2013 Articles

Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials

Makani, Harikrishna Jayantilal; Desouza, Kavit Alan; Shah, Arpit Falgun; Bangalore, Sripal

The concept of dual blockade of the renin-angiotensin system originated from an experimental model purporting to show a “synergistic” effect between angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers.The concept seemed so logical and appealing that seemingly beneficial changes in surrogate endpoints such as blood pressure, proteinuria, and endothelial dysfunction became accepted as a free pass for dual blockade having cardioprotective and nephroprotective effects. Despite a lack of solid evidence on the safety and efficacy of dual blockade of the renin-angiotensin system this type of therapy has been mentioned in several sets of guidelines. Thus dual therapy was commonly used in patients with hypertension and with diabetes or proteinuria, or both and also to a lesser extent in those with heart failure resistant to treatment. Even patients with uncomplicated essential hypertension were not entirely able to escape this fashionable trend. In the United States more than 200,000 patients are currently treated with dual blockade of the renin-angiotensin system, most of them by the combination of an angiotensin receptor blocker and ACE inhibitor (70%). Some other combinations are also used, such as two ACE inhibitors (15%), two angiotensin receptor blockers (5%), and ACE inhibitors or angiotensin receptor blockers in combination with a direct renin inhibitor (8%). The long term efficacy and safety of dual blockade is not, however, well defined. We compared the long term efficacy of dual blockade of the renin-angiotensin system (any two of ACE inhibitors, angiotensin receptor blockers, or aliskiren) with monotherapy and evaluated adverse events in patients receiving dual therapy compared with monotherapy.