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... were followed for a median of 18.6 months (interquartile range, 18.2 to 18.9) and a mean (SD) of 16 (6) months; patients allocated to glipizide were adherent (took 80% and 120% of their study medications) at 90.7% of visits, and those allocated to rosiglitazone were adherent at 92.7% of visits. Adverse effects that were either of interest on the basis of prior studies, that occurred in 5% of partici- pants in either group, or that significantly differed in fre- quency between groups are noted in Table 2. Compared with patients in the glipizide group, those allocated to rosiglitazone had less hypoglycemia and more anemia. ...
Context 2
... were followed for a median of 18.6 months (interquartile range, 18.2 to 18.9) and a mean (SD) of 16 (6) months; patients allocated to glipizide were adherent (took 80% and 120% of their study medications) at 90.7% of visits, and those allocated to rosiglitazone were adherent at 92.7% of visits. Adverse effects that were either of interest on the basis of prior studies, that occurred in 5% of participants in either group, or that significantly differed in frequency between groups are noted in Table 2. Compared with patients in the glipizide group, those allocated to rosiglitazone had less hypoglycemia and more anemia. ...
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Background
Ranolazine is an antianginal drug reported to have hypoglycaemic effects.
Objectives
To assess the effect of ranolazine versus placebo on glycaemic control for adults with and without diabetes.
Methods
A systematic search of seven databases was conducted to identify all randomised controlled trials that compared the effect of ranolazin...
Citations
... The result also has been reported in SYMPHONY substudy [51]. Although these studies highlighted the central role of insulin resistance in progression of atherothrombotic events in DM patients, these outcomes have not been established in the later published APPROACH trial [52]. In this study, there was no significant difference between the group treated with thiazolinedione rosiglitazone and the group treated with glipizide, an insulin secretagogue, in patients with type-2 DM and CAD [52]. ...
... Although these studies highlighted the central role of insulin resistance in progression of atherothrombotic events in DM patients, these outcomes have not been established in the later published APPROACH trial [52]. In this study, there was no significant difference between the group treated with thiazolinedione rosiglitazone and the group treated with glipizide, an insulin secretagogue, in patients with type-2 DM and CAD [52]. ...
Patients with Diabetes Mellitus (DM) have accelerated atherosclerosis, which is the main essential factor contributing to the high risk of atherothrombotic events in these patients. Atherothrombotic complications are the principal cause of morbidity and mortality in patients with DM. Both atherosclerosis and the increased risk of thrombotic vascular events may result from dyslipidaemia, endothelial dysfunction, platelet hyperreactivity, an impaired fibrinolytic balance, and abnormal blood flow. Platelets of DM patients are characterised by dysregulation of several signalling pathways causing increased adhesion, activation and aggregation. Platelet function of patients with DM is complicated by several mechanisms, such as hyperglycaemia, insulin deficiency and resistance, associated metabolic conditions, and cellular abnormalities. The present manuscript purposes to provide a review on the up-to-date status of data on platelet abnormalities that characterise patients with DM.
... 23 Studies have shown that the administration of statins and thiazolidinedione (pioglitazone and rosiglitazone) causes a significant regression of the coronary atherosclerotic plaques and they can be used in the secondary prevention of cardiovascular disease. [24][25][26] A wide angle between the LM and LAD could predict in-stent restenosis after stenting of the proximal LAD, as reported by Konishi et al. 27 The effect of the bifurcation angle on 12-month outcome after stenting of the LM-LAD was investigated by Amemiya et al. 28 The angle was evaluated by three-dimensional quantitative coronary angiography analysis. They reported a significant relationship between the pre-procedure bifurcation angle and adverse cardiac events. ...
Aim:
The aim of this study was to evaluate the association between the left main coronary artery (LM) bifurcation angle and the severity of the proximal left anterior descending coronary artery (LAD) stenosis.
