title: Indomethacin does not attenuate the hypotensive effect of trandolapril.
abstract: This is a randomised, double-blind, placebo-controlled, four-way crossover study to determine if indomethacin attenuates the hypotensive effect of trandolapril. Twenty-three hypertensive patients (diastolic blood pressure (DBP) 95-115) requiring NSAID were recruited. Seventeen completed the study. Three week treatment periods: trandolapril 2 mg od and indomethacin 25 mg tds, trandolapril 2 mg and placebo, indomethacin and placebo, placebo and placebo. Clinic and ambulatory BP after 3 weeks of each treatment. Study had 85% power to detect a 5 mm Hg difference in BP (s.d. 7 mm Hg). End of treatment clinic BPs were: 152.9/98 mm Hg (95% CI 147.2, 158.6/95.8, 101.4) with placebo and placebo; 150.4/94.9 mm Hg (95% CI 144.7, 156.1/92.1, 97.7) with trandolapril and indomethacin; 148.2/96.5 mm Hg (95% CI 142.5, 153.9/93.7, 99.3) with trandolapril and placebo; and 156.6/97.4 mm Hg (95% CI 150.9, 162.3/94.6, 100.2) with indomethacin and placebo. There were no significant interactions between trandolapril and indomethacin for clinic systolic BP (SBP) (P = 0.79) or clinic DBP (P = 0.87). When trandolapril treatments (placebo or with indomethacin) were compared to treatments without trandolapril (placebo or indomethacin), trandolapril lowered clinic SBP by 5.4 mm Hg (P = 0.047) and DBP by 2.3 mm Hg (P = 0.08). Mean ambulatory BP was: 140.6/88.2 mm Hg (trandolapril and placebo); 142.8/89.7 mm Hg (trandolapril and indomethacin); 149.6/95.0 mm Hg, (indomethacin and placebo); 147.7/94.0 mm Hg (placebo and placebo). Compared with placebo, trandolapril and placebo lowered BP by 6.5/7.5 mm Hg (P < 0.001, SBP; P < 0.001, DBP). Compared with indomethacin, trandolapril and indomethacin lowered BP by 5.0/5.5 mm Hg (P = 0.001, SBP; P < 0.001, DBP). In the present study trandolapril 2 mg lowered clinic SBP and ambulatory BP, but indomethacin did not attenuate this. Indomethacin had no significant effect on either clinic or ambulatory BP. The antihypertensive effects of trandolapril in this study were modest. Patient selection factors may have contributed to the observed responses, but it seems unlikely from these data that a clinically important drug interaction has occurred.
authors.affiliation: Clinical Pharmacology Unit, University of Aberdeen, UK.
authors.forename: G
authors.initials: G
authors.lastname: Pritchard
authors.forename: D
authors.initials: D
authors.lastname: Lyons
authors.forename: J
authors.initials: J
authors.lastname: Webster
authors.forename: J C
authors.initials: JC
authors.lastname: Petrie
authors.forename: T M
authors.initials: TM
authors.lastname: MacDonald
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced*; D007211:Indoles / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; C052035:trandolapril; D007213:Indomethacin