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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:425-430.)
© 1996 American Heart Association, Inc.

Articles

Evidence for a Synergistic Effect of Calcium Channel Blockers With Lipid-Lowering Therapy in Retarding Progression of Coronary Atherosclerosis in Symptomatic Patients With Normal to Moderately Raised Cholesterol Levels

J. Wouter Jukema; Aeilko H. Zwinderman; Ad J. van Boven; Johan H.C. Reiber; Arnoud Van der Laarse; Kong I. Lie; Albert V.G. Bruschke; for the REGRESS Study Group

From the Department of Cardiology (J.W.J., A. Van der L., A.V.G.B.) and the Department of Diagnostic Radiology and Nuclear Medicine (J.H.C.R.), University Hospital, Leiden; the Department of Medical Statistics, Leiden University (A.H.Z.); and the Department of Cardiology, University Hospital, Groningen (A.J. van B., K.I.L.), The Netherlands.

Correspondence to J.W. Jukema, MD, Department of Cardiology, University Hospital, Leiden, Bldg 1, C5-P, Rijnsburgerweg 10, 2333 AA Leiden, the Netherlands.

Abstract To date, lipid-lowering therapy appears to be the most effective medical intervention to retard progression of coronary atherosclerosis. In spite of promising experimental results, clinical trials completed so far have failed to demonstrate that calcium channel blockers (CCBs) alone influence the evolution of established coronary atherosclerosis. To assess whether the two therapies may have an additive or synergistic beneficial effect on human atherosclerosis, we reviewed in this regard the data of the angiographic Regression Growth Evaluation Statin Study (REGRESS) trial. REGRESS was designed to determine the effect of lipid-lowering therapy with pravastatin in symptomatic patients with normal to moderately raised cholesterol levels. Angiographically, with respect to the minimum obstruction diameter, in the pravastatin group, patients had on average 0.05 mm (95% confidence interval [CI]: 0.01-0.09) less progression if cotreated with CCBs compared with no CCB cotreatment, whereas in the placebo (no pravastatin) group, no effect of CCB treatment was observed (interaction test for differential effect of CCB treatment in patients with pravastatin compared with patients receiving placebo: P=.0016). With respect to the mean segment diameter, similar although not significant (P=.33) results were found. With respect to new lesion formation, in the pravastatin group, there were 50% (CI: 25-83) fewer patients with new angiographic lesions if cotreated with CCBs compared with no CCB cotreatment, whereas in the placebo (no pravastatin) group, no significant effect of CCB treatment was observed (interaction test: P=.0026). No beneficial effects of CCB treatment on clinical events were observed. Although the REGRESS trial was not designed to evaluate combination therapy, the results suggest strongly that addition of CCBs to 3-hydroxy-3-methylglutaryl–coenzyme reductase inhibitor therapy (pravastatin) acts synergistically in retarding the progression of established coronary atherosclerosis.

Key Words: calcium channel blockers • pravastatin • lipids • atherosclerosis • clinical trials

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