P-302: Blood pressure and cardiovascular effects of tadalafil, a new PDE5 inhibitor

• Published in: American journal of hypertension 2002-04, Vol.15 (S3), p.140A-140A
• Main Authors: Hutter, A.M., Kloner, R.A., Watkins, V., Costigan, T., Bedding, A., Mitchell, M., Emmick, J.
• Format: Article
• Language: English
• Subjects: Erectile Dysfunction; PDE5 Inhibition; Tadalafil
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/S0895-7061(02)02653-5

In the Massachusetts Male Aging Study, the age-adjusted probability for complete impotence in men with treated hypertension was 14%, vs 9.6% in the entire sample of 1,290 men aged 40 to 70 (Feldman et al. N Engl J Med. 1994;151:54-61). Tadalafil, a selective and potent inhibitor of PDE5, is a new treatment for men with erectile dysfunction (ED). Tadalafil and other PDE5 inhibitors potentiate vascular smooth muscle relaxation; therefore, they may affect the cardiovascular (CV) system as well. PDE5 inhibitors have been shown to augment the hypotensive effects of nitrates; PDE5 inhibitors and nitrates both act through the nitric oxide-cGMP pathway. This report summarizes the CV profile of tadalafil based on clinical pharmacology and large-scale clinical trials. In healthy subjects receiving 20 mg of tadalafil, there was no significant difference in standing systolic and diastolic blood pressure compared to subjects receiving placebo (mean maximal decrease of 0.2 and 4.6 mm Hg, respectively). There was also no change in heart rate. Sadovsky et al determined an incidence rate of myocardial infarction (MI) of 0.6 per 100 patient-years in age-standardized men (Sadovsky et al. Int J Clin Pract. 2001;55:115-128). Across all clinical studies of tadalafil, the rate of MI in treated patients (N>4000) was 0.39, vs 1.1 in patients receiving placebo (N>1200). The phase 3 clinical trials included patients with a wide variety of stable CV conditions, including patients taking multiple antihypertensive agents. Overall, the incidence of CV adverse events (AEs) in these trials was low, and the rate of AEs reported by patients on tadalafil was similar to placebo. There were no reports of hypotension for tadalafil-treated patients and 1 report for a placebo-treated patient. (The table shows treatment-emergent CV AEs occurring in at least 0.5% of patients receiving placebo or tadalafil. The number of syncope reports was too small for calculation of significance.) Event Placebo (N = 379) Tadalafil (N = 949) P Value (All NS) Flushing 1.6% 3.7% 0.089 Dizziness 1.9% 2.4% 0.873 Hypertension 1.6% 1.1% 0.912 Syncope 0.5% 0.1% NA In conclusion, tadalafil treatment has not been associated with an increased incidence of CV events. In addition, tadalafil has little effect on systemic arterial pressure.