June 27, 2005Archives of Internal Medicine295 citations
View Full PaperClinical Outcomes in Antihypertensive Treatment of Type 2 Diabetes, Impaired Fasting Glucose Concentration, and Normoglycemia
Key Result
Amlodipine and lisinopril showed no superiority over chlorthalidone for fatal CHD or nonfatal MI in diabetes or normoglycemia, though amlodipine increased risk in impaired fasting glucose (RR 1.73).
Study Design
Type
RCT (n=31,512)
Blinding
double-blind
Randomization
randomly assigned
PICO
P
Population
31,512 adults aged 55 years or older with hypertension and at least 1 other CHD risk factor, stratified by diabetes, impaired fasting glucose, and normoglycemia.
I
Intervention / Comparator
Amlodipine or lisinopril vs Chlorthalidone 12.5 to 25 mg/d (Amlodipine 2.5 to 10 mg/d or lisinopril 10 to 40 mg/d)
O
Primary Outcome
Fatal coronary heart disease or nonfatal myocardial infarction — RR 1.73 (1.10-2.72)
Main Result
Relative Risk: 1.73 (95% CI 1.1–2.72)
Abstract
BACKGROUND: Optimal first-step antihypertensive drug therapy in type 2 diabetes mellitus (DM) or impaired fasting glucose levels (IFG) is uncertain. We wished to determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor decreases clinical complications compared with treatment with a thiazide-type diuretic in DM, IFG, and normoglycemia (NG). METHODS: Active-controlled trial in 31 512 adults, 55 years or older, with hypertension and at least 1 other risk factor for coronary heart disease, stratified into DM (n = 13 101), IFG (n = 1399), and NG (n = 17 012) groups on the basis of national guidelines. Participants were randomly assigned to double-blind first-step treatment with chlorthalidone, 12.5 to 25 mg/d, amlodipine besylate, 2.5 to 10 mg/d, or lisinopril, 10 to 40 mg/d. We conducted an intention-to-treat analysis of fatal coronary heart disease or nonfatal myocardial infarction (primary outcome), total mortality, and other clinical complications. RESULTS: There was no significant difference in relative risk (RR) for the primary outcome in DM or NG participants assigned to amlodipine or lisinopril vs chlorthalidone or in IFG participants assigned to lisinopril vs chlorthalidone. A significantly higher RR (95% confidence interval) was noted for the primary outcome in IFG participants assigned to amlodipine vs chlorthalidone (1.73 1.10-2.72). Stroke was more common in NG participants assigned to lisinopril vs chlorthalidone (1.31 1.10-1.57). Heart failure was more common in DM and NG participants assigned to amlodipine (1.39 1.22-1.59 and 1.30 1.12-1.51, respectively) or lisinopril (1.15 1.00-1.32 and 1.19 1.02-1.39, respectively) vs chlorthalidone. CONCLUSION: Our results provide no evidence of superiority for treatment with calcium channel blockers or angiotensin-converting enzyme inhibitors compared with a thiazide-type diuretic during first-step antihypertensive therapy in DM, IFG, or NG.