Stéphane Rinfret

The Metabolic Syndrome and Cardiovascular Risk : A Systematic Review and Meta-Analysis

OBJECTIVES We sought to conduct a systematic review and meta-analysis of the cardiovascular risk associated with the metabolic syndrome as defined by the 2001 National Cholesterol Education Program (NCEP) and 2004 revised National Cholesterol Education Program (rNCEP) definitions. BACKGROUND Numerous studies have investigated the cardiovascular risk associated with the NCEP and rNCEP definitions of the metabolic syndrome. There is debate regarding the prognostic significance of the metabolic syndrome for cardiovascular outcomes. METHODS We searched the Cochrane Library, EMBASE, and Medline databases through June 2009 for prospective observational studies investigating the cardiovascular effects of the metabolic syndrome. Two reviewers extracted data, which were aggregated using random-effects models. RESULTS We identified 87 studies, which included 951,083 patients (NCEP: 63 studies, 497,651 patients; rNCEP: 33 studies, 453,432 patients). There was little variation between the cardiovascular risk associated with NCEP and rNCEP definitions. When both definitions were pooled, the metabolic syndrome was associated with an increased risk of cardiovascular disease (CVD) (relative risk [RR]: 2.35; 95% confidence interval [CI]: 2.02 to 2.73), CVD mortality (RR: 2.40; 95% CI: 1.87 to 3.08), all-cause mortality (RR: 1.58; 95% CI: 1.39 to 1.78), myocardial infarction (RR: 1.99; 95% CI: 1.61 to 2.46), and stroke (RR: 2.27; 95% CI: 1.80 to 2.85). Patients with the metabolic syndrome, but without diabetes, maintained a high cardiovascular risk. CONCLUSIONS The metabolic syndrome is associated with a 2-fold increase in cardiovascular outcomes and a 1.5-fold increase in all-cause mortality. Studies are needed to investigate whether or not the prognostic significance of the metabolic syndrome exceeds the risk associated with the sum of its individual components. Furthermore, studies are needed to elucidate the mechanisms by which the metabolic syndrome increases cardiovascular risk.

Effectiveness of recanalization of chronic total occlusions: A systematic review and meta-analysis

BACKGROUND Chronic total occlusion (CTO) recanalizations remain extremely challenging procedures. With improvements in technology and techniques, success rates for recanalization of CTO continue to improve. However, the clinical benefits of this practice remain unclear. The aim of the study was to determine the effectiveness of CTO recanalization on clinical outcomes. METHODS We performed a systematic review and meta-analysis of published studies comparing CTO recanalization to medical management. Data were extracted in duplicate and analyzed by a random effects model. RESULTS We did not identify any randomized controlled trials or observational studies comparing CTO recanalization to a planned medical management. We did identify 13 observational studies comparing outcomes after successful vs failed CTO recanalization attempt. These studies encompassed 7,288 patients observed over a weighted average follow-up of 6 years. There were 721 (14.3%) deaths of 5,056 patients after successful CTO recanalization compared to 390 deaths (17.5%) of 2,232 patients after failed CTO recanalization (odds ratio [OR] 0.56, 95% CI 0.43-0.72). Successful recanalization was associated with a significant reduction in subsequent coronary artery bypass graft surgery (CABG) (OR 0.22, 95% CI 0.17-0.27) but not in myocardial infarction (OR 0.74, 95% CI 0.44-1.25) or major adverse cardiac events (OR 0.81, 95% CI 0.55-1.21). In the 6 studies that reported angina status, successful recanalization was associated with a significant reduction in residual/recurrent angina (OR 0.45, 95% CI 0.30-0.67). CONCLUSIONS In highly selected patients considered for CTO recanalization, successful attempts appear to be associated with an improvement in mortality and with a reduction for the need for CABG as compared to failed recanalization. However, given the observational nature of the reviewed evidence, randomized clinical trials are needed to confirm these findings.

Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials

Background: Many placebo-controlled trials have demonstrated the efficacy of individual pharmacotherapies approved for smoking cessation. However, few direct or indirect comparisons of such interventions have been conducted. We performed a meta-analysis to compare the treatment effects of 7 approved pharmacologic interventions for smoking cessation. Methods: We searched the US Centers for Disease Control and Preventions Tobacco Information and Prevention database as well as MEDLINE, EMBASE and the Cochrane Library for published reports of placebo-controlled, double-blind randomized controlled trials of pharmacotherapies for smoking cessation. We included studies that reported biochemically validated measures of abstinence at 6 and 12 months. We used a hierarchical Bayesian random-effects model to summarize the results for each intervention. Results: We identified 70 published reports of 69 trials involving a total of 32 908 patients. Six of the 7 pharmacotherapies studied were found to be more efficacious than placebo: varenicline (odds ratio [OR] 2.41, 95% credible interval [CrI] 1.91–3.12), nicotine nasal spray (OR 2.37, 95% CrI 1.12–5.13), bupropion (OR 2.07, 95% CrI 1.73–2.55), transdermal nicotine (OR 2.07, 95% CrI 1.69–2.62), nicotine tablet (OR 2.06, 95% CrI 1.12–5.13) and nicotine gum (OR 1.71, 95% CrI 1.35–2.21). Similar results were obtained regardless of which measure of abstinence was used. Although the point estimate favoured nicotine inhaler over placebo (OR 2.17), these results were not conclusive because the credible interval included unity (95% CrI 0.95–5.43). When all 7 interventions were included in the same model, all were more efficacious than placebo. In our analysis of data from the varenicline trials that included bupropion control arms, we found that varenicline was superior to bupropion (OR 2.18, 95% CrI 1.09–4.08). Interpretation: Varenicline, bupropion and the 5 nicotine replacement therapies were all more efficacious than placebo at promoting smoking abstinence at 6 and 12 months.

Predicting Late Myocardial Recovery and Outcomes in the Early Hours of ST-Segment Elevation Myocardial Infarction : Traditional Measures Compared With Microvascular Obstruction, Salvaged Myocardium, and Necrosis Characteristics by Cardiovascular Magnetic Resonance

OBJECTIVES The aim of this study was to determine whether a very early imaging strategy improves the prediction of late systolic dysfunction and poor outcomes in ST-segment elevation myocardial infarction (STEMI) compared with traditional predictors. BACKGROUND Earlier prediction of poor outcomes after STEMI is desirable, because it will allow tailored therapy at the earliest possible time, when benefits might be greatest. METHODS One hundred and three patients with acute STEMI were studied by contrast-enhanced cardiovascular magnetic resonance within 12 h of primary angioplasty and at 6 months and followed >2 years. The primary end point was left ventricular (LV) dysfunction, whereas poor outcomes were a key secondary end point. RESULTS Traditional risk factors were only modest predictors of late LV dysfunction. Late gadolinium enhancement (LGE) volume maintained a stronger association to LV ejection fraction change than infarct transmurality, microvascular obstruction, or myocardial salvage during STEMI (p = 0.02). Multivariable logistic regression identified LGE volume during STEMI as the best predictor of late LV dysfunction (odds ratio: 1.36, p = 0.03). An LGE >or=23% of LV during STEMI accurately predicted late LV dysfunction (sensitivity 89%, specificity 74%). The LGE volume provided important incremental benefit for predicting late dysfunction (area under the curve = 0.92, p <or= 0.03 vs. traditional risk factors). Twenty-three patients developed poor outcomes (1 death, 2 myocardial infarctions, 5 malignant arrhythmias, 4 severe LV dysfunction <35%, 11 hospital stays for heart failure) over 2.6 +/- 0.9 years; LGE volume remained a strong independent predictor of poor outcomes, whereas LGE >or=23% carried a hazard ratio of 6.1 for adverse events (p < 0.0001). CONCLUSIONS During the hyperacute phase of STEMI, LGE volume provides the strongest association and incremental predictive value for late systolic dysfunction and discerns poor late outcomes.