Methods:
Two hundred patients with suspected coronary artery disease who had coronary angiography were included in this observational study. The severity of coronary artery stenosis was analysed using quantitative coronary angiography software (QCA analysis). The LM-LAD and LAD-left circumflex artery (LCX) angles were measured using software (IC MEASURE) in two-dimensional axial images.
Results:
The patients were divided into two groups. The first group included 100 patients with significant proximal LAD stenosis (≥ 50%) and the second, those with LAD stenosis < 50% (100 patients). Patients with significant proximal LAD stenosis were older and had a higher frequency of diabetes mellitus, and higher serum creatinine and low-density lipoprotein levels than those with non-significant LAD stenosis. The LM-LAD and LAD-LCX angles in patients with significant proximal LAD stenosis were wider than in patients with non-significant LAD stenosis (p < 0.001). The cut-off value of 42° of the LM-LAD angle had a sensitivity of 73% and specificity of 70% to predict significant proximal LAD stenosis. The cut-off value of 68° of the LAD-LCX angle had a sensitivity of 68% and specificity of 62% to predict significant proximal LAD disease. In a multivariate logistic regression analysis, LM-LAD and LAD-LCX angles were independent factors for the development of significant proximal LAD stenosis.
Conclusions:
Wider LM-LAD and LAD-LCX angles were associated with the severity of proximal LAD disease. Preventative measures and close follow up are needed in such cases to improve their cardiovascular outcome.
... In the Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation (PERISCOPE) study, 110 pioglitazone was superior to glimepiride in inhibiting plaque progression (PAV: −0.16% vs. +0.73%, P = 0.02), whereas the Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in Diabetes Patients With Cardiovascular History (APPROACH) study 111 showed no difference between the effect of rosiglitazone and glipizide on PAV (see Supplementary material online, Table S1). ...
Intravascular imaging has been often used over the recent years to examine the efficacy of emerging therapies targeting plaque evolution. Serial intravascular ultrasound, optical coherence tomography, or near infrared spectroscopy-intravascular ultrasound studies have allowed us to evaluate the effects of different therapies on plaque burden and morphology, providing unique mechanistic insights about the mode of action of these treatments. Plaque burden reduction, a decrease in necrotic core component or macrophages accumulation – that have been associated with inflammation - and an increase in fibrous cap thickness over fibroatheromas have been used as surrogate endpoints to assess the value of several drugs in inhibiting plaque evolution and improving clinical outcomes.
However, some reports have demonstrated weak associations between the effects of novel treatments on coronary atheroma and composition and their prognostic implications. This review examines the value of invasive imaging in assessing pharmacotherapies targeting atherosclerosis. It summarizes the findings of serial intravascular imaging studies assessing the effects of different drugs on atheroma burden and morphology and compares them with the results of large-scale trials evaluating their impact on clinical outcome. Furthermore, it highlights the limited efficacy of established intravascular imaging surrogate endpoints in predicting the prognostic value of these pharmacotherapies and introduces alternative imaging endpoints based on multimodality/hybrid intravascular imaging that may enable more accurate assessment of the athero-protective and prognostic effects of emerging therapies.
... Sulphonylureas were associated with a significantly increased risk of cardiovascular mortality. [103][104][105][106][107][108][109] Adapted with permission from Phung et al. 101 ...
