Long-term Anti-hypertensive Therapy and Stroke Prevention

A Meta-analysis

Bertrand N. Mukete; Mark Cassidy; Keith C. Ferdinand; Thierry H. Le Jemtel


Am J Cardiovasc Drugs. 2015;15(4):243-257. 

In This Article

Abstract and Introduction


Background Stroke causes approximately 6.7 million 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.

Methods 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. Results The 251,853 subjects (46 ± 11.4 % female; mean age 67.2 ± 6.8 years), 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 ± 15 months. 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).

Conclusion 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


Hypertension is a major risk factor for cardiovascular disease (CVD) and stroke, affecting one in three US adults.[1] Hypertension is an independent risk factor for stroke, heart failure (HF), atherosclerotic CVD, renal failure, and death.

According to data from NHANES (National Health and Nutrition Examination Survey) (2007–2010), an estimated 6.8 million adults aged ≥20 years have experienced a stroke in the USA. The prevalence of stroke in this timeframe is estimated to be 2.8 %. An additional 3.4 million Americans are projected to have had a stroke at age 18 or older by 2030.[2] Cerebrovascular disease is the second leading cause of death worldwide, with approximately 5 million deaths annually.[3]

The BPLTTC (Blood Pressure Lowering Treatment Trialists' Collaboration) was a systematic review that included 29 randomized antihypertensive trials that examined the effects of different blood pressure (BP)-lowering regimens on major cardiovascular events, including stroke. All outcome data collected were from between July 1995 and June 2003.[4,5] A statistically significant reduction in risk of stroke was seen with regimens based on angiotensinconverting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs) when compared with placebo. The BP trials showed no statistically significant difference in stroke risk reduction between the active treatment regimens.

Thus far, it is not clear which antihypertensive regimen is better long term for primary and/or secondary reduction of stroke risk. We performed a systematic review using meta-analytic methods evaluating the efficacy of long-term antihypertensive regimens on primary and/or secondary stroke risk reduction.