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Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration BMJ 1994 308 81 106 2539220 8298418
... We requested data between each participant's randomisation date and November 30, 2018. We mapped recurrent ICH and components of the composite outcome of all MACE (defined by the Antithrombotic Trialists' Collaboration) to ICD-10 codes (Table 1), with reference to the CALIBER chronological map of human health [24], the Antithrombotic Triallists [25] and 2002 meta-analyses [25,26], UK Biobank definitions of stroke and myocardial infarction [27,28], and record linkage studies of ICH [29,30]. We searched for these pre-specified codes in fields for the disease or condition leading directly to death or the first/main diagnostic code for each hospital admission. ...
... We requested data between each participant's randomisation date and November 30, 2018. We mapped recurrent ICH and components of the composite outcome of all MACE (defined by the Antithrombotic Trialists' Collaboration) to ICD-10 codes (Table 1), with reference to the CALIBER chronological map of human health [24], the Antithrombotic Triallists [25] and 2002 meta-analyses [25,26], UK Biobank definitions of stroke and myocardial infarction [27,28], and record linkage studies of ICH [29,30]. We searched for these pre-specified codes in fields for the disease or condition leading directly to death or the first/main diagnostic code for each hospital admission. ...
Background
Healthcare systems data (HCSD) could improve the efficiency of clinical trials, but their accuracy and validity are uncertain. Our objective was to assess the accuracy of HCSD as the sole method of outcome detection in the REstart or STop Antithrombotics Randomised Trial (RESTART; ISRCTN71907627) compared with adjudicated questionnaire follow-up and compare estimates of treatment effect.
Methods
RESTART was a prospective, open, assessor-blind, parallel-group randomised controlled trial (RCT) of antiplatelet therapy after intracerebral haemorrhage (ICH) in the UK.
We included 496 (92%) of 537 RESTART participants, who were resident in England or Scotland at randomisation. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy.
RESTART used annual questionnaires to detect its primary outcome (recurrent ICH) and secondary outcome (a composite of haemorrhagic or ischemic major adverse cardiovascular events [MACE]) over a median of 2.0 years; an independent adjudication committee verified outcomes using medical records and brain imaging. We obtained ICD10-coded HCSD on hospital admissions and deaths in England and Scotland to identify primary and secondary outcomes. We compared HCSD with a reference standard of adjudicated outcomes. We estimated the effects of antiplatelet therapy using HCSD alone in a Cox proportional hazards model adjusted for minimisation variables.
Results
In the original RESTART trial, 31 people experienced a primary outcome event. HCSD had sensitivity of 84% (95% CI 66 to 95%) and positive predictive value of 68% (51 to 82%) for recurrent ICH. HCSD estimated an effect of antiplatelet therapy (adjusted hazard ratio [aHR] 0.51, 95% CI 0.27 to 0.98; p = 0.044) that was almost identical to adjudicated outcomes (aHR 0.51, 95% CI 0.25 to 1.03; p = 0.060). HCSD had sensitivity of 84% (76 to 91%) and positive predictive value of 78% (69 to 85%) for MACE, on which HCSD estimated an effect of antiplatelet therapy (aHR 0.81, 95% CI 0.56 to 1.16; p = 0.247) that was similar to adjudicated outcomes (aHR 0.65, 95% CI 0.44 to 0.95; p = 0.025).
Conclusions
In a RCT of antiplatelet therapy for people with ICH, HCSD was reasonably accurate and provided similar estimates of treatment effect compared with adjudicated outcomes.
Trial registration
ISRCTN71907627. Registered on 25 April 2013.
... The most common indication for aspirin is secondary prevention of cardiovascular events. 4 Platelets are principally involved in primary hemostasis, and naturally, we must consider how aspirin interferes with this process and augments the risk of bleeding. 5 The "washout period" of aspirin is a product of its half-life (15-20 min) and the time it takes to replace the circulating platelet pool (approximately 7-10 d). ...
... Preventive and therapeutic measures have improved the prognosis of patients with CAD or other cardiovascular diseases in the past few decades [4,5]. However, there is still a high risk and a need for methods of prevention and treatment. ...
Purpose
This study aimed to evaluate the acute effects of beetroot extract and resveratrol supplementation (isolated and combined) on cardiac autonomic modulation and cardiovascular parameters recovery after exercise in individuals with coronary artery disease (CAD).
Methods
14 males with CAD were submitted to 4 protocols consisting of 30 min (min) of rest, 30 min of aerobic exercise on a treadmill (60% of the heart rate reserve HRR), followed by 30 min of recovery. Before each protocol, the subjects consumed 500 mg of starch (placebo protocol), 500 mg of beetroot (beetroot protocol), or 500 mg of resveratrol (resveratrol protocol), or 500 mg of beetroot and 500 mg of resveratrol (combined protocol). Heart rate variability (HRV) indices and cardiorespiratory parameters were determined at different times during the protocols.
Results
Regarding HR, significantly higher values about rest in the placebo protocol at all recovery moments (1st to 30th min) were observed. Significant differences were observed in the other protocols (beetroot, resveratrol and combined) from the first to the 20th min recovery. For SBP, significantly higher values concerning rest were observed at the first minute of recovery for all protocols. No differences were found for the HRV index between time and protocols.
Conclusions
The single supplementation of beetroot and resveratrol (isolated and combined) did not alter HRV and cardiovascular parameter responses between protocols. The consumption of beetroot extract and resveratrol enhanced vagal modulation and heart rate recovery compared to rest.
... Through the formation of aggregates involving endothelial cells or leukocytes, or directly through cross-reactive antibodies, substantial damage to platelets can take place. The primary cause of this damage is thought to be the molecular resemblance that exists between host blood clotting components, endothelial cells, platelets, and virus proteins such as E, NS1, and prM [32,33]. Coagulation deficits, macrophage activation, platelet dysfunction, and endothelial cell death can be triggered by antibodies generated against these virus proteins that are cross-reactive [34]. ...
Dengue fever is currently a major global issue, especially in tropical and subtropical countries. The absence of specific antiviral medications supports alternative dengue treatment strategies. South Asian countries have been using Carica papaya leaves as a traditional remedy for dengue for many years. Carica papaya possesses several biological features, including anti-inflammatory, antiviral, cancer-fighting, anti-diabetic, and antioxidant qualities. Additionally, numerous studies have demonstrated that bioactive compounds found in papaya leaf extracts, including carpaine, dehydrocarpaine I and II, chymopapain, and papain, significantly influence platelet counts, while phenolic compounds, such as chlorogenic acid, kaemferol, protocatechuic acid, quercetin, and 5,7-dimethoxycoumarin significantly inhibit viral replication in dengue patients, with negligible side effects. Carica papaya may be considered a viable pharmacological candidate with several targets for treating dengue. It has been shown to prevent infections, reduce oxidative stress, control cytokine storms and the immune system, lessen thrombocytopenia, and increase the body’s protein and hemoglobin levels. This literature review highlights the pathophysiological mechanism of dengue, as well as the pharmacological action of Carica papaya, both of which combat this debilitating disease. Despite these findings, additional investigation, including clinical studies, is necessary to confirm the effectiveness and safety of papaya-based treatments. It is necessary to address issues like standardizing papaya extracts, figuring out the best dosages, and assessing any drug interactions.
... We calculated a weighted estimate of the odds for each outcome event across studies using the Peto odds ratio method. We calculated ORs with 95% CIs using the Peto fixed-effect method 29 as done in the prior versions of this review. 20,22 We assessed the heterogeneity between trial results using the I2 statistic. ...
Introduction
Extracranial internal carotid artery dissection (eICAD) is a leading cause of stroke in younger patients. In this Cochrane Review update we compared benefits and harms of eICAD-patients treated with either antiplatelets or anticoagulants.
Patients and methods
Eligible studies were identified through Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, and EMBASE and personal search until December 2023. We included randomized-controlled trials (RCTs) and non-randomized studies comparing anticoagulants with antiplatelets in eICAD-patients. Co-primary outcomes were (i) death (all causes) and (ii) death or disability. Secondary outcomes were ischemic stroke, symptomatic intracranial hemorrhage, and major extracranial hemorrhage. Odds ratios (OR) with 95% CIs were calculated for (i) all studies and (ii) separately for RCTs and non-randomized studies.
Results
We meta-analyzed a total of 42 studies (2624 patients) including 2 RCTs (213 patients) for the primary outcome of death and 31 studies (1953 patients) including 1 RCT (115 patients) for the primary outcome of death or disability. Antiplatelet-treated patients had higher odds for death (OR all-studies 2.70, 95% CI 1.27–5.72; OR RTCs 6.80, 95% CI 0.14–345; OR non-randomized studies 2.60, 95% CI 1.20–5.60) and death or disability (OR all-studies 2.1, 95% CI 1.58–2.66; OR RTCs 2.2, 95% CI 0.29–16.05; OR non-randomized studies 2.1, 95% CI 1.58–2.66) than anticoagulated patients. Antiplatelet-treated patients had also higher odds for ischemic stroke, though this reached statistical significance only in the subgroup of RCTs (OR RTC 4.60, 95% CI 1.36–15.51). In turn, antiplatelet-treated patients had less symptomatic intracranial hemorrhage (OR all-studies 0.25, 95% CI 0.07–0.86) and a tendency toward less major extracranial hemorrhage (OR all-studies 0.17, 95% CI 0.03–1.03).
Discussion and conclusion
The evidence considering antiplatelets as standard of care in eICAD is weak. Individualized treatment decisions balancing risks versus harms seem recommendable.
Aim
The “2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes” incorporates new evidence since the “2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction” and the corresponding “2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes” and the “2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction.” The “2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes” and the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization” retire and replace, respectively, the “2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease.”
Methods
A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.
Structure
Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.
Background
Up to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia and impaired cognitive function, termed post-COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice.
Objective
To create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID.
Methods
Eligible trials will randomise adults with long COVID to pharmacologic or non-pharmacologic interventions, placebo, sham or usual care. We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, PsycINFO, AMED and CENTRAL from inception, without language restrictions.
Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest and assess risk of bias. Our outcomes of interest will include patient-reported fatigue, pain, postexertional malaise, changes in education or employment status, cognitive function, mental health, dyspnoea, quality of life, physical function, recovery and serious adverse events.
For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach will guide our assessment of the certainty of evidence.
We will update our living review biannually, on the publication of a seminal trial, or when new evidence emerges that may change clinical practice.
Conclusion
This living systematic review and network meta-analysis will provide comprehensive, trustworthy and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline-producing organisations to inform their recommendations.
Ethics and dissemination
The study describes the protocol for a systematic review that uses data from published trial reports. Therefore, the study is exempt from ethics review. We intend to deposit all data in a public repository and publish each iteration of the living review online.
Peripheral arterial disease (PAD) is defined as atherosclerotic disease of the aorta and arteries of the lower extremities. The most frequent manifestations of ischemia occur in the lower extremity arteries, with intermittent claudication as the most common symptom. Intermittent claudication, which is characterized by temporary pain brought on by muscle exertion, is usually experienced in the calf muscles and typically subsides with rest. The atherosclerotic nature of PAD/intermittent claudication makes it an important predictor of risk for cardio- and cerebrovascular disease, as well as limb loss. Thus, active screening and early diagnosis of PAD/intermittent claudication, in addition to aggressive management that incorporates risk factor modification, exercise therapy, platelet inhibition and other appropriate pharmacotherapy, and potential lifestyle changes, play important roles in overall patient management. Pharmacotherapy with cilostazol has been shown to improve maximal and pain-free walking distances. Uncontrolled and severely debilitating intermittent claudication may require revascularization.
Background
Heart failure with reduced ejection fraction (HFrEF) is a growing health concern, with an increased risk of thromboembolic events. Oral anticoagulants (OACs) are commonly used in HFrEF patients with atrial fibrillation, but their role in patients with sinus rhythm is unclear.
Objective
To assess the safety and efficacy of OACs in HFrEF patients with sinus rhythm.
Methods
A systematic review of seven studies involving 17 051 patients was conducted. Outcomes included mortality, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalization rates.
Results
OACs significantly reduced non-fatal strokes compared to antiplatelets and placebo. A measurable reduction in nonfatal MIs was observed in most studies. However, no conclusive benefit was found regarding all-cause fatality and rehospitalization rates. The benefit of OACs in stroke prevention was counterbalanced by an increased risk of major bleeding episodes.
Conclusion
OACs may have a role in reducing nonfatal cardiovascular events in HFrEF patients with sinus rhythm, particularly those with ischemic etiologies or underlying thrombotic states. However, further research is needed to establish their efficacy and safety in this population.
Carotid artery stenosis is a common and potentially treatable cause of stroke. Stroke risk is increased as the degree of carotid stenosis increases, as well as in patients with neurological symptoms referable to the stenosed carotid artery. Carotid stenosis can be quantified by ultrasound imaging, magnetic resonance angiography, or conventional angiography. Medical treatment with platelet antiaggregants reduces stroke risk in some patients; other patients are best treated with carotid endarterectomy. Experimental treatments for carotid stenosis, including carotid angioplasty with or without stenting, are under investigation. We summarize the current literature and provide treatment recommendations for patients with atherosclerotic carotid artery disease.
Background
Myocardial infarction (MI) remains a leading cause of mortality globally, often resulting in irreversible damage to cardiomyocytes. Ferroptosis, a recently identified form of regulated cell death driven by iron-dependent lipid peroxidation, has emerged as a significant contributor to post-MI cardiac injury. The endoplasmic reticulum (ER) stress response has been implicated in exacerbating ferroptosis.
Methods
Here, we investigated the potential of Dioscin, a natural compound known for its diverse pharmacological properties, in mitigating ferroptosis in cardiomyocytes following MI by targeting ER stress.
Results
In animal models subjected to MI, administration of Dioscin notably improved cardiac function, reduced infarct size by approximately 24%, and prevented adverse remodeling, highlighting its therapeutic potential. Through in vitro and in vivo models of MI, we demonstrated that Dioscin treatment significantly attenuates ferroptosis in cardiomyocytes, as evidenced by a decrease in lipid peroxidation by about 19% and preserved mitochondrial integrity. Moreover, Dioscin exerted its protective effects by inhibiting ER stress markers, such as the phosphorylation levels of PERK and eIF2α proteins, and the expression levels of BIP and ATF4 proteins, thus disrupting the ER stress-mediated signaling cascade associated with ferroptosis.
Conclusion
Overall, our findings suggested that Dioscin holds promise as a therapeutic agent against post-MI cardiac injury by mitigating ferroptosis via the suppression of ER stress. Further investigations into the precise molecular mechanisms and clinical translation of Dioscin’s cardioprotective effects are warranted, offering a potential avenue for novel therapeutic interventions in MI-related cardiac complications.
Graphical Abstract
Of all of the known risk factors for coronary artery disease, age remains the most potent. Yet, the specific processes that accompany increasing age and that render it such an important risk factor for cardiovascular disease are not clearly elucidated. Age-associated changes in cardiovascular structure and physiologic function alter the substrate on which disease is superimposed. (See Chapter 9 for a discussion on age-related cardiovascular changes) These alterations include increased central arterial stiffness, decreased responsiveness to β-adrenergic stimulation, delayed early left-ventricular diastolic filling, and endothelial dysfunction (1–3). Such changes impact the presentation, diagnosis, clinical manifestations, therapeutic management, and prognosis of cardiovascular disease. Although it is thought that these changes occur universally, the rate at which they change is highly variable. The resultant heterogeneity of the aging process adds further challenge to the clinical care of older patients because no clear markers exist to discern biologic from chronologic age.
The human brain changes as it ages, and the elderly are increasingly susceptible to many neurological diseases and symptoms. Neurological disorders are the leading source of serious disability among the elderly and one of the major reasons for institutionalization of elderly individuals. As many as 90% of institutionalized elderly persons have disabilities caused by neurological disease, and as many as 50% of the elderly living in the community have neurological problems. This burden of age-related neurological disease in the population is only expected to increase as the population ages.
Cardiovascular disease is the leading cause of death in the United States as well as other developed societies. It has been the leading cause of mortality in men and in women since 1900. According to the 1999 Heart and Stroke Statistical Update, cardiovascular-related deaths in women accounted for more than the next 16 leading causes of death combined (1). Efforts to reduce cardiovascular disease risk remains one of the most important challenges in medicine. Guidance is provided by literature evaluating use of medications for reduction of both primary and secondary cardiovascular events.
According to data from the prethrombolytic era, a patient who survives a first myocardial infarction (MI) faces nearly an 80% chance of another cardiovascular disease (CVD) event within the next 5 yr (1). More contemporary data indicate that within 6 yr of an MI, approx 20% of men and 35% of women will sustain another heart attack with similar percentages developing congestive heart failure (CHF) (2). Thus, the diagnosis of an MI brings with it the high likelihood of recurrent cardiovascular events, compounding morbidity, and probable ultimate fatality. Viewed in this way, CVD is, in fact, much like many forms of cancer, although the reaction of many patients to those two diagnoses can be quite different. Perhaps this is related to antiquated notions, propagated at times by physicians, that mechanical cardiovascular therapies, such as bypass surgery and angioplasty, can “fix” the cardiovascular problem. The myriad of therapeutic options available to the cardiologist and their patients might further fuel such concepts. In reality, modern medicine might be better at “curing” some types of cancer than reversing advanced atherosclerosis. CVD patients suffer a chronic insidious disease that requires aggressive interventions to alter the complex process that led to its generation, propagation, and recurrence; steps untouched by acute mechanical treatments restoring patency or providing alternate paths of blood flow. Fortunately, the number of interventions, both medical and lifestyle, for so-called secondary prevention also continues to grow. Similarly, our understanding of atherogenesis and the development of acute coronary syndromes is also progressing, creating hope for the development of new, and perhaps more effective, therapeutic approaches. We are also left with the considerable challenge of applying those interventions known to reduce cardiovascular risk.
Both insulin-dependent (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) are powerful and independent risk factors for coronary artery disease (CAD), stroke, and peripheral arterial disease (1–3). Furthermore, when patients with diabetes develop clinical events, they sustain a worse prognosis compared with nondiabetics (4). Ultimately, atherosclerosis accounts for 65–80% of all deaths among North American diabetic patients, compared with one-third of all deaths in the general North American population (3, 5, 6). A two- to fourfold excess in CAD mortality among diabetic individuals has been noted in a number of prospective studies encompassing a variety of ethnic and racial groups (7). Diabetes also increases the likelihood of severe carotid atherosclerosis (8,9) and mortality from stroke is increased almost threefold in diabetic patients (1).