Despite the importance of individualised strategies for patients with type 2 diabetes mellitus (T2DM) and the availability of alternative treatments, including glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), sulphonylureas are still widely used in practice. Clinical evidence shows that GLP‐1 RAs may provide better and more durable glycaemic control than sulphonylureas, with lower risk of hypoglycaemia. Other reported benefits of GLP‐1 RAs include weight loss rather than weight gain (as observed with sulphonylureas), blood pressure reductions and improvements in lipid profiles. In general, the main adverse events with GLP‐1 RAs are gastrointestinal in nature. The respective modes of action of GLP‐1 RAs and sulphonylureas contribute to differences in durability of glycaemic control (related to effects on beta‐cells) and effects on body weight. Moreover, the glucose‐dependent mode of action of GLP‐1 RAs, which favours a low incidence of hypoglycaemia, contrasts with the glucose‐independent mode of action of sulphonylureas. Evidence from cardiovascular outcomes trials indicates a consistent finding of cardiovascular safety across the GLP‐1 RAs and suggests a class benefit for the long‐acting GLP‐1 RAs in reducing three‐point major adverse cardiovascular events, cardiovascular mortality and all‐cause mortality. In contrast, potential concerns relating to an increased incidence of adverse cardiovascular events with sulphonylureas have yet to be fully resolved. Recent updates to management guidelines recommend that treatment selection for patients with T2DM should consider clinical trial evidence of cardiovascular safety. Available evidence suggests that this selection should give preference to GLP‐1 RAs over sulphonylureas, especially for patients at high cardiovascular risk.
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... It was noted that statin therapy was significantly less administered in patients who developed ACS. This observation corresponds with the results of recent studies which have shown that aggressive lipid reduction therapy (high dosages of atorvastatin or rosuvastatin) induces a regression of plaques and that pioglitazone has favorable effects on coronary atherosclerosis [14, 15, 16]. Almost 2/3 of the total number was located in the left anterior descending artery (LAD) which, in addition to the number of plaques we tested in other coronary arteries , corresponded with the frequency of certain coronary arteries involvement in the development of ACS [14]. ...
Rupture of vulnerable atherosclerotic plaques is the cause of most acute coronary syndromes (ACS). Postmortem studies which compared stable coronary lesions and atherosclerotic plaques in patients who have died because of ACS indicated high lipid-core content as one of the major determinants of plaque vulnerability.
Our primary goal was to assess the potential relations of plaque composition determined by IVUS-VH (Intravascular Ultrasound -Virtual Histology) in patients with stable angina and subjects in acute phase of ACS without ST segment elevation.
The study comprised of 40 patients who underwent preintervention IVUS examination.Tissue maps were reconstructed from radio frequency data using IVUS-VH software.
We analyzed 53 lesions in 40 patients. Stable angina was diagnosed in 24 patients (29 lesions), while acute phase of ACS without ST elevation was diagnosed in 16 patients (24 lesions). In the patients in acute phase of ACS without ST segment elevation IVUS-VH examination showed a significantly larger area of the necrotic core at the site of minimal lumen area and a larger mean of the necrotic core volume in the entire lesion comparing to stable angina subjects (1.84+/-0.90 mm2 vs. 0.96+/-0.69 mm2; p<0.001 and 20.94+/-15.79 mm3 vs. 11.54+/-14.15 mm3; p<0.05 respectively).
IVUS-VH detected that the necrotic core was significantly larger in atherosclerotic lesions in patients in acute phase of ACS without ST elevation comparing to the stable angina subjects and that it could be considered as a marker of plaque vulnerability.
... In the Pioglitazone Effect on Progression of Intravascular Sonographic Obstruction Prospective Evaluation (PERISCOPE) trial [32], pioglitazone significantly reduced the primary outcome of percent atheroma volume (PAV) after 18 months of treatment as compared with glimepiride [32] . The Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in Diabetes Patients with Cardiovascular History (APPROACH) trial [33] showed a nonsignificant effect of rosiglitazone on PAV, suggesting that rosiglitazone, in contrast to pioglitazone, cannot delay the progression of coronary atherosclerosis in patients with type 2 DM and coronary artery disease during a similar treatment pe- riod [33]. ...
... In the Pioglitazone Effect on Progression of Intravascular Sonographic Obstruction Prospective Evaluation (PERISCOPE) trial [32], pioglitazone significantly reduced the primary outcome of percent atheroma volume (PAV) after 18 months of treatment as compared with glimepiride [32] . The Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in Diabetes Patients with Cardiovascular History (APPROACH) trial [33] showed a nonsignificant effect of rosiglitazone on PAV, suggesting that rosiglitazone, in contrast to pioglitazone, cannot delay the progression of coronary atherosclerosis in patients with type 2 DM and coronary artery disease during a similar treatment pe- riod [33]. ...
