[show abstract][hide abstract] ABSTRACT: Patients needing surgery within 1 year after drug-eluting cardiac stent implantation are challenging to manage because of an increased thrombotic and bleeding risk. A "bridge therapy" with short-acting antiplatelet agents in the perioperative period is an option. We assessed the outcome and safety of such a bridge therapy in cardiovascular and non-cardiovascular surgery. We performed a comprehensive search of MEDLINE, EMBASE, the Cochrane Library, and ongoing trial registers, irrespective of type of design. Our primary outcome was the success rate of bridge therapy in terms of freedom from cardiac ischaemic adverse events, whereas secondary outcome was freedom from bleeding/transfusion. We also performed combined success rate for each bridge therapy drug (tirofiban, eptifibatide, and cangrelor). We included eight case series and one randomised controlled trial. Among the 420 patients included, the technique was effective 96.2 % of the times [95 % confidence interval (CI) 94.4-98.0 %]. The success rate was 100 % for tirofiban (4 studies), 93.8 % for eptifibatide (4 studies), and 96.2 % for cangrelor (1 study). Freedom from bleeding/transfusion events was observed in 72.6 % of the times (95 % CI 68.4-76.9 %), and was higher with cangrelor (88.7 %; 95 % CI 82.7-94.7 %) than with other drugs (81.0 % for tirofiban and 58.6 % for eptifibatide). Evidence from case series and one randomised controlled trial suggests that, in patients with recent coronary stenting undergoing major surgery, perioperative bridge therapy with intravenous antiplatelet agents is an effective and safe treatment option to ensure low rate of ischaemic events.
Internal and Emergency Medicine 01/2014; · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Clopidogrel is a prodrug that undergoes extensive enteric clearance and requires two-stage hepatic activation by cytochrome P450 (CYP) enzymes. This metabolic pathway is susceptible to genetic polymorphisms, resulting in a variable platelet inhibitory effect. A growing number of studies have linked poor antiplatelet response to clopidogrel to adverse clinical outcomes, particularly coronary ischemic events and stent thrombosis. This has prompted the development of new ADP receptor antagonists that inhibit platelets more effectively. Two of these agents, prasugrel and ticagrelor, have been investigated in two large randomized clinical trials, and both have shown superiority versus clopidogrel in reducing ischemic endpoints, with an increase in bleeding events, but a favorable final net clinical outcome. Since the publication of the main articles, several sub-analyses have been performed on the same data, and Guideline recommendations have largely endorsed these subgroup findings. Most clinicians have accepted the concept that we might consider approaching the patient differently, deserving a specific agent for each different settings. However, subgroup analyses of randomized trials are often post hoc, underpowered and prone to bias. Weighing efficacy and safety of the most commonly used antiplatelet agents will represent a clinical challenge over the next few years. Furthermore, individuals and organizations involved in formulary decisions will have to face economic constraints, also taking into account the availability of low-cost generic clopidogrel. In the following review, we have performed a critical appraisal of the current literature in order to outline lights and shadows on the most relevant clinical scenarios.
Journal of Cardiovascular Medicine 01/2014; 15(1):8-18. · 2.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: Abstract Baseline thrombocytopenia (TP) is relatively common in patients referred for percutaneous coronary intervention (PCI). Its detection may have implications for long-term antiplatelet medication prescription and adherence. The aim of this article is to review several practical aspects in managing patients with baseline TP and stable coronary artery disease (CAD). Moving from two clinical cases, we tried to picture cardiological scenarios associated with baseline TP and to provide flow charts for patient's management which take into consideration both the cardiological and the hematological conditions. TP in patients with stable CAD on antiplatelet treatment may follow diverse clinical courses depending upon TP inferred etiology, baseline degree of thrombocytopenia and its time course as outlined by previous complete blood counts, when available. Evaluation of these three parameters may guide the planning of further patient work-up and the choice of the most appropriate cardiological treatment (medical, invasive with stent implantation or coronary artery bypass). A multidisciplinary evaluation comprehensive of hematological counseling is also recommended in these patients before planning prolonged dual anti-platelet therapy.
