Physicians' Academy for Cardiovascular Education

EMA reviews combined use RAS-inhibitors

News - May 21, 2013

The European Medicines Agency (EMA) has initiated a review  of combining agents that block the renin-angiotensin system (RAS)[1]. These drugs are used in the treatment of hypertension and congestive heart failure and include ACE-inhibitors, ARBs, and direct renin inhibitors.
The review is performed due to concerns that combined RAS-blocking agents could increase the risk of hyperkalemia, hypotension and kidney failure, compared with using a single agent. Moreover, using multiple RAS-acting agents failed to reduce mortality and was associated with an excessive risk of adverse events, arguing against the use of dual therapy, as shown in a recent meta-analysis in the BMJ [2].
The current review follows a decision of EMA’s Committee for Medicinal Products for Human Use (CHMP) that the combination of aliskiren with an ACE inhibitor or ARB is not recommended and should be contraindicated in patients with diabetes or moderate to severe kidney impairment, due to increased risk of side effects affecting the heart and blood vessels or the kidneys.
The European Medicines Agency will evaluate the impact of the latest available evidence on the benefit-risk balance of combining RAS-acting agents in the treatment of hypertension and congestive heart failure.

1. Referral on Renin-angiotensin system (RAS) acting agents, EMA
2. Makani H, Bangalore S, Desouza KA, Shah A, Messerli FH. Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomized trials. BMJ. 2013 Jan 28;346:f360. doi: 10.1136/bmj.f360.