Diabetes mellitus is an established risk factor for cardiovascular disease and the leading cause of end-stage renal disease in the Western World. Thiazolidinediones (TZDs) represent a class of antidiabetic agents that exert their glucose-lowering effects by reducing insulin resistance, through stimulation of a type of nuclear receptor, called peroxisome proliferator-activated receptor-γ. Apart from improving glycemic control, TZDs were shown to exert beneficial effects on several components of the metabolic syndrome and cardiovascular risk markers. Furthermore, background and human studies have shown that TZDs reduce urinary albumin and protein excretion and interfere with most of the pathogenentic pathways involved in the development and progression of diabetic nephropathy. On the other hand, currently used TZDs have side effects, most important of which is fluid retention leading to wait gain and heart failure deterioration. With regards to cardiovascular outcomes, the anticipated benefit of TZDs was demonstrated for pioglitazone, whereas a series of previous meta-analyses linking rosiglitazone treatment with increased risk of myocardial infarction and cardiovascular death raised uncertainty around the cardiovascular safety of rosiglitazone. This article will discuss the effects of TZDs on established and emerging cardiovascular risk factors, the data on possible beneficial renal effects of these compounds, and the existing evidence from large-scale clinical trials and meta-analyses on their effects on cardiovascular outcomes, aiming to provide an overview of the cardio- and renoprotective properties of these drugs.
... The APPROACH (Assessment on the Prevention of Progression by Rosiglitazone On Atherosclerosis in diabetes patients with Cardiovascular History) study was a double-blind randomized clinical trial comparing the effects of rosiglitazone with glipizide on the progression of coronary atherosclerosis[1,2]. Patients with Type 2 diabetes mellitus (T2DM) are at increased risk for restenosis after intracoronary stent placement[3][4][5][6]. ...
To determine (1) the medium-term effect of rosiglitazone and glipizide on intra-stent neointima hyperplasia, (2) restenosis pattern as assessed by intra-vascular ultrasound (IVUS) and quantitative coronary angiography (QCA) in patients with T2DM and coronary artery disease. A total of 462 patients with T2DM were randomized to rosiglitazone or glipizide for up to 18 months in the APPROACH trial, and had evaluable baseline and follow-up IVUS examinations. There was no significant difference in the size of plaque behind stent between the rosiglitazone and glipizide groups at 18 months among those treated with a bare metal stent (-5.6 mm(3) vs. 1.9 mm(3); P = 0.61) or with a drug-eluting stent (12.1 mm(3) vs. 5.5 mm(3); P = 0.09). Similarly, there was no significant difference in percentage intimal hyperplasia volume between the rosiglitazone and glipizide groups at 18 months among those treated with a bare metal stent (24.1% vs. 19.8%; P = 0.38) or with a drug-eluting stent (9.8% vs. 8.3%; P = 0.57). QCA data (intra-stent late loss, intra-stent diameter stenosis or binary restenosis) were not different between the rosiglitazone and glipizide groups. This study suggests that both rosiglitazone and glipizide have a similar effect on neointimal growth at medium term follow-up, a finding that warrants investigation in dedicated randomized trials.
... Based on the well documented association between excess visceral adipose tissue/ectopic fat vs. insulin resistance, glucose intolerance and features of the so-called metabolic syndrome, such shift in regional energy storage could represent an important " remodeling " mechanism by which TZD therapy could improve not only insulin resistance and glycemic control, but also the global cardiometabolic risk profile of patients with type 2 diabetes [16]. Recent evidence suggests that TZDs could affect atherosclerosis progression and in-stent restenosis [17][18][19] . TZDs have numerous biological effects with anti-inflammatory effects at the cellular and molecular level and in plasma [20,21] . ...
