Blood pressure lowering effects of a new long-acting inhibitor of phosphodiesterase 5 in patients with mild to moderate hypertension

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1091-1097
Number of pages7
JournalHypertension
Volume53
Issue number6
DOIs
StatePublished - Jun 1 2009
Externally publishedYes

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Phosphodiesterase 5 Inhibitors
Blood Pressure
Hypertension
Placebos
Type 5 Cyclic Nucleotide Phosphodiesterases
Ambulatory Blood Pressure Monitoring
Dyspepsia
Incidence
Gastroesophageal Reflux
Headache

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Blood pressure lowering effects of a new long-acting inhibitor of phosphodiesterase 5 in patients with mild to moderate hypertension. / Wolk, Robert; Smith, William; Neutel, Joel M.; Rubino, John; Xuan, Dawei; Mancuso, James; Gilbert, James; Pressler, Milton L.

In: Hypertension, Vol. 53, No. 6, 01.06.2009, p. 1091-1097.

Research output: Contribution to journalArticle

Wolk, Robert ; Smith, William ; Neutel, Joel M. ; Rubino, John ; Xuan, Dawei ; Mancuso, James ; Gilbert, James ; Pressler, Milton L. / Blood pressure lowering effects of a new long-acting inhibitor of phosphodiesterase 5 in patients with mild to moderate hypertension. In: Hypertension. 2009 ; Vol. 53, No. 6. pp. 1091-1097.
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