The European Medicines Agency (EMA) has recommended that angiotensin-receptor blockers (ARBs), ACE inhibitors, and direct renin inhibitors should not routinely be combined. EMA also recommended that particularly in patients with diabetic nephropathy ARBs and ACE inhibitors should not be used in combination. In their press release EMA indicates that “Where such combination (dual blockade) is considered absolutely necessary, it must be carried out under specialist supervision with close monitoring of kidney function, fluid and salt balance, and blood pressure”. “The combination of aliskiren (Tekturna, Novartis) with an ARB or ACE inhibitor is strictly contraindicated in those with kidney impairment or diabetes.” The EMA in their deliberations took notice of data published from a large meta-analysis by Makani et al, published in the BMJ in 2013 (1). The EMA took into account the fact that the combined use of pharmacological agents acting on the RAS can lead to severe hyperkalemia, worsening of kidney function and marked hypotension. This increased risk of serious side effects seen with the use of these drugs in combination is not accompanied by measurable clinical benefits.
1. Makani H, Bangalore S, Desouza KA, Shah A, Franz H Messerli FH. Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials. BMJ. 2013; 346: f360.
The concurrent use of Angiotensin Convertin Enzyme inhibitors (ACEi) and Angiotensin Receptor II Blockers (ARBs) has been implemented in clinical practice mainly by the nephrologists who had suggested greater nephro-protection with dual blockade as compared to single blockade.
However, clinical studies conducted to show benefit of dual blockade of the Renin Angiotensin System with dual ACEi/ARBs or through direct renin inhibition have failed to show beneficial long term effect and have, on the other hand, shown an increased risk of adverse events including worsening renal failure, severe hypotension and hyperkalaemia. Therefore, in the absence of a clear prognostic benefit, the European Medicines Agency felt that the risks outweigh the benefit of using double blockade of the Renin Angiotensin System and has contraindicated the concurrent use of aliskiren and/or an ACEi and/or an ARB. This decision has been made in the interest of patients and it is based on sound scientific rationale.