Dual renin-angiotensin system (RAS) blockade with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improves some surrogate outcomes, but does not reduce mortality and may increase the risk of renal failure and other adverse outcomes, concludes a report in the British Medical Journal.
The researchers performed a meta-analysis of data on 68,405 patients from 33 randomized trials of dual versus single RAS blocker therapy. Mortality and adverse events were assessed, with stratification of studies that did and did not include patients with heart failure.
The analysis found no reduction in mortality with dual RAS blockade. All-cause mortality was 15.3 percent with dual therapy and 15.0 percent with monotherapy. Cardiovascular mortality was 14.7 percent and 15.7 percent, respectively. The rate of hospitalization for heart failure was 10.9 percent with dual therapy versus 10.3 percent with monotherapy (risk ratio 0.82). Several adverse events were more frequent with dual RAS blockade, including hyperkalemia and hypotension—risk ratios 1.55 and 1.66, respectively.
Dual blockade was also associated with a higher rate of renal failure: 8.3 percent versus 6.4 percent, (risk ratio 1.41). Most outcomes were similar in study cohorts with and without heart failure. The exceptions were higher all-cause mortality in cohorts without heart failure and a higher risk of kidney failure in those with heart failure.
Despite a lack of long-term safety and efficacy data, dual RAS blockade is widely used in certain groups, including patients with hypertension and diabetes and/or proteinuria. The new meta-analysis questions this practice, showing no reduction in mortality with dual blockade versus monotherapy.
Dual RAS blockade is also associated with higher rates of certain adverse outcomes, including a 41 percent increase in renal failure. The investigators conclude, “The overall risk to benefit ratio argues against the use of dual therapy” [Makani H, et al:Efficacy and safety of dual blockade of the renin-angiotensin system: meta-analysis of randomised trials. BMJ 2013; 346:f360].