Effect of indomethacin on blood pressure lowering by captopril and losartan in hypertensive patients.
NSAIDs are known to attenuate the effects of some antihypertensive medications. It is not known whether the new class of angiotensin II receptor antagonists is similarly affected. We conducted a multicenter study assessing the effect of indomethacin on the antihypertensive effects of losartan and captopril. After 4 weeks of placebo washout, hypertensive patients received 6 weeks of active antihypertensive therapy with either 50 mg losartan once daily (n=111) or 25 mg captopril twice daily for 1 week, which was increased to 50 mg twice daily for 5 weeks (n=105). This was followed by 1 week of concomitant therapy with indomethacin (75 mg daily). The primary outcome measure was the change in mean 24-hour ambulatory diastolic blood pressure after the addition of indomethacin. Both captopril and losartan significantly lowered ambulatory diastolic blood pressure (losartan -5.3 mm Hg, P:<0.001; captopril -5.6 mm Hg, P:<0.001) after 6 weeks of therapy. Indomethacin significantly attenuated the 24-hour ambulatory diastolic blood pressure for both losartan (2.2 mm Hg, P:<0.05) and captopril (2.7 mm Hg, P:<0.001) and also attenuated the effect of captopril on trough sitting diastolic blood pressure. Changes in daytime diastolic blood pressure (7:00 AM to 11:00 PM) were similar to the 24-hour response in both groups. Nighttime diastolic blood pressure (11:01 PM to 6:59 AM) was significantly attenuated in captopril-treated patients (2.0 mm Hg, P:<0.05), but losartan was unaffected (0.4 mm Hg). Thus, concurrent treatment with indomethacin similarly attenuates the 24-hour antihypertensive response to losartan and captopril.
Conlin
P R
PR
Endocrinology-Hypertension Division, Brigham and Women's Hospital, Medical Service, Brockton/West Roxbury VA Medical Center, and Harvard Medical School, Boston, MA 02115, USA. pconlin@rics.bwh.harvard.edu
Moore
T J
TJ
Swartz
S L
SL
Barr
E
E
Gazdick
L
L
Fletcher
C
C
DeLucca
P
P
Demopoulos
L
L
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002940:Circadian Rhythm; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D002317:Cardiovascular Agents; D002216:Captopril; D019808:Losartan; D007213:Indomethacin