Metabolic and clinical outcomes in nondiabetic individuals with the metabolic syndrome assigned to chlorthalidone, amlodipine, or lisinopril as initial treatment for hypertension: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
OBJECTIVE
Optimal initial antihypertensive drug therapy in people with the metabolic syndrome is unknown.


METHODS
We conducted a subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) to compare metabolic, cardiovascular, and renal outcomes in individuals assigned to initial hypertension treatment with a thiazide-like diuretic (chlorthalidone), a calcium channel blocker (CCB; amlodipine), or an ACE inhibitor (lisinopril) in nondiabetic individuals with or without metabolic syndrome.


RESULTS
In participants with metabolic syndrome, at 4 years of follow-up, the incidence of newly diagnosed diabetes (fasting glucose >or=126 mg/dl) was 17.1% for chlorthalidone, 16.0% for amlodipine (P = 0.49, chlorthalidone vs. amlodipine) and 12.6% for lisinopril (P < 0.05, lisinopril vs. chlorthalidone). For those without metabolic syndrome, the rate of newly diagnosed diabetes was 7.7% for chlorthalidone, 4.2% for amlodipine, and 4.7% for lisinopril (P < 0.05 for both comparisons). There were no differences in relative risks (RRs) for outcomes with amlodipine compared with chlorthalidone in those with metabolic syndrome; in those without metabolic syndrome, there was a higher risk for heart failure (RR 1.55 [95% CI 1.25-1.35]). In comparison with lisinopril, chlorthalidone was superior in those with metabolic syndrome with respect to heart failure (1.31 [1.04-1.64]) and combined cardiovascular disease (CVD) (1.19 [1.07-1.32]). No significant treatment group-metabolic syndrome interaction was noted.


CONCLUSIONS
Despite a less favorable metabolic profile, thiazide-like diuretic initial therapy for hypertension offers similar, and in some instances possibly superior, CVD outcomes in older hypertensive adults with metabolic syndrome, as compared with treatment with CCBs and ACE inhibitors.
Black
Henry R
HR
New York University School of Medicine, New York, New York, USA.
Davis
Barry
B
Barzilay
Joshua
J
Nwachuku
Chuke
C
Baimbridge
Charles
C
Marginean
Horia
H
Wright
Jackson T
JT
Basile
Jan
J
Wong
Nathan D
ND
Whelton
Paul
P
Dart
Richard A
RA
Thadani
Udho
U
D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000453:epidemiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002752:Chlorthalidone / Q000627:therapeutic use*; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000188:drug therapy; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control*; D012307:Risk Factors
D000959:Antihypertensive Agents; D000960:Hypolipidemic Agents; D017311:Amlodipine; D017706:Lisinopril; D002752:Chlorthalidone