Long-Term Anti-Hypertensive Therapy and Stroke Prevention: A Meta-Analysis.

Abstract

Stroke causes approximately 6.7million deaths worldwide per year and is the second leading cause of death. Pharmacotherapy for hypertension, an independent risk factor for stroke, significantly reduces the incidence of stroke. Although prior meta-analyses demonstrate various antihypertensive classes are superior to placebo in reducing stroke risk, which class is most effective is unclear. We conducted a systematic MEDLINE search including only randomized controlled trials (RCT) of antihypertensive medications published between 1999 and 2014 in adults with stroke as a primary or secondary outcome. Five classes compared against all others were angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-adrenoceptor antagonists (β-blockers), calcium channel blockers (CCBs), and thiazide or thiazide-like diuretics (T-TLDs). Among 17 RCTs with 31 comparative arms, risk ratio was used to assess effect size, and a fixed- and random-effect model was used to calculate summary effect size, utilizing comprehensive meta-analysis statistical software version 2.0. The 251,853 subjects (46±11.4% female; mean age 67.2±6.8years), were grouped as follows: ACEI 52,887; ARB 7278; ACEI/ARB 60,165; β-blocker 24,099; CCB 98,950; and T-TLD 68,639. The mean follow-up was 42.9±15months. A random-effect model was used to assess for summary effect size in ACEI, ACEI/ARB, ARB, and T-TLD groups. The summary risk ratio for stroke occurrence in the different antihypertensive drug classes were as follows: ACEIs 1.01 (95% confidence interval [CI] 0.81-1.27; p=0.92); ACEIs/ARBs 0.94 (95% CI 0.78-1.13; p=0.51); T-TLDs 0.90 (95% CI 0.75-1.08; p=0.25); ARBs 0.83 (95% CI 0.59-1.18; p=0.30); β-blockers 1.42 (95% CI 1.26-1.61; p<0.01); and CCBs 0.83 (95% CI 0.79-0.89; p<0.01). Among the antihypertensive classes, CCBs were most effective in reducing the long-term incidence of stroke, whereas β-blockers were associated with significantly increased risk.