Hypertension with metabolic syndrome: Think thiazides are old hat? ALLHAT says think again

,; Stevermer, James

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Hypertension with metabolic syndrome: Think thiazides are old hat? ALLHAT says think again

J Fam Pract. 2008 May;57(5):306-310

References

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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.

Anecdotally, we know many physicians who have adopted thiazide-type diuretics as the first-line treatment for hypertension in metabolic syndrome, but until now, data have been inadequate to support this decision.

How is conflicting information playing out in practice?

It is unclear to us how this conflicting information has played out in current practice. We know that many physicians already choose thiazides as their first-line agent for hypertensive patients with metabolic syndrome. And we suspect that many choose other agents.

We analyzed the National Ambulatory Medical Care Survey data (http://www.cdc.gov/nchs/about/major/ahcd/ahcd1.htm) from 2004 and 2005 and found that only 3% to 5% of outpatients with diabetes and hypertension were taking thiazides at all (unpublished data). Metabolic syndrome is not a variable in this dataset, so we could not determine the use of thiazides in hypertension and metabolic syndrome.

Our informal polling of colleagues suggested that large numbers of hypertensive patients with metabolic syndrome are not currently receiving the more beneficial thiazides.

STUDY SUMMARY: Chlorthalidone outcomes were equivalent or better

Wright and colleagues analyzed a sub-group¹ of the ALLHAT cohort, which consisted of 42,418 participants, aged ≥55, with hypertension and at least 1 other cardiovascular risk factor ( FIGURE ).

Patients were randomly assigned to therapy with chlorthalidone, amlodipine, lisinopril, or doxazosin. After randomization, if patients failed to reach the target blood pressure (<140/90 mm Hg) with their assigned therapy, they were started on atenolol, clonidine, or reserpine. If they required a third agent, they received hydralazine. The doxazosin arm was stopped early due to increased stroke and heart failure risk.

The ALLHAT was well done and designed for adequate power to evaluate clinical outcomes in racial subgroups, as well as the general population.

Outcomes were compared by race in hypertensive patients with and without metabolic syndrome.

A total of 23,077 (54%) patients met all criteria; 12,818 were black, 7327 (57%) of whom had metabolic syndrome.

Not surprisingly in a study of this size, the expected metabolic effects of all 4 antihypertensive agents were detected. Patients taking chlorthalidone had higher glucose levels (1–4 mg/dL) and higher levels of cholesterol, although these higher glucose and cholesterol levels were not statistically significant for all comparisons over time and between different drugs.

Outcomes in the chlorthalidone group were equivalent or superior to the 3 other therapies, generally. This pattern held true regardless of race ( TABLE ):

Heart failure rates were significantly higher in patients with metabolic syndrome across all treatments compared with chlorthalidone.

Combined cardiovascular disease rates were higher with lisinopril and doxazosin compared with chlorthalidone.

Stroke rates were higher among black participants only in the lisinopril group.

TABLE
Number needed to treat to prevent blood pressure-related adverse outcomes in patients with hypertension and metabolic syndrome

NUMBER NEEDED TO TREAT (NNT)= number of patients that would need to take chlorthalidone to prevent 1 outcome, compared with the alternate drug (4.9 years of chlorthalidone instead of lisinopril or amlodipine or 3.2 years of chlorthalidone instead of doxazosin). Smaller numbers indicate a bigger effect.
OUTCOME	CHLORTHALIDONE VS AMLODIPINE		CHLORTHALIDONE VS LISINOPRIL		CHLORTHALIDONE VS DOXAZOSIN
	Black	Non-black	Black	Non-black	Black	Non-black
Combined cardiovascular disease	22	NS	18	53	14	34
Stroke	NS	-111	59	NS	37	NS
Heart failure	29	48	28	143	28	25
All-cause mortality	NS	NS	NS	NS	NS	NS
NS=not significant.
Source: The authors calculated the NNTs from the event rates reported.¹