Objectives: A 2007 comparative effectiveness review (CER) evaluated the long-term benefits and harms of angiotensin-converting enzyme inhibitors (ACEIs) versus angiotensin II receptor blockers/antagonists (ARBs) for treating essential hypertension in adults. Since then, significant additional research has been published comparing these agents, and direct renin inhibitors (DRIs) have been introduced to the market. We sought to update 2007 CER on ACEIs versus ARBs and expand this to include comparisons with DRIs.
Data Sources: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, a list of systematic reviews underway in the Cochrane Hypertension Review Group, and selected gray literature sources.
Review Methods: We included studies that directly compared ACEIs, ARBs, and/or DRIs in at least 20 total adults with essential hypertension; had at least 12 weeks of followup; and reported at least one outcome of interest. Two investigators reviewed each article, and a standard protocol was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality; and summarize the evidence. When appropriate, quantitative meta-analysis was performed.
Results: We 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 remains high for equivalence between ACEIs and ARBs for blood pressure lowering and use of a single antihypertensive agent, and for superiority of ARBs over ACEIs for short-term adverse events (primarily due to cough). The new evidence did not strengthen our 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. For DRIs, we were not able to reach definitive conclusions for any of the outcomes of interest. Few studies involved a representative 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.
Conclusion: Evidence does not support a meaningful difference between ACEIs and ARBs for any outcome except short-term adverse events. Few, if any, of the questions that were not answered in the 2007 CER have been addressed by the 39 new studies. Future research in this area should consider areas of uncertainty and be prioritized accordingly.