CU-Boulder IPHY 3700 - Comparison of 26-Week Efficacy and Tolerability of Telmisartan and Atenolol

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CLINICAL THERAPEUTICSWOL. 23, NO. I, 2001 Comparison of 26-Week Efficacy and Tolerability of Telmisartan and Atenolol, in Combination with Hydrochlorothiazide as Required, in the Treatment of Mild to Moderate Hypertension: A Randomized, Multicenter Study Frank Freytag, MD,’ Adre Schelling, MD,2 Thomas Meinicke, MD,3 and Guntram Deichsel, PhD,4 for the Telmisartan Hypertension Experience in a Randomized European Study Versus Atenolol Study Group* ‘Kreiskrankenhaus Gunzenhausen, Gunzenhausen, Germany, 2Sint Franciscus Gasthuis, Department of Cardiology, Rotterdam, the Netherlands, jClinica1 Research, and 4Medical Data Services, Boehringer Ingelheim Pharma KG, Biberach, Germany ABSTRACT Objective: This study was undertaken to compare the efficacy and tolerability of telmi- sartan, a novel antihypertensive agent, and atenolol, a well-established beta-blocker, in the treatment of mild to moderate hypertension. Methods: This 26-week, multicenter, randomized, double-blind, double-dummy, parallel- group, titration-to-response study compared doses of telmisartan (40 mg titrated to 80 mg titrated to 120 mg) with atenolol (50 mg titrated to 100 mg) required to achieve diastolic blood pressure (DBP) control (590 mm Hg or a decrease from baseline of 210 mm Hg). Open-label hydrochlorothiazide (HCTZ) 12.5 or 25 mg was added if needed according to a prespecified titration rule. Men and women aged ~18 years with mild to moderate hy- pertension (morning mean supine DBP [SDBP] 295 mm Hg and 5114 mm Hg) were el- igible to participate. Patients with significant cardiovascular, metabolic, hepatic, or renal dysfunction or chronic obstructive pulmonary disease were excluded. The primary efft- cacy end point was trough SDBP response at 26 weeks; secondary efficacy end points in- cluded changes from baseline at trough in both standing and supine DBP and systolic blood pressure (SBP), and heart rate after 4, 8, 16, and 26 weeks; SBP control (reduction from baseline of 210 mm Hg); normalization of supine SDBP to 590 mm Hg; and the need for add-on HCTZ. Changes in quality of life were also examined. Adverse events were obtained from spontaneous reporting and recorded. Serious adverse events were re- ported to the sponsor according to predefined timelines. *The study group members are listed in the Acknowledgments. Accepted for publication October 1 I, 2000. Printed in the USA. Reproduction in whole or part is not permitted 108 0149-2918/01/$19.00F. FREYTAG ET AL. Results: A total of 533 patients from 49 centers participated. Patients’ mean age was 57.9 years (range, 22-79 years); 55.9% (298/533) of the population was male and 98.1% (523/533) was white. Of the 533 patients randomly assigned to treatment and included in the safety analy- sis, 520 (97.6%) were included in the ef- ficacy analysis; 346 received telmisartan and 174 received atenolol. A total of 489 patients (91.7%) completed the study (325 [93.9%1, telmisartan; 164 [94.2%], atenolol). Full SDBP response (trough SDBP 590 mm Hg and/or a reduction from baseline of ~10 mm Hg) was observed in 84% and 78% of telmisartan- and atenolol- treated patients, respectively; this differ- ence was not statistically significant. Final SBP/DBP reductions of 20.9/14.4 mm Hg were observed for the telmisartan regimen versus 16.7/13.3 mm Hg for the atenolol regimen; only the difference in SBP was significant (P = 0.005). Reduction from baseline in SBP of 210 mm Hg was achieved by 80% of telmisartan-treated and 68% of atenolol-treated patients (P = 0.003). Adverse events were reported by 52.1% of patients given telmisartan and 61.2% of patients given atenolol; this dif- ference was not statistically significant. Most events were mild or moderate. Al- though fatigue and male impotence were more common in atenolol-treated patients (3.4% and 4.0%, respectively), the inci- dence of these adverse events was too low to differentiate statistically. Conclusions: Telmisartan appears to be at least as effective as atenolol in the treat- ment of mild to moderate hypertension and may be better tolerated. Key words: telmisartan, angiotensin II antagonist, atenolol, hydrochlorothiazide, efficacy, tolerability. (Clin Ther: 200 1;23: 108-123) INTRODUCTION Angiotensin II (AII), the principal effec- tor hormone in the renin-angiotensin- aldosterone system, activates several pow- erful physiologic responses that help regulate blood pressure, including sys- temic and renal vasoconstriction, sodium reabsorption by the renal proximal tubule, and stimulation of aldosterone and adren- ergic hormone release by the adrenal glands.’ These actions are mediated prin- cipally via a specific AI1 receptor sub- type, AT,, which is located on the cell- wall surfaces of a variety of tissues including the heart, kidneys, and arteries.* Telmisartan belongs to a new class of orally active and highly selective nonpep- tide substituted benzimidazole AT,-receptor antagonists.3” Preclinical pharmacology studies have demonstrated that telmisartan specifically and potently inhibits the AI1 receptor subtype AT,.5 Telmisartan does not affect other aspects of the renin- angiotensin-aldosterone system, such as angiotensin-converting enzyme (ACE) ac- tivity; nor does it interact with the AT,- receptor subtype or other receptor systems, including those for catecholamines, sero- tonin, histamine, or adenosine.5 Telmisartan has high bioavailability (40%60%), a half-life of 24 hours, and a volume of distribution of 600 L&g; binds tightly and specifically to AT, receptors; and may have some inherent natriuretic ac- tivity.&s It has been shown in previous stud- ies to be an extremely effective antihyper- tensive agent, producing high response rates compared with other commonly used agents.7-9 For example, in a 52-week, ran- domized,


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CU-Boulder IPHY 3700 - Comparison of 26-Week Efficacy and Tolerability of Telmisartan and Atenolol

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