Combination Use of Clopidogrel and Proton Pump Inhibitors Increases Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease: A Meta-Analysis.

BACKGROUND: Published data indicated that combination use of clopidogrel and proton pump inhibitors (PPIs) may increase the incidence of major adverse cardiovascular events (MACEs). This has been a highly controversial topic for years. DESIGN: The present study was performed to evaluate whether combination therapy of clopidogrel and PPIs is associated with increased risk of MACEs than with clopidogrel alone in patients with coronary artery disease. METHODS: A systematic search of MEDLINE, EMBASE, and the Cochrane Library was conducted for studies recording the occurrence of MACEs in patients with exposure to concomitant use of clopidogrel and PPIs up to February 2015. Odds ratios (ORs) were combined using a random-effects model. RESULTS: Patients receiving combination therapy with PPIs and clopidogrel were at significantly increased risk of MACEs (OR: 1.42; 95% confidence interval [CI]: 1.30-1.55). Adding a PPI to clopidogrel treatment was associated with a higher rate of MACE occurrence in rapid metabolizers (RMs, *1/*1) of CYP2C19 (OR: 1.42; 95% CI: 1.12-1.81), but there was no obviously increased rate (OR: 1.43; 95% CI: 0.89-2.28) in decreased metabolizers (with 1 or 2 loss-of-function allele). The increased risk of MACEs was similar in 4 classes of PPIs (omeprazole, lansoprazole, esomeprazole, and pantoprazole), but rabeprazole (OR: 1.03; 95% CI: 0.55-1.95) wasn't. CONCLUSION: The combination use of clopidogrel and certain types of PPIs (omeprazole, lansoprazole, esomeprazole, pantoprazole) increases the risk of MACE in patients with coronary artery disease. Only in the RMs of CYP2C19, PPIs were associated with significantly increased MACE in patients coadministered with clopidogrel.

The safety and efficacy of antithrombotic therapy in patients undergoing cardiac rhythm device implantation: a meta-analysis.

AIMS: The meta-analysis was to assess the safety and efficacy of periprocedural antithrombotic therapy and to evaluate the risk factors potentially associated with bleeding among patients undergoing cardiac implantable electronic devices implantations. METHODS AND RESULTS: A systematic literature search of PubMed, EMBASE, and Cochrane Controlled Trials Register was performed. Anticoagulation and antiplatelet therapies were assessed separately. Uninterrupted anticoagulation was associated with significant lower bleeding risk compared with heparin bridging strategy [odds ratio (OR) = 0.31, 95% confidence interval (CI) 0.18-0.53, and P < 0.0001], but there was no significant difference in thromboembolic risk between these two strategies (OR = 0.82, 95% CI 0.32-2.09, and P = 0.65). The haematoma rate was significantly increased in dual antiplatelet therapy group (OR = 6.84, 95% CI 4.16-11.25, and P < 0.00001), but not in single antiplatelet therapy (OR = 1.52, 95% CI 0.93-2.46, and P = 0.09). Clopidogrel increased the risk of haematoma vs. aspirin (OR = 2.91, 95% CI 1.27-6.69, and P = 0.01). Otherwise, a lower risk of haematoma was observed in pacemaker group vs. cardiac resynchronization therapy and/or implantable cardioverter defibrillator group (OR = 0.64, 95% CI 0.50-0.82, and P = 0.0004). CONCLUSION: This meta-analysis suggested that uninterrupted oral anticoagulation seems to be the better strategy, associated with a lower risk of bleeding complications rather than heparin bridging, and dual antiplatelet therapy carried a significant risk of bleeding whereas single antiplatelet therapy was relatively safe among patients undergoing cardiac implantable electronic devices implantations. Meanwhile, cardiac resynchronization therapy and/or implantable cardioverter defibrillator implantations increase the bleeding.

Effects of radiofrequency catheter ablation on left ventricular structure and function in patients with atrial fibrillation: a meta-analysis.

INTRODUCTION: Radiofrequency catheter ablation (RFCA) is an effective therapy for atrial fibrillation (AF). This study was designed to investigate the effects of RFCA on left ventricular (LV) structure and function in AF patients. METHODS AND RESULTS: A systematic literature search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was performed to identify trials involving changes of LV structure and function in AF patients undergoing RFCA. Effect size was expressed as weighted mean difference (WMD) with 95% confidence interval (CI). LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were estimated. A total of 21 trials including 1,135 participants were qualified for this meta-analysis. Compared to the baseline values, there were significant decreases in LVEDV (WMD, -6.39 ml; 95%CI, -12.46 to -0.33) and LVESV (WMD, -6.39 ml; 95%CI, -11.35 to -1.42) and a significant improvement in LVEF (WMD, 6.23%; 95%CI, 3.70 to 8.75), but no significant changes were observed in LVEDD (WMD, -0.64 mm; 95%CI, -2.40 to 1.13) and LVESD (WMD, -0.38 mm; 95%CI, -1.32 to 0.56) after RFCA. Subgroup analysis demonstrated that patients with low LVEF (WMD, 11.90%; 95%CI, 9.16 to 14.64) gained more benefits than those with normal LVEF (WMD, 1.56%; 95%CI, 0.38 to 2.74). Besides, patients with chronic AF (WMD, 10.96%; 95%CI, 4.92 to 17.01) improved more than those with paroxysmal AF (WMD, 1.93%; 95%CI, -0.27 to 4.12). CONCLUSIONS: RFCA in AF patients could reverse LV structural remodeling and improve LV systolic function, especially in patients with low LVEF and chronic AF.

Renin-angiotensin system inhibitors prevent the recurrence of atrial fibrillation: a meta-analysis of randomized controlled trials.

OBJECTIVE: This study was designed to assess whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could prevent the recurrence of atrial fibrillation (AF). METHODS: A systemic literature search of PubMed, EMBASE, and Cochrane Controlled Trials Register till 2012 was performed to identify randomized controlled trials involving the prevention of recurrence of AF with renin-angiotensin system blockade therapy. Subgroup analysis and meta-regression were performed. Publication bias was checked through funnel plot and Egger's test. RESULTS: Twenty-one randomized controlled trials including 13,184 patients with AF were identified. Overall, the recurrence of AF was significantly reduced in patients using ACEI/ARBs [odds ratio (OR), 0.43; 95% confidence interval (CI), 0.32-0.56; P < 0.00001], especially both in irbesartan subgroup (OR, 0.38; 95% CI, 0.21-0.68; P = 0.001) and in patients receiving antiarrhythmic drug (AAD) (OR, 0.37; 95% CI, 0.29-0.48; P < 0.00001), and there was no significant difference between ACEIs and ARBs (ACEIs: OR, 0.42; 95% CI, 0.31-0.57 and ARBs: OR, 0.42; 95% CI, 0.31-0.57). Moreover, it was found that the benefits of ACEI/ARBs revealed positive correlation to systolic blood pressure (regression coefficient: -0.0700257, P = 0.000) in no-AAD users. CONCLUSIONS: ACEI/ARBs are effective on the secondary prevention of AF, especially in patients receiving AAD and suffering from hypertension.