title: Effects of combination of perindopril, indapamide, and calcium channel blockers in patients with type 2 diabetes mellitus: results from the Action In Diabetes and Vascular Disease: Preterax and Diamicron Controlled Evaluation (ADVANCE) trial.
abstract: The objective of the present analysis was to determine the effects of a fixed combination of perindopril and indapamide in combination with calcium channel blockers (CCBs) in patients with type 2 diabetes mellitus. The Action in Diabetes and Vascular Disease: Preterax and Diamicron Controlled Evaluation (ADVANCE) trial was a factorial randomized controlled trial. A total of 11 140 patients with type 2 diabetes mellitus were randomly assigned to fixed combination of perindopril-indapamide (4/1.25 mg) or placebo. Effects of randomized treatment on mortality and major cardiovascular outcomes were examined in subgroups defined by baseline use of CCBs. Patients on CCB at baseline (n=3427) constituted a higher risk group compared with those not on CCB (n=7713), with more extensive use of antihypertensive and other protective therapies. Active treatment reduced the relative risk of death by 28% (95% confidence interval, 10%-43%) among patients with CCB at baseline compared with 5% (-12% to 20%) among those without CCB (P homogeneity=0.02) and 14% (2%-25%) for the whole population. Similarly, the relative risk reduction for major cardiovascular events was 12% (-8% to 28%) versus 6% (-10% to 19%) for those with and without CCB at baseline although the difference was not statistically significant (P homogeneity=0.38). There was no detectable increase in adverse effects in those receiving CCB. The combination of perindopril and indapamide with CCBs seems to provide further protection against mortality in patients with type 2 diabetes mellitus.
authors: The George Institute for Global Health, PO Box M201, Camperdown, NSW 2050, Australia. chalmers@georgeinstitute.org.au.
authors: John
authors: J
authors: Chalmers
authors: Hisatomi
authors: H
authors: Arima
authors: Mark
authors: M
authors: Woodward
authors: Giuseppe
authors: G
authors: Mancia
authors: Neil
authors: N
authors: Poulter
authors: Yoichiro
authors: Y
authors: Hirakawa
authors: Sophia
authors: S
authors: Zoungas
authors: Anushka
authors: A
authors: Patel
authors: Bryan
authors: B
authors: Williams
authors: Stephen
authors: S
authors: Harrap
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000009:adverse effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality; D004095:Dihydropyridines / Q000008:administration & dosage* / Q000009:adverse effects; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005907:Gliclazide / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007190:Indapamide / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004338:Drug Combinations; D007004:Hypoglycemic Agents; C494243:indapamide, perindopril drug combination; C038806:1,4-dihydropyridine; D007190:Indapamide; D005907:Gliclazide; D020913:Perindopril
keywords: angiotensin-converting enzyme inhibitors; blood pressure; calcium channel blockers; combination; diabetes mellitus; diuretics; drug therapy; randomized controlled trial