MODULE 2: Rethinking the Role of Thiazide-Type Diuretics in the Management of Hypertension: Which Diuretic Is Best?

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Medical Education Library

MODULE 2: Rethinking the Role of Thiazide-Type Diuretics in the Management of Hypertension: Which Diuretic Is Best?

August 2012 · Vol. 61, No. 08 Suppl: S15-S19

By

William C. Cushman, MD

References

1. Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment, and control of hypertension, 1988-2008. JAMA. 2010;303(20):2043-2050.

2. Chobanian AV, Bakris GL, Black HR, et al. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206-1252.

3. Aronow WS, Fleg JL, Pepine CJ, et al. ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus documents developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension. J Am Coll Cardiol. 2011;57(20):2037-2114.

4. Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA. 1970;213(7):1143-1152.

5. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. 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) [published corrections appear in JAMA. 2003;289(2):178; JAMA. 2004;291(18):2196]. JAMA. 2002;288(23):2981-2997.

6. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;265(24):3255-3264.

7. Petitti DB, Xie F, Barzilay JI. Prescribing patterns for thiazide diuretics in a large health maintenance organization: relationship to participation as an ALLHAT clinical center. Contemporary Clin Trials. 2006;27(5):397-403.

8. Dahlöf B, Devereux RB, Kjeldsen SE, et al. LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359(9311):995-1003.

9. Psaty BM, Manolio TA, Smith NL, et al. Cardiovascular Health Study. Time trends in high blood pressure control and the use of antihypertensive medications in older adults: the Cardiovascular Health Study. Arch Intern Med. 2002;162(20):2325-2332.

10. Glasser SP, Basile JN, Lackland DT. Does prehypertension represent an increased risk for incident hypertension and adverse cardiovascular outcome? Hypertension. 2009;54(5):954-955.

11. Stafford RS, Bartholomew LK, Cushman WC, et al. ALLHAT Collaborative Research Group. Impact of the ALLHAT/JNC7 Dissemination Project on thiazide-type diuretic use. Arch Intern Med. 2010;170(10):851-858.

12. Furmaga EM, Cunningham FE, Cushman WC, et al. National utilization of antihypertensive medications from 2000 to 2006 in the Veterans Health Administration: focus on thiazide diuretics. J Clin Hypertens (Greenwich). 2008;10(10):770-778.

13. Pitt B. The role of chlorthalidone in patients with high-risk hypertension. J Clin Hypertens (Greenwich). 2009;11(9):460-461.

14. Ernst ME, Carter BL, Basile JN. All thiazide-like diuretics are not chlorthalidone: putting the ACCOMPLISH study into perspective. J Clin Hypertens (Greenwich). 2009;11(1):5-10.

15. Sica DA. Chlorthalidone—a renaissance in use? Expert Opin Pharmacother. 2009;10(13):2037-2039.

16. Kaplan NM. Chlorthalidone versus hydrochlorothiazide: a tale of tortoises and a hare. Hypertension. 2011;58(6):994-995.

17. Carter BL, Ernst ME, Cohen JD. Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability. Hypertension. 2004;43(1):4-9.

18. Carter BL, Malone DC, Ellis SL, Dombrowski RC. Antihypertensive drug utilization in hypertensive veterans with complex medication profiles. J Clin Hypertens (Greenwich). 2000;2(3):172-180.

19. Ernst ME, Lund BC. Renewed interest in chlorthalidone: evidence from the Veterans Health Administration. J Clin Hypertens (Greenwich). 2010;12(12):927-934.

20. Neaton JD, Grimm RH Jr, Prineas RJ, et al. Treatment of Mild Hypertension Study Research Group. Treatment of Mild Hypertension Study. Final results. JAMA. 1993;270(6):713-724.

21. Ford RV. Therapy of edema and hypertension, Comparative clinical effects of chlorothiazide and chlorthalidone. Tex State J Med. 1960;56:343-346.

22. Mach RS, Veyrat R. Clinical experiences with some of the newer diuretics, especially chlorthalidone. Ann N Y Acad Sci. 1960;88:841-863.

23. Dyrda I, Dufault C, Herbert JG, Tremblay G, Genest J. Studies on a new diuretic: chlorthalidone. Can Med Assoc J. 1962;86:475-482.

24. Kakaviatos N, Finnerty FA, Jr. Comparison of chlorthalidone, a long-acting antihypertensive and diuretic agent, with chlorothiazide. Analysis of one hundred twenty-three cases. Am J Cardiol. 1962;10:570-574.

25. Materson BJ, Oster JR, Michael UF, et al. Dose response to chlorthalidone in patients with mild hypertension. Efficacy of a lower dose. Clin Pharmacol Ther. 1978;24(2):192-198.

26. Ernst ME, Carter BL, Goerdt CJ, et al. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension. 2006;47(3):352-358.

27. Dunbar-Jacob J, Erlen JA, Schlenk EA, Ryan CM, Sereika SM, Doswell WM. Adherence in chronic disease. Annu Rev Nurs Res. 2000;18:48-90.

28. Hypertension Detection and Follow-up Program Cooperative Group. Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. JAMA. 1979;242(23):2562-2571.

29. Multiple Risk Factor Intervention Trial Research Group. Multiple risk factor intervention trial. Risk factor changes and mortality results. JAMA. 1982;248(12):1465-1477.

30. Dorsch MP, Gillespie BW, Erickson SR, Bleske BE, Weder AB. Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis. Hypertension. 2011;57(4):689-694.

31. Ernst ME, Carter BL, Zheng S, Grimm RH, Jr. Meta-analysis of dose-response characteristics of hydrochlorothiazide and chlorthalidone: effects on systolic blood pressure and potassium. Am J Hypertens. 2010;23(4):440-446.

