Cardiovascular Safety of Vardenafil in Patients on Antihypertensives and/or Alpha-Blockers: Analysis of 17 Placebo-Controlled Trials.

Cardiovascular Safety of Vardenafil in Patients on Antihypertensives and/or Alpha-Blockers: Analysis of 17 Placebo-Controlled Trials, William B. White, University of Connecticut School of Medicine; Wayne Hellstrom, Tulane University School of Medicine; Christiane Norenberg, Bayer HealthCare, Germany; Hartmut Porst, Practice of Urology and Andrology, Germany

We evaluated the cardiovascular (CV) safety of vardenafil when used concomitantly with antihypertensive therapies (AHT) and/or alpha-blockers. Drug-related CV adverse event (AE) data were compiled from 5,091 vardenafil- and 2,949 placebo-treated patients in 17 phase III studies in men with erectile dysfunction (ED) for greater than 6 months receiving vardenafil 2.5, 5, 10, or 20mg or placebo for 12 to 26 weeks. Event data were defined using updated MedDRA terms and stratified by (a) no AHT (placebo n = 1,917, vardenafil n = 3,359); (b) more than 1 AHT excluding alpha-blockers (placebo n = 828, vardenafil n = 1,355); and (c) alpha-blockers alone or with more than 1 AHT (placebo n = 204, vardenafil n = 377). The incidence rate of drug-related dizziness was slightly higher in vardenafil-treated vs. placebo patients, but without additive effects by AHT or alpha-blocker use. In the vardenafil group, drug-related dizziness was reported by 50 (1.5%) patients receiving no AHT, 21 (1.5%) patients receiving more than 1 AHT excluding alpha-blockers, and 7 patients (2%) receiving alpha-blockers with or without more than 1 AHT. Corresponding incidences in the placebo group were 8 (0.5%), 3 (0.5%), and 1 (0.5%) patient in the three subgroups, respectively. No patient experienced drug-related myocardial infarction (MI), and 1 patient receiving placebo plus alpha-blockers with or without more than 1 AHT experienced drug-related cerebrovascular accident (CVA). For all serious AEs (regardless of relationship to study drug), MI, CVA, and syncope occurred with frequencies ranging from 0 to 1% with no predilection for treatment group or AHT use. Two patients in the placebo group experienced syncope while on AHT (not alpha-blockers). Three vardenafil-treated patients experienced syncope while receiving alpha-blockers and one while receiving another type of AHT. Overall, pooled safety data from 17 placebo-controlled trials demonstrated no increase in drug-related CV-AEs other than dizziness for vardenafil. Neither alpha-blockers nor AHT increased drug-related CV-AE rates in vardenafil-treated patients.