Effect of indomethacin on the antihypertensive efficacy of valsartan and lisinopril: a multicentre study.
OBJECTIVE
To compare the effect on antihypertensive efficacy produced by the addition of indomethacin to the angiotensin II (Ang II) antagonist, valsartan, or to the angiotensin-converting enzyme inhibitor, lisinopril, in hypertensive patients with chronic osteoarthritis.


METHODS
One hundred and twenty-eight patients (52 men and 76 women) aged 25-82 years (mean age 55.7 years), with diastolic blood pressure (DBP) > 100 mmHg at the end of a 2-week placebo washout period were allocated randomly to groups to receive valsartan (80-160 mg once daily) or lisinopril (10-20 mg once daily). At the end of 10 weeks of treatment, patients with DBP < 90 mmHg, while continuing to receive valsartan or lisinopril treatment, were allocated randomly to groups to receive either indomethacin (50 mg three times a day) or the corresponding placebo for 2 weeks, with a 1-week washout period between the two treatments, according to a double-blind, crossover design. After the initial washout period, patients were examined at the end of the 4th, 8th and 10th weeks of randomized treatment with valsartan and lisinopril, at the end of the first crossover period and then at the beginning and at the end of the second crossover period. At each visit, sitting and standing blood pressure were measured by standard mercury sphygmomanometer.


RESULTS
The addition of indomethacin blunted the blood pressure-decreasing effect of both antihypertensive drugs. Although indomethacin produced greater increases in both systolic and DBP values in the lisinopril-treated patients (5.45/3.22 mmHg) than in the valsartan-treated ones (2.12/1.87 mmHg), no significant difference between the two drugs was found.


CONCLUSIONS
From a theoretical standpoint, these findings suggest that prostaglandins may play a part in the antihypertensive action of Ang II antagonists. From a practical standpoint, hypertensive patients treated with valsartan or with lisinopril should be monitored to detect changes in blood pressure control while receiving indomethacin.
Fogari
Roberto
R
Dipartimento di Medicina Interna, IRCCS Policlinico S. Matteo, Università di Pavia, Pavia, Italy. r.fogari@smatteo.pv.it
Zoppi
Annalisa
A
Carretta
Renzo
R
Veglio
F
F
Salvetti
Antonio
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy*; D007213:Indomethacin / Q000627:therapeutic use*; D017706:Lisinopril / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000150:complications* / Q000188:drug therapy*; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D013777:Tetrazoles; D000068756:Valsartan; D017706:Lisinopril; D014633:Valine; D007213:Indomethacin