RESUMEN
Aims: To evaluate changes in electrolyte profiles during combination treatment with amlodipine (AML) and hydrochlorothiazide (HCZ) in hypertensive Nigerians. Study Design: Randomized, open-label, prospective, two-centre, outpatient, 48-week study. Methodology: We enrolled 90 male and female Nigerians aged 31-86 years with uncomplicated essential hypertension (blood pressure [BP] > 160/90 ≤ 180/120mmHg). Patients, who were 30 each (15males [M] and 15females [F]) in AML, HCZ and AMLHCZ groups, were treated, respectively, with 5mg AML for 6 weeks (wks) and the dose increased to 10mg till wk 12 (monotherapy) after which HCZ 25mg was added; HCZ 25mg till wk 6 (monotherapy) after which AML 5-10mg was added; and AML 5-10mg + HCZ 25mg. Body mass index (BMI), BP, 24h urine volume, serum and urine electrolytes (Na+, K+, Cl-) were assessed at baseline and at the end of wks 1, 3, 6, 12, 24, 36 and 48 during treatment. Results: The 3 regimens comparably significantly (P= .05) reduced BP. Diuresis was greatest and significant (P= .05) in HCZ group. A time dependent significant (P< .0001) hyponatraemic changes were observed in all subgroups except AML M subgroup such that the mean maximum M/F decrease in AML, HCZ and AML-HCZ groups, respectively, were 5.07/14.74, 17.40/16.40 and 10.93/16.86 mmol/L. A parallel significant (P< .01) increase in urine Na+ was observed in all groups with maximum mean M/F increase in AML, HCZ and AML-HCZ groups being, respectively, 26.00/24.40, 28.07/40.94 and 30.47/27.67 mmol/L. A baseline hypokalaemia was observed in all groups except in the AML M subgroup. Significant (P< .0001) M/F hypokalaemic changes were 0.23/0.35, 0.76/0.53 and 0.18/0.19 mmol/L for AML, HCZ and AML-HCZ groups, respectively. Corresponding significant (P< .0001) M/F increase in urine K+ were 4.60/5.71, 10.67/18.60 and 8.2/9.3 mmol/L for AML, HCZ and AML-HCZ groups, respectively. Significant (P= .05) disproportionate chloraemia was observed at baseline in all groups. The observed significant (P< .0001) M/F hypochloraemic changes in AML, HCZ and AML-HCZ groups were, respectively, 10.60/11.46, 25.60/26.94 and 22.93/17.67. A significant (P < .0001) parallel hyperchloriuria was evident in all groups and M/F values in AML, HCZ and AML-HCZ groups were, respectively, 8.09/6.46, 26.00/39.86 and 24.53/18.00 mmol/L. Conclusion: Long-term AML and HCZ combination therapy, though effective, is associated with biochemical changes – Na+, K+ and Cl- depletion, thus making serum electrolytes monitoring and K+ supplementation or concomitant use of a K+-sparing diuretic clinically imperative.
RESUMEN
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 longterm 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.