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.

Contents

• Preface
• Acknowledgments
• Stakeholders
• Executive Summary
• Background
• Methods
  • Overview
  • Analytic Framework
  • Initial List of Research Needs
  • Creation of Stakeholder Group
  • Expansion of Research Gaps
  • Review of the Current Literature
  • Research Prioritization
• Results
• Discussion
• Conclusions
• References
• Abbreviations
• Appendixes
  • Appendix A Exact Search Strings
  • Appendix B Table of Research Priorities Linked to Recent Publications and Ongoing Studies
  • Appendix C Criteria for Research Prioritization

Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services¹, . Contract No. 290-2008-10066-I. Prepared by: Duke Evidence-based Practice Center, Durham, NC

Suggested citation:

Powers BJ, Crowley MJ, McCrory DC, Pendergast K, Posey R, Hadley C, Gray R, Sanders GD. Future Research Needs for Comparing Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), and Direct Renin Inhibitors (DRIs) in the Treatment of Hypertension. (Prepared by the Duke Evidence-based Practice Center under contract No. 290-2008-10066-I). AHRQ Publication No. 12-EHC046-EF. Rockville, MD: Agency for Healthcare Research and Quality; March 2012.

This report is based on research conducted by the Duke Evidence-based Practice Center (EPC) under contract to the Agency for healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2008-10066-I). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help health care researchers and funders of research make well-informed decisions in designing and funding research and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of scientific judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical research and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances.

None of the investigators has any affiliations or financial involvement that conflicts with the material presented in this report.

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