Updates on the treatment of essential hypertension: a summary of AHRQ's comparative effectiveness review of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and direct renin inhibitors

Benjamin Powers, Laurence Greene, Lisa M Balfe
Journal of Managed Care Pharmacy: JMCP 2011, 17 (8 Suppl): S1-14

BACKGROUND: In 2007, the Agency for Healthcare Research and Quality (AHRQ) published a comparative effectiveness review (CER) on the benefits and risks of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) for treating essential hypertension in adults. The main findings indicated that the 2 classes of antihypertensive medications caused similar reductions in blood pressure, although higher rates of adverse events, especially cough, were reported by patients treated with ACEIs. In addition, the 2007 review indicated no treatment related differences in lipid levels, glycemic control, or progression of kidney disease among the agents. Since 2007, 39 relevant studies have been published that compare outcomes for adults treated with ACEIs versus ARBs or a drug in one of these 2 classes versus a direct renin inhibitor (DRI). To systematically analyze findings from the new research, AHRQ commissioned and, in June 2011, published an updated comparative effectiveness review on the benefits and risks of agents that target the renin-angiotensin- aldosterone system (RAAS), specifically ACEIs, ARBs, and DRIs.

OBJECTIVES: To (a) familiarize health care professionals with the methods and findings from AHRQ's 2011 comparative effectiveness review on ACEIs, ARBs, and DRIs for adults with essential hypertension; (b) provide commentary and encourage consideration of the clinical and managed care applications of the review findings; and (c) identify limitations to the existing research on the benefits and risks of ACEIs, ARBs, and DRIs.

SUMMARY: Consistent with the findings from AHRQ's 2007 report, the 2011 update indicated no overall differences in blood pressure control, mortality rates, and major cardiovascular events in patients treated with ACEIs versus ARBs. With a low strength of evidence, 2 studies reported a small significantly greater blood pressure reduction for patients treated with the DRI aliskiren versus the ACEI ramipril. Studies evaluating the DRI aliskiren versus ACEIs and ARBs on mortality and morbidity outcomes were relatively short, and few deaths or cardiovascular events occurred, resulting in insufficient evidence to discern differences. A random-effects meta-analysis of 23 RCTs comparing ACEIs and ARBs found no significant difference in the proportion of patients who achieved successful blood pressure control on a single antihypertensive agent. Compared with ARBs and the DRI aliskiren, ACEIs were consistently associated with higher rates of cough. Withdrawals due to adverse events were modestly more frequent for patients receiving ACEI rather than ARBs or DRIs; this is consistent with the differential rates of cough. There was no evidence of differential effects of ACEIs, ARBs, or DRIs on the outcomes of lipids, renal outcomes, carbohydrate metabolism or diabetes, or left ventricular mass; however, there was not a high strength of evidence for any of these outcomes. Regarding the question of whether ACEIs, ARBs, or DRIs are associated with better outcomes in specific patient subgroups, the evidence was insufficient to reach firm conclusions.

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