Thiazide Diuretics First-Line Antihypertensives for Diabetic Patients

ALLHAT study demonstrates that chlorthalidone is at least equivalent to lisinopril and amlodipine in the management of hypertension in patients with DM, and it may be superior for the prevention of congestive heart failure. Thiazide diuretics are suitable as first-line antihypertensives for diabetic patients, according to the results of a randomized trial
"Optimal first-step antihypertensive drug therapy in type 2 diabetes or impaired fasting glucose levels is uncertain," write Paul K. Whelton, MD, MSc, from Tulane University in New Orleans, Louisiana, and colleagues from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group. "Agents that interfere with the renin-angiotensin system, especially angiotensin-converting enzyme inhibitors (ACEIs), have been recommended as first-step antihypertensive treatment in patients with DM and proteinuria. There is less certainty, however, regarding the optimal choice of first-step antihypertensives in patients with DM and hypertension who have little or no renal damage."

The ALLHAT trial enrolled 31,512 adults age 55 years and older who had hypertension and at least one other risk factor for coronary heart disease (CHD). On the basis of national guidelines, patients were stratified into DM (n = 13,101), IFG (n = 1,399), and normoglycemia (NG; n = 17,012) groups. Patients were randomized to double-blind first-step treatment with 12.5 to 25 mg of chlorthalidone per day, 2.5 to 10 mg of amlodipine besylate per day, or 10 to 40 mg of lisinopril per day. The primary outcome was fatal CHD or nonfatal myocardial infarction (MI). Analysis of the primary endpoint, total mortality, and other clinical complications was by intent-to-treat.

Relative risk (RR) for the primary outcome was not significantly different in patients with DM or normoglycemic patients randomized to amlodipine or lisinopril vs chlorthalidone or in participants with IFG randomized to lisinopril vs chlorthalidone. However, RR (95% confidence interval [CI]) for the primary outcome was significantly higher in participants with IFG randomized to amlodipine vs chlorthalidone (RR, 1.73; 95% [CI], 1.10 – 2.72).

Stroke was more frequent in normoglycemic patients randomized to lisinopril vs chlorthalidone. Compared with patients with DM and normoglycemic patients randomized to chlorthalidone, heart failure was more frequent in those randomized to amlodipine or lisinopril.

"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," the authors write.

"Recognizing the constraints in the interpretation of clinical trials, the ALLHAT findings suggest that thiazide-type diuretics should be strongly considered as first-step agents for therapy in patients with hypertension and DM or IFG," the authors conclude. "These agents are not only efficacious but have been evaluated in many trials and are the least expensive medications to prescribe."

Practice Pearls

· The ABCD trial demonstrated that ACE inhibitors were superior to calcium channel blockers in preventing MI among patients with hypertension and DM, but the two treatments were similar in terms of rates of stroke, congestive heart failure, death from cardiovascular causes, and deaths from any cause.

· ALLHAT demonstrates that chlorthalidone is at least equivalent to lisinopril and amlodipine in the management of hypertension in patients with DM, and it may be superior for some outcomes such as the prevention of congestive heart failure.

Arch Intern Med. June 2005;165:1401-1409

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