Renin angiotensin system inhibitors in patients with stable coronary artery disease and preserved left ventricular function: to use or not to use?

Guidelines advise use of renin angiotensin system inhibitors (RASi) in all patients with stable ischaemic heart disease. In the early trials including HOPE and EUROPA, RASi significantly reduced cardiovascular events compared with placebo. However, the later trials including PEACE and CAMELOT were unable to affirm this benefit. This was possibly due to lower event rates in more contemporary populations with higher rates of coronary revascularisation and lipid lowering therapy. There is plenty of evidence for the benefit of RASi in patients with heart failure and chronic kidney disease but how about in those with stable coronary artery disease with preserved left ventricular function?

A recent meta-analysis published by Bangalore et al. in the BMJ questions the benefit of RASi in this group (1). Randomised trials of RASi vs placebo or RASi vs active controls in patients with stable coronary artery disease without heart failure (left ventricular ejection fraction ≥40% or without clinical heart failure) were included. The authors examined 24 trials with 198,275 patient-years of follow-up. RASi reduced cardiovascular outcomes (all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina, heart failure and revascularisation) when compared with placebo but not when compared with active controls (calcium antagonists, thiazide diuretics or conventional treatment). Consistent with other trial data however, RASi reduced incident diabetes when compared with both placebo and active controls. Bayesian meta-regression analysis showed that among the RASi vs placebo trials, the beneficial effects of RASi on all cause and cardiovascular mortality were restricted to trials with higher event rates (>14.1 deaths and >7.7 cardiovascular deaths per 1000 patient years).

The authors note that this meta-analysis has limitations, including inability to control for differences between trials, incomplete datasets for ejection fraction and that active controls were predominantly calcium antagonists (therefore results cannot be extrapolated to other drugs). However, the universal endorsement of RASi for all patients with stable coronary artery disease was not supported by this data and may apply only to patients with higher baseline risk. This lack of benefit could have implications for patients with stable coronary artery disease, preserved left ventricular function and aggressive management of risk factors, such as hypertension and hypercholesterolaemia, with consequent lower residual baseline risk.

References

1. Bangalore S, Fakheri R, Wandel S, et al. Renin angiotensin system inhibitors for patients with stable coronary artery disease without heart failure: A systematic review and meta-analysis of randomized trials. BMJ2017; DOI:10.1136/bmj.j4.