A multicenter, randomized, double-blind study of the antihypertensive efficacy and tolerability of irbesartan in patients aged >= 65 years with mild to moderate hypertension

Background: Blockade of the renin-angiotensin-aldosterone system (RAAS) is the preferred mechanism of action for controlling hypertension in select gr oups of patients, including those with diabetic nephropathy and heart failu re. Currently, 2 classes of drugs work by blocking the RAAS, albeit by diff ering mechanisms: angiotensin-converting enzyme (ACE) inhibitors and angiot ensin II angiotensin type 1 receptor blockers (ARBs). Objective: The goal of this study was to assess the comparative efficacy an d tolerability of the ARE irbesartan and the ACE inhibitor enalapril in pat ients greater than or equal to 65 years of age with mild to moderate hypert ension (sitting diastolic blood pressure [DBP], 95 to 110 mm Hg). Methods: Elderly (greater than or equal to 65 years of age) patients were r ecruited from 26 Canadian study centers for a randomized, double-blind, 8-w eek clinical trial. Exclusion criteria included sitting DBP >110 mm Hg or s itting systolic blood pressure (SBP) >200 mm Hg, angina pectoris, myocardia l infarction, cardiac procedure, stroke, or transient ischemic attack withi n 6 months of randomization, as well as other preexisting or present severe medical or psychologic conditions. Patients were randomly assigned to rece ive a single daily dose of irbesartan 150 mg (n = 70) or enalapril 10 mg (n = 71) with treatment doses of study drugs doubled at week 4 for sitting DB P greater than or equal to 90 mm Hg. Reductions from baseline blood pressur e measurements at trough (24 +/- 3 hours after the last dose of medication) were assessed for sitting DBP and sitting SEP. Comparative tolerability to study drugs was also assessed. Results: The intent-to-treat analysis demonstrated similar reductions at we ek 8 in both DBP and SEP for both groups. For the primary efficacy analysis of sitting DBP, there was a mean reduction from baseline of 9.6 mm Hg and 9.8 mm Hg for the irbesartan and enalapril groups, respectively (P = 0.93). The mean reduction from baseline in sitting SEP was 10.1 mm Hg and 11.6 mm Hg for the irbesartan and enalapril groups, respectively (P = 0.54). Norma lization rates (sitting DBP <90 mm Hg) at week 8 did not differ between gro ups (52.9% in the irbesartan group and 54.9% in the enalapril group; P = 0. 81). No statistical difference existed between the 2 groups with respect to serious adverse events or discontinuations due to adverse events. Irbesart an was associated with a significantly lower incidence of cough than was en alapril (4.3% vs 15.5%, respectively; P = 0.046). Conclusions: Irbesartan is an effective and well-tolerated antihypertensive for elderly patients with mild to moderate hypertension. This study establ ishes that irbesartan has better torerability than enalapril with respect t o cough and suggests that irbesartan is as effective at lowering blood pres sure but better tolerated than an ACE inhibitor in hypertensive patients <g reater than or equal to>65 years of age.