Recent research suggests that dual blockade of the Renin-angiotensin system (RAS) results in increased adverse events in hypertensive patients.

A meta-analysis of randomized controlled trials published between 1990 and 2011 compared dual RAS blockade with a single RAS blocker. The analysis included 28 trials with a mean follow-up of 53 weeks, and 58,849 patients were enrolled (11 trials with 24,861 patients with heart failure).

In 19 of the trials, patients were administered an ACE inhibitor with an angiotensin receptor blocker (ARB) – six trials combined an ARB with aliskiren, and three combined an ACE inhibitor with aliskiren. The meta-analysis found a greater potential for harm than benefit when two agents were used for RAS blockade.

Even when the combination decreased hospitalizations in patients with heart failure (RR 0.78, 95% CI 0.70 to 0.87), it increased the risk of renal failure, hyperkalemia (RR 1.67, 95% CI 1.36 to 2.06) and hypotension (RR 1.74, 95% CI 1.38 to 2.19). The combination treatment had no effect on all-cause (RR 0.98, 95% CI 0.89 to 1.08) or cardiovascular mortality (RR 0.94, 95% CI 0.86 to 1.03).

Among patients with heart failure only, there were greater risks of renal failure (RR 2.19, 95% CI 1.82 to 2.65) and of withdrawal due to adverse events (RR 1.35, 95% CI 1.24 to 1.46). It can be concluded that the use of two agents to block the RAS offers little benefit, but has significant negative effects.


1. Makani H, et al. Efficacy and safety of dual renin-angiotensin system blockade — a meta-analysis of randomized trials. ASH 2012; Abstract LB-PO-06.