Effect of statins and ACE inhibitors alone and in combination on clinical outcome in patients with coronary heart disease

We assessed the 'synergy' of statins and angiotensin-converting enzyme inhibitors (ACEI) in reducing vascular events in patients with coronary heart disease (CHD). The GREek Atorvastatin and CHD Evaluation (GREACE) Study, suggested that aggressive reduction of low density lipoprotein cholesterol to 2.59 mmol/l (<100 mg/dl) significantly reduces morbidity and mortality in CHD patients, in comparison to undertreated patients. In this post hoc analysis of GREACE the patients (n=1600) were divided into four groups according to long-term treatment: Group A (n=460 statin+ACEI), B (n=420; statin, no ACEI), C (n=371; no 371; no statin, on ACEI), and D (n=349; no statin, no ACEI). Analysis of variance was used to assess differences in the relative risk reduction (RRR) in 'all events' (primary end point) between groups. During the 3-year follow-up there were 292 cardiovascular events; 45 (10% of patients) in group A, 61 (14.5%) in group B, 91 in group C (24.5%) and 95 events in group D (27%). The RRR (95% confidence interval (CI) in the primary end point in group A was 31%, (95% CI -48 to -6%, P=0.01) in comparison to group B, 59% (95% CI -72 to -48%, P<0.0001) to group C and 63% (95% CI -74 to -51%, P<0.0001) to group D. There was no significant difference in RRR between groups C and D (9%, CI -27 -10%, P=0.1). Other factors (eg the blood pressure) that can influence clinical outcome did not differ significantly between the four treatment groups. In conclusion, the statin+ACEI combination reduces cardiovascular events more than a statin alone and considerably more than an ACEI alone. Aggressive statin use in the absence of an ACEI also substantially reduced cardiovascular events. Treatment with an ACEI in the absence of a statin use reduced clinical events in comparison to patients not treated with an ACEI but not significantly, at least in these small groups of patients.