Type 2 diabetes mellitus is increasing significantly in westernized, industrialized societies as the populations become more obese, sedentary, and older (1–5). Four of five persons with type 2 diabetes will die of cardiovascular diseases (CVDs) (1, 2, 5–7). Many factors contribute to increased CVD in persons with diabetes. These include hypertension, dyslipidemia, platelet hyperactivity, endothelial abnormalities, and hypercoagulability, as well as hyperglycemia, microalbuminuria, and hyperinsulinemia (1–9). The Multiple Risk Factor Intervention Trial (4) (MRFIT) followed over 5000 diabetic persons were followed for 12 year and compared them with over 350,000 persons without diabetes. The risk of cardiovascular death at the 12-year follow-up was approximately three times higher in diabetic men as compared with their nondiabetic controls, regardless of age, ethnic group, cholesterol level, systolic blood pressure, or tobacco use. When patients had optimal control of systolic blood pressure and were nonsmokers, the relative risk of CVD was still 2.5 times higher in the diabetic men. The MRFIT study confirmed that diabetes is a strong independent risk factor for CVD mortality above the risk incurred from hypercholesterolemia, systolic hypertension, and cigarette use. In addition, it confirmed that hypercholesterolemia, systolic hypertension, and cigarette smoking are also important independent predictors of mortality in men with and without diabetes. The presence of one or more of these risk factors had a greater impact on increasing CVD risk in diabetics than in nondiabetics.
Traditionally, ischemic heart disease has been divided into several separate syndromes: stable coronary artery disease, unstable angina (UA)(1,2), non-Q wave myocardial infarction (MI), and Q wave MI. However, the understanding of the conversion of a stable atherosclerotic lesion to a ruptured plaque with thrombosis has provided a unifying hypothesis for the etiology of acute coronary syndromes (ACS)(3–7). The concept of myocardial ischemia as a spectrum provides a framework for understanding the pathogenesis, clinical features, treatment and outcome of patients across the nexus of myocardial ischemia (Fig. 1).
Acute coronary syndromes, including acute myocardial infarction (AMI), have a common underlying pathophysiologic mechanism initiated by atherosclerotic plaque disruption and followed by platelet aggregation and thrombus formation. Exposure of thrombogenic plaque components, including collagen, fibronectin, and von Willebrand factor, to circulating platelets, together with local high shear stress, lead to platelet adhesion, activation, and aggregation. In turn, platelet aggregation facilitates thrombin generation and conversion of fibrinogen to fibrin. Thrombin further stimulates platelet activation and aggregation, leading to a vicious cycle. Ultimately, a thrombus composed of platelets and fibrin causes complete occlusion of the coronary artery and results in AMI (1).
The factors that predispose to atherosclerotic disease of the lower extremity arteries have been evaluated in numerous case-control and prospective studies. Data continue to accumulate that modification of these risk factors is essential to prevent progression of disease, not only in the lower extremities, but also in the coronary and cerebrovascular systems. The following sections detail these risk factors and medical strategies for modification of atherosclerotic disease risk.
Fifteen years ago the Gruppo Italialono per lo Studio della Streptochianasi nell’Infarto Miocardico (GISSI) trial firmly established the benefit of fibrinolytic therapy in acute myocardial infarction (1). Several years later, the importance of adjunctive antiplatelet therapy with aspirin was demonstrated in the Second International Study of Infarct Survival (ISIS-2) (2). The need for concomitant anticoagulant therapy with heparin remains less clear, but indirect evidence in the setting of fibrin-specific lytics has led to widespread adoption (3,4).
BACKGROUND
Preinjury antithrombotic (AT) use is associated with worse outcomes for geriatric (65 years or older) patients with traumatic brain injury (TBI). Previous studies have found that use of AT outside established guidelines is widespread in TBI patients.
METHODS
In this single-center retrospective cross-sectional study, we examined inappropriate AT use among geriatric patients presenting with traumatic intracranial hemorrhage. We reviewed records of patients 65 years or older with preinjury AT use who presented to a Level 1 trauma center with traumatic intracranial hemorrhage between 2016 and 2023. Patient demographics and AT indications/types were extracted. Appropriateness of AT use was determined using established guidelines.
RESULTS
The cohort comprised 207 patients (56.5% male; median age, 77 years). Fall was the most common mechanism of injury (87.9%). At initial presentation, 87.0% of patients had mild TBI (Glasgow Coma Scale scores 13–15). The two most common indications for AT use were atrial fibrillation (41.5%) and venous thromboembolism (14.5%). Anticoagulation therapy was used by 51.7% of patients, antiplatelet therapy by 40.1%, and both by 8.2%. Prescribed AT agents included warfarin (23.2%), direct oral anticoagulants (36.2%), aspirin (32.4%), and clopidogrel (15.0%). Per clinical guidelines, 31 patients (15.0%) were determined to be inappropriately on AT therapy. On multivariable analysis, venous thromboembolism (odds ratio [OR], 5.32; 95% confidence interval [CI], 1.80–15.71; p = 0.002) and arterial stent (OR, 4.69; 95% CI, 1.53–14.37; p = 0.007) were associated with inappropriate AT use; aspirin was the most common inappropriately prescribed AT (OR, 3.59; 95% CI, 1.45–8.91; p = 0.006).
CONCLUSION
Overall, 15% of geriatric TBI patients with preinjury AT use were prescribed this therapy outside of current guidelines. Trauma providers should remain vigilant in identifying such patients and collaborate across multidisciplinary teams to implement interventions that minimize inappropriate AT use.
LEVEL OF EVIDENCE
Prognostic and Epidemiological Study; Level IV.
Aim
Potassium 2‐(1‐hydroxypentyl)‐benzoate (dl‐PHPB), puerarin and salvianolic acid B are three natural products or derivatives that can inhibit platelet aggregation. However, the mechanisms of dl‐PHPB, puerarin and salvianolic acid B to inhibit platelet aggregation are still not clear.
Method
Here, 2‐methylthioadenosine diphosphate (2‐MeSADP) was used as an inducer to confirm the effects of three drugs on platelet aggregation and illustrate the corresponding mechanisms.
Result
The results indicated that dl‐PHPB, puerarin and salvianolic acid B significantly inhibited platelet aggregation both in vivo and in vitro. In addition, the content of IP3, cAMP and intracellular [Ca²⁺]i were measured in HEK293 cell lines overexpressing P2Y1 and P2Y12. Dl‐PHPB and puerarin could obviously reduce 2‐MeSADP‐induced IP3 increase, but salvianolic acid B showed no effects. Unlike dl‐PHPB and puerarin, which had no effects on 2‐MeSADP‐induced cAMP decrease, salvianolic acid B significantly reversed the reduction of cAMP. Both dl‐PHPB and puerarin could decrease the enhanced intracellular [Ca²⁺]i induced by 2‐MeSADP; however, salvianolic acid B showed no effect on intracellular [Ca²⁺]i elevation.
Conclusion
These results suggested that dl‐PHPB and puerarin inhibited platelet aggregation via targeting at P2Y1 receptor and P2Y1‐Gq‐IP3‐Ca²⁺ signal pathway. Differently, salvianolic acid B inhibited platelet aggregation via targeting at P2Y12 receptor and via Gi‐AC‐cAMP signal pathway.
Objective
To investigate the most common causes of death and trends in cause-specific long-term mortality in patients hospitalized for acute myocardial infarction (AMI).
Methods
This analysis was based on 10,718 patients, aged 25–74 years, recorded by the population-based Myocardial Infarction Registry Augsburg between 2000 and 2017. All hospitalized cases of AMI occurring in the study region during this period were included. If a patient died during follow-up (median: 6.6 years, IQR: 2.8–11.2) the death certificate was obtained and coded using the ICD-10 to determine the main cause of death. Cause-specific mortality was calculated for three 6-year periods. Multivariable adjusted Cox regression models stratified by time interval were calculated.
Results
The most common cause of death was cardiovascular disease (CVD), more precisely ischemic-heart disease (IHD), followed by cancer. The proportions of CVD deaths and IHD deaths were stable over time. An increasing trend was observed in cancer mortality in post-AMI patients. In male patients, the hazard ratio for cancer mortality was 44.4% higher in 2012–2017 compared to 2000–2005, in female patients, it was more than twice as high in 2006–2012 compared to 2000–2005.
Conclusion
This study revealed consistent CVD and IHD long-term mortality and increasing trends in long-term cancer mortality in patients post-AMI. Thus, post-AMI patients should emphasize tertiary prevention of CVD by minimizing risk factors. Furthermore, patients should regularly undergo cancer screening programs. The reasons for the unfavorable development in terms of increasing cancer mortality should be investigated in further studies.
Carotid artery stenosis causes approximately 10% of all strokes. Knowing how to best reduce this risk is important for public health and health economy. The objective here was to capture fundamental elements in how to best manage carotid artery stenosis (narrowing due to atherosclerosis). This concise review draws upon multinational, multispecialty reviews and key original research. Given the lack of current evidence for procedural benefits with respect to stroke risk reduction associated with carotid stenosis, this document focuses on the effectiveness and nature of current best practice noninvasive arterial care.
