Antihypertensive Classes Show Different Real-World Outcomes

A systematic review and meta-analysis of real-world observational studies found that angiotensin receptor blockers (ARBs) and diuretics were associated with more favorable outcomes than angiotensin-converting enzyme inhibitors (ACEIs) for selected endpoints. ARBs also showed favorable associations compared with calcium channel blockers (CCBs), whereas beta-blockers were associated with greater heart failure risk than renin-angiotensin-aldosterone system inhibitors (RASIs). The article-in-press findings were published online in Scientific Reports.

Investigators searched MEDLINE and Scopus through November 26, 2025, for observational studies that used propensity score methods to compare antihypertensive drug classes in adults with hypertension. The analysis included 49 retrospective cohort studies representing approximately 13 million patients before propensity score adjustment. Outcomes included mortality, cardiovascular events, and blood pressure.

Compared with ACEIs, ARBs were associated with lower risks of all-cause mortality (adjusted hazard ratio [aHR], 0.89; 95% CI, 0.84-0.95), cardiovascular mortality (aHR, 0.74; 95% CI, 0.58-0.95), heart failure (aHR, 0.94; 95% CI, 0.90-0.98), composite cardiovascular events (aHR, 0.87; 95% CI, 0.85-0.88), and myocardial infarction (aHR, 0.89; 95% CI, 0.79-0.99).

Diuretics were associated with lower risks of all-cause mortality and stroke than ACEIs. Compared with CCBs, ARBs were associated with lower risks of all-cause mortality, stroke, and myocardial infarction. Beta-blockers were associated with a higher risk of heart failure than RASIs (aHR, 1.91; 95% CI, 1.07-3.39).

The authors cautioned that the findings are associative rather than causal. Forty-seven percent of studies had a serious risk of bias, and 4% had a critical risk; evidence certainty was low or very low for all comparisons. Residual confounding, clinical heterogeneity, small numbers of contributing studies for several comparisons, and limited blood pressure data further constrained interpretation. The authors said the results do not support definitive changes to clinical guidelines or first-line treatment recommendations.

Source: Ta ANP, Turongkaravee S, Chaikledkaew U, et al. Comparative real-world effectiveness of antihypertensive agents on complications: a systematic review and meta-analysis of observational studies employing propensity score methods. Sci Rep. Published online August 26, 2026. doi:10.1038/s41598-026-65046-x