Effects of Initiating Antihypertensive Therapy with Amlodipine or Hydrochlorothiazide on Creatinine Clearance in Hypertensive Nigerians with Type 2 Diabetes Mellitus

Aims: To assess the effects of initiating antihypertensive therapy with amlodipine (AML) or hydrochlorothiazide (HCZ) for 48 weeks on creatinine clearance (Clcr) in hypertensive Nigerians with type 2 diabetes mellitus (DM).

Study Design: Randomized, open-label, prospective, outpatient study.

Place and Duration of Study: Department of Pharmacology and Therapeutics, College of Medicine, Ambrose Alli University, Ekpoma, Edo State, Nigeria between March 2008 and March 2009.

Methodology: We randomized 40 newly diagnosed hypertensive subjects with controlled type 2 diabetes mellitus (DM) aged 43-68 years to AML and HCZ treatment groups of 20 patients each (20 males (M) and 20 females (F)) and they were treated monotherapeutically, respectively, with AML 10mg and HCZ 25mg, all given once daily for 48 weeks. Body mass index (BMI), blood pressure (BP), 24h urine volume, urine creatinine, serum creatinine and the corresponding Clcr for each day were evaluated at baseline before treatment and at the end of weeks 1, 3, 6, 12, 24, 36 and 48 during treatment.

Results: The 2 drugs significantly reduced BP and at week 48, the mean M vs F systolic BP (SBP)/Diastolic BP (DBP) decrease from baseline for AML group (27.0/17.5 vs 29.5/20.0 mmHg) was more significant than that of HCZ group (23.5/17.5 vs 22.0/16.5 mmHg, P < .01). HCZ caused maximum M vs F diuresis (1593.00 +/- 27.21 vs 1587.00 +/- 30.60 ml) at week 3 and this was significantly higher than that (1526.00 +/- 27.10 vs 1516.00 +/- 22.76 ml, P < .01) produced by AML. Although the treatment effect exerted by the 2 drugs on Clcr was significant (P =.05), time-dependent changes in the mean values, which were higher in AML group, were not significantly different.

Conclusion: It is demonstrated that in hypertensive Nigerians with type 2 DM, single daily doses of these medications do not have a clinically significant effect on Clcr over a long-term monotherapy. Accordingly, with regard to HCZ greater diuresis which may cause problems particularly in the elderly, AML appears to be a preferred logical alternative to substitute for low dose HCZ therapy.