The Treatment of Adults with Essential Hypertension

,

Applied Evidence

The Treatment of Adults with Essential Hypertension

J Fam Pract. 2002 January;51(1):74-80

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References

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9. Furberg C, Psaty B, Meyer J. Nifedipine: dose related increase in mortality in patients with coronary heart disease. Circulation 1995;92:1326-31.

10. Kizer J, Kimmel S. Epidemiologic review of the calcium channel blocker drugs. Arch Intern Med 2001;161:1145-58.

11. Braun S, Boyo V, Behar S, et al. Calcium antagonists did not increase mortality in patients with coronary artery disease. J Am Coll Cardiol 1996;28:7-11.

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13. Hansson L, Lindholm L, Ekbohm T, Dahlof B. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity. The Swedish trial in old patients with hypertension-2 study. Lancet 1999;354:1751-56.

14. Wright J, Lee C, Chambers G. Systematic review of antihypertensive therapies: does evidence assist in choosing a first-line drug? Can Med Assoc J 1999;161:25-32.

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17. Gueyffier F, Froment A, Gouton M. New meta-analysis of treatment trials of hypertension: improving the estimate of therapeutic benefit. J Hum Hypertens 1996;10:1-8.

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20. Peterson J, Adler S, Burkart J, Greene J. Blood pressure control, proteinuria, and the progression of renal disease. Ann Intern Med 1995;123:754-62.

21. Psaty B, Smith N, Siscovick D, Koepsell T, Weiss N. Health outcomes associated with antihypertensive therapies used as first-line agents: A systematic review and meta-analysis. J Am Med Assoc 1197;277:739-45.

22. Staessen J, Fagard R, Celis H, Arabidze C, Birkenhager W. Randomised double-blind comparison of placebo and active treatment in older patients with isolated systolic hypertension. Lancet 1997;350:757-64.

23. Investigators THOPES. Effect of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. New Eng J Med 2000;342:145-53.

24. Masterson B, Reda D, Preston R, et al. Response to a second single antihypertensive agent used as monotherapy for hypertension after failure of the initial drug. Arch Intern Med 1995;155:1757-62.

25. Tuomilehto J, Rastenyte D, Birkenhager W, et al. Systolic hypertension in Europe trial investigators. Effects of calcium-channel blockers in older patients with diabetes and systolic hypertension. New Eng J Med 1999;340:677-84.

26. Yakovlevitch M, Black HR. Resistant hypertension in a tertiary care clinic. Arch Intern Med 1991;151:1786-92.

27. Halbert J, Silagy C, Finucane P, Withers R. The effectiveness of exercise training in lowering blood pressure: a metaanalysis of randomized controlled trials of 4 weeks or longer. J Human Hypertension 1997;10:641-49.

28. Ebrahim S, Davey G. Lowering blood pressure: a systematic review of sustained effects of non-pharmacologic interventions. J Public Health Med 1998;4:441-48.

29. Appel L, Moore T, Obarzanek E, Vollmer W. A clinical trail of the effects of dietary patterns on blood pressure. New Eng J Med 1997;336:1117-24.

30. Appel L, Espeland M, Easter L, Wilson A, Folmar S, Lacy C. Effects of reduced sodium intake on hypertension control in older individuals. Results from the trial of nonpharmacologic interventions in the elderly (TONE). Arch Intern Med 2001;161:685-93.

31. Beilin L, Puddey I, Burke V. Alcohol and hypertension: kill or cure? J Human Hypertension 1996;10(Suppl 2):1-5.

32. Corrigan S, Raczynski J, Swencionis C, Jennings S. Weight reduction in the prevention and treatment of hypertension: a review of representative clinical trials. Am J Health Promo 1991;5:208-14.

33. Mulrow C, Chiquette E, Angel L, Cornell J. Dieting to reduce body weight for controlling hypertension in adults. The Cochrane Library 2001.

34. Whelton P, He J, Cutler J, Brancati F, Appel L. Effects of oral potassium on blood pressure: meta-analysis of randomized controlled trials. JAMA 1997;277:1624-32.

35. Morris M, Sacks F, Rosner B. Regulation on blood pressure: does fish oil lower blood pressure?: analysis of controlled trials. Circulation 1993;88:523-33.

36. Sugioka K, Woods M, Mueller R. An unsuccessful attempt to treat hypertension with acupuncture. Am J Chinese Med 1977;5:39-44.

37. Kraft K, Coulon S. Effect of a standardized acupuncture treatment on complaints, blood pressure, and serum lipids of hypertensive, postmenopausal women. A randomized controlled clinical study. Forschende Komplementarmedizin 1999;6:74-79.

38. Eisenberg D, Delblanco T, Berkey C, et al. Cognitive and behavioral techniques and hypertension: a meta-analysis. Ann Intern Med 1993;118:964-72.

39. Hunyor S, Henderson R, Saroj K, Carter N, et al. Placebo-controlled biofeedback blood pressure effect in hypertensive humans. Hypertension 1997;29:1225-31.

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41. Ackerman R, Mulrow C, Ramirez G, Gardner C, Mobidoni L, Lawrence V. Garlic shows promise for improving some cardiovascular risk factors. Arch Intern Med 2001;161:813-24.

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43. Sundar S, Agrawal S, Singh V, Bhattacharya S, et al. Role of yoga in management of essential hypertension. Acta Cardiologica 1984;39:203-08.

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45. Staessen J, Byttebier G, Butinx F, Celis H, O’Brien E. Antihypertensive treatment based on conventional or ambulatory blood pressure measurement. J Am Med Assoc 1997;278:1065-72.

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FIGURE 1
ALGORITHM FOR INITIAL MANAGEMENT OF HYPERTENSION

FIGURE 2
ALGORITHM FOR SUBSEQUENT MANAGEMENT OF HYPERTENSION

TABLE 2
NUMBER NEEDED TO TREAT (NNT) FOR SPECIFIC ANTIHYPERTENSIVE TREATMENTS

Medication	Level of Evidence	NNT (95% CI)*	Comment
Low-Dose Thiazide	1a	18 (14-23)	Adults with systolic blood pressure
			≥ 160 or diastolic blood pressure
			≥90 regardless of age or comorbidities.
High-Dose Thiazide	1a	67 (48-111)
Beta-Blocker	1a	142 (71-1000)	Drug vs no treatment comparison.¹⁴
Calcium-Channel Blockers	1b	45 (30-102)	Isolated systolic hypertension in older patients, drug vs no treatment comparison.²²
ACE inhibitors	1b	NS	Captopril versus diuretic or ß-blocker.
Alpha-agonists	1b	NS	Doxazosin versus chlorthalidone, increased congestive heart in doxazosin group.⁷
ARBs	NA	NA	Patient-oriented outcomes not available.
Sodium Restriction	1a	NA	May reduce blood pressure but lacks evidence of reduced morbidity or mortality.^27-35
Weight Loss	1a	NA
Exercise	1a	NA
Low-Fat Diet	1b	NA
Limited Alcohol	5	NA
Potassium Supplement	1a	NA
Fish Oil Supplement	1a	NA
Acupuncture	NA	NA	No evidence of blood pressure reduction or reduced morbidity or mortality.^36-43
Biofeedback	NA	NA
Herbal Medicine	NA	NA
Transcendental Meditation	NA	NA
Yoga	NA	NA
*For total cardiovascular events over 5 years.
NS denotes no significant difference from comparison drug; NA, not applicable; ACE, angiotensin-converting enzyme; ARBs, angiotensin-receptor blockers.

