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Effective Health Care Program

Future Research Needs for Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), or Direct Renin Inhibitors (DRIs) for Treating Hypertension

Systematic Review Archived

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Archived: This report is greater than 3 years old. Findings may be used for research purposes, but should not be considered current.

This report is from AHRQ's series on Future Research Needs Projects.


Almost 75 million American adults have hypertension. Advances in antihypertensive therapy have dramatically reduced cardiovascular, cerebrovascular, and renal events. Among the effective pharmacotherapies are inhibitors of the renin-angiotensin-aldosterone system (RAS). In 2007, the Agency for Healthcare Research and Quality (AHRQ) sponsored a comparative effectiveness review (CER) of the two most common renin system inhibitors, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), to answer the following three Key Questions for adults with essential hypertension: do ACEIs and ARBs differ in their (1) blood pressure control, cardiovascular events, quality of life, and other outcomes; (2) safety, tolerability, persistence with therapy, or treatment adherence; and (3) effects within important subgroups of patients? This 2007 CER was updated in 2011 to incorporate the significant additional direct comparison research published in the interval and to include direct renin inhibitors (DRIs), which are the newest class of RAS inhibitors.

The results of the updated CER included 97 studies (36 new since 2007) directly comparing ACEIs versus ARBs and 3 studies directly comparing DRIs to ACEIs or ARBs. The strength of evidence remained high for equivalence between ACEIs and ARBs for blood pressure lowering, and for superiority of ARBs over ACEIs for short-term adverse events (primarily cough). The new evidence did not strengthen the conclusions regarding long-term cardiovascular outcomes, quality of life, progression of renal disease, medication adherence or persistence, rates of angioedema, or differences in key patient subgroups; the strength of evidence for these outcomes remained low to moderate. Evidence on the comparative effectiveness of DRIs versus either ACEIs or ARBs was limited to 3 studies with 2,049 patients and did not allow definitive conclusions on any of the included outcomes. Few studies involved a representative patient sample treated in a typical clinical setting over a long duration; treatment protocols had marked heterogeneity; and significant amounts of data about important outcomes and patient subgroups were missing.

Given the clinical and economic importance of these medications, the ongoing investment in research, and the remaining areas of uncertainty, we sought to create a prioritized research agenda representing the interests of diverse stakeholders in order to address the remaining areas of uncertainty.