Abstract
Background: Dihydropyridine calcium channel blockers are a heterogeneous group of antihypertensive drugs. Long acting dihydropyridine agent Amlodipine is widely used for mono and combination therapy for hypertension in clinical practice, while intermediate acting dihydropyridine agents such as Felodipine, Nifedipine-GITS etc. have shown inconsistent results in randomized clinical trials (RCTs). Methods and Results: A meta-analysis of 18 prospective, actively controlled RCTs enrolling a total of 80,069 hypertensive patients followed for a mean of 51.7 months was performed. Amlodipine therapy was associated with 24% higher risk of heart failure (RR: 1.24, [95%CI: 1.04 to 1.48], p= 0.019) but 16% lower risk of stroke (RR: 0.84, [95%CI: 0.73 to 0.95], p=0.009) without statistically significant effect on acute myocardial infarction (AMI) (RR: 0.90, [95%CI: 0.78 to 1.03], p=0.128) or cardiovascular event (CVE) (RR: 0.99, [95%CI: 0.93 to 1.06], p=0.814). Intermediate acting dihydropyridine calcium channel blocker therapy was associated with 24% higher risk of heart failure (RR: 1.24, [95%CI: 1.07 to 1.44], p=0.005), 27% higher risk of AMI (RR: 1.27, [95%CI: 1.04 to 1.55], p=0.019), 14% higher risk of CVE (RR: 1.14, [95%CI: 1.01 to 1.29], p=0.034) without statistically significant effect against stroke (RR: 1.03, [95%CI: 0.87 to 1.21], p=0.580). Amlodipine showed higher risk of heart failure (RR: 1.20, [95%CI: 1.00 to 1.43], p=0.045) and lower risk of stroke (RR; 0.85, [95%CI: 0.75 to 0.96], p= 0.007) compared to Renin-angiotensin-system (RAS) blockers. Intermediate acting dihydropyridine calcium channel blocker showed higher risk of heart failure (RR: 1.31, [95%CI: 1.09 to 1.57], p=0.004) and AMI (RR: 1.46, [95%CI: 1.00 to 2.14], p=0.050) compared to RAS blockers. Multivariate meta-regression suggested that the effect size may differ between intermediate and long acting agents for stroke (B: -0.27, [95%CI: -0.50 to -0.05], p=0.012) and AMI (B: -0.42, [95%CI: -0.69 to -0.16], p=0.002) after adjustment for baseline presence of diabetes. Conclusions: This study suggests that Amlodipine offers greater protection against major complications of hypertension compared to intermediate acting dihydropyridine calcium channel blockers.
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