Scientific rationale for combination of a calcium channel antagonist and an HMG-CoA reductase inhibitor: a new approach to risk factor management.

Cardiovascular disease is the leading cause of morbidity and mortality throughout the developed world. Risk factors for cardiovascular disease commonly coexist, which multiplies the overall or absolute risk of clinical events. Furthermore, evidence from observational and intervention trials suggest that the numerical risk associated with factors such as cholesterol level and blood pressure increases continuously. These findings concur with results from large-scale clinical trials showing that clinical benefits can be achieved with lowering cholesterol levels, irrespective of the initial levels. Cardiovascular risk factors have been shown to adversely influence vascular endothelial function. In particular, reduced bioavailability of endothelial-dependent nitric oxide production as a result of enhanced oxidative stress represents a common pathological mechanism of cardiovascular risk factors. This contributes to the observation that risk factors increase the overall risk of clinical events in an apparent additive fashion. Treatment guidelines now reflect these advances in our knowledge of risk factors by encouraging approaches that aim to reduce absolute risk, rather than addressing single risk factors in isolation. In response to this, a single pill combination of a calcium channel antagonist and an HMG-CoA reductase inhibitor (statin) has emerged as a means of addressing the suboptimal rates of goal attainment for concomitant hypertension and dyslipidaemia. Moreover, it can be viewed as a new therapeutic approach that seeks to comprehensively manage risk factors and enhance cardiovascular protection for patients at risk. Both experimental and clinical studies indicate that this approach is effective for reducing both the pathophysiological markers of atherosclerotic disease and its clinical consequences. This article provides an overview of the evidence for this new approach and recommends applications for use in clinical settings.