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(Circulation. 1998;97:937.)
© 1998 American Heart Association, Inc.

Correspondence

Does 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase Inhibitor Therapy Exert a Direct Anti-Ischemic Effect?

Pericle Di Napoli, MD; ; Prof Antonio Barsotti, MD

Istituto di Clinica Cardiovascolare, Università degli Studi G. D'Annunzio, Chieti, Italy

To the Editor:

We read with great interest the recent well-written article by Andrews et al¹ in Circulation, and we would like to add a comment to the editorial observation of Dr Frye.²

The most important finding of the study is that in selected patients with documented coronary artery disease associated with myocardial ischemia on ambulatory ECG monitoring, dietary treatment and lovastatin therapy induced, after 4 to 6 months, a significant reduction of ischemic events compared with the control group (dietary treatment). Andrews et al¹ concluded that the importance of their study is the evidence that cholesterol lowering is related to clinical manifestations of coronary artery disease and reduces cardiac events in the medium term.

Two points we would consider in the discussion of these results:

(1) In long-term follow-up, several clinical studies^{3 4} reported that cholesterol lowering results in an improvement of prognosis or coronary atheroma regression.

(2) Clinical and experimental data^{5 6} suggest that hypercholesterolemia affects endothelial function (abnormal constriction provoked by acetylcholine, reduction of endothelial nitric oxide production), but the time course of these alterations is still unknown.

In our opinion, the positive effects of statin therapy on myocardial ischemia may also be related to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition rather than only to the total and LDL cholesterol reduction. This hypothesis, at least in part, is supported by the evidence of best result, regarding mortality and ischemic events, obtained by statin therapy with respect to dietary treatment or therapy with fibrates.

We think that an important . . . [Full Text of this Article]