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Evidence summaries

First-Line Renin Angiotensin System Inhibitors Versus other Drug Classes for Hypertension

First-line renin angiotensin system (RAS) inhibitors appear not to differ for all-cause death compared to calcium channel blockers, thiazides, or beta-blockers for hypertension. They appear to increase heart failure and stroke compared with thiazides. Level of evidence: "B"

The quality of evidence is downgraded by study limitations (unclear allocation concealment).

Summary

A Cochrane review [Abstract] 1 included 45 studies with a total of 66 625 subjects with a mean age of 66 years to evaluate the benefits and harms of first-line renin-angiotensin system (RAS) inhibitors (angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and renin inhibitors) compared to other first-line antihypertensive drugs in people with hypertension.

First-line RAS inhibitors compared with first-line thiazides: RAS inhibitors increased heart failure (HF)(RR 1.19, 95% CI 1.07 to 1.31; 1 study, n=24 309; ARI 1.0%), increased stroke (RR 1.14, 95% CI 1.02 to 1.28; 1 study, n=24 309; ARI 0.6%), did not differ for all-cause death (RR 1.00, 95% CI 0.94 to 1.07; 1 study, n=24 309), total cardiovascular (CV) events (RR 1.05, 95% CI 1.00 to 1.11; 2 studies, n=24 379), total myocardial infarction (MI)(RR 0.93, 95% CI 0.86 to 1.01; 2 studies, n=24 379), and for end stage renal failure (ESRF)(RR 1.10, 95% CI 0.88 to 1.37; 1 study, n=24 309) compared with thiazides.

First-line RAS inhibitors compared with first-line calcium channel blockers (CCBs): RAS inhibitors decreased HF (RR 0.83, 95% CI 0.77 to 0.90; 5 studies, n=35 143; absolute risk reduction, ARR 1.2%), increased stroke (RR 1.19, 95% CI 1.08 to 1.32; 4 studies, n=34 673; absolute risk increase, ARI 0.7%), did not differ for all-cause death (RR 1.03, 95% CI 0.98 to 1.09; 5 studies, n=35 226), total CV events (RR 0.98, 95% CI 0.93 to 1.02; 6 studies, n=35 223), total MI (RR 1.01, 95% CI 0.93 to 1.09; 5 studies, n=35 043), and for ESRF (RR 0.88, 95% CI 0.74 to 1.05; 4 studies, n=19 551) compared with CCBs.

First-line RAS inhibitors compared with with first-line beta-blockersbeta-blockers: RAS inhibitors decreased total CV events (RR 0.88, 95% CI 0.80 to 0.98; 2 studies, n=9 239; ARR 1.7%), decreased stroke (RR 0.75, 95% CI 0.63 to 0.88; 1 study, n=9 193; ARR 1.7%), did not differ for all-cause death (RR 0.89, 95% CI 0.78 to 1.01; 1 study, n=9 193), HF (RR 0.95, 95% CI 0.76 to 1.18; 1 study, n=9 193), and total MI (RR 1.05, 95% CI 0.86 to 1.27; 2 studies, n=9 239) compared with beta-blockers.

Blood pressure comparisons between first-line RAS inhibitors and other first-line classes showed either no differences or small differences which did not correlate with the differences in the morbidity outcomes. None of the studies reported on the outcome of non-fatal serious adverse events.

Clinical comments

Note

The mortality and morbidity comparisons studied here involved predominately ACE inhibitors versus thiazides and ARBs versus beta-blockers. The comparison with CCBs involved both ACE inhibitors and ARBs.

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References

  • Chen YJ, Li LJ, Tang WL et al. First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension. Cochrane Database Syst Rev 2018;(11):CD008170. [PubMed]

Primary/Secondary Keywords