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Updated Report on Comparative Effectiveness of ACE inhibitors, ARBs, and Direct Renin Inhibitors for Patients with Essential Hypertension: Much More Data, Little New Information

Journal of General Internal Medicine volume 27, pages 716–729 (2012)Cite this article

Abstract

OBJECTIVES

A 2007 systematic review compared angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) in patients with hypertension. Direct renin inhibitors (DRIs) have since been introduced, and significant new research has been published. We sought to update and expand the 2007 review.

DATA SOURCES

We searched MEDLINE and EMBASE (through December 2010) and selected other sources for relevant English-language trials.

STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS

We included studies that directly compared ACE inhibitors, ARBs, and/or DRIs in at least 20 total adults with essential hypertension; had at least 12 weeks of follow-up; and reported at least one outcome of interest. Ninety-seven (97) studies (36 new since 2007) directly comparing ACE inhibitors versus ARBs and three studies directly comparing DRIs to ACE inhibitor inhibitors or ARBs were included.

STUDY APPRAISAL AND SYNTHESIS METHODS

A standard protocol was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality; and summarize the evidence.

RESULTS

In spite of substantial new evidence, none of the conclusions from the 2007 review changed. The level of evidence remains high for equivalence between ACE inhibitors and ARBs for blood pressure lowering and use as single antihypertensive agents, as well as for superiority of ARBs for short-term adverse events (primarily cough). However, the new evidence was insufficient on long-term cardiovascular outcomes, quality of life, progression of renal disease, medication adherence or persistence, rates of angioedema, and differences in key patient subgroups.

LIMITATIONS

Included studies were limited by follow-up duration, protocol heterogeneity, and infrequent reporting on patient subgroups.

CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS

Evidence does not support a meaningful difference between ACE inhibitors and ARBs for any outcome except medication side effects. Few, if any, of the questions that were not answered in the 2007 report have been addressed by the 36 new studies. Future research in this area should consider areas of uncertainty and be prioritized accordingly.

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Acknowledgements

Disclaimer

This project was funded under Contract No. Contract No. 290-02-0025 from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsements by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

Funders

This project was funded under Contract No. Contract No. 290-02-0025 from the Agency for Healthcare Research and Quality (AHRQ), U.S. Department of Health and Human Services. AHRQ commented on the planned methods and draft report, but did not participate in the search of the literature, data abstraction, or evaluation of individual studies. The first author is funded by a HSR&D career development award from the Department of Veterans Affairs.

Prior presentations

This work was presented at the Academy Health Annual Research Meeting in Seattle, WA on June 14th, 2011.

Conflict of Interest

None disclosed.

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Affiliations

  1. Center for Health Services Research In Primary Care, Durham VA Medical Center, 508 Fulton Street, Durham, NC, 27705, USA

    Benjamin J. Powers MD, MHS, Rowena J. Dolor M.D., M.H.S., Uptal D. Patel M.D. & William S. Yancy Jr. M.D., MHS

  2. Duke Evidence-based Practice Center, Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA

    Benjamin J. Powers MD, MHS, Remy R. Coeytaux M.D., Ph.D., Rowena J. Dolor M.D., M.H.S., Vic Hasselblad Ph.D., Uptal D. Patel M.D., William S. Yancy Jr. M.D., MHS, Rebecca N. Gray D. Phil., R. Julian Irvine M.C.M., Amy S. Kendrick R.N, M.S.N & Gillian D. Sanders PhD

  3. Department of Medicine, Duke University School of Medicine, Durham, NC, USA

    Benjamin J. Powers MD, MHS, Rowena J. Dolor M.D., M.H.S., Uptal D. Patel M.D., William S. Yancy Jr. M.D., MHS & Gillian D. Sanders PhD

  4. Department of Community and Family Medicine, Duke University School of Medicine, Durham, NC, USA

    Remy R. Coeytaux M.D., Ph.D.

  5. Department of Biostatistics & Bioinformatics, Duke University School of Medicine, Durham, NC, USA

    Vic Hasselblad Ph.D.

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  1. Benjamin J. Powers MD, MHS
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Correspondence to Benjamin J. Powers MD, MHS.

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Powers, B.J., Coeytaux, R.R., Dolor, R.J. et al. Updated Report on Comparative Effectiveness of ACE inhibitors, ARBs, and Direct Renin Inhibitors for Patients with Essential Hypertension: Much More Data, Little New Information. J GEN INTERN MED 27, 716–729 (2012). https://doi.org/10.1007/s11606-011-1938-8

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KEY WORDS

  • angiotensin converting enzyme inhibitors
  • angiotensin receptor blockers
  • direct renin inhibitors
  • hypertension
  • systematic review