Published in:
01-05-2000 | Clinical Use
A Comparative Evaluation of Amlodipine and Hydrochlorothiazide as Monotherapy in the Treatment of Isolated Systolic Hypertension in the Elderly
Published in: Clinical Drug Investigation | Issue 5/2000
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Objective: The purpose of this 8-week, randomised, single-blind, parallel group, multicentre, comparative study was to evaluate the efficacy, safety and tolerability of the dihydropyridine calcium antagonist amlodipine versus the thiazide diuretic hydrochlorothiazide for control of isolated systolic hypertension (ISH) in elderly patients aged 60 years or more.
Design: This was a phase IV, multicentre, single-blind, comparative, parallel group, randomised clinical trial, divided into two phases.
Setting, Patients and Interventions: Following a 4-week placebo wash-out period (phase I), outpatients aged 60 to 87 years with systolic blood pressure (SBP) ≥ 160mm Hg and diastolic blood pressure (DBP) ≤ 95mm Hg were randomised to receive amlodipine 5 mg/day or hydrochlorothiazide 50 mg/day for 8 weeks (phase II). After 4 weeks of active treatment, if sitting SBP (sSBP) still was above 150mm Hg, the dose had to be doubled. Demographic and safety data were assessed in all patients and efficacy only in the evaluable patients according to pre-specified criteria.
Results: 197 patients (66.5% women) were assigned to received amlodipine (n = 97) or hydrochlorothiazide (n = 100). 86 patients treated with amlodipine and 98 patients treated with hydrochlorothiazide were considered evaluable for efficacy. Two (2%) and five patients (5%) from each group, respectively, did not complete the study treatment. At the end of the active treatment phase, 80% of the patients treated with amlodipine were considered therapeutic successes (sSBP ≤ 150mm Hg) compared with 54% in the hydrochlorothiazide group (p = 0.0003). The mean reduction in sitting SBP/DBP in the amlodipine group was 32.5/8.4mm Hg and 24.0/4.7mm Hg in the hydrochlorothiazide group. The difference between groups was statistically significant (p < 0.001). There were no clinically significant changes in mean heart rate values between the two treatment groups. Laboratory findings showed that amlodipine had a neutral effect on haematological and biochemical values with an improvement in serum triglyceride and creatinine levels, while in the hydrochlorothiazide group, due to the high doses studied (50 to 100 mg/day), there were some metabolic adverse effects (e.g. in blood glucose levels and serum levels of lipids, uric acid and electrolytes). Safety and tolerability data showed that both treatments were well tolerated. Only one serious adverse event occurred during the course of the trial, and it was not related to treatment. The percentage of adverse events and discontinuations was 36 and 2% with amlodipine versus 44 and 4% with hydrochlorothiazide, respectively.
Conclusion: These results showed that for treatment of ISH in patients aged 60 years or more, amlodipine is significantly more effective than hydrochlorothiazide in reducing sitting SBP/DBP in monotherapy, and both drugs are well tolerated.