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Rapid response to:


Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study

BMJ 2017; 356 doi: (Published 09 March 2017) Cite this as: BMJ 2017;356:j791

Rapid Response:

Harms caused by overtreatment with renin-angiotensin-aldosterone blockers.

Some circulating or tissue angiotensin II - a defense molecule - concentrations seem paramount in keeping best possible function shape not only in glomerular filtration rate (GFR), but also in systemic blood pressure levels, vital organ & body perfusion, such as cerebral autoregulation of blood flow, and salt balance, among other homeostatic functions in human health and disease (1-2).

To illustrate the above concept/s, every single randomized clinical trial, so far, of purposeful higher degrees of renin-angiotensin-aldosterone system (RAAS) blockade have ended up interrupted earlier than predicted because of increased harms such as hypotension, syncope, hyperkalemia, renal function deterioration, and even cardiac arrest (3-4).

Schmidt et al add evidence that is more realistic – because they used data from registries instead of clinical trial frequencies. And their well done statistics showed that unnoticed overtreatment with RAAS blockers is more common than previously generally thought, being without clinical benefits but with dose graded serious harms (5).


1. De'Oliveira JM1, Price DA, Fisher ND, ET AL. Autonomy of the renin system in type II diabetes mellitus: dietary sodium and renal hemodynamic responses to ACE inhibition. Kidney Int. 1997 Sep;52(3) and
2. Lesogor A, Cohn JN, Latini R, et al. Interaction between baseline and early worsening of renal function and efcacy of renin-angiotensinaldosterone system blockade in patients with heart failure: insights from the Val-HeFT study. Eur J Heart Fail 2013;15:1236-44.
3. “The ONTARGET Investigators”. Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events. N Engl J Med 2008;358:1547-59.
4. Hans-Henrik Parving, M.D., D.M.Sc., Barry M. Brenner, M.D., Ph.D., John J.V. McMurray, M.D, et al. Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes. N Engl J Med 2012;367:2204-13.
5. Ray Moynihan, senior research fellow 1, Jenny Doust, professor of clinical epidemiology2, David Henry, chief executive officer3. MEDICALISATION. Preventing overdiagnosis: how to stop harming the healthy BMJ 2012; 344 doi:

Competing interests: No competing interests

12 March 2017
Jose Mario de Oliveira
Associate Professor of Medicine.
Department of Medicine. Universidade Federal Fluminense.
Rua Senador Vergueiro # 2 Apt. 202.., Flamengo. Rio de Janeiro, RJ, Brazil.