title: Vasodilator monotherapy in the treatment of hypertension: comparative efficacy and safety of pinacidil, a potassium channel opener, and prazosin.
abstract: We compared antihypertensive effects of monotherapy with pinacidil (N = 197) or prazosin (N = 204) in a randomized, parallel, double-blind dose-titration study in which hydrochlorothiazide or propranolol could be added for adverse events or lack of efficacy. Pinacidil (12.5 to 75 mg b.i.d.) was a more potent vasodilator, producing a mean decrease in supine diastolic blood pressure (baseline = 102 to 103 +/- 9 mm Hg) of 18.8 +/- 10.0 (SD) mm Hg compared with 15.5 +/- 9.2 mm Hg with prazosin (1 to 10 mg b.i.d.; p less than 0.001). Patients responding to each drug had similar average blood pressure levels during 12-hour monitoring (137/85 mm Hg). More patients taking pinacidil required hydrochlorothiazide for edema (p = 0.008) and more taking prazosin required hydrochlorothiazide and propranolol for lack of efficacy (p less than 0.001). Tachycardia (15% to 20%) and palpitation (13% to 15%) were frequent events with both drugs. Edema (38.2% vs 22.3%) was more frequent with pinacidil (p less than 0.001) and postural hypotension (4.7% vs 1.0%) and asthenia (20.2% vs 13.2%) were more frequent with prazosin (p = 0.025; 0.062). No significant laboratory toxicity was noted. In conclusion, both pinacidil and prazosin are effective as monotherapy for hypertension. Monotherapy with pinacidil is limited by adverse events related to vasodilatation and monotherapy with prazosin is limited by lack of efficacy.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN.
authors.forename: M R
authors.initials: MR
authors.lastname: Goldberg
authors.forename: C S
authors.initials: CS
authors.lastname: Sushak
authors.forename: F W
authors.initials: FW
authors.lastname: Rockhold
authors.forename: W L
authors.initials: WL
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002986:Clinical Trials as Topic; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D005260:Female; D006146:Guanidines / Q000009:adverse effects / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020110:Pinacidil; D011224:Prazosin / Q000627:therapeutic use; D011897:Random Allocation; D013610:Tachycardia / Q000139:chemically induced; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D006146:Guanidines; D014665:Vasodilator Agents; D020110:Pinacidil; D011224:Prazosin