[show abstract][hide abstract] ABSTRACT: The causes of death within 1 year of hospital admission in patients with non-ST-segment elevation acute coronary syndromes are ill defined, particularly in patients aged ≥75 years. From January 2008 through May 2010, we enrolled 645 patients aged ≥75 years with non-ST-segment elevation acute coronary syndromes: 313 in a randomized trial comparing an early aggressive versus an initially conservative approach, and 332, excluded from the trial for specific reasons, in a parallel registry. Each death occurring during 1 year of follow-up was adjudicated by an independent committee. The mean age was 82 years in both study cohorts, and 53% were men. By the end of the follow-up period (median 369 days, interquartile range 345 to 391), 120 patients (18.6%) had died. The mortality was significantly greater in the registry (23.8% vs 13.1%, p = 0.001). The deaths were classified as cardiac in 94% of the cases during the index admission and 68% of the cases during the follow-up period. Eighty-six percent of the cardiac deaths were of ischemic origin. In a multivariate logistic regression model that included the variables present on admission in the whole study population, the ejection fraction (hazard ratio 0.95, 95% confidence interval 0.94 to 0.97; p <0.001), hemoglobin level (hazard ratio 0.85, 95% confidence interval 0.76 to 0.94; p = 0.001), older age (hazard ratio 1.05, 95% confidence interval 1.01 to 1.10, p = 0.010), and creatinine clearance (hazard ratio 0.99, 95% confidence interval 0.97 to 0.99; p = 0.030) were the independent predictors of all-cause death at 1 year. In conclusion, within 1 year after admission for non-ST-segment elevation acute coronary syndromes, most deaths in patients aged ≥75 years have a cardiac origin, mostly owing to myocardial ischemia.
The American journal of cardiology 03/2013; · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Adenosine di-phosphate receptor antagonists (ADPRAs) blunt hemostasis for several days after administration. This effect, aimed at preventing cardiac ischemic complications particularly in patients with acute coronary syndromes (ACS), may increase perioperative bleeding in the case of cardiac surgery. Practice Guidelines recommend withholding ADPRAs for at least 5days prior to surgery, though with a weak base of evidence. The purpose of this study was to systematically review observational and experimental studies of early or late preoperative discontinuation of ADPRAs prior to coronary artery bypass grafting (CABG) for patients with ACS. METHODS: MEDLINE, EMBASE, the Cochrane Library databases up to December 2011; and reference lists. Observational and experimental studies that compared early ADPRA discontinuation with late discontinuation, or no discontinuation, in patients with ACS undergoing CABG. RESULTS: There were 19 studies, including 14,046 participants, 395 deaths and 309 reoperations due to bleeding. ADPRA late discontinuation up to CABG was associated with an increased risk of postoperative mortality (OR 1.46, 95% confidence interval (CI) 1.10 to 1.93) and reoperations due to bleeding (OR 2.18; 95% CI 1.47 to 2.62). Between-study heterogeneity was low. Meta-analysis limited to high quality or prospective studies gave consistent results. In most instances, the 95% prediction intervals for summary risk estimates confirmed the risk across study groups. CONCLUSIONS: ADPRA late discontinuation prior to CABG is associated with an increased risk of death and reoperations due to bleeding in patients with ACS. The confidence in the estimates of risk for late discontinuation is moderate to high.
International journal of cardiology 01/2013; · 7.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background
Recurrent ST-segment elevations in acute coronary syndromes have been attributed to coronary cyclic flow variations (CCFV) possibly due to coronary vasospasm and unstable platelet aggregation in partially occluded arteries.
We describe the case of a patient with an acute myocardial infarction, recurrent ST-segment elevations and diffuse disease of the left anterior descending artery.
The post-angiography 12-lead continuous ECG monitoring revealed cyclic anterior ST-segment elevations that were completely abolished with continuous intravenous infusion of low-dose isosorbide-dinitrate.
The complete and sustained response to low-dose nitrate suggests that vasoconstriction plays a crucial role to provoke CCFV. This case underlines the importance of continuous 12-lead ECG monitoring with ST-segment trend analysis in the CCU.
Journal of electrocardiology 01/2013; · 1.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Elderly patients account for one third of those admitted to cardiac care units with non-ST-elevation acute coronary syndromes, but are largely underrepresented in randomized clinical trials which form the basis of practice guidelines. Conducting trials in this patient population is especially difficult due to coexisting pathologies, informed consent issues, a perceived higher risk of interventional procedures, and complexity of follow-up. The Italian Elderly ACS Study has been a positive experience in terms of accepting this challenge, carrying it on with limited resources and delineating convincing results, although not statistically conclusive due to its final limited sample size. The indications from the study are straightforward in patients with elevated troponin levels on admission and other high-risk characteristics: in these patients, an early invasive approach has reduced by 40% to 60% the risk of fatal and nonfatal ischemic complications at 1-year follow-up. This result has been achieved with an incidence of bleeding complications which was by far lower than previously reported in the literature, probably due to a systematic radial approach to vascular interventions and a cautious use of antithrombotic treatments in the acute phase.