Treatment

Drug Therapy

Patients who require drug treatment for hypertension should begin with a low dose of the initial medication, and that dose should be slowly titrated upward every 1 to 2 months (Figure 2). The JNC-VI recommends a diuretic or a ß-blocker with once daily dosing and 24-hour efficacy as the initial treatment for most hypertensive patients. However, the choice of initial medication will be affected by concomitant illnesses: (1) ß-blockers are recommended for the initial treatment of patients with hypertension and a history of coronary artery disease; (2) diuretics are suggested for the initial treatment of isolated systolic hypertension; (3) and angiotensin-converting enzyme (ACE) inhibitors are recommended for hypertensive patients who have systolic dysfunction after myocardial infarction, diabetic nephropathy, or congestive heart failure. Angiotensin II receptor blockers may be used in patients who cannot tolerate ACE inhibitors because of cough or rash. Alpha-adrenergic blockers should be used with caution in light of evidence that they may increase the risk of cardiovascular events (especially congestive heart failure).⁷

Among patients who do not have concomitant illness, the choice of drug therapy is controversial. A case-control study and a meta-analysis suggested that short-acting calcium channel blockers (CCBs) increase cardiovascular mortality.^8,9 Unfortunately, these studies were not designed to establish a causal relationship. A recent nonsystematic review suggested that short-acting CCBs should be avoided and that conventional therapies were more effective than long-acting CCBs.¹⁰ An earlier non-systematic review suggested that short- and intermediate-acting CCBs were associated with increased cardiovascular mortality and morbidity. However, a well-designed cohort study of patients with coronary artery disease failed to reveal an increase in adverse effects among patients taking short-acting CCBs.¹¹ Furthermore, randomized controlled trials suggest that diuretics, ß-blockers, and long-acting CCBs are equally effective in preventing cardiovascular mortality and morbidity.^12,13 Physicians who treat hypertension must choose the best initial treatment for patients who do not have concomitant illness. Fortunately, safety, tolerability, efficacy, price, and simplicity can guide the physician to an ideal drug for most hypertensive patients.

Low-dose thiazide diuretics (the equivalent of 25 to 50 mg of hydrochlorothiazide) appear better tolerated than ß-blockers or CCBs.¹⁴ Treatment with ß-blockers, CCBs, and ACE inhibitors is also more expensive (75% to 85% more) than diuretic therapy.¹⁵ The cost savings offered by diuretics complement the fact that diuretics are safe, effective, and may be dosed once daily. In short, in addition to being the drug of choice for isolated systolic hypertension, low-dose thiazide diuretics are the ideal initial drug treatment of patients without concomitant illness. It should be noted that higher doses of thiazide diuretics offer proportionately less blood pressure reduction and greater risk of hypokalemia.¹⁶

Antihypertensive treatment reduces morbidity and mortality for all stages of hypertension, but people with the greatest baseline cardiovascular risk (eg, older patients and patients with higher levels of blood pressure) have the most to gain from treatment.^17,18 There is no conclusive evidence to suggest that lowering blood pressure to below 140/80 reduces morbidity or mortality in most patients. However, patients who have diabetes or renal failure benefit from more aggressive management of blood pressure.^19,20 Therefore, the JNC-VI recommends a target blood pressure of less than 130/85 for these patients.

The JNC-VI recommendation to start with a low-dose diuretic is supported by the evidence across a spectrum of patient-oriented outcomes. The effectiveness of diuretics and ß-blockers as first-line agents has been confirmed by long-term clinical trials.^14,21 However, low-dose thiazides appear effective against a broader range of outcomes than high-dose thiazides and ß-blockers (Table 3). There is also evidence to suggest that CCBs and ACE inhibitors may be effective first-line agents, but fewer patients have been studied who take CCBs and ACE inhibitors than those who take diuretics and ß-blockers.^22,23

Most patients with hypertension will respond to 1 (approximately 50%) or 2 (approximately 30%) antihypertensive medications.^19,24,25 As noted earlier, failure to respond to treatment suggests an identifiable cause of hypertension. Among patients who do not have a secondary cause of hypertension, inadequate drug treatment (often failure to start a diuretic) and noncompliance are among the most common causes of resistant hypertension.²⁶