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

,; Stevermer, James

PURLs

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

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

References

1. 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.

2. Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003;326:1427.-

3. Eberly LE, Cohen JD, Prineas R, Yang L. Intervention Trial Research group. Impact of incident diabetes and incident nonfatal cardiovascular disease on 18-year mortality: the Multiple Risk Factor Intervention Trial experience. Diabetes Care. 2003;26:848-854.

4. Pollare T, Lithell H, Berne C. A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hyper-tension. N Engl J Med. 1989;321:868-873.

5. Mancia G, Grassi G, Zanchetti A. New-onset diabetes and antihypertensive drugs. J Hypertens. 2006;24:3-10.

6. Skarfors ET, Lithell HO, Selinus I, Aberg H. Do antihypertensive drugs precipitate diabetes? BMJ. 1989;298:1147-1152

7. Scholze J, Grimm E, Herrmann D, Unger T, Kintscher U. Optimal treatment of obesity-related hypertension: the Hypertension-Obesity-Sibutra-mine (HOS) study. Circulation. 2007;115:1991-1998.

8. Bakris G, Molitch M, Hewkin A, et al. STAR Investigators. Differences in glucose tolerance between fixed-dose antihypertensive drug combinations in people with metabolic syndrome. Diabetes Care. 2006;29:2592-2597.

9. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993;329:1456-1462.

10. Gianni M, Bosch J, Pogue J, et al. Effect of long-term ACE-inhibitor therapy in elderly vascular disease patients. Eur Heart J. 2007;28:1382-1388.

11. Abuissa H, Jones PG, Marso SP, O’Keefe JH Jr. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials. J Am Coll Cardiol. 2005;46:821-826.

12. Mykkänen L, Kuusisto J, Pyörälä K, Laakso M, Haffner SM. Increased risk of non-insulin-dependent diabetes mellitus in elderly hypertensive subjects. J Hypertens. 1994;12:1425-1432.

13. Giles TD, Sander GE. Pathophysiologic, diagnostic, and therapeutic aspects of the metabolic syndrome. J Clin Hypertens (Greenwich). 2005;7:669-678.

14. Mancia G. The association of hypertension and diabetes: prevalence, cardiovascular risk and protection by blood pressure reduction. Acta Diabetol. 2005;42(suppl 1):S17-S25.

15. Wagh A, Stone NJ. Treatment of metabolic syndrome. Expert Rev Cardiovasc Ther. 2004;2:213-228.

16. Hall WD, Clark LT, Wenger NK, et al. African-American Lipid and Cardiovascular Council. The metabolic syndrome in African Americans: a review. Ethn Dis. 2003;13:414-428.

17. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981-2997.

18. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). Bethesda, MD: US Department of Health and Human Services, National Heart, Lung, and Blood Institute; December 2003. Available at: http://www.nhlbi.nih.gov/guidelines/hypertension. Accessed March 31, 2008.

19. Black HR, Davis B, Barzilay J, et al. Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. 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). Diabetes Care. 2008;31:353-360.

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 obesity⁷ 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 al¹¹ 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

FAST TRACK

ACE inhibitors, ARBs, calcium-channel blockers, and alpha-blockers have better metabolic profiles than thiazides

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 sub-group analyses stratified by race, diabetic status, and level of renal function, but ALLHAT did not identify patients with metabolic syndrome a priori.

FAST TRACK

Some physicians already use thiazides for hypertension with metabolic syndrome

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