Background: Combining statins with antihypertensive therapy has been demonstrated to provide an early reduction in cardiovascular events. This nested substudy of the AVALON trial assessed the effects of coadministered amlodipine and atorvastatin vs. either therapy alone or placebo on arterial compliance, to evaluate the vascular benefits of coadministered therapy. Methods: During an initial 8-week, double-blind phase, patients with concomitant hypertension and dyslipidemia were randomized into four treatment groups (placebo, amlodipine 5 mg, atorvastatin 10 mg, or coadministered amlodipine 5 mg and atorvastatin 10 mg). The sustained effect of combined therapy was evaluated during subsequent 8-week, single-blind, and 12-week, open-label periods. In the single-blind phase, all patients were coadministered amlodipine 5 mg and atorvastatin 10 mg, which were then titrated to optimize blood pressure and low-density lipoprotein cholesterol control during the open-label phase. Arterial compliance was assessed every 4 weeks using the HDI/Pulsewave CR-2000. Results: Overall, 668 patients (61% male, mean age 55 years) were randomized to treatment. A 19% improvement in small artery compliance (C2) was observed with coadministered amlodipine and atorvastatin from baseline to week 8, which was significantly greater than with either treatment alone or with placebo (P = 0.03 to 0.0001). After 28 weeks, C2 was increased from baseline in all groups, but the overall improvement was greatest in the group receiving coadministered drugs for the entire study period (P < 0.05). Conclusions: Early and sustained improvement in small artery compliance was observed following coadministration of amlodipine and atorvastatin, thus demonstrating a vascular benefit with simultaneous treatment of hypertension and dyslipidemia.
Bibliographical noteFunding Information:
acknowledgments:This study was sponsored by Pfizer Inc., Newyork. J.N. and D.H.G.S. are founders of Integrium, LLC; Integrium, LLC were paid consultants to Pfizer Inc. in connection with the design and conduct of this study. Editorial support was provided by Sarah Shearing and Elizabeth Harvey of Envision Pharma and funded by Pfizeer Inc. Logistical support included contributions to protocol development, clinical research site selection, regulatory management, and clinical monitoring.W.S., an employee of Pfizer Inc., was responsible for the statistical analysis of the data. all authors were involved in the collation and interpretation of the data; contributed to reviewing and editing the manuscript, approval of the final version, and the decision to submit the article for publication without constraints from the sponsor and inline with Good Publication Practice. J.N.C. had full access to the data and takes responsibility for the final version of the manuscript.
Disclosure: J.N.C. holds an equity position in Hypertension Diagnostics; M.H.W. has received research grants from Pfizer Inc. and honoraria for serving on the Speaker’s Bureau for Pfizer Inc.; D.J.W. andW.S. were employees of Pfizer Inc. at the time this study was conducted.