Brenda J. Wilson, BSc, MB, ChB, MSc; Nadeem Qureshi, MBBS, MSc, DM; Pasqualina Santaguida, BSc, PT, PhD; Julian Little, MA, PhD; June C. Carroll, MD; Judith Allanson, MB, ChB; Parminder Raina, BSc, PhD
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Jose R Banegas
Department of Preventive Medicine, School of Medicine, Autonomous University of Madrid, Spain
January 2, 2010
Suppression of renin-angiotensin system (RAS) and cardiovascular protection
TO THE EDITOR: We read with great interest the paper published by Baker et al in Ann Intern Med comparing effectiveness of angiotensin- converting enzyme inhibitors (ACEi) or angiotensin II-receptor blockers (ARB) for ischemic heart disease (1). The topic of suppression of renin- angiotensin system (RAS) and cardiovascular and renal protection has been objective of different reviews and meta-analyses in the last years. In fact, one of the topics of discussion when ACEi and ARB were compared was a potential difference in the protection of myocardial infarction in favour of ACEi (2), but this possibility has been denied by others (3).
The reality is that when studies using ACEi or ARB have been compared, little or no attention was paid to the fact that the circumstances under which those studies were performed differed. Most if not all patients entering ACEi studies were performed naive of having received a drug suppressing the RAS, which is not the case for those patients entering ARB studies. A clear example is the ONTARGET-TRANSCEND project (4). In TRANSCEND, every body had received and ACEi for periods of time not defined, but it could have been years. In ONTARGET, almost two thirds had received an ACEi before admission in the study. Hence, the development of cardiorenal disease in many of those patients entering ARB studies took place while on suppression of the RAS. Should this be the case, the capacity of a new RAS suppressor to modify the evolution of cardiorenal disease should be diminished in a very important amount. This is the most important argument to perform studies in patients having developed cardiorenal disease under suppression of the RAS and to reconsider the different possible ways to increase the degree of suppression of the RAS (ACEi plus ARB, ACEi or ARB plus aliskiren, ACEi or ARB uptitration, ACEi or ARB plus aldosterone blockers).
On the other hand, many more patients were taking lipid-lowering drugs in trials testing the capacity of ARB to protect cardiovascular and kidney systems (4), which could have interfered in the interpretation of the outcome data, in particular in patients non naive of RAS suppression before entering the study.
In summary, conclusions of the comparison of studies with ACEi and ARB have to be considered with caution. Design of new studies must contemplate all possible confounders.
References 1. Baker WL, Coleman CI, Kluger J, Reinhart KM, Talati R, Quercia R, et al. Systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers for ischemic heart disease. Ann Intern Med. 2009;151:861-71.
2. Strauss MH, Hall AS. Angiotensin receptor blockers may increase risk of myocardial infarction: unraveling the ARB-MI paradox. Circulation. 2006;114: 838-54.
3. Volpe M, Tocci G, Sciarretta S, Verdecchia P, Trimarco B, Mancia G. Angiotensin II receptor blockers and myocardial infarction: an updated analysis of randomized clinical trials. J Hypertens. 2009;27:941-46.
4. Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, et al. ONTARGET Investigators. Telmisartan, ramipril or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547-59.
Authors Julian Segura, MDa; Jose R. Banegas, MD, MPHb; Luis M. Ruilope, MD, PhDa a.Hypertension Unit. Hospital 12 de Octubre. Madrid. Spain. b.Department of Preventive Medicine and Public Health, Universidad Autonoma de Madrid. CIBERESP. Madrid, Spain.
Wilson BJ, Qureshi N, Santaguida P, et al. Systematic Review: Family History in Risk Assessment for Common Diseases. Ann Intern Med. 2009;151:878–885. doi: https://doi.org/10.7326/0000605-200912150-00177
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Published: Ann Intern Med. 2009;151(12):878-885.
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