Bevezetés: A lipidcsökkentés – a mögötte felhalmozódott klinikai vizsgálati bizonyítékok és az irányelvekben tükröződő jelentős prevenciós szerepe ellenére – sem a betegek, sem az orvosok értékrendjében nem áll az őt megillető helyen, nagy távolság van a gyakorlat és az elvek között. Célkitűzés: A lipidcsökkentő kezelés presztízsének emelése érdekében az LDL-koleszterin csökkentésének potenciális nyereségét összehasonlítottuk az általánosan jobban elfogadott thrombocytaaggregáció-gátló kezelésével. Módszer: A gyulai Békés Megyei Központi Kórház Pándy Kálmán Tagkórházában 2020. április 1-jétől kezdődően egy éven át akut coronaria szindróma miatt percutan coronariaintervención átesett 531 beteg adatait dolgoztuk fel. Szimulációs vizsgálatot végeztünk, melynek során a nagy klinikai vizsgálatok alapján megbecsültük az optimális lipidcsökkentés és thrombocytaaggregáció-gátlás egy évre vonatkozó cardiovascularis prevenciós hatását. Eredmények: Az akut coronaria szindróma miatt kezelt 531 összes beteg esetében, ha az LDL-koleszterin a felvételkor talált 3,37 mmol/l átlagos szinten maradt volna, az indexesemény után egy év alatt 59 nagy cardiovascularis esemény bekövetkeztével lehetett volna számolni. Ha az LDL-koleszterint az Európai Kardiológusok Társaságának lipidajánlásában igen nagy kockázatú célértéknek megadott 1,4 mmol/l-re csökkentenénk le, akkor az események száma 13-mal, a teoretikus, igen alacsonynak minősíthető, nem célérték 0,5 mmol/l elérésekor pedig 16-tal kevesebb lenne. Az LDL-koleszterin-szint csökkentésével tehát várhatóan elkerülhető lenne 13, illetve 16 nagy cardiovascularis esemény. Ha thrombocytaaggregáció-gátlásra csak aszpirint kapnának a betegek, egy év alatt 14, aszpirin és klopidogrél kombinációval 17, aszpirint és praszugrélt vagy tikagrelort együtt adva 20-20 esemény lenne megelőzhető. Megbeszélés: Az LDL-koleszterin-célértékek elérésének alacsony arányai alapján a lipidcsökkentő kezelés optimalizálásában világszerte jelentős tartalékok vannak. A kardiológiai gyakorlat egyik legsérülékenyebb betegcsoportjában, az akut coronaria szindrómán átesett betegekben a vizsgálat eredményei szerint a lipidcsökkentéssel és a thrombocytaaggregáció-gátlással hasonló mértékű csökkenést lehetne elérni a nagy cardiovascularis események számában. Következtetés: A szimulációs vizsgálat a kétféle beavatkozás összemérhető cardiovascularis hasznát igazolja. Mivel az irányelvekben előírt LDL-koleszterin-célértékek elérési aránya nem megfelelő – amiben az orvosok terápiás tehetetlensége nagy szerepet játszik –, reményeink szerint eredményeink meggyőzik a kollégákat arról, hogy nagyobb figyelmet kell fordítani az optimálisabb lipidcsökkentésre. Orv Hetil. 2024; 165(44): 1746–1752.
The integration of nanoparticles with classical drugs to create biocompatible delivery platforms for the treatment of cardiovascular diseases can make a major impact on patient welfare.
Traditional drug delivery systems are not selective and induce severe collateral damage to surrounding non-diseased cells and tissues. Nanoparticles, however, can be bio-conjugated with antibodies to encapsulate cardiovascular drugs, gaseous molecules and biomolecules to selectively deliver them in a safe, targeted and cost-effective manner.
This book provides in-depth and insightful discussion on the mechanistic, pre-clinical and clinical applications of nanomedicine in cardiovascular disease. It not only discusses core chemical concepts via the synthesis of novel nanotechnology-based drug formulations, but also covers the latest drug delivery advances including innovative therapeutic targets in cardiovascular lesions at an early, curable and reversible stage.
Written by experts in the field, students and researchers will find this book equally useful for understanding the trends and challenges of the clinical translation of cardiovascular nanomedicine.
Background Healthcare systems data (HCSD) could improve the efficiency of clinical trials, but their accuracy and validity are uncertain. Our objective was to assess the accuracy of HCSD as the sole method of outcome detection in the REstart or STop Antithrombotics Randomised Trial (RESTART; ISRCTN71907627) compared with adjudicated questionnaire follow-up; and compare estimates of treatment effect. Methods RESTART was a prospective, open, assessor-blind, parallel-group randomized controlled trial (RCT) of antiplatelet therapy after intracerebral haemorrhage (ICH) in the UK. We included 496 (92%) of 537 RESTART participants, who were resident in England or Scotland at randomization. Computerized randomization incorporating minimization allocated participants (1:1) to start or avoid antiplatelet therapy. RESTART used annual questionnaires to detect its primary outcome (recurrent ICH) and secondary outcome (a composite of haemorrhagic or ischemic major adverse cardiovascular events [MACE]) over a median of 2.0 years; an independent adjudication committee verified outcomes using medical records and brain imaging. We obtained ICD10-coded HCSD on hospital admissions and deaths in England and Scotland to identify primary and secondary outcomes. We compared HCSD with a reference standard of adjudicated outcomes. We estimated the effects of antiplatelet therapy using HCSD alone in a Cox proportional hazards model adjusted for minimization variables. Results In the original RESTART trial, 31 people experienced a primary outcome event. HCSD had sensitivity of 84% (95% CI 66% to 95%) and positive predictive value of 68% (51% to 82%) for recurrent ICH. HCSD estimated an effect of antiplatelet therapy (adjusted hazard ratio [aHR] 0.51, 95% CI 0.27 to 0.98; p=0.044) that was almost identical to adjudicated outcomes (aHR 0.51, 95% CI 0.25 to 1.03; p=0.060). HCSD had sensitivity of 84% (76% to 91%) and positive predictive value of 78% (69% to 85%) for MACE, on which HCSD estimated an effect of antiplatelet therapy (aHR 0.81, 95% CI 0.56 to 1.16; p=0.247) that was similar to adjudicated outcomes (aHR 0.65, 95% CI 0.44 to 0.95; p=0.025). Conclusions In a RCT of antiplatelet therapy for people with ICH, HCSD was reasonably accurate and provided similar estimates of treatment effect compared with adjudicated outcomes. Trial registration: RESTART; ISRCTN71907627
A randomized controlled trial is reported in which a single dose of aspirin (300 mg) was given to patients with myocardial infarction on first contact with a general practitioner. A total of 1,705 patients with confirmed infarction were studied, and survival ascertained. There was no evidence of benefit from the aspirin.
Background. Patients with peripheral vascular disease (PVD) undergo a clinical course that can be
complicated by cardiovascular events occurring in several areas of the circulation. Methods and Results. In the present study we investigated the ability of picotamide, a substance that inhibits platelet thromboxane A2 (TxA2) synthase and antagonizes TxA2 receptors, to reduce cardiovascular complications in PVD patients. The study was double blind and placebo controlled. After a 1-month run-in period, 2,304 patients were randomly allocated to either placebo or picotamide (300 mg t.i.d.) and followed for 18 months. Major and minor events were analyzed. Results of an "intention-to-treat analysis" were that patients on picotamide suffered 45 major events (3.9%) and 77 minor events (6.7%), whereas those taking placebo suffered 52 major (4.5%) and 99 minor events (8.6%). There was borderline statistical difference between the two groups with respect to the sum of the major and minor events (risk reduction, 18.9o; p=0.056, log-rank test). Results of an "on-treatment" analysis were that patients on picotamide suffered 40 major (3.8%) and 66 minor events (6.3%), whereas those taking placebo suffered 45 major (4.2%) and 95 minor events (8.9%o). The sum of both major and minor events was 106 (10.1%) in the picotamide group and 140 (13.1%) in the placebo group. This difference was significant (risk reduction, 23%; p=0.029, log-rank test). Conclusions. The results of this study indicate that picotamide reduces cardiovascular complications in PVD patients. The apparently low effect of this drug in reducing major events suggests that further studies be made with picotamide in PVD patients who are at high risk of cardiovascular complications so as to further assess its clinical efficacy.
Within 3 weeks of the event, 505 patients with cerebral infarction, minor or major stroke, were randomly assigned to treatment with acetylsalicylic acid (ASA) 1.5 g/day or placebo in a double-blind clinical trial with a follow-up of 2 years in all patients. Primary events were considered to be recurrent stroke or death; secondary events, myocardial infarction and transient ischemic attack. There was no difference in stroke recurrence rate in the ASA and placebo groups (12 and 13%, respectively), nor was there any significant difference in the rate of recurrent stroke or death, first event counted (23% in the ASA and 22% in the placebo group). The risk of transient ischemic attack and myocardial infarction was not reduced in the ASA group. In the present study there was no prophylactic effect of high-dose ASA after cerebral infarction. A compilation of the major trials of ASA after transient ischemic attack and cerebral infarction is presented.
