What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Hypertension (n=180342). Intervention: Antihypertensive drug classes (ACEIs, ARBs, BBs, CCBs, diuretics) vs. Another antihypertensive drug class or placebo. Primary outcome: Fatal or non-fatal stroke incidence (RR 0.94, 95% CI 0.83-1.05, p=>0.05).

What does this research mean for the field?

Major antihypertensive drug classes show no significant difference in overall stroke prevention, as the magnitude of systolic blood pressure reduction is the primary determinant of benefit. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The review aims to systematically compare the effects of different antihypertensive drug classes on stroke prevention.

March 21, 2026Open Access

Effect of Antihypertensive Drug Classes on Stroke Prevention: A Systematic Review and Meta-Analysis

Key Result

Major antihypertensive drug classes showed no significant difference in overall stroke prevention (RR 0.94), as the magnitude of systolic blood pressure reduction was the primary determinant of benefit.

Key Points

The review aims to systematically compare the effects of different antihypertensive drug classes on stroke prevention.
Conducted a systematic review following PRISMA guidelines.
Analyzed randomized controlled trials published since January 2000.
Compared different antihypertensive classes including ACEIs, ARBs, BBs, CCBs, and diuretics.
Used random-effects model for data pooling and conducted subgroup analyses.
No significant difference in stroke risk among drug classes with RR: 0.94; 95% CI: 0.83-1.05.
Substantial heterogeneity in results (I²=65%).
Moderate SBP differences (>2 mmHg) led to a significant stroke risk reduction (RR: 0.78; 95% CI: 0.71-0.85).
Minimal SBP differences (<2 mmHg) did not affect stroke risk (RR: 1.02; 95% CI: 0.90-1.14).
Overall, no drug class was superior for stroke prevention.

Study Design

Type

Meta-Analysis (n=180,342)

Structured PICO

Does the choice of specific antihypertensive drug class reduce stroke incidence in adults with hypertension?

Population

Adults with diagnosed primary hypertension or a history of cerebrovascular event/TIA

Intervention

Antihypertensive drug classes (ACEIs, ARBs, beta-blockers, CCBs, or diuretics)

Comparator

Another antihypertensive drug class or placebo

Outcome

Stroke incidence (fatal and non-fatal)hard clinical

The magnitude of achieved systolic blood pressure reduction, rather than the specific antihypertensive drug class used, is the primary determinant of stroke prevention in hypertensive patients.

Main Result

Effect estimate: RR 0.94 (95% CI 0.83-1.05)

p-value: p=>0.05

Limitations

Considerable clinical and methodological heterogeneity among the included studies
Potential performance bias from PROBE designs or treatment strategy trials
Inclusion of fixed-dose combinations may confound the effect of a single drug class
Ecological fallacy risk due to reliance on study-level aggregate data for SBP differences
Inability to perform time-to-event analyses or adjust for patient-level covariates due to lack of individual patient data
Inability to analyze stroke outcomes by pathological subtype (ischemic vs. hemorrhagic)
Restriction to English-language publications

Abstract

Hypertension is the most common modifiable risk factor for stroke. However, whether different classes of antihypertensive drugs provide equal protection against stroke remains controversial. This review aimed to systematically compare the effects of various antihypertensive drug classes on stroke prevention through a contemporary meta-analysis of randomized controlled trials (RCTs). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search was conducted in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus for studies published since January 2000. Eligible RCTs compared angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), or diuretics with another drug class or placebo and reported stroke incidence. Data were pooled using a random-effects model. Subgroup analyses were performed based on prevention type, baseline risk, and differences in achieved blood pressure. A total of 10 RCTs (N=180,342 participants) were included. The pooled meta-analysis showed no statistically significant difference in stroke risk among the drug classes (risk ratio (RR): 0.94; 95% confidence interval (CI): 0.83-1.05), although heterogeneity was substantial (I²=65%). Subgroup analyses revealed no effect modification by prevention type or baseline risk. However, studies with a moderate to significant between-group difference in systolic blood pressure (SBP) (>2 mmHg) demonstrated a substantial reduction in stroke risk (RR: 0.78; 95% CI: 0.71-0.85), whereas studies with a minimal difference (<2 mmHg) did not (RR: 1.02: 95% CI: 0.90-1.14; p for subgroup difference=0.001). No antihypertensive drug class was found to be superior for stroke prevention overall. The magnitude of achieved SBP reduction, rather than the drug class itself, appears to be the primary determinant of benefit.

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