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

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Medical Education Library

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

August 2012 · Vol. 61, No. 08 Suppl: S5-S14

References

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18. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998;317(7160):713-720.

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20. Liu L, Wang JG, Gong L, Liu G, Staessen JA. Systolic Hypertension in China (Syst-China) Collaborative Group. Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension. J Hypertens. 1998;16(12 Pt 1):1823-1829.

21. Hansson L, Hedner T, Lindholm L, et al. The Captopril Prevention Project (CAPPP) in hypertension—baseline data and current status. Blood Press. 1997;6(6):365-367.

22. Hansson L, Lindholm LH, Ekbom T, et al. 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(9192):1751-1756.

23. Brown MJ, Palmer CR, Castaigne A, et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT) [published correction appears in Lancet. 2000;356(9228):514]. Lancet. 2000;356(9227):366-372.

24. Hansson L, Hedner T, Lund-Johansen P, et al. Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study. Lancet. 2000;356(9227):359-365.

25. Lithell H, Hansson L, Skoog I, et al. SCOPE Study Group. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens. 2003;21(5):875-886.

26. Black HR, Elliott WJ, Grandits G, et al. CONVINCE Research Group. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA. 2003;289(16):2073-2082.

27. 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.

28. Wing LM, Reid CM, Ryan P, et al. Second Australian National Blood Pressure Study Group. A comparison of outcomes with angiotensin-converting– enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med. 2003;348(7):583-592.

29. 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.

30. The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547-1559.

31. Weber MA, Julius S, Kjeldsen SE, et al. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial. Lancet. 2004;363(9426):2049-2051.

32. Dahlöf B, Sever PS, Poulter NR, et al. ASCOT Investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet. 2005;366(9489):895-906.

33. Jamerson K, Bakris GL, Dahlöf B, et al. ACCOMPLISH Investigators. Exceptional early blood pressure control rates: the ACCOMPLISH trial. Blood Press. 2007;16(2):80-86.

34. Julius S, Nesbitt SD, Egan BM, et al. Trial of Preventing Hypertension (TROPHY) Study Investigators. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med. 2006;354(16):1685-1697.

35. ATMOSPHERE study, [NCT00853658] ongoing trial. Trial-Results Center Web site. http://www.trialresultscenter.org/study9503-ATMOSPHERE.htm. Accessed March 28, 2012.

36. Parving HH, Brenner BM, McMurray JJ, et al. Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design. Nephrol Dial Transplant. 2009;24(5):1663-1671.

37. Massie BM, Carson PE, McMurray JJ, et al. I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359(23):2456-2467.

38. US National Library of Medicine. The Edward D. Freis Papers: the VA Cooperative Study and the Beginning of Routine Hypertension Screening, 1964-1980. http://profiles.nlm.nih.gov/ps/retrieve/Narrative/XF/p-nid/172. Accessed March 26, 2012.

39. Comberg HU, Heyden S, Knowles M, et al. Long-term survey of 450 hypertensives of the HDFP. Munch Med Wochenschr. 1991;133:32-38.

40. Skoog I, Lithell H, Hansson L, et al. SCOPE Study Group. Effect of baseline cognitive function and antihypertensive treatment on cognitive and cardiovascular outcomes: Study on COgnition and Prognosis in the Elderly (SCOPE). Am J Hypertens. 2005;18(8):1052-1059.

41. 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.

42. Beckett NS, Peters R, Fletcher AE, et al. HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358(18):1887-1898.

43. Weber MA, Neutel JM, Frishman WH. Combination drug therapy. In: Frishman WH, Sonnenblick EH, Sica DA, eds. Cardiovascular Pharmacotherapeutics. 2nd ed. New York, NY: McGraw-Hill; 2003:355–368.

44. Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. INVEST Investigators. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil- Trandolapril Study (INVEST): a randomized controlled trial. JAMA. 2003;290(21):2805-2816.

