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Practice changer
Use thiazide-type diuretics for hypertension in patients with metabolic syndrome to reduce stroke and heart failure.
Strength of recommendation
B: Single well done randomized controlled trial
Wright JT Jr, Harris-Haywood S, Pressel S, et al. Clinical outcomes by race in hypertensive patients with and without the metabolic syndrome: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med. 2008; 168:207-217. (1)
ILLUSTRATIVE CASE

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Your new patient is a 57-year-old African American man. His blood pressure is 150/95 mm Hg, fasting glucose 115 mg/dL, body mass index 32, and triglycerides 155 mg/dL; he is on no prior medications. During the course of his care you diagnose hypertension with metabolic syndrome and decide to recommend an antihypertensive. Thiazidetype diuretics are your standard initial therapy, but this patient has metabolic syndrome, and you know that certain antihypertensive agents have a more favorable metabolic profile than thiazide diuretics. Furthermore, metabolic differences among races have been touted as reason to use other agents in black patients. Should you recommend a thiazide diuretic, or another agent?
Until now, we’ve had no simple approach to treating hypertension in patients with metabolic syndrome–and half or more of our hypertensive patients over the age of 55 have this disorder.
Now, however, we can base decisions on clinical outcomes data from a subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). (1) This new subgroup analysis supports use of thiazide-type diuretics in these patients–particularly in black patients–despite the more favorable metabolic profile of calcium channel blockers, alpha-blockers, and angiotensin-converting enzyme (ACE) inhibitors.
Cost is no longer as big a factor as it once was, now that ACE inhibitors and alpha-blockers, as well as thiazide diuretics, are available generically.
* Does a better metabolic profile improve outcomes?
We have had reason to be concerned about the metabolic adverse effects of thiazide-type diuretics in the past. Studies published before this ALLHAT subgroup analysis showed that hydrochlorothiazide for essential hypertension had adverse effects on potassium, glucose, and lipid metabolism. Some speculated that these changes aggravate the metabolic changes in early diabetes (2-4) and may contribute to increased coronary heart disease risk. (5,6)
ACE inhibitors and ARBs
The metabolic benefits of ACE inhibitors and angiotensin-receptor blockers (ARBs) are widely known. In comparative studies prior to this ALLHAT subgroup analysis, ACE inhibitors were thought to be preferable to thiazide diuretics and beta-blockers for patients with obesity (7) or the metabolic syndrome. (8) These agents also protect against diabetic nephropathy. (9) Other studies attribute additional vascular benefits to ACE inhibitors, (10) beyond that of lowering blood pressure.
A 2005 meta-analysis by Abuissa et al (11) showed that ACE inhibitors and ARBs were associated with significant reductions in the incidence of newly diagnosed diabetes, which, in turn, might lead to reduced heart disease. That report concluded that use of ACE inhibitors or ARBs should be considered in patients with prediabetic conditions such as metabolic syndrome, hypertension, impaired fasting glucose, family history of diabetes, obesity, congestive heart failure, or coronary heart disease.
Calcium-channel blockers and alpha-blockers
Calcium-channel blockers and alpha-blockers also do not appear to have the adverse metabolic effects of thiazides, and have also been advocated over beta-blockers and thiazides for hypertensive patients with metabolic syndrome. (12-15)
Racial differences
In a consensus statement developed before the findings from the ALLHAT subgroup analysis were available, it was noted that racial differences in metabolic syndrome may make the selection of antihypertensive agents particularly important in African American patients. (16)
* ALLHAT and JNC7 recommendations
The 2002 ALLHAT demonstrated that chlorthalidone (a thiazide-type diuretic) is superior to lisinopril, amlodipine, and doxazosin in preventing 1 or more major forms of cardiovascular disease. No difference was observed, however, for fatal coronary heart disease, nonfatal myocardial infarction, or all-cause mortality. (17) These findings persisted in subgroup analyses stratified by race, diabetic status, and level of renal function, but ALLHAT did not identify patients with metabolic syndrome a priori.
The ALLHAT influenced the 2003 Joint National Commission VII (JNC7) Report, which recommends thiazide diuretics for first-line treatment of hypertension in the absence of compelling indications to begin an alternative antihypertensive agent. (18)
Special consideration, but no recommendation. The JNC7 Report mentions the metabolic syndrome as a special consideration, but does not explicitly recommend a first-line therapy other than thiazides.