Behavioural interventions for smoking cessation : a meta-analysis of randomized controlled trials

AIMS Widely varying estimates of treatment effects have been reported in randomized controlled trials (RCTs) investigating the efficacy of behavioural interventions for smoking cessation. Previous meta-analyses investigating behavioural interventions have important limitations and do not include recently published RCTs. We undertook a meta-analysis of RCTs to synthesize the treatment effects of four behavioural interventions, including minimal clinical intervention (brief advice from a healthcare worker), and intensive interventions, including individual, group, and telephone counselling. METHODS AND RESULTS We searched the CDC Tobacco Information and Prevention, Cochrane Library, EMBASE, Medline, and PsycINFO databases. We included only RCTs that reported biochemically validated smoking cessation outcomes at 6 and/or 12 months after the target quit date. Outcomes were aggregated using hierarchical Bayesian random-effects models. We identified 50 RCTs, which randomized n = 26 927 patients (minimal clinical intervention: 9 RCTs, n = 6456; individual counselling: 23 RCTs, n = 8646; group counselling: 12 RCTs, n = 3600; telephone counselling: 10 RCTs, n = 8225). The estimated mean treatment effects were minimal clinical intervention [odds ratio (OR) 1.50, 95% credible interval (CrI) 0.84-2.78], individual counselling (OR 1.49, 95% CrI 1.08-2.07), group counselling (OR 1.76, 95% CrI 1.11-2.93), and telephone counselling (OR 1.58, 95% CrI 1.15-2.29). CONCLUSION Intensive behavioural interventions result in substantial increases in smoking abstinence compared with control. Although minimal clinical intervention may increase smoking abstinence, there is insufficient evidence to draw strong conclusions regarding its efficacy.

Effect of Fibrates on Lipid Profiles and Cardiovascular Outcomes: A Systematic Review

OBJECTIVE Fibrates might represent a viable treatment option for patients who do not meet their target low-density lipoprotein levels on statins or who are resistant or intolerant to statins. New data from fibrate trials can be synthesized with the existing literature to better estimate their effects. METHODS We systematically searched the literature to identify randomized, double-blind, placebo-controlled trials examining the effect of fibrates on lipid profiles or cardiovascular outcomes. We estimated the effect of fibrates on the incidence of nonfatal myocardial infarction and all-cause mortality using random effects models. RESULTS Compared with placebo, fibrates were associated with greater reductions in total cholesterol (range: -101.3 mg/dL to -5.0 mg/dL) and triglycerides (range: -321.3 mg/dL to -20.8 mg/dL), and a greater increase in high-density lipoprotein (range: +1.1 mg/dL to +17.9 mg/dL) in all trials. Fibrates tended to be associated with a greater reduction in low-density lipoprotein (range: -76.3 mg/dL to +38.7 mg/dL) than placebo, although these results were not consistent across all trials. Fibrates were more efficacious than placebo at preventing nonfatal myocardial infarction (odds ratio=0.78; 95% confidence interval, 0.69-0.89), but not all-cause mortality (odds ratio=1.05; 95% confidence interval, 0.95-1.15). CONCLUSION In addition to improving lipid profiles, fibrates are associated with an important decrease in nonfatal myocardial infarction, but do not substantially affect all-cause mortality. Potential applications include treatment for patients with statin resistance or isolated hypertriglyceridemia, or as an adjunct to other lipid-lowering therapies.

Meta-analysis of ten trials on the effectiveness of the radial versus the femoral approach in primary percutaneous coronary intervention.

The radial approach in primary percutaneous coronary intervention (PCI) has been recently assessed in both randomized and observational studies. However, observational studies have several biases that favor the radial approach. We conducted a meta-analysis of randomized controlled trials to compare the clinical outcomes of radial and femoral approach in primary PCI for ST-segment elevation myocardial infarction. The outcomes of interest included death, major bleeding, vascular complications/hematoma, and procedure time. The data were pooled using random-effects models. Ten randomized controlled trials involving 3,347 patients met our inclusion criteria. The radial approach was associated with improved survival (odds ratio 0.53, 95% confidence interval 0.33-0.84) and reduced vascular complications/hematoma (odds ratio 0.35, 95% confidence interval 0.24-0.53). A nonsignificant trend was found toward reduced major bleeding with the radial approach (odds ratio 0.63, 95% confidence interval 0.35-1.12). The procedural time with the radial approach was longer by < 2 minutes (mean difference 1.76 minutes, 95% confidence interval 0.59-2.92). In conclusion, in patients undergoing primary PCI, the radial approach is associated with lower short-term mortality. When feasible, the radial approach should be the favored route in primary PCI.

