Synergistic protection against vascular inflammation with a calcium channel blocker and a statin

Abstract

C ardiovascular disease (CVD) is a leading cause of death worldwide. As CVD drives high healthcare costs in surviving events such as stroke and heart failure, better strategies to facilitate to prevent CVD have become priorities for most healthcare systems. Modification of cardiovascular risk factors is essential to reduce incidence of CVD. Cardiovascular risk factors are highly interactive and thereby contribute synergistically to the pathogenesis of atherosclerotic diseases. 1 Epidemiologic studies revealed that hypertension usually occurs in conjunction with other metabolically linked risk factors; such as glucose intolerance, obesity, left ventricular hypertrophy and dislipidemia. 2 Cowie estimated that over half of the hypertensive population also has dyslipidemia. 3 It has also become clear that CVD risk factors tend to increase the total or absolute CVD risk in a multiplicative rather than additive manner. 4 Thus, individual treatment strategies should be based on absolute cardiovascular risk, which could be determined by the synergistic effect of all cardiovascular risk factors rather than on individual risk factors. 5 To effectively reduce CVD risk in hypertensive patients at high cardiovascular risk, concomitant lipid-lowering therapy with HMG-CoA reductase inhibitors, stains, would be necessary as well as rigorous blood pressure control with two or more antihypertensive agents. These recommendations concur with the results of large clinical trials that demonstrated clinical benefit of statin therapy in hypertensive patients with normal lipid levels. 6 The antihypertensive efficacy of amlodipine and the lipid-lowering efficacy of atorvastatin are well established. The efficacy of the combined administration of amlodipine and atorvastatin in reducing coronary risk factors and cardiovascular morbidity has been evaluated in adult patients in several trials. Two randomized, double-blind, double-dummy, multicenter trials (AVALON, RESPOND) compared the efficacy of the coadministration of amlodipine and atorvastatin with that of single-agent therapy or placebo over 8 weeks. Five non-comparative, titration-to-goal, multicenter studies (GEMINI, GEMINI-ALAA, JEWEL I, JEWEL II, CAPABLE) evaluated the efficacy of the fixed-dose combination amlodipine/ atorvastatin in a clinical-practice setting over 14, 16 and 20 weeks.A 2Â2 factorial analysis of the data from the randomized, double-blind, multicenter trial evaluated the efficacy of amlodipine plus atorvastatin over 3.3 years (ASCOT-LLA). The randomized ASCOTT-LLA included patients with a total cholesterol concentration p250 mg dl À1 who were already enrolled in ASCOT-BPLA. 6 ASCOT-BPLA was a large, multicenter trial that used a PROBE (prospective, randomized, open-label and blinded endpoint) evaluation design to compare amlodipine-based with atenololbased therapy in hypertensive patients. 7 Patients eligible for ASCOT-LLA were further randomized to receive atorvastatin or placebo in addition to the blood pressure lowering medication in a double-blind manner. A pr...