The EPPAC (Etude de la permeabilite des pontages aorto-coronaires) is a randomised prospective (18 centres) double blind trial designed to compare the patency of coronary bypass grafts in two groups of coronary patients after surgery : one group treated with oral vitamin-K antagonists and placebo (n = 196, age 57 ± 5 years, 2.09 grafts/patient) and the other group with vitamin-K antagonists and dipyridamole (n = 182, age 56 ± 6 years, 1.99 grafts/patient), the principal criterion of evaluation being the patency of the grafts at coronary angiography performed 6 months after surgery, interpreted by two independent observers. Of the 469 patients included (average ejection fraction 59.5 ± 2.2%), 378 underwent the control coronary angiography at the 6th month and 773 saphenous vein grafts were evaluated. At the end of the study, there were 12 deaths, 10 due to perioperative myocardial infarction, and 24 nonlethal myocardial infarctions. The frequency of occlusion of at least one graft per patient was 18.2%, the patency of the graft at the distal anastomosis was 89.9%. The following factors played a major role: the cardiological center : the occlusion rate per patient ranged from 7.1 to 57.1% and per anastomosis from 2.8 to 28.6%; the internal diameter of the artery grafted : when 2 mm or more, the occlusion rate was 17.6% compared with 42.3% (p < 0.001); the technique used for distal anastomosis : 9.2% of grafts with single outflow sites occluded, compared with 4.3% of grafts with multiple outflow sites. Early occlusion of saphenous vein aorto-coronary grafts is the main problem of this form of therapy and the addition of dipyridamole to oral anticoagulants does not seem to reinforce the anti-thrombotic effect at 6 months after surgery.
The distribution volume and the total clearance of inulin and [51Cr]EDTA (etylene-diamine-tetraacetic-acid labelled with 51Cr) was compared using a single injection technique without urine sampling in 22 measurements in patients. The distribution volume of [51Cr]EDTA exceeded the distribution volume of inulin by 75 per cent, while the total clearances were not significantly different. In five nephrectomized dogs the [51Cr]EDTA distribution volume was 90 per cent higher than inulin distribution volume, while the extrarenal clearance was not significantly different. © 1972 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
Cardiopulmonary bypass induces platelet activation and dysfunction, which result in platelet deposition and depletion. Reduced platelet numbers and abnormal platelet function may contribute to postoperative bleeding. A membrane oxygenator may preserve platelets and reduce bleeding more than a bubble oxygenator, and the antiplatelet agent dipyridamole may protect platelets intraoperatively and reduce bleeding postoperatively. A prospective randomized trial was performed in 44 patients undergoing elective coronary artery bypass grafting to assess the effects of the membrane oxygenator and dipyridamole on platelet counts, platelet activation products, and postoperative bleeding. Patients who were randomized to receive a bubble oxygenator and no dipyridamole had the lowest postoperative platelet counts, the greatest blood loss, and the most blood products transfused. Platelet counts were highest and blood loss was least in patients randomized to receive a membrane oxygenator and dipyridamole (p < .05). A bubble oxygenator with dipyridamole and a membrane oxygenator without dipyridamole resulted in intermediate postoperative platelet counts and blood loss. Arterial thromboxane B2 and platelet factor 4 concentrations were elevated on cardiopulmonary bypass in all groups. Both the membrane oxygenator and dipyridamole were independently effective (by multivariate analysis) in preserving platelets. Optimal blood conservation was achieved with a membrane oxygenator and dipyridamole.
Clinical test of the acetylsalicylic acid preparation micristin concerning effect and side-effect on the postoperative rate of thromboembolism in general surgery and traumatology. Prospective, randomized, checked double-blind study in 802 operated patients: 401 patients with micristin and 401 patients with placebo. Objectivization of findings in highly endangered patients by the radiofibrinogen test, ultrasonic doubler, venography of contrast medium, section. In total there were 149 thromboembolic complications = 18.6%. The placebo control group (401 patients) had 52 ensured deep venothrombosises and 8 fatal pulmonary embolisms. The group with micristin treatment (401 patients) had 23 ensured deep venothrombosises and 4 fatal pulmonary embolisms. Significant decrease of the thromboembolism rate by micristin (p = 0.001). Failures concerning the effect of micristin included fractures near the hip. Favourable effects concerned intra-abdominal surgery. Frequent side-effect: increased intra-operative and postoperative bleeding tendency.
A report is presented on the prospective trial for prophylaxis of myocardial reinfarction by means of acetylsalicyclic acid. For the first time it was organized on the basis of population. 1,340 patients were treated with acetylsalicylic acid or placebo respectively for 22 months on an average. There were 24 cases of reinfarction in the group of treatment and 51 in the placebo group. The difference is significant.
Since platelet cyclo-oxygenase is much more sensitive to inactivation by aspirin than is the enzyme in the arterial wall and low doses of aspirin may prevent thrombosis by blocking thromboxane synthesis, we conducted a randomized, double-blind trial of aspirin (160 mg per day) vs. placebo in 44 patients on chronic hemodialysis. The study was continued until there were 24 patients with thrombi and both groups had been under observation for a mean of nearly five months. Thrombi occurred in 18 of 25 (72 per cent) of patients given placebo and 16 of 19 (32 per cent) of those given aspirin (P less than 0.01). The incidence of thrombosis was reduced from 0.46 thrombi per patient month in the placebo group to 0.16 thrombi per patient month in the aspirin group (p less than 0.005). A dose of 160 mg of aspirin per day is an effective, nontoxic antithrombotic regimen in patients on hemodialysis.
Adouble-blind trial of aspirin for the treatment of cerebral ischemia was begun in 1972 and continued for 37 months. This was accomplished despite difficulties in controlling a long-term study of a drug which has widespread availability and consumption. The study design, criteria for selection of patients, follow-up surveillance, and methods of data analysis are presented. We report only subjects without carotid surgery before randomization. Patients (178) who had carotid transient ischemic attacks (TIAs) were randomly allocated to aspirin or placebo and followed to determine the incidence of subsequent TIAs,death, cerebral infarction or retinal infarction. Analysis of the first six months of follow-up revealed a statistically significant differential in favar of aspirin when death or cerebral or retinal infarction and the occurrence of TIAs were grouped and considered together as end points. Significance in favor of aspirin treatment was mainly revealed in patients with a history of multiple TIAs and was most evident in those individuals having carotid lesions appropriate to the TIA symptoms. It cannot be inferred from this study that aspirin prevents stroke because when end points were restriced to death or cerebral or retinal infarction, there was no statistically significant differential between the aspirin and placebo treatments.
Prevention of arterial thromboembolism with acetylsalicylic acid (ASA) was studied in 148 patients with single Starr-Edwards aortic ball-valve prostheses. These patients are suitable for such a study because they have a high incidence of arterial emboli derived mainly from thrombi formed on the valves. They were given either 1 Gm. of ASA daily or placebo in combination with anticoagulants, and were observed for 2 years. Only two emboli occurred in patients receiving ASA, none of them severe. In the placebo group 12 thromboembolic episodes were diagnosed in 10 patients, and three with cerebral emboli died; in one a subdural hematoma unrelated to the embolus was found. In addition, one fatal and the one nonfatal intracranial bleeding occurred in each group, whereas gastrointestinal complications were seen more frequently in patients taking ASA. It is concluded that ASA combined with anticoagulants offered a significantly better protection against arterial thromboembolism than did anticoagulant therapy alone.
Suspecting that platelet thromboemboli could play a role in the pathogenesis of myocardial ischemia, we did a random-order, double-blind, crossover study of the effect of the platelet aggregation inhibitor, aspirin, on treadmill exercise-induced angina in 13 men with coronary artery disease. Although collagen-induced platelet aggregation and the second phase of adenosine diphosphate (ADP)-induced platelet aggregation were significantly decreased and the rate of disaggregation of ADP-induced platelet aggregates was significantly increased after 650 mg aspirin in buffered solution, there was no delay in onset of exercise-induced angina, change in heart rate-blood pressure product at onset of angina, or change in S-T segment depression at onset of angina. Regardless of whether the patients had received placebo or aspirin on the preceding day, treadmill exercise until angina was followed by no changes in platelet aggregation or disaggregation, platelet count in blood or platelet-rich plasma, or of the plasma concentration of nonesterified fatty acids.
Abnormalities of platelet survival time, fibrinogen survival time or fibrinolytic activity have been observed in patients with recurrent venous thrombosis. In the present study these measurements were undertaken in 41 patients with idiopathic recurrent venous thrombosis and repeated after treatment with sulfinpyrazone, ethylestrenol and phenformin or placebo. An additional 10 patients were studied before and after discontinuation of warfarin therapy. Platelet survival (autologous labelling with chromium-51) was shortened in 41 (80 percent); fibrinogen survival (autologous labelling with iodine-125) was shortened in 28 (55 per cent) and abnormal lytic activity (preocclusion and postvenous occlusion euglobulin lysis time) was present in 22 (43 per cent). All patients had at least one abnormal value, and two patients had abnormalities of all three measurements. The administration of sulfinpyrazone increased platelet survival (N = 14) but did not alter either fibrinogen survival or lytic activity. Lytic therapy (N = 7) decreased euglobulin lysis time but did not alter either platelet or fibrinogen survival, and placebo therapy (N = 11) did not alter any measurement. Discontinuation of warfarin therapy was associated with a decrease in fibrinogen survival (N = 10) but no alteration in platelet survival or lytic activity. During therapy (three months) with placebo, venous thrombosis occurred in four of 11 patients; with lytic agents, in three of seven; with sulfinpyrazone, in none of 14; and following discontinuation of warfarin therapy, in one of 10. Results suggest that abnormalities of platelet and fibrinogen survival, and of blood lytic activity are frequently observed in patients with recurrent venous thrombosis and that these measurements behave independently of each other. Platelet suppressant therapy appears to be superior to lytic therapy or to placebo therapy in preventing venous thrombosis in these patients.
