Some 30 years ago, captopril became the first angiotensin converting enzyme (ACE) inhibitor available for clinical use. Since then, several other ACE inhibitors have been introduced, as well as drugs from the angiotensin II type 1 receptor blocker (ARB) family. More recently, an orally active renin inhibitor, aliskiren, has become available. It is now possible to block renin itself, to inhibit the conversion of angiotensin I into angiotensin II, and to block the main target receptors of angiotensin II in a single patient. In the linked systematic review and meta-analysis of randomised controlled trials (doi:10.1136/bmj.e42), Harel and colleagues examined the safety of dual blockade of the renin-angiotensin system using the renin inhibitor aliskiren and an ACE inhibitor or ARB.1

Many investigators have evaluated whether delivering a combination of drugs that interfere with specific functions of the renin-angiotensin system would be more effective at reducing blood pressure or protecting target organs (or both) than giving one drug only. Both dual and triple renin-angiotensin blockade have been investigated. Most trials did not consider the potential pathophysiological consequences of blocking the system at multiple levels. A meta-analysis that compared combinations of an ACE inhibitor and ARB with single drug treatment—mainly in patients with diabetes or kidney disease—showed …