45. Mancia G, Messerli F, Bakris G, Zhou Q, Champion A, Pepine CJ. Blood pressure control and improved cardiovascular outcomes in the International Verapamil SR-Trandolapril Study. Hypertension. 2007;50(2):299-305.

46. Wald DS, Law M, Morris JK, Bestwick JP, Wald NJ. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med. 2009;122(3):290-300.

47. Gradman AH, Basile JN, Carter BL, et al. Combination therapy in hypertension. J Am Soc Hypertens. 2010;4(2):90-98.

48. Weir MR, Levy D, Crikelair N, Rocha R, Meng X, Glazer R. Time to achieve blood-pressure goal: influence of dose of valsartan monotherapy and valsartan and hydrochlorothiazide combination therapy. Am J Hypertens. 2007;20(7):807-815.

49. National Heart, . Lung, and Blood Institute. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. http://www.nhlbi.nih.gov/guidelines/hypertension/. Published 2003. Accessed March 27, 2012.

50. National Institute for Health and Clinical Excellence. Hypertension: Clinical management of primary hypertension in adults. http://www.nice.org.uk/nicemedia/live/13561/56008/56008.pdf. Published August 2011. Accessed March 27, 2012.

TABLE 2

Antihypertensive treatment in patients with compelling indications^41,49

Indication	Diuretic	BB	ACEI	ARB	Calcium antagonist	Aldosterone antagonist
Heart failure
Post MI
CVD or high CVD risk
Angina^a
Aortopathy/aortic aneurysm^a
Diabetes
Recurrent stroke prevention
CKD^b
Early dementia^a
= ACCF/AHA recommendation; = JNC-7 Express recommendation. ACCF, American College of Cardiology Foundation; ACEI, angiotensin-converting enzyme inhibitor; AHA, American Heart Association; ARB, angiotensin-receptor blocker; BB, beta-blocker; CVD, cardiovascular disease; CKD, chronic kidney disease; MI, myocardial infarction. ^aNot considered “compelling” indication in JNC-7 Express guidelines. ^bNot considered “compelling” recommendation in ACCF/AHA recommendations. Source: Journal of the American College of Cardiology by American College of Cardiology. Reproduced with permission of Elsevier Inc. in the format Journal via Copyright Clearance Center.

Recent guidelines from ASH describe combination therapies of hypertension in categories of preferred, acceptable, and less effective, based on efficacy in lowering BP, safety and tolerability, and certain known outcomes from longer-term trials (TABLE 3).⁴⁷

TABLE 3

Drug combinations in hypertension: Recommendations from the American Society of Hypertension⁴⁷

Preferred	Acceptable	Less Effective
ACEI + diuretic^a	BB + diuretic^a	ACEI + ARB
ARB + diuretic^a	Calcium antagonist + diuretic	ACEI + BB
ACEI + CCB^a	Renin inhibitor + diuretic	ARB + BB
ARB + CCB^a	Renin inhibitor + ARB^a,^b	CCB (non-dihydropyridine) + BB
	Thiazide diuretic + potassium-sparing diuretic^a	Centrally acting agent + BB
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; BB, beta-blocker; CCB, calcium channel blocker. ^aAvailable as single-pill combination. ^bThis may be medically inappropriate in patients with diabetes and chronic diabetic nephropathy. Source: Journal of the American Society of Hypertension: JASH by American Society of Hypertension. Reproduced with permission of Elsevier Inc. in the format Journal via Copyright Clearance Center.

In 2010, the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) published an expert consensus document on hypertension in the elderly. It recommends single therapy or combination therapy with an ACEI, ARB, calcium antagonist, or diuretic for patients 65 years of age and older with stage 1 hypertension and no “compelling” indications (eg, HF, post-MI, known coronary disease, angina, aortopathy/aortic aneurysm, diabetes, recurrent stroke prevention, chronic kidney disease, and early vascular dementia), but combination therapy for those with stage 2 hypertension and no compelling indications. