Comparative metabolic effects of hydrochlorothiazide and indapamide in hypertensive diabetic patients receiving ACE inhibitor therapy.
BACKGROUND
ACE inhibitors, when used as monotherapy, are frequently unable to adequately control blood pressure in diabetic patients. A diuretic may be added; however, thiazide diuretics, but not indapamide, have been associated with adverse metabolic effects. Whether these effects also apply to thiazides when administered in the currently used lower doses, and whether they differ from indapamide in their metabolic effects, particularly when used in combination with an ACE inhibitor in diabetic patients, has not been previously studied.


METHODS
We conducted a prospective, randomized, open-label, blinded endpoint crossover study comparing the metabolic responses to the addition of either hydrochlorothiazide (HCTZ) or indapamide, in 18 diabetic hypertensive patients receiving ACE inhibitor monotherapy for hypertension. Patients stabilized on fosinopril 20 mg/day were randomized to receive either HCTZ 12.5 mg od or indapamide 2.5 mg od for 8 weeks, then crossed over to the alternate therapy for a further 8-week period. Blood pressure, heart rate and metabolic assessments were performed at the end of each 8-week treatment period.


RESULTS
Seated and standing systolic and diastolic blood pressures were not different between HCTZ or indapamide when added to fosinopril, nor was the fasting lipid profile or urinary albumin : creatinine ratio. Plasma potassium was lower with indapamide compared with HCTZ treatment (indapamide 4.3+/-0.1 mmol/l; HCTZ 4.5+/-0.1 mmol/l, P<0.01) and HbA1c was higher with indapamide than with HCTZ therapy (indapamide 7.8+/-0.4%; HCTZ 7.2+/-0.3%, P<0.01).


CONCLUSIONS
Hydrochlorothiazide 12.5 mg/day, when added to background ACE inhibitor therapy with fosinopril in hypertensive diabetic patients, resulted in a metabolic profile that was similar, if not superior on certain parameters, in comparison with indapamide 2.5 mg/day.
Krum
H
H
National Health & Medical Research Council of Australia Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology & Preventive Medicine, Monash University/Alfred Hospital, Prahran, Victoria, Australia. henry.krum@med.monash.edu.au
Skiba
M
M
Gilbert
R E
RE
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000378:metabolism; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D017328:Fosinopril / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007190:Indapamide / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016037:Single-Blind Method; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D007190:Indapamide; D017328:Fosinopril