EFFICACY, TOLERABILITY, AND QUALITY-OF-LIFE OF LOSARTAN, ALONE OR WITH HYDROCHLOROTHIAZIDE, VERSUS NIFEDIPINE GITS IN PATIENTS WITH ESSENTIAL-HYPERTENSION

A randomized, double-masked, parallel-group, multicenter clinical tria l was conducted to compare the efficacy, tolerability, and effects on quality oflife associated with the angiotensin II receptor antagonist losartan, alone or with hydrochlorothiazide (HCTZ), and the dihydropyr idine calcium channel blocker nifedipine gastrointestinal therapeutic system (GITS) in patients whose sitting diastolic blood pressure measu rements were between 95 and 115 mm Hg, inclusive, while receiving plac ebo. Patients were randomized to receive either losartan or nifedipine GITS in a double-masked, double-dummy fashion. A 4-week placebo washo ut period established baseline untreated blood pressure measurements a nd was followed by a 12-week active treatment period. Patients receivi ng losartan (n = 110) were initially given 50 mg once a day (QD) and c ould be titrated to losartan/HCTZ 50 mg/12.5 mg QD after 4 weeks follo wed by losartan/HCTZ 50 mg/25 mg QD after 8 weeks, as necessary. Patie nts in the nifedipine GITS group (n = 113) received 30 mg QD, which co uld be titrated to 60 mg QD after 4 weeks followed by 90 mg QD after 8 weeks. Medication was titrated upward as necessary to achieve a sitti ng trough diastolic blood pressure < 90 mm Hg. Efficacy, tolerability, and quality-of-life scores were assessed after 12 weeks of each thera py. Trough sitting diastolic blood pressure reductions after 4, 8, and 12 weeks of therapy were clinically comparable: losartan, -8.9, -11.6 , and -12.7 mm Hg, respectively, and nifedipine GITS, -9.3, -11.0, and -11.1 mm Hg, respectively, with the mean reduction in sitting diastol ic blood pressure at 12 weeks in the losartan group 1.6 mm Hg lower (9 5% confidence interval, 3.4 mm Hg lower to 0.3 mm Hg higher) than the mean reduction in sitting diastolic blood pressure in the nifedipine G ETS group. Similarly, reductions in systolic blood pressure between th e two treatment groups were comparable at all time points. The percent age of patients reaching the goal trough sitting diastolic blood press ure was comparable for the two treatment groups, with 74% of patients in the losartan regimen and 68% of patients in the nifedipine GETS reg imen reaching the goat. Of patients reporting adverse events in the tw o groups (75 patients receiving losartan and 69 receiving nifedipine G ITS), there was significantly more edema in the nifedipine GETS group (15% vs 4%; P = 0.005). Fourteen (12%) patients in the nifedipine GETS group were withdrawn due to an adverse event (eight of these were for edema). Six patients (5%) in the losartan group were withdrawn due to an adverse event (none of these patients had edema). There were signi ficant differences in the patient-reported quality-of-life symptom bot her inventory with respect to edema, with nifedipine GETS therapy caus ing significantly more bother due to edema in patients, regardless of whether that symptom was present at baseline (27% vs 9%; P = 0.0004. N o statistically significant differences for bother due to the other sy mptoms in the inventory were noted. Of note, while the incidence of pa tient-reported symptom bother due to edema in the nifedipine GITS grou p was 27%, the incidence of physician-reported drug-related edema was 12%. This difference points to the need for improved physician-patient communication regarding adverse effects and their impact on patients' quality of life. In conclusion, a regimen of losartan, when compared with a regimen of nifedipine GITS, provides comparable efficacy, and w ith respect to edema, superior tolerability, less bother to patients, and fewer therapy dropouts.