Patients (125) who had carotid transient ischemic attacks (TIAs) and one or more accessible carotid lesions visualized angiographically had reconstructive operations of the carotid artery and were then randomly assigned to aspirin or placebo treatment. The were followed to determine the incidence of subsecquent TIAs, death, cerebral infarction, or retinal infarction. Life table analysis (for 24 months follow up) that eliminated deaths which were not stroke-related revealed a significant difference in favor of aspirin. Because of the small number of patients and the short period of follow up, these results should be interpreted only as consistent with those reported in the initial publication but not conclusive of an aspirin effect in preventing cerebral infarction.
A randomized, double-blind controlled trial of low-dose heparin combined with sulfinpyrazone to prevent deep-vein thrombosis after operation on the hip was carried out. In a group of seventy-three patients after arthroplasty, postoperative thrombosis of the veins of the lower limbs occurred in 51 per cent of the control patients and in 36 per cent of the treated patients. In a fracture group of thirty patients, thrombosis occurred in 75 per cent of the control patients and in 36 per cent of the treated patients. These differences are of borderline statistical significance in the fracture group and are of no statistical significance in the arthroplasty group. However, a 36 per cent incidence of venous thrombosis in the drug-treated patients is too high to justify recommendation of the regimen tested without careful monitoring of patients by tests designed to detect thrombosis. Then, appropriate anticoagulant therapy can be instituted if necessary.
A prospective, double-blind clinical study was performed to evaluate the combination of dipyridamole 225 mg/day and acetylsalicylic acid 1 gm/day prophylaxis of postoperative venous thromboembolism in elective total hip replacement. Patients were stratified according to age, and randomly assigned to receive drug or placebo. All patients were followed with 125I-labeled fibrinogen scanning for one week postoperatively, or until fully mobile. Venography was performed in 79/132 patients; in 36 patients the venogram was obtained to confirm a positive fibrinogen scan, in 43 patients an elective venogram was obtained on the seventh postoperative day to evaluate the operated thigh (a blind area for scanning). Thrombosis (by scan or venogram) was found in 17/68 (25%) in the control group, and in 23/64 (36%) in the treated group. Overall incidence was 40/132 (30%). Correlation of scan with venography was 90%. There were no clinically significant pulmonary emboli in either group. The combination of acetylsalicylic acid (ASA) and dipyridamole as given in this study is not effective prophylaxis in elective total hip replacement.
Among the 62 patients in the double-blind portion of the study, 31 received aspirin pretreatment and showed inhibited platelet aggregation. Four of these patients (13 per cent) sustained post-cannulation radial-artery occlusion. Among the other 31 patients who received placebo and had normal platelet aggregation, 12 (39 per cent) experienced arterial occlusion (P<0.05 versus aspirin-treated group). The mean thrombus scores assigned after arteriography were 1.3 ± .2 SE in the aspirin-treated group and 1.9 ± .3 SE in the placebo group (P<0.05). An unexpected finding was that women appeared to benefit more from aspirin pretreatment than did the men. Among all women in the study the incidence of arterial occlusion was 63 per cent (12 of 19) for those who did not receive aspirin, compared with 27 per cent (7 of 26) for men in the control group. This discrepancy is probably related to the smaller size of women's arteries (2.0 mm ± 0.1 SEM versus 2.3 mm ± 0.1 SEM, P < 0.05).
Fifty patients who underwent aortocoronary saphenous-vein bypass-graft surgery were randomly assigned to one of three groups to determine the effects of antiplatelet or anticoagulant therapy on graft patency. Twenty-four patients served as controls; 13 patients received aspirin (325 mg three times a day) and dipyridamole (75 mg three times a day); and 13 patients received closely regulated warfarin therapy. Medications were begun on the third post-operative day. Six months after surgery, all patients underwent coronary angiography to assess graft patency. There were no statistically significant differences between groups in various clinical, hemodynamic and angios, 27 of 33 grafts (82 per cent) with aspirin and dipyridamole and 29 of 37 grafts (78 per cent) with warfarin (P less than 0.5), all patients had at least one patent graft. Postoperative treatment either with aspirin and dipyridamole or with warfarin failed to improve the patency of the grafts.
Deep vein thrombosis (DVT) following hip surgery occurs in more than 50% of cases because most patients undergo hip replacement are under unfavourable conditions due to preexistent cardiovascular and respiratory diseases. The clinical diagnosis of DVT and pulmonary embolism (PE) is not sufficient. The majority of DVT and PE occurs without any preceding clinical sign. The 125-J-fibrinogen uptake test seems a simple and most efficient tool for detecting DVT in the earliest stage. Additional methods are sonography and venography. Review of the literature and our investigations show that 75% of the thrombi start intraoperatively. 80% of the PE appeared within the first week after surgery. In 1973 we started prospective trials on prophylactic efficacy of 5 drugs: combination of aspirin and dipyridamol (group I - 95 patients), dextran 60 (group II - 43 patients), dihydroergotamin (group III - 61 patients), low-dose-heparin (group IV - 63 patients) and combination of dihydroergotamin and low-dose-heparin (group V - 61 patients). The trials included 323 patients all undergoing total hip replacement. They all underwent the same operative procedure and the same routine physiotherapy. All patients were screened with the 125-J-fibrinogen uptake test, venography and a careful clinical evaluation before and after surgery. A lung perfusion scan was performed pre- and postoperatively in groups III, IV and V. In case of established DVT simultaneous anticoagulation with heparin and coumarin was started. In group I (aspirin/dihyridamol) 32 DVT (34%) and 3 PE were detected - I patient did not survive. In the dextran group II 24 patients (54%) got DVT and 1 non fatal PE. The dihydroergotamin group III showed 33 DVT (54%) and 7 PE (Scan). In the low-dose-heparin-group IV we had 29 DVT (46%) and 3 PE. Only the combination of low-dose-heparin and dehydroergotamin (V) reduced the incidence of thromboembolic complications significantly: 15 DVT (25%) were detected and no PE.
71 patients operated upon for total hip replacement were randomly assigned to two treatment groups. Group I daily received 1.8 g acetylsalicylic-lysine i.v., group II received perioperatively 3 × 5000 U heparin s.c. and 3 × 7500 U heparin from the 2nd until the 15th postoperative day.Deep vein thrombosis diagnosed by the 125-I-fibrinogen test and verified by venography were found in 19 of 31 patients of group I and in 4 patients of group II; the different incidence is significant (p < 0.001). Major wound haematomas occurred in one patient of group I and in two patients of group II.
In a double-blind study, prevention of re-thrombosis was tested on 101 patients in whom stenosis or segmental occlusion of a large artery of the lower limbs had been successfully removed by the intraluminal catheter method. The combination of 75 mg dipyridamol and 330 mg acetylsalicylic acid, three times daily by mouth, proved to be slightly more effective than acetylsalicylic acid alone at the same dosage. In the group with the combined treatment 84% of the arteries remained open, compared with 70% on acetylsalicylic acid alone.
Forty-five patients suffering from intermittent claudication were admitted to a double-blind non-crossover study. Three groups were constituted at random and treated for 2 months with either 100 mg suloctidil t.i.d. or 1.5 mg dihydroergotoxine methylate t.i.d. or placebo. From the results of measurements of pain-free walking distance and venous occlusion plethysmography recordings, suloctidil was shown to be active and significantly superior to dehydroergotoxine and placebo: in the two latter groups a decrease in calf blood perfusion after 2 months was also noted. The physician's overall assessment of response to treatment showed that suloctidil and dihydroergotoxine were significantly superior to placebo, and that suloctidil was significantly better than dihydroergotoxine.
30 Patienten mit operativem Ersatz des Hüftgelenkes wurden täglich 3,6 g Acetylsalicyl-lysin injiziert. Postoperativ wurde eine Lungenembolie und mit dem Radiojod-Fibrinogentest wurden bei 19 Patienten tiefe Venenthrombosen diagnostiziert. Bei Verabreichung von niedrig dosiertem Heparin (dreimal 5000 I.E./24 h) entwickelten sich bei zehn von 30 Patienten tiefe Venenthrombosen; die Frequenz ist signifikant (P < 0,05) niedriger als in der Acetylsalicylsäure-Gruppe. Abgesehen vom unzureichenden Thromboseschutz durch Acetylsalicylsäure zeigen die Ergebnisse, daß die Wirksamkeit der »Low-dose«-Heparinprophylaxe bei diesen besonders gefährdeten Patienten begrenzt ist.
Summary
3.6 g acetylsalicylic lysin was injected into 30 patients daily after operative replacement of the hip-joint. Pulmonary embolism and (or) deep-vein thrombosis were diagnosed in 19 patients. Low-dose heparin (3 X 5000 IU/24 h) significantly reduced the incidence of deep-vein thrombosis (ten of thirty patients: P < 0.05) compared with the acetylsalicylic acid group. The results demonstrate not only the inadequate thrombosis prophylaxis provided by acetylsalicylic acid, but also that low-dose heparin prophylaxis in these specially at risk patients is of limited efficacy.
