Diuretics Most Effective Blood Pressure Medication For People With Metabolic Syndrome

Commentaries:

The ALLHAT study originally reported in 2002 that diuretics were the most beneficial of the drug classes studied for treating high blood pressure and for protecting against adverse cardiovascular outcomes. The study compare a diuretic (chlorthalidone) with three classes of medications to treat high blood pressure: a calcium-channel blocker (amlodipine besylate), an alpha-blocker (doxazosin mesylate), and an angiotensin-converting enzyme (ACE) inhibitor (lisinopril).

Diuretic-based treatment was more protective against heart failure and also against overall cardiovascular disease (coronary heart disease, stroke, heart failure, or peripheral arterial disease combined) when compared with the ACE-inhibitor and alpha-blocker-based treatments.
Diuretic-based treatment was more protective against heart failure when compared with the calcium channel blocker-based treatment.

Clinical Outcomes by Race in Hypertensive Patients With and Without the Metabolic Syndrome Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Jackson T. Wright Jr, MD, PhD; Sonja Harris-Haywood, MD; Sara Pressel, MS; Joshua Barzilay, MD; Charles Baimbridge, MS; Charles J. Bareis, MD; Jan N. Basile, MD; Henry R. Black, MD; Richard Dart, MD; Alok K. Gupta, MD; Bruce P. Hamilton, MD; Paula T. Einhorn, MD, MS; L. Julian Haywood, MD; Syed Z. A. Jafri, MD; Gail T. Louis, RN, BA; Paul K. Whelton, MD, MSc; Cranford L. Scott, MD; Debra L. Simmons, MD; Carol Stanford, MD; Barry R. Davis, MD, PhD

Arch Intern Med. 2008;168(2):207-217.

Background Antihypertensive drugs with favorable metabolic effects are advocated for first-line therapy in hypertensive patients with metabolic/cardiometabolic syndrome (MetS). We compared outcomes by race in hypertensive individuals with and without MetS treated with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), an -blocker (doxazosin mesylate), or an angiotensin-converting enzyme inhibitor (lisinopril).

Methods A subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind hypertension treatment trial of 42 418 participants. We defined MetS as hypertension plus at least 2 of the following: fasting serum glucose level of at least 100 mg/dL, body mass index (calculated as weight in kilograms divided by height in meters squared) of at least 30, fasting triglyceride levels of at least 150 mg/dL, and high-density lipoprotein cholesterol levels of less than 40 mg/dL in men or less than 50 mg/dL in women.

Results Significantly higher rates of heart failure were consistent across all treatment comparisons in those with MetS. Relative risks (RRs) were 1.50 (95% confidence interval, 1.18-1.90), 1.49 (1.17-1.90), and 1.88 (1.42-2.47) in black participants and 1.25 (1.06-1.47), 1.20 (1.01-1.41), and 1.82 (1.51-2.19) in nonblack participants for amlodipine, lisinopril, and doxazosin comparisons with chlorthalidone, respectively. Higher rates for combined cardiovascular disease were observed with lisinopril-chlorthalidone (RRs, 1.24 [1.09-1.40] and 1.10 [1.02-1.19], respectively) and doxazosin-chlorthalidone comparisons (RRs, 1.37 [1.19-1.58] and 1.18 [1.08-1.30], respectively) in black and nonblack participants with MetS. Higher rates of stroke were seen in black participants only (RR, 1.37 [1.07-1.76] for the lisinopril-chlorthalidone comparison, and RR, 1.49 [1.09-2.03] for the doxazosin-chlorthalidone comparison). Black patients with MetS also had higher rates of end-stage renal disease (RR, 1.70 [1.13-2.55]) with lisinopril compared with chlorthalidone.

Conclusions The ALLHAT findings fail to support the preference for calcium channel blockers, -blockers, or angiotensin-converting enzyme inhibitors compared with thiazide-type diuretics in patients with the MetS, despite their more favorable metabolic profiles. This was particularly true for black participants.