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(Hypertension. 2009;53:1091.)
© 2009 American Heart Association, Inc.

Original Articles

Blood Pressure Lowering Effects of a New Long-Acting Inhibitor of Phosphodiesterase 5 in Patients With Mild to Moderate Hypertension

Robert Wolk; William B. Smith; Joel M. Neutel; John Rubino; Dawei Xuan; James Mancuso; James Gilbert; Milton L. Pressler

From Pfizer Global Research & Development (R.W., D.X., J.M., J.G., M.L.P.), Pfizer Inc, New London, Conn; Volunteer Research Group (W.B.S.), Knoxville, Tenn; Orange County Research Center (J.M.N.), Tustin, Calif; and Triangle Medical Research (J.R.), Raleigh, NC.

Correspondence to Robert Wolk, MD, PhD, DSc, Pfizer Global Research & Development, Pfizer Inc., MS 6025-A4162, 50 Pequot Ave, New London, CT 06320. E-mail Robert.Wolk{at}pfizer.com

Inhibition of phosphodiesterase 5 is an attractive candidate mechanism for blood pressure (BP) lowering. In this study, a novel long-acting phosphodiesterase 5 inhibitor, PF-00489791, was evaluated in 133 patients with mild to moderate hypertension, randomized into 1 of 4 groups: placebo, 4 mg, 10 mg, and 20 mg titrated after 14 days of dosing to 40 mg. Study medication was administered once daily for 28 days. Ambulatory BP monitoring was used. There was a statistically significant decrease (compared with placebo) in mean daytime systolic BP on day 28 at the 10 and 20/40 mg doses (by 5 and 7 mm Hg, respectively). Changes in mean daytime diastolic BP corresponded with those in systolic BP. The magnitude of BP lowering was greater on day 1 than on days 14 and 28, but the response was sustained between days 14 and 28. PF-00489791 also exerted BP lowering effects on mean 24-hour ambulatory BP. There was a dose-related increase in plasma cGMP concentration (statistically significant at the 20/40 mg dose). There was an increased incidence of headaches at the 10 and 20/40 mg doses (22% and 21%, respectively, compared with 12% with placebo) and an increased incidence of dyspepsia/gastroesophageal reflux disease and musculoskeletal adverse events at the 20/40 mg dose. In conclusion, PF-00489791 causes a clinically meaningful and sustained BP lowering in patients with hypertension. It is generally safe and well tolerated at the clinically efficacious doses.

Key Words: hypertension • phosphodiesterase 5 • PDE-5 inhibition • PF-00489791 • ABPM • cGMP • blood pressure