Profiles of Serum and Urine Electrolytes Following Dual Pharmacotherapy with Amlodipine and Hydrochlorothiazide in Hypertensive Nigerians

Abstract

Aims: To evaluate changes in electrolyte profiles during dual pharmacotherapy with amlodipine (AML) and hydrochlorothiazide (HCZ) in hypertensive Nigerians.Introduction: In Nigeria, hypertension is the commonest non-communicable disease representing the commonest cardiovascular cause of hospitalisation and mortality among the indigenous people.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 \(\le\) 180/120mmHg). Patients, who were 30 each (15males [M] and 15females [F]) in AML, HCZ and AML-HCZ 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. The associated robust natriuresis and diuresis suggest that the patients were salt-sensitive and so may benefit from salt restriction as a lifestyle intervention to control hypertension.