A Rationale for Combined Therapy with a Calcium Channel Blocker and a Statin: Evaluation of Basic and Clinical Evidence

Abstract

Calcium channel blockers and HMG-CoA reductase inhibitors are widely used for the management of hypertension and dyslipidemia, respectively. The use of these agents in the prevention and treatment of cardiovascular disease remains largely based on their actions in lowering blood pressure and lipids. Recent clinical trials, however, indicate that certain members of these two drug classes may slow progression of disease to an extent that cannot be solely attributed to risk factor reduction. The proposed mechanisms for such pleiotropic actions include enhancement of endothelial-dependent nitric oxide bioavailability, anti-inflammatory activity, and inhibition of oxidative stress. To understand the basis for such effects, along with potential synergies, we will review the basic and clinical evidence that indicate a broader opportunity for treatment and protection of cardiovascular events by atheroprotection with these agents beyond risk factor management.

Effect of atorvastatin on the intravenous and oral pharmacokinetics of verapamil in rats

“…The multiple prescription of drugs is increasingly common in current medical practice and cholesterol-lowering agents such as HMG-CoA reductase inhibitors could be coadministered with drugs used for the treatment of hypertension such as calcium channel blockers in clinics [20]. Considering that those drugs used in the combination therapy often share the metabolic pathways or cellular transport pathways, there could be high potential for pharmacokinetic as well as pharmacodynamic drug interactions between calcium channel antagonists and HMG-CoA reductase inhibitors.…”

Effects of HMG-CoA reductase inhibitors on the pharmacokinetics of nifedipine in rats: Possible role of P-gp and CYP3A4 inhibition by HMG-CoA reductase inhibitors

“…The prescription of more than one drug as a combination therapy is increasingly common in current medical practice. Cholesterol-lowering agents such as HMG-CoA reductase inhibitors could be co-administered with calcium channel blockers for the treatment of hypertension [39].…”

Effects of lovastatin on the pharmacokinetics of verapamil and its active metabolite, norverapamil in rats: Possible role of P-glycoprotein inhibition by lovastatin

“…The multiple prescriptions of drugs is increasingly common in current medical practice and cholesterol-lowering agents such as HMG-CoA reductase inhibitors could be co-administered with calcium channel blockers in clinics for the treatment of hypertension (Mason et al, 2005). Considering that those drugs used in the combination therapy often share same metabolic pathways or cellular transport pathways, there could be a high potential for pharmacokinetic as well as pharmacodynamic drug interactions between calcium channel antagonists and 0.92 ± 0.20 1.08 ± 0.49 1.08 ± 0.49* t 1/2 (h) 9.8 ± 2.40 10.4 ± 2.60 11.0 ± 2.90* M.R.…”