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Cardiovascular Safety Update of Tadalafil: Retrospective Analysis of Data from Placebo-Controlled and Open-Label Clinical Trials of Tadalafil With As Needed, Three Times-per-Week or Once-a-Day Dosing

https://doi.org/10.1016/j.amjcard.2005.12.073Get rights and content

Because most men with erectile dysfunction have underlying vascular disease, it is important to update the cardiovascular safety profile of medications used in the treatment of erectile dysfunction. This retrospective analysis evaluated serious cardiovascular treatment-emergent adverse events (CVTEAEs) reported in 36 clinical trials of tadalafil, a phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction. A serious CVTEAE was defined as myocardial infarction, cardiovascular death, or cerebrovascular death. In the 36 trials, 12,487 men (mean age 55 years) with erectile dysfunction received tadalafil, with 5,771 patient-years (PYs) of exposure, and 2,047 men (mean age 56 years) received placebo, with 460 PYs of exposure. Tadalafil 2 to 50 mg was taken as needed, 3 times/week, or once a day. Co-morbidities at baseline included hypertension (31%), diabetes (21%), hyperlipidemia (17%), and coronary artery disease (5%). Across all trials, the incidence rate of serious CVTEAEs was 0.40/100 PYs in tadalafil-treated patients and 0.43/100 PYs in placebo-treated patients. In patients taking tadalafil as needed, 3 times/week, or once a day, the incidence rates of serious CVTEAEs ranged from 0.17 to 0.54/100 PYs across placebo-controlled and open-label trials. In conclusion, the incidence rates of serious CVTEAEs were comparable among men with erectile dysfunction taking tadalafil as needed, 3 times/week, or once a day, and these rates were also comparable with those in placebo-treated patients. In this clinical trial population of men with erectile dysfunction, tadalafil was not associated with an increased risk for serious cardiovascular adverse events.

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Methods

Studies were approved by institutional review boards, and each patient gave informed consent. Studies were conducted in accordance with the Helsinki Declaration and the Guidelines for Good Clinical Practice.

Baseline demographics

There were 12,487 tadalafil-treated and 2,047 placebo-treated men with erectile dysfunction across the 36 clinical trials. The mean age of patients receiving tadalafil was 55 years (19% were >65 years old), and the mean age of patients receiving placebo was 56 years (21% were >65 years old). The body mass index was ≥30 kg/m2 in 2,998 tadalafil-treated patients (24%) and 464 placebo-treated patients (23%). The ethnicities of patients receiving tadalafil (n = 12,487) were Caucasian (81%), Asian

Discussion

This was a retrospective analysis of pooled data from 36 clinical trials of tadalafil using placebo-controlled and open-label study designs. The analysis included 12,487 tadalafil-treated and 2,047 placebo-treated men with erectile dysfunction. Across the trials, dosing regimens of tadalafil included as needed, 3 times/week, and once a day. The incidence rate of serious CVTEAEs was low in all groups evaluated, with comparable incidence rates in tadalafil- and placebo-treated patients. In

Acknowledgment

The authors thank Yi Xia, MS, Lingling Xie, MS, and Shuhuan Zhang, MS, Lilly Research Laboratories, Eli Lilly and Company, for their assistance with statistical analyses.

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This study was supported by Lilly ICOS LLC, Indianapolis, Indiana, and Bothell, Washington.

Conflict of interest statement: Dr. Kloner was a speaker and consultant to Bayer GSJ, Lilly ICOS, and Pfizer, a Consultant to Schering Plough and Platin-King, and received research support from Lilly LCOS. Dr. Jackson was a consultant to Lilly LCOS and Pfizer and received educational grants from Bayer, Lilly LCOS, and Pfizer. Dr Hutter was a consultant to Lilly LCOS. Dr. Mittleman was a consultant to Bayer, Lilly LCOS, and Pfizer. Ms. Chan and Drs. Costigan, Vail, and Warner are stockholders of Eli Lilly and Company.

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