Giornale italiano di cardiologia (2006) 10/2012; 13(10):59-64.
[show abstract][hide abstract] ABSTRACT: This study sought to determine the risk versus benefit ratio of an early aggressive (EA) approach in elderly patients with non-ST-segment elevation acute coronary syndromes (NSTEACS).
Elderly patients have been scarcely represented in trials comparing treatment strategies in NSTEACS.
A total of 313 patients ≥75 years of age (mean 82 years) with NSTEACS within 48 h from qualifying symptoms were randomly allocated to an EA strategy (coronary angiography and, when indicated, revascularization within 72 h) or an initially conservative (IC) strategy (angiography and revascularization only for recurrent ischemia). The primary endpoint was the composite of death, myocardial infarction, disabling stroke, and repeat hospital stay for cardiovascular causes or severe bleeding within 1 year.
During admission, 88% of the patients in the EA group underwent angiography (55% revascularization), compared with 29% (23% revascularization) in the IC group. The primary outcome occurred in 43 patients (27.9%) in the EA group and 55 (34.6%) in the IC group (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.53 to 1.19; p = 0.26). The rates of mortality (HR: 0.87; 95% CI: 0.49 to 1.56), myocardial infarction (HR: 0.67; 95% CI: 0.33 to 1.36), and repeat hospital stay (HR: 0.81; 95% CI: 0.45 to 1.46) did not differ between groups. The primary endpoint was significantly reduced in patients with elevated troponin on admission (HR: 0.43; 95% CI: 0.23 to 0.80), but not in those with normal troponin (HR: 1.67; 95% CI: 0.75 to 3.70; p for interaction = 0.03).
The present study does not allow a definite conclusion about the benefit of an EA approach when applied systematically among elderly patients with NSTEACS. The finding of a significant interaction for the treatment effect according to troponin status at baseline should be confirmed in a larger size trial. (Italian Elderly ACS Study; NCT00510185).
[show abstract][hide abstract] ABSTRACT: The management of antiplatelet therapy in patients with coronary stents undergoing surgery is a growing clinical problem and often represents a matter of debate between cardiologists and surgeons. It has been estimated that about 4-8% of patients undergoing coronary stenting need to undergo surgery within the next year. Surgery represents one of the most common reasons for premature antiplatelet therapy discontinuation, which is associated with a significant increase in mortality and major adverse cardiac events, in particular stent thrombosis. In addition, surgery confers an additional risk of perioperative cardiac ischemic events, being high in these patients because of the pro-inflammatory and pro-thrombotic effects of surgery. Current international guidelines recommend to postpone non-urgent surgery for at least 6 weeks after bare metal stent implantation and for 6-12 months after drug-eluting stent implantation. However, these recommendations provide little support with regard to managing antiplatelet therapy in the perioperative phase in case of urgent operations and/or high hemorrhagic risk. Furthermore, ischemic and hemorrhagic risk is not defined in detail on the basis of clinical and procedural characteristics. Finally, guidelines shared with cardiologists and surgeons are lacking. The present consensus document provides practical recommendations on the management of antiplatelet therapy in the perioperative period in patients with coronary stents undergoing surgery. Cardiologists and surgeons contributed equally to its creation. An ischemic risk stratification has been provided on the basis of clinical and procedural data. All surgical interventions have been defined on the basis of the hemorrhagic risk. A consensus on the most appropriate antiplatelet regimen in the perioperative phase has been reached on the basis of the ischemic and hemorrhagic risk. Dual antiplatelet therapy should not be withdrawn for surgery at low bleeding risk, whereas aspirin should be continued perioperatively in the majority of surgical operations. In the event of interventions at high risk for both bleeding and ischemic events, when oral antiplatelet therapy withdrawal is required, perioperative treatment with short-acting intravenous glycoprotein IIb/IIIa inhibitors (tirofiban or eptifibatide) should be considered.
Giornale italiano di cardiologia (2006) 07/2012; 13(7-8):528-51.
[show abstract][hide abstract] ABSTRACT: To assess and promote compliance of Italian cardiological intensive care units (CCUs) with evidence-based guidelines for the management of acute myocardial infarction (MI).
