Blood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system

L. Agodoa, C. Anderson, F. Asseibergs, C. Baigent, H. Black, B. Brenner, M. Brown, C. Bulpitt, R. Byington, J. Chalmers, R. Collins, J. Cutler, B. Dahlof, B. Davis, D. De Zeeuw, J. Dens, R. Estacio, R. Fagard, K. Fox, T. FukuiL. Hansson, R. Holman, L. Hunsicker, Y. Imai, M. Ishii, Y. Kanno, J. Kostis, K. Kuramoto, E. Lewis, M. Lièvre, L. H. Lindholm, L. Liu, J. Lubsen, S. Lueders, S. MacMahon, E. Malacco, G. Mancia, M. Matsuzaki, B. Neal, S. Nissen, T. Ohkubo, T. Ogihara, C. Pepine, M. Pfeffer, B. Pitt, P. Poole-Wilson, M. Rahman, W. Remme, G. Remuzzi, A. Rodgers, P. Ruggenenti, T. Saruta, J. Schrader, R. Schrier, P. Sever, P. Sleight, J. Staessen, K. Teo, G. Viberti, J. Wang, P. Whelton, L. Wing, Y. Yui, S. Yusuf, A. Zanchetti, F. Turnbull, J. Kostis, C. Algert, M. Woodward, A. Zanchetti

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337 Scopus citations


OBJECTIVES: To evaluate the blood pressure-dependent and independent effects of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) on major cardiovascular events. METHODS: Using data from 26 large-scale trials comparing an ACEI or an ARB with placebo or another drug class, meta-regression analyses were conducted in which treatment-specific relative risks for major cause-specific outcomes [stroke, major coronary heart disease (CHD) events and heart failure] were regressed against follow-up blood pressure differences. RESULTS: From a total of 146 838 individuals with high blood pressure or an elevated risk of cardiovascular disease, 22 666 major cardiovascular events were documented during follow-up. The analyses showed comparable blood pressure-dependent reductions in risk with ACEI and ARB (P ≥ 0.3 for all three outcomes). The analyses also showed that ACEI produced a blood pressure-independent reduction in the relative risk of CHD of approximately 9% (95% confidence interval 3-14%). No similar effect was detected for ARB, and there was some evidence of a difference between ACEI and ARB in this regard (P = 0.002). For both stroke and heart failure there was no evidence of any blood pressure-independent effects of either ACEI or ARB. CONCLUSION: There are similar blood pressure-dependent effects of ACEI and ARB for the risks of stroke, CHD and heart failure. For ACEI, but not ARB, there is evidence of blood pressure-independent effects on the risk of major coronary disease events.

Original languageEnglish (US)
Pages (from-to)951-958
Number of pages8
JournalJournal of Hypertension
Issue number5
StatePublished - May 1 2007

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine


  • Blood pressure
  • Coronary heart disease
  • Heart failure
  • Meta-regression analyses
  • Metaanalyses
  • Stroke


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