A meta analysis published in the Archives of Internal Medicines has examined the safety of prescribing combinations of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) in patients with heart failure.
A search strategy revealed four randomised studies involving 17,337 patients that met the pre-defined inclusion criteria. The data were analysed for adverse events including symptomatic hypotension, worsening renal function, hyperkalaemia and treatment discontinuation.
The risk of:
- Treatment discontinuation was 28% higher [95% CI 1.17-1.40] in the combination cohort
- Symptomatic hypotension was 48% higher [95% CI 1.34-1.62] in the combination cohort
- Worsening renal function was 76% higher [95% CI 1.49-2.09] in the combination cohort
- Hyperkalaemia was 246% higher [95% CI 0.68-8.87 Not Significant] in the combination cohort
The authors conclude that, "Combination ARB plus ACE inhibitor therapy was accompanied by marked increases in adverse effects". It is also stated that these results are consistent with HF Guidelines that have expressed reservations about the place in therapy for the combination.
Action: Clinicians should ensure that single agents are used and titrated to maximum tolerated doses before considering combination treatment. It may be appropriate to seek specialist advice before starting combination therapy.