Angiotensin-converting enzyme inhibitors and outcome among patients with heart failure and renal insufficiency: need for a prospective study.

Ezekowitz et al. (1) recently reported lack of benefit of angiotensin-converting enzyme (ACE) inhibitors on mortality in patients with chronic heart failure (CHF) in whom estimated creatinine clearance was below 60 ml/min, as opposed to a beneficial effect in those with creatinine clearance above 60 ml/min. The researchers attribute this lack of benefit to a possible interaction between aspirin and ACE inhibitor use, suggesting that aspirin might blunt the effects of ACE inhibitors. Whereas this might be true, in our opinion another explanation should be considered as well, namely prescription bias. In CHF, ACE inhibition should be prescribed to all patients, especially in those with severe CHF. Regretfully, this is not always true in daily practice. In the cohort studied by Ezekowitz et al. (1), only 60% were using ACE inhibitors. It has been reported that physicians are reluctant to prescribe ACE inhibitors in the presence of severe renal dysfunction (2). Physicians are more willing to prescribe ACE inhibitors to CHF patients if such patients are more symptomatic (3). In CHF, renal function impairment can elicit a clinically more unstable condition—for instance, by fluid retention. Accordingly, in the present study by Ezekowitz et al. (1), confounding by prescription may have occurred among the patients with renal function impairment, with ACE inhibitors being preferentially prescribed to subjects with a more unstable cardiac condition and a worse prognosis. In view of the prognostic importance of renal function in subjects with CHF, it might be relevant that, in subjects with primary renal disease and severely impaired renal function, ACE inhibition protects against further worsening of renal function (4). Whether this might be of benefit in CHF patients has not been studied so far. Taken together, the data by Ezekowitz et al. (1) argue for prospective studies into the role of ACE inhibitors in CHF subjects with renal function impairment.