European Medicines Agency Starts Review of Combined Use Of Drugs That Block The Renin-Angiotensin System

The European Medicines Agency said last week that it was initiating a review of the combined use of agents that block the renin-angiotensin system (RAS). The three classes of RAS-blocking drugs (ACE inhibitors, ARBs, and direct renin inhibitors) are used to treat hypertension and congestive heart failure.

The EMA said that the review was being performed to address concerns that combined RAS-blocking drugs could increase the risk for hyperkalemia, hypotension, and kidney failure when compared with a single agent.  A recent meta-analysis of 33 clinical studies published in the British Medical Journal concluded that “although dual blockade of the renin-angiotensin system may have seemingly beneficial effects on certain surrogate endpoints, it failed to reduce mortality and was associated with an excessive risk of adverse events… The risk to benefit ratio argues against the use of dual therapy.”

Franz Messerli, senior author of the BMJ meta-analysis, applauded the EMA action and said that “as usual the FDA is dragging its feet.”

Click here to read the full story on Forbes.





  1. Jean E. Sealey D.Sc and John H. Laragh MD says

    Multiple antihypertensive drugs should be used only when absolutely necessary. But, high renin hypertensives (who are at greatest risk of a cardiovascular event) should not be deprived of the option of dual renin-angiotensin system blockade. The conclusion by Messerli et al that dual blockade should be discouraged was based on a meta analysis of clinical trials, most of which paradoxically revealed net benefit from the first blocker but net risk from the second. But, even positive clinical trials are the result of net effect of benefit in some and increased risk in others. Moreover package inserts warn that sodium depleted patients are at increased risk from renin-angiotensin system blockers of hypotension, hyperkalemia and deteriorating renin function. The problem is that some sodium depleted patients were likely present in the clinical trials, since they are difficult to detect. Therefore, the results can be explained as follows: the first blocker benefits most patients but puts sodium depleted patients at increased risk. The second blocker adds no more benefit to most, but increases the risk of the sodium depleted patients. In sum, sodium depleted patients are at risk from both single and dual renin-angiotensin system blockade. Thus, dual blockade is not the problem, it is giving renin-angiotensin system blockers to sodium depleted patients. Every effort should be made to avoid or reverse sodium depletion before giving even one renin-angiotensin system blocking drug. This can be done by subtracting low salt diets and natriuretic drugs while monitoring plasma renin and blood pressure levels (Amer J Hypertens 2013;26:727. Renin-angiotensin system blockers may create more risk than reward for sodium depleted cardiovascular patients with high PRA levels.).

Speak Your Mind