... Plasma adiponectin concentration, whose production is negatively related to adipose cell size, was remarkably increased in the present study, a finding concordant with the view that the gain in subcutaneous adiposity observed in VICTORY is due to adipose tissue hyperplasia rather than to fat cell hypertrophy [24]. Recently, two studies using IVUS to assess atherosclerosis progression after 18 months have been completed in coronary arteries of patients with type 2 diabetes [18,19]. In the PERISCOPE study, the authors found a significant difference in change of % atheroma volume (but not in absolute changes in plaque volume) between baseline and follow-up favoring pioglitazone compared to glimepiride [18] . ...
... In the PERISCOPE study, the authors found a significant difference in change of % atheroma volume (but not in absolute changes in plaque volume) between baseline and follow-up favoring pioglitazone compared to glimepiride [18] . In contrast, in the APPROACH study, the authors found a non-significant difference between rosiglitazone and glipizide in change of % atheroma volume (and a significant effect on absolute change in plaque volume) [19]. These two studies differ from VICTORY as they included different study population, assessed different vascular beds and, baseline and follow-up IVUS exams were 18 months apart compared to 12 months in our study. ...
Objectives:
To assess the efficacy and safety of rosiglitazone on saphenous vein graft (SVG) atherosclerosis prevention and on modification of the global cardiometabolic risk profile.
Methods and results:
This was a double-blind, randomized, placebo-controlled, multicenter trial which enrolled 193 post-CABG patients with type 2 diabetes. Atherosclerosis changes in one SVG were assessed with intravascular ultrasound at baseline and at 12 months. Serial cardiometabolic assessments were performed. At baseline, both groups had mean HbA(1C)<7%, LDL-cholesterol (LDL-C)<2.3 mmol/l, HDL-cholesterol (HDL-C)>1.0 mmol/l and blood pressure<130/75 mmHg. After 12 months, plaque volume in SVG had increased (median [interquartile range]) by 7.7 mm(3) (-17.2 to 37.9) in the placebo group and decreased by 0.3mm(3) (-19.1 to 22.3) in the rosiglitazone group (P=0.22). Compared to placebo, rosiglitazone treated patients had a higher (mean + or - SD) body weight (89 + or - 15 kg vs. 84 + or - 15 kg, P=0.02) at the end of the study, mostly related to an increment in subcutaneous adipose tissue. Rosiglitazone treated patients also displayed further improvements in glycemic control compared to placebo (HbA(1C): 6.4 + or - 0.7% vs. 7.0 + or - 0.9%, P<0.001) as well as in several cardiometabolic parameters such as lipids (HDL-C: 1.16 + or - 0.28 mmol/l vs. 1.06 + or - 0.23 mmol/l, P=0.003), inflammatory profile (C-reactive protein: 0.92 mg/l [0.51-1.56] vs. 1.37 mg/l [0.79-3.08], P=0.02), and adiponectin levels (11.1 microg/ml [8.19-17.9] vs. 4.65 microg/ml [3.27-7.15], P<0.001). There was no significant difference in the incidence of serious adverse cardiovascular events. However, more patients in the rosiglitazone group had peripheral oedema (33% vs. 18%, P=0.0019).
Conclusion:
After a 12-month follow-up, we found no evidence for a statistically significant effect of rosiglitazone on SVG atherosclerosis whereas significant effects on glycemic control and on the cardiometabolic risk profile appeared to be modulated in part by changes in subcutaneous adiposity.
Objective
To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk.
Design
Network meta-analysis.
Data sources
Medline, Embase, and Cochrane CENTRAL up to 11 August 2020.
Eligibility criteria for selecting studies
Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias.
Main outcome measures
Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review.
Results
764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced mortality and admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 5 to 48 fewer deaths in 1000 patients over five years; see interactive decision support tool ( https://magicevidence.org/match-it/200820dist/#!/ ) for all outcomes.
Conclusions
In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review.
Systematic review registration
PROSPERO CRD42019153180.
