Renin-angiotensin system (RAS) inhibitors including angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are widely prescribed to patients, but how does their safety and efficacy compare to other antihypertensive drug classes? A review published in the Cochrane Library evaluated 42 studies involving 65,733 patients (mean age 66 years) with primary elevated blood pressure ≥130/85mmHg) on the effect of various first-line antihypertensives on primary outcomes that included all-cause mortality, fatal and non-fatal stroke, fatal and non-fatal myocardial infarction (MI), fatal and non-fatal congestive heart failure (CHF) requiring hospitalization, total cardiovascular (CV) events (consisting of fatal and non-fatal stroke, fatal and non-fatal MI, and fatal and non-fatal CHF requiring hospitalizations), and ESRF. All studies were randomized-controlled trials with parallel design, double-blind, and had a minimum follow-up of six months.

The results were as follows:

  • All-cause mortality is similar for both first-line RAS inhibitors and other first-line antihypertensives (moderate quality evidence)
  • Compared with calcium channel blockers (CCBs), RAS inhibitors decreased HF risk but increased stroke risk (moderate quality evidence). The reduction in HF risk however exceeded the risk of stroke.
  • Compared to thiazides, RAS inhibitors increased the risk of HF and stroke (moderate quality evidence)
  • Compared to beta-blockers, RAS inhibitors decreased risk total CV events and stroke (low quality evidence).

Small differences in effect on blood pressure were seen with different drug classes, which did not appear to correlate with the differences in the hard outcomes.

This review suggests that first-line RAS inhibitors are a better first-line choice than first-line beta-blockers and first-line CCBs for hypertension, but are inferior to first-line thiazides. Clinicians should weigh the risks and benefits associated with these outcomes when selecting a first-line treatment for hypertension based on the individual patient risk.