2136 patients in general surgery, gynaecology and urology were investigated by the 125I-fibrinogen-uptake-test for detection of postoperative deep vein thrombosis (DVT). They received at random one of low-dose heparin, dihydroergotamine, the fixed combination of both drugs (Heparin-Dihydergot), low molecular weight dextran and acetylsalicylic-acid (ASS). When DVT was detected repeated lung perfusion scintigraphies were carried out for diagnosis of embolic pulmonary perfusion defects. Results demonstrate the outstanding effect of Heparin-Dihydergot, which is not only 2-3 times better than the anti-thrombotic standard low-dose heparin but also eliminates almost completely the risk of postoperative embolism. The preventive efficacy of ASS and dextran must be considered to be poor and not comparable to that obtained when using heparin, dihydroergotamine or the combination. Now Heparin-Dihydergot is the new standard with which all prophylactic procedures should be compared.
Small doses of subcutaneous heparin and infusions of dextran both reduce the incidence of fatal pulmonary embolism after elective general surgery. But both methods have disadvantages. Therefore, the protection against deep vein thrombosis afforded by sulfinpyrazone, a drug which can be taken by mouth as well as by injection, was assessed in a prospective study of 119 patients undergoing elective general or urological surgery. The prophylactic administration of sulfinpyrazone was compared with the effects of small doses of sodium heparin and infusions of dextran-70. The 125I-fibrinogen test was carried out in all patients during their hospitalization. Deep vein thrombosis was diagnosed in 13 of 30 patients (43%) who received sulfinpyrazone, in 9 of 29 (31%) receiving dextran-70 and in 2 of 22 (9%) having subcutaneous heparin. The difference between the sulfinpyrazone and heparin groups was statistically significant (p less than 0.01). Sulfinpyrazone in the dose used in this trial was not effective in reducing the incidence of deep vein thrombosis during elective general surgery.
The study was carried out on 75 patients undergoing hip joint surgery. The efficacy of a prophylaxis of deep vein thrombosis (DVT) by acetylsalicyclic lysine (ASL) and by a low dose heparin (LDH) combined with the ASL treatment was investigated using the 125I-fibrinogen test. DVT was not significantly decreased by the ASL application (53%) compared to the controls (60%). DVT occurred significantly less under the combined administration (27%) than in the other two groups.
Anticoagulation therapy with acenocoumarin or with anticoagulants plus aspirin was given to 65 and 57 patients, respectively, with cardiac valve replacement. The follow-up was 1,462 months (22.5 months per patient) for the first group and 1,411 months (24.7 months per patient) for the second group. The frequency of embolic accidents was significantly lower in the group taking aspirin: Thirteen thromboembolic accidents were detected in patients receiving the anticoagulant and 3 in the group receiving the anticoagulant plus aspirin. These figures represent a 20.3 per cent incidence (one each 9.3 years of treatment) for the anticoagulant group and a 5.2 per cent incidence (one accident each 39.1 years of treatment) for the other group. The statistical significance between groups is p less than 0.005. There was no difference in the hemorrhagic risk between the two groups. We conclude that the use of an anticoagulant plus aspirin is a good and safe therapy for the prevention of thromboembolism in these patients.
The effect of sulfinpyrazone on the incidence of thrombosis of arterio-venous shunts was investigated in a double-blind crossover study in 45 patients on chronic hemodialysis over a period of 12 months. The incidence of thrombosis was reduced from 0.64 thrombi per patient month when on placebo to 0.21 thrombi per patient month when on sulfinpryazone (P less than 0.001). The therapeutic effect was more striking in men than in women and became evident within a week of starting the drug. The side effects were minimal, requiring withdrawal from the study of only one patient. This crossover study strengthens the findings in the previous report that sulfinpyrazone is of value in the prevention of thrombosis.
In order to prevent thrombo-embolism after prosthetic valve replacement, a high dose therapy with 450 mg/day of Dipyridamole and 3,000 mg/day of Aspirin was carried out for 1 year and 2 months in 91 cases (26 cases with aortic valve replacement, 40 cases with mitral valve replacement and 25 cases with multiple valve replacement). In the treated group, the incidence was 1.9% in cases more than 5 years after valve replacement and 2.9% in cases less than 5 years after valve replacement. In contrast, in the control group of 89 cases (47 cases of aortic valve replacement, 30 cases of mitral valve replacement and 12 cases of multiple valve replacement), the incidence was 9.1% and 14.7%, respectively. Thus, in both time intervals following prosthetic valve replacement the incidence of thrombo-embolism in the treated group was significantly lower than in the control group.
On exercise testing after an episode of unstable coronary artery disease (CAD; unstable angina or non-Q-wave myocardial infarction), a proportion of patients show ST-segment depression, indicating myocardial ischaemia, but do not report concomitant symptoms of angina. Treatment of such "silent" ischaemia aims mainly to reduce the risk of subsequent cardiac events. We have studied the effect of low-dose aspirin in patients with myocardial ischaemia defined at the predischarge test as silent (though patients might have had symptomatic ischaemia at other times) or symptomatic. 740 men with unstable CAD aged 70 years or less underwent symptom-limited exercise testing before hospital discharge; 144 showed ST depression without pain and 230 ST depression with simultaneous chest pain. Of the silent ischaemia group, 67 were randomly assigned placebo and 77 aspirin (75 mg daily); the corresponding numbers in the symptomatic group were 125 and 105. Angina symptoms were less common in the silent than in the symptomatic ischaemia group both before inclusion and during follow-up, and a greater proportion of the silent ischaemia group were included because of myocardial infarction. In both ischaemia groups aspirin treatment reduced the risk of subsequent myocardial infarction or death by 3 months' follow-up (silent 4% of aspirin-treated vs 21% of placebo-treated patients, p = 0.004; symptomatic 9% vs 18%, p = 0.05); at 12 months' follow-up a significant benefit of aspirin was still apparent in the silent ischaemia group (9% vs 28%, p = 0.005) but not in the symptomatic group (13% vs 22%, p = 0.109). Low-dose aspirin reduced the risk of subsequent myocardial infarction at least as well in silent as in symptomatic myocardial ischaemia. Since improvement of outlook is the main treatment objective in symptom-free patients, aspirin should be a mainstay of their treatment.
Clinical trials have demonstrated a prophylactic role for aspirin in myocardial infarction and in unstable angina pectoris. The Swedish Angina Pectoris Aspirin Trial (SAPAT) is the first prospective study of aspirin in stable angina. 2035 patients were randomised double-blind to treatment with aspirin 75 mg daily or placebo. All patients were treated with sotalol for control of symptoms. The median duration of follow-up was 50 months. Compared with the placebo+sotalol group, the aspirin+sotalol group had a 34% (81 vs 124 patients) reduction in primary outcome events (myocardial infarction and sudden death; 95% confidence interval 24-49%; p = 0.003) and the reduction observed in secondary outcome events (vascular events, vascular death, all cause mortality, stroke) ranged from 22% to 32%. Treatment withdrawal caused by adverse events occurred in 109 patients in the aspirin+sotalol group and 100 in patients in the placebo+sotalol group; major bleeds, including haemorrhagic stroke, occurred in 20 and 13 patients, respectively (not significant). The addition of a low dose of aspirin to sotalol treatment showed significant benefit in terms of cardiovascular events, including a significant reduction in the incidence of first myocardial infarction in patients with symptoms of stable angina pectoris.
32 patients (mean age 65 years, range 51-75 years) were included in this controlled, double blind study to evaluate the effect of dipyridamole in patients with intermittent claudication. Following a run-in phase of one month, 15 patients received 400 mg dipyridamole per day and 17 patients placebo. Patient characteristics (risk factors, age, clinical and apparative tests) of both groups did not differ significantly before and during the study period. Mean pain free und absolute walking distance on the treadmill (3.2 km/h, 12.5 degrees gradient) increased significantly in both groups during study period (p < 0.001 and p < 0.01). Explanations are more intensive physical activity and increasing adaptation to treadmill exercise. However, dipyridamole did not induce a significantly longer walking distance in comparison with placebo. The working hypothesis that the drug with inhibiting properties of thrombocyte function prolongs walking distance in intermittent claudication, could not be confirmed.
Patients with atherosclerotic disease of the lower limbs are at high risk of thrombotic events not only in the peripheral circulation, but also in the coronary and cerebral arteries. Ticlopidine, a potent inhibitor of platelet aggregation, can reduce the incidence of arterial thrombosis in patients suffering from intermittent claudication, as shown by a meta-analysis performed in 1987. In order to confirm these findings, we undertook a randomized, stratified, placebo-controlled, double-blind multicentre trial in Argentina in two parallel groups of patients suffering from intermittent claudication. Twenty-one clinical centres participated in the trial and 615 patients were enrolled. Patients were eligible if they had presented obstructive arterial disease of the upper part of the lower limb (popliteal or above) for at least 12 months, confirmed by either angiography or Doppler studies, and intermittent claudication (stage II) assessed by treadmill testing. Non insulin treated diabetic patients were eligible if they fulfilled the other inclusion criteria and two strata, diabetic and non diabetic, were established. Patients enrolled were treated with either ticlopidine (500 mg/day) or placebo for 24 weeks. In this paper, we report the design and organization of the study and the baseline characteristics of the patient population at inclusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Data from the early stages of the thrombosis prevention trial (TPT) have been used to establish and quantify the risk of extracranial bleeding due to low dose aspirin (75 mg) and low intensity oral anticoagulation with warfarin (international normalised ratio, INR, 1.5) singly or in combination, in men aged between 45 and 69 who are at high risk of ischaemic heart disease (IHD). The design of the trial is factorial, the four treatments being combined low dose aspirin and low intensity anticoagulation (WA), low intensity anticoagulation alone (W), low dose aspirin alone (A) and double placebo treatment (P). The trial is being carried out through the Medical Research Council's General Practice Research Framework, with participating practices throughout the United Kingdom. Results are based on the first 3,667 men entered. The risk of major gastrointestinal bleeding due to active treatment is probably about 1 in 500 man-years of treatment, there currently being no difference between the three active regimes (WA, W, A). Intermediate and minor bleeding episodes occur more frequently with WA than with W or A on their own, the excess being mainly due to minor nose bleeds and bruises. In turn, both W and A on their own cause more such minor episodes than placebo treatment, P. There is no evidence that any of the three active regimens increases the risk of peptic ulceration, nor do they increase reports of indigestion. Aspirin increases reports of constipation and reduces reports of blurred vision. Minor bleeding occurs less frequently in smokers than in non-smokers but is not influenced by age. The antithrombotic regimes used are feasible and acceptable.
To evaluate therapy with aspirin plus dipyridamole in reducing restenosis after carotid endarterectomy.
A total of 163 patients having 175 surgical carotid endarterectomies.
Eighty-three patients (90 endarterectomies) were randomly assigned to receive oral aspirin, 325 mg, plus dipyridamole, 75 mg, beginning 12 hours preoperatively, followed by a second dose administered within 8 hours after the operation, and given three times daily thereafter for 1 year. Eighty patients (85 endarterectomies) received placebo medication that was identical in appearance to the study drugs.
After the adequacy of the surgical procedure was confirmed by intraoperative angiography, restenosis at the endarterectomy sites was evaluated using serial duplex ultrasound studies before hospital discharge and at 3-month intervals postoperatively for 1 year.
Based on the time for developing identifiable restenosis and on efficacy analysis, greater than 50% restenosis developed in 11 operated vessels (16%) in the treated group and in 10 arteries (14%) in the placebo group, yielding an observed risk increase of 14% (95% CI, -52% to 167%; P greater than 0.2). By intention-to-treat analysis, greater than 50% restenosis developed in 16 of 90 operated vessels in treated patients and in 10 of 85 arteries in patients receiving placebo (26% for the treated group and 12% for the placebo group; P = 0.18, Mantel-Haenszel statistic), representing an observed risk increase of 110% (CI, -5% to 365%). Similar differences were observed for greater than 20% restenosis and for the comparison of patients rather than operated vessels by either intention-to-treat or efficacy analyses.
Because therapy not only failed to reduce carotid restenosis but may have actually increased its frequency, treatment with aspirin plus dipyridamole probably has no clinically important benefit on restenosis in patients having carotid endarterectomy.
Experiments in animals and two epidemiologic studies in humans suggest that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) may be protective against colon cancer. We tested this hypothesis in a prospective mortality study of 662,424 adults who provided information in 1982 on the frequency and duration of their aspirin use. Death rates from colon cancer were measured through 1988. The possible influence of other risk factors for colon cancer was examined in multivariate analyses for 598 case patients and 3058 matched control subjects drawn from the cohort.
Death rates from colon cancer decreased with more frequent aspirin use in both men and women. The relative risk among persons who used aspirin 16 or more times per month for at least one year was 0.60 in men (95 percent confidence interval, 0.40 to 0.89) and 0.58 in women (95 percent confidence interval, 0.37 to 0.90). The risk estimates were unaffected when we excluded persons who reported at entry into the study that they had cancer, heart disease, stroke, or another condition that might influence both their aspirin use and their mortality. Adjustment for dietary factors, obesity, physical activity, and family history did not alter the findings significantly. No association was found between the use of acetaminophen and the risk of colon cancer.
Regular aspirin use at low doses may reduce the risk of fatal colon cancer. Whether this is due to a direct effect of aspirin, perhaps mediated by the inhibition of prostaglandin synthesis, or to other factors indirectly associated with aspirin use is unclear.
In order to assess the usefulness of a combination of low-dose aspirin (25 mg b.i.d.) with dipyridamole (200 mg b.i.d.) in the prevention of major coronary events in patients with acute unstable angina, we performed a prospective, double-blind, placebo-controlled study involving 88 consecutive patients admitted to three Hospital Departments of Cardiology. The patients entered the study as soon as possible after hospital admission, and were treated and followed up to one year. There was no appreciable difference in side effects and adverse reactions between the treatment and control group. The incidence of cardiac death and/or nonfatal myocardial infarction during the whole period of observation was 14% (6/44) in the treatment group and 25% (11/44) in the placebo group by "intention-to-treat" analysis; 16% (4/25) and 32% (10/31), respectively, by "drug-efficacy" analysis (p = 0.21 by Fisher's exact test, non significant difference). However, when considering the only events occurred in the first month (2/44 in the treatment group and 9/44 in the placebo group, amounting to 4.5 and 20 percent, respectively), the combination of dipyridamole with low-dose aspirin reached a statistically significant protective effect (p = 0.04). The results of this pilot study provide strong evidence for a beneficial effect of the regimen tested in patients with acute unstable angina, at least in the first weeks of treatment, while at the same time suggesting a safe alternative for patients with contraindications to higher doses of aspirin.
The authors report the results of a randomised double-blind study comparing the antithrombotic activity of a new anti-platelet drug (Triflusal) with that of acetylsalicylic acid (ASA). 99 patients who underwent hip surgery were included in the study (total hip replacement, osteosynthesis of a pertrochanter fracture or Moore's prosthesis for intracapsular fracture of the femoral neck). Of the 48 patients having received Triflusal, 7 (14.5%) developed deep vein thrombosis as indicated by 125I-fibrinogen isotopic scanning and confirmed by phlebography. Of the 51 patients treated with ASA, 11 (21.6%) presented the same complication as diagnosed by the same techniques. This difference is not statistically significant, considering the number of cases studied. Nevertheless, Triflusal appears to provide prevention of thromboembolic risk to patients who have undergone hip surgery, particularly total hip replacement.
All 701 heart infarction patients admitted to 15 hospitals in the district of Cottbus between 1981 and 1983 were randomly administered 30, 60 or 1000 mg aspirin daily according to the territorial affiliation of their local hospitals. The physical and drug therapy during the 2 years follow-up was highly standardized; deviations--as far as they occurred--were documented. Lower all-cause mortality was statistically demonstrated in patients over 60 and a lower fatal reinfarction rate in patients over 50 as well as in men. Deaths and fatal reinfarctions were significantly lower among patients with a history of angina pectoris, marked ST-depression, with an infarction location except for the posterior wall and among hypercholesterolemic patients. The preventive effect of 60 mg aspirin daily was less than that of 30 mg in comparison to the 1000 mg group. Side effects were seen in 4 and 8% (first and second year), respectively, of the patients administered 30 mg aspirin as opposed to 22 and 17% in patients allocated 1000 mg. We conclude that the optimum dose of aspirin for preventing reinfarctions could be as low as 30 mg daily.
GR32191B is a novel thromboxane A2-receptor antagonist with potent antiagregational and antivasoconstrictive properties. We have conducted a randomized, double-blind placebo-controlled trial to study its usefulness in restenosis prevention.
Patients received either GR32191B (80 mg orally before angioplasty and 80 mg/day orally for 6 months) or 250 mg i.v. aspirin before angioplasty and placebo for 6 months. Coronary angiograms before angioplasty, after angioplasty, and at 6-month follow-up were quantitatively analyzed. Angioplasty was attempted in 697 patients. For efficacy analysis, quantitative angiography at follow-up was available in 522 compliant patients (261 in each group). Baseline clinical and angiographic parameters did not differ between the two treatment groups. The mean difference in coronary diameter between postangioplasty and follow-up angiogram (primary end point) was -0.31 +/- 0.54 mm in the control group and -0.31 +/- 0.55 mm in the GR32191B group. Clinical events during 6-month follow-up, analyzed on intention-to-treat basis, were ranked according to the highest category on a scale ranging from death (control, six; GR32191B, four) to nonfatal infarction (control, 22; GR32191B, 18), bypass grafting (control, 19; GR32191B, 22) and repeat angioplasty (control, 52; GR32191B, 48). No significant difference in ranking was detected. Six months after angioplasty, 75% of patients in the GR32191B group and 72% of patients in the control group were symptom free.
Long-term thromboxane A2-receptor blockade with GR32191B does not prevent restenosis and does not favorably influence the clinical course after angioplasty.
Since platelet interactions appear to play an important role in the development of restenosis, attenuation of thromboxane-mediated reactions may improve the long-term outcome following coronary angioplasty. Phase II of the Multi-Hospital Eastern Atlantic Restenosis Trial (M-HEART) is a prospective, randomized, placebo-controlled study of thromboxane blockade in the prevention of restenosis following successful coronary angioplasty. Two forms of thromboxane blockade are evaluated: aspirin (a nonspecific inhibitor of thromboxane synthesis) and sulotroban (a specific thromboxane receptor antagonist). The design of this multicenter trial and the rationale for use of sulotroban in the prevention of restenosis are reviewed in this report.
