Effects of lipid-lowering drugs on left ventricular function and exercise tolerance in dyslipidemic coronary patients

Previous studies suggested that certain lipid-lowering drugs such as statin s suppress ubiquinone, affect mitochondrial function, and may have deleteri ous effect on skeletal or cardiac muscles with potentially serious clinical consequences, especially in patients with established coronary heart disea se and left ventricular dysfunction. In this double-blind study, we assesse d the effects of 20 mg simvastatin (S, n = 32) or 200 mg micronized fenofib rate (F, n = 32, control group) on rest and exercise left ventricular funct ion in hypercholesterolemic survivors of a previous Q-wave acute myocardial infarction. Left ventricular radionuclide imaging was performed at rest an d during submaximal exercise and global and segmental (nine segment regiona l wall-motion score) ejection fractions were measured before treatment and 12 weeks later. Serum ubiquinone was reduced after treatment (p = 0.03) in the S but not the F group, whereas total and low-density lipoprotein (LDL) cholesterol were significantly reduced in both groups. Before treatment, me an global ejection fraction was 52.1 +/- 12.2% and 49.3 +/- 11.8% at rest i n F and S patients, respectively, and increased (56.0 +/- 13.7% in F and 52 .1 +/- 12.9% in S) at peak exercise (no difference between groups). After t reatment, the increase in ejection fraction tended to be lower in S (0) tha n in F (+3.5%) but not significantly. However, ejection fraction at rest in creased after treatment in S (p = 0.009) but not in F. Subgroup analyses in dicated that the improvement in rest ejection fraction in S was essentially observed in patients with ejection fraction <40% (n = 8, +6%), whereas it was stable in patients with ejection fraction >40% (+1.8%). Finally, the nu mbers of akinetic or hypokinetic segments at rest and during exercise were not different in the two groups before and after treatment. Mean maximal ex ercise load (113 +/- 23 watts in F vs. 104 +/- 27 W in S before treatment) was not modified by the treatment (111 +/- 21 and 104 +/- 27 W). Thus a 12- week lipid-lowering treatment with either S or F did not negatively alter l eft ventricular function during exercise in dyslipidemic patients with esta blished coronary heart disease and did not affect their ability to exercise . The improvement in left ventricular function at rest after simvastatin in patients with left ventricular dysfunction warrants confirmation in furthe r studies with large sample size.