The retrograde technique for recanalization of chronic total occlusions: a step-by-step approach.

Chronic total occlusion recanalization still represents the final frontier in percutaneous coronary intervention. Retrograde chronic total occlusion recanalization has recently become an essential complement to the classical antegrade approach. In experienced hands, the retrograde technique currently has a high success rate with a low complication profile, despite frequent utilization in the most anatomically and clinically complex patients. Since its initial description, important changes have occurred that make the technique faster and more successful. We propose a step-by-step approach of the technique as practiced at experienced centers in North America. Because the technique can vary substantially, we describe the different alternatives to each step and offer what we perceived to be the most efficient techniques.

Meta-analysis of clinical outcomes of patients who underwent percutaneous coronary interventions for chronic total occlusions

Successful percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) has been associated with clinical benefit. There are no randomized controlled trials on long-term clinical outcomes after CTO PCI, limiting the available evidence to observational cohort studies. We sought to perform a weighted meta-analysis of the long-term outcomes of successful versus failed CTO PCI. A total of 25 studies, published from 1990 to 2014, with 28,486 patients (29,315 CTO PCI procedures) were included. We analyzed data on mortality, subsequent coronary artery bypass grafting (CABG), myocardial infarction, major adverse cardiac events, angina pectoris, stroke, and target vessel revascularization using random-effects models. Procedural success was 71% (range 51% to 87%). During a weighted mean follow-up of 3.11 years, compared with unsuccessful, successful CTO PCI was associated with lower mortality (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.43 to 0.63), less residual angina (OR 0.38, 95% CI 0.24 to 0.60), lower risk for stroke (OR 0.72, 95% CI 0.60 to 0.88), less need for subsequent coronary artery bypass grafting (OR 0.18, 95% CI 0.14 to 0.22), and lower risk for major adverse cardiac events (0.59, 95% CI 0.44 to 0.79). There was no difference in the incidence of target vessel revascularization (OR 0.66, 95% CI 0.36 to 1.23) or myocardial infarction (OR 0.73, 95% CI 0.52 to 1.03). Outcomes were similar in patients who underwent balloon angioplasty only or stenting with bare metal or drug-eluting stents. Compared with failed procedures, successful CTO PCIs are associated with a lower risk of death, stroke, and coronary artery bypass grafting and less recurrent angina pectoris.

Adjunctive Thrombectomy for Acute Myocardial Infarction A Bayesian Meta-Analysis

Background—In available trials and meta-analyses, adjunctive thrombectomy in acute myocardial infarction (MI) improves markers of myocardial reperfusion but has limited effects on clinical outcomes. Thrombectomy devices simply aspirate thrombus or mechanically fragment it before aspiration. Simple aspiration thrombectomy may offer a distinct advantage. Methods and Results—We identified 21 eligible trials (16 that used a simple aspiration thrombectomy device) involving 4299 patients with ST-segment elevation MI randomized to reperfusion therapy by primary percutaneous coronary intervention with or without thrombectomy. By using Bayesian meta-analysis methods, we found that thrombectomy yielded substantially less no-reflow (odds ratio [OR], 0.39; 95% credible interval [CrI], 0.18 to 0.69), more ST-segment resolution ≥50% (OR, 2.22; 95% CrI, 1.60 to 3.23), and more thrombolysis in myocardial infarction/myocardial perfusion grade 3 (OR, 2.50; 95% CrI, 1.48 to 4.41). There was no evidence for a decrease in death (OR, 0.94; 95% CrI, 0.47 to 1.80), death, recurrent MI, or stroke (OR, 1.07; 95% CrI, 0.63 to 1.92) with thrombectomy. Restriction of the analysis to trials that used simple aspiration thrombectomy devices did not yield substantially different results, except for a positive effect on postprocedure thrombolysis in myocardial infarction grade 3 flow (OR, 1.49; 95% CrI, 1.14 to 1.99). Conclusions—In this Bayesian meta-analysis, adjunctive thrombectomy improves early markers of reperfusion but does not substantially effect 30-day post-MI mortality, reinfarction, and stroke. The use of aspiration thrombectomy devices is not associated with a reduction in post-MI clinical outcomes. Thrombectomy is one of the rare effective preventive measures against no-reflow.