A Comparative Evaluation of Amlodipine and Hydrochlorothiazide as Monotherapy in the Treatment of Isolated Systolic Hypertension in the Elderly

C. Calvo, F. Gude, Hypertension Unit and Epidemiology Department, Hospital Clínico Universitario, Santiago de Compostela, Spain; J. Abellán, Murcia S. Andrés Primary Care Center, Murcia, Spain; J. Oliván, Hypertension Unit, Hospital Virgen Macarena, Seville, Spain; M. Olmos, Department of Nephrology, Hospital Universitario La Fe, Valencia, Spain; L. Pita, Department of Internal Medicine, Hospital Universitario Santa Cristina, Madrid, Spain; D. Sánz, Department of Clinical Nephrology, Clínica Puerta de Hierro, Madrid, Spain; J. Sarasa, Department of Preventive Medicine, Hospital Miguel Servet, Zaragoza, Spain; J. Bueno, Department of Internal Medicine, Hospital Clínico Universitario, Zaragoza, Spain; J. Herrera, Department of Nephrology, Hospital Central de Asturias, Oviedo, Spain; J. Macías, Department of Nephrology, Hospital Clinico, Salamanca, Spain; T. Sagastagoitia, Department of Cardiology, Hospital Civil de Basurto, Bilbao, Spain; B. Ferro, A. Vega, J. Martínez, Medical Division, Pfizer, S.A., Madrid, Spain

Clin Drug Invest. 2000;19(5) 

In This Article

Abstract and Introduction

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 washout 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.

High blood pressure is one of the most wide-spread diseases in the world population and, more specifically, isolated systolic hypertension (ISH) is the most common form of high blood pressure in elderly patients.[1,2,3,4,5] This variety of high blood pressure, which is simply an isolated elevation of systolic blood pressure (SBP) while maintaining normal diastolic blood pressure (DBP) values, is closely related to the age of patients and is a 'natural' consequence of ageing, so that the prevalence of ISH increases with age.[1,6] The Framingham study[6] set the prevalence of ISH in elderly hypertensives at 60 to 65%.

Not so long ago, some physicians proposed that high blood pressure should not be treated in elderly patients unless it was very severe (SBP/DBP > 200/110mm Hg) and symptomatic. However, data from the Framingham study[6] and other studies[7,8] have demonstrated that high blood pressure increases cardiovascular risk in elderly patients.

In recent years, more persuasive data have been obtained on the beneficial effects of pharmacological intervention and sustained reduction of SBP. Specifically, reductions of up to 42%in stroke and of about 14% in coronary events have been reported.[1,9,10]

However, it should be stressed that despite the different existing antihypertensive therapies, not all drugs show the same efficacy in reducing or adequately controlling ISH.

Beta-Blockers and diuretics have traditionally been the treatments used in patients with ISH. More recently, the fifth report of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC V report)[11] recommended diuretics as the first choice agents, and the sixth (JNC VI) report[12] has extended its recommendation to include both diuretics and long-acting dihydropyridine calcium antagonists.

The purpose of this study was to compare the efficacy, safety and tolerability of these two classes of drugs in a population of elderly patients aged 60 years or older with high SBP. For this purpose, the long-acting calcium antagonist amlodipine and the thiazide diuretic hydrochlorothiazide were chosen.

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