The process of diagnosis and treatment of MI was prospectively evaluated in 163 CCUs by use of 30 indicators during two enrolment phases, each followed by a feedback of both local and general performance. Overall, 5854 patients with ST-segment elevation MI (STEMI) and 5852 with non-ST-segment elevation MI (NSTEMI) were consecutively enrolled. The target for each indicator was defined as compliance with the relevant recommendations in ≥90% of suitable patients and it was met for nine (30%) and 10 (33.3%) indicators in the first and second phases, respectively. Regardless of target, a significant improvement in compliance was observed in the second phase in 10 out of 30 indicators (33.3%). Use of pre-hospital ECG, expedite delivery of reperfusion therapy, dosage of antithrombotic drugs, and non-pharmacological implementation of secondary prevention were often off target. Similar in-hospital mortality was observed in phases I and II, both in patients with STEMI (4.0 vs. 4.2%, p=0.79) and NSTEMI (1.8 vs. 2.4%, p=0.11). Overall, 30-day mortality were 5.7% for patients with STEMI and 3.4% with NSTEMI.
Performance indicators can accurately weigh the whole process of diagnosis and treatment of patients with MI and monitor the improvements in the quality of care. In our large population of consecutive patients, satisfactory 30-day outcomes were observed despite suboptimal adherence to guidelines for some indicators of recognised prognostic relevance.
European heart journal. Acute cardiovascular care. 06/2012; 1(2):143-52.
[show abstract][hide abstract] ABSTRACT: The 2011 edition of the ESC guidelines on non-ST-segment elevation acute coronary syndromes (NSTE-ACS) maintains the approach strongly based upon risk stratification, following the concept that "the higher the risk of ischemic events, the larger will be the benefit of an aggressive pharmaco-interventional approach". This concept applies both to the indication and timing of angiography/revascularization and to the choice of concomitant pharmacological therapies. The proofs of efficacy of the most recent drug treatments are solid, but the choice among the several available options and the evaluation of the efficacy/safety ratios in patient subsets require clinical wisdom, especially for the management of the most complex and frail patients. The indication for performing coronary angiography within 24h in high-risk patients would imply extending to NSTE-ACS patients the networks already in place for primary percutaneous coronary intervention in ST-elevation myocardial infarction.
Giornale italiano di cardiologia (2006) 03/2012; 13(3):157-68.
[show abstract][hide abstract] ABSTRACT: Acute coronary syndromes (ACS) are the leading cause of mortality in Western countries. Until a few years ago, the antiplatelet drug to be administered in association with aspirin was indisputably clopidogrel. Recent data from randomized trials conducted in ACS patients have shown that the new oral antiplatelet regimens, prasugrel and ticagrelor, are associated with a significant reduction in cardiovascular events, as compared to clopidogrel. Moreover ticagrelor reduced both all-cause and cardiovascular mortality as compared to clopidogrel in the PLATO trial. However, there are intrinsic differences between the trials design and among the enrolled ACS populations, that make complex the generalization of the mortality results in the whole spectrum of ACS patients. We aimed to provide further insights into the unresolved mortality issues raised in the PLATO and TRITON-TIMI 38 trials, by analysing the effects of ticagrelor and prasugrel in the ACS populations included in the respective trials.
Current Medical Research and Opinion 09/2011; 27(11):2117-22. · 2.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: About 5% of patients undergoing coronary stenting need to undergo surgery within the next year. The risk of perioperative cardiac ischemic events, particularly stent thrombosis (ST), is high in these patients, because surgery has a prothrombotic effect and antiplatelet therapy is often withdrawn in order to avoid bleeding. The clinical and angiographic predictors of ST are well known, and the proximity to an acute coronary syndrome adds to the risk. The current guidelines recommend delaying non-urgent surgery for at least 6 weeks after the placement of a bare metal stent and for 6-12 months after the placement of a drug-eluting stent, when the risk of ST is reduced. However, in the absence of formal evidence, these recommendations provide little support with regard to managing urgent operations. When surgery cannot be postponed, stratifying the risk of surgical bleeding and cardiac ischemic events is crucial in order to manage perioperative antiplatelet therapy in individual cases. Dual antiplatelet therapy should not be withdrawn for minor surgery or most gastrointestinal endoscopic procedures. Aspirin can be safely continued perioperatively in the case of most major surgery, and provides coronary protection. In the case of interventions at high risk for both bleeding and ischemic events, when clopidogrel withdrawal is required in order to reduce perioperative bleeding, perioperative treatment with the short-acting intravenous glycoprotein IIb-IIIa inhibitor tirofiban is safe in terms of bleeding, and provides strong antithrombotic protection. Such surgical interventions should be performed at hospitals capable of performing an immediate percutaneous coronary intervention at any time in the case of acute myocardial ischemia.
Journal of Thrombosis and Haemostasis 08/2011; 9(11):2133-42. · 6.08 Impact Factor