ANTIHYPERTENSIVE EFFICACY OF OLMESARTAN MEDOXOMIL, A NEW ANGIOTENSIN II RECEPTOR ANTAGONIST, AS ASSESSED BY AMBULATORY BLOOD PRESSURE MEASUREMENTS

Olmesartan medoxomil is a new angiotensin II receptor blocker. In this randomized, double-blind, placebo-controlled study, the efficacy and safety of olmesartan medoxomil was assessed in 334 patients with moderate to severe essential hypertension. Patients were randomized to receive placebo; 5, 20, or 80 mg olmesartan medoxomil q.d.; or 2,5, 10, or 40 mg olmesartan medoxomil b.i.d. Ambulatory and cuff blood pressure were measured prior to and after 8 weeks of treatment. Treatment with olmesartan medoxomil resulted in a significant placebo-adjusted reduction of mean 24-hour ambulatory diastolic blood pressure of 9,6 mm Hg, 12,2 mm Hg, and 10,6 mm Hg in the 5-, 20-, and 80-mg q.d. groups, respectively. Corresponding reductions in mean ambulatory systolic blood pressure were 14,5 mm Hg, 16,5 mm Hg, and 15,4 mm Hg. Similar reductions of diastolic and systolic blood pressure were seen with b.i.d. dosing. The diastolic trough-to-peak ratios of the q.d. doses of olmesartan medoxomil ranged from 57% to 70%, indicating 24-hour effectiveness. The safety profile of olmesartan medoxomil was similar to that of placebo. Olmesartan medoxomil appears to be a safe and effective once-a-day treatment for hypertension.

Moderate to severe essential hypertension, olmesartan medoxomil, antihypertensive efficacy, safety, 24-hour ambulatory blood pressure monitoring

1. Burnier M, Brunner HR. Angiotensin II receptor antagonists. Lancet. 2000;355:637–645.

2. Yanagisawa H, Amemiya Y, Kanazaki T, et al. Nonpeptide angiotensin II receptor antagonists: synthesis, biological activities, and structure–activity relationships of imidazole-5-carboxyliv acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-posotion and their related compounds. J Med Chem. 1996;39:323–338.

3. Anonymous. Olmesartan medoxomil. Drugs Future. 1997;22:1205– 1209.

4. Mizuno M, Sada T, Ikeda M, et al. Pharmacology of olmesartan medoxomil, a novel nonpeptide angiotensin II receptor antagonist. Eur J Pharmacol. 1995;285:181–188.

5. Püchler K, Nussberger J, Laeis P, et al. Blood pressure and endocrine effects of single doses of olmesartan medoxomil, a novel angiotensin II antagonist, in salt-restricted hypertensive patients. J Hypertens. 1997;15:1809–1812.

6. Diamant M, Idema RN, Vincent HH. The use of Fourier analysis in the calculation of trough to peak ratio from ambulatory blood pressure measurements. J Hum Hypertens. 1998;12:61–67.

7. Andrejak M, Genes N, Vaur L, et al. Electronic pill-boxes in the evaluation of antihypertensive treatment compliance: comparison of once daily versus twice daily regimen. Am J Hypertens. 2000;13:184–190.

8. White WB. Circadian variation of blood pressure: clinical relevance and implications for cardiovascular chronotherapeutics. Blood Press Monit. 1997;2:47–51.

9. Staessen JA, Beilin L, Parati G, et al. Task force IV: clinical use of ambulatory blood pressure monitoring. Participants of the 1999 Consensus Conference on Ambulatory Blood Pressure Monitoring. Blood Press Monit. 1999;4:319–331.

10. US Food and Drug Administration (FDA). Draft ICH principle: principles for clinical evaluation of new antihypertensive drugs. Available at www.fda.gov/cder/guidance/3774dft.pdf. Accessed January 23, 2001.

11. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med. 1997;157:2413–2446.

12. Mazzolai L, Burnier M. Comparative safety and tolerability of angiotensin II receptor antagonists. Drug Saf. 1999;21:23–33.

13. Hansson L, Smith DH, Reeves R, et al. Headache in mildtomoderate hypertension and its reduction by irbesartan therapy. Arch Intern Med. 2000;160:1654–1658.

14. McIntyre M, Caffe SE, Michalak RA, et al. Losartan, an orally angiotensin (AT1) receptor antagonist: a review of its efficacy and safety in essential hypertension. Pharmacol Ther. 1997;74:181–194.

15. McClellan KJ, Goa KL. Candesartan cilexetil. A review of its use in essential hypertension. Drugs. 1998;56:847–869.