32. Woodman R, Brown C, Lockette W. Chlorthalidone decreases platelet aggregation and vascular permeability and promotes angiogenesis. Hypertension. 2010;56(3):463-470.

33. Messerli FH, Makani H, Benjo A, Romero J, Alviar C, Bangalore S. Antihypertensive efficacy of hydrochlorothiazide as evaluated by ambulatory blood pressure monitoring: a meta-analysis of randomized trials. J Am Coll Cardiol. 2011;57(5):590-600.

34. Demirovic J, Prineas R, Rudolph M. Epidemiology of congestive heart failure in three ethnic groups. Congest Heart Fail. 2001;7(2):93-96.

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36. Epstein M. Re-examining RAS-blocking treatment regimens for abrogating progression of chronic kidney disease. Nat Clin Pract Nephrol. 2008;5(1):12-13.

37. Jamerson K, Weber MA, Bakris GL, et al. ACCOMPLISH Trial Investigators. Ben-azepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359(23):2417-2428.

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Table of Contents

MODULE 1: Historical Review of Evidence-Based Treatment of Hypertension

MODULE 2: Rethinking the Role of Thiazide-Type Diuretics in the Management of Hypertension: Which Diuretic Is Best?

MODULE 3: Using Thiazide-Type Diuretics in African Americans with Hypertension

MODULE 4: Enhancing Adherence with Antihypertensives: The Role of Fixed-Dose Combinations and Home Blood Pressure Monitoring

Post-Tests and Evaluations

DISCLOSURE

Dr Cushman is a paid consultant to Daiichi-Sankyo, Inc; Merck & Co, Inc; Omron Healthcare, Inc; and Takeda Pharmaceuticals International, Inc. He has performed contracted research for Merck & Co, Inc.

Background

Despite the availability of 7 major classes of effective and safe antihypertensive medications and numerous combination drugs designed to reduce pill burden and improve adherence, just 50.1% of the estimated 76.4 million US adults with hypertension (33.5% of the population) have their condition under control.¹

One of the greatest challenges for clinicians who manage patients with hypertension is choosing the most appropriate drug, whether as initial treatment or add-on therapy. Clinicians may be guided in this decision, however, by guidelines and algorithms that are provided for hypertension management. These algorithms are reviewed in the first article in this supplement by Dr William B. White.

National guidelines recommend thiazide-type diuretics as initial therapy for most patients with hypertension, regardless of the severity of the condition, either alone or in combination with 1 of the other classes of hypertension medications that have also been shown to reduce 1 or more hypertensive complications in randomized controlled outcome trials.^2,3 These recommendations are based primarily on more than 50 years of data on the safety and efficacy of thiazide-type diuretics.

The first evidence of the benefits of thiazide-type diuretics came from publications of the VA (Veterans Administration) Cooperative Study in 1967 and 1970. It was the first trial to demonstrate reduced stroke, heart failure (HF), and progressive kidney damage in patients receiving antihypertensive treatment, including the then-newly released hydrochlorothiazide (HCTZ), a thiazide diuretic.⁴

Since then, hundreds of clinical trials have demonstrated the efficacy of thiazide-type diuretics. During that time, however, numerous other classes of antihypertensive medications were introduced, leading to the question of the appropriate place of thiazides within the antihypertensive arsenal. The seminal trial to answer this question was the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). This randomized, double-blind, multicenter, clinical trial was designed to determine whether the occurrence of fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI) was lower for high-risk hypertensive patients 55 years of age and older who were treated with the calcium channel blocker amlodipine, the angiotensin-converting enzyme inhibitor (ACEI) lisinopril, or the alpha-blocker doxazosin compared with the thiazide-type diuretic chlorthalidone (CTD).⁵ Investigators could add atenolol, clonidine, reserpine, and/or hydralazine as necessary to achieve blood pressure (BP) goal. The trial randomized 42,418 patients, 90% of whom had been previously treated.

At a mean follow-up of 4.9 years, there was no significant difference in the primary outcome or mortality between the 4 drugs.⁵ There was a 38% higher rate of HF with amlodipine, and a 10%, 15%, and 19% higher rate of cardiovascular disease (CVD), stroke, and HF, respectively, with lisinopril compared with CTD. For stroke, there was a statistically significant race-by-treatment interaction (40% higher stroke rate with lisinopril vs CTD in black participants). Participants in the doxazosin treatment group (n = 9061) were followed for a mean of 3.2 years. This arm was terminated early because of a 25% higher incidence of CVD events, including a nearly 2-fold higher risk of HF, accompanied by a low probability of reaching a statistically significant difference in the primary endpoint.⁵

Additional rationale for the use of diuretics in elderly populations came from the Systolic Hypertension in the Elderly Program (SHEP), a multicenter, randomized, double- blind, placebo-controlled trial of patients aged 60 years and older.⁶ Participants were randomized to either CTD 12.5 to 25 mg once daily±atenolol 25 to 50 mg once daily, or reserpine 0.05 mg once daily, or placebo. Treatment reduced the incidence of all fatal and nonfatal strokes by 36%, MI by 27%, all CHD by 27%, and all CVD by 32%.⁶

Underuse of diuretics

Despite trials such as SHEP and ALLHAT, and despite the long record of safety and efficacy in numerous patient populations, thiazide-type diuretics remain significantly under-used in clinical practice.^7-10

Even intensive academic detailing designed to increase the use of thiazide-type diuretics found that the prescribing rates of 37.1% immediately before the intervention only increased to 39.6% overall after the intervention (46.5% in areas that received the most intensive intervention), reflecting what appears to be clinical resistance to this class of drugs (FIGURE 1).¹¹ Even 4 years after the ALLHAT results were published, national use of thiazide-type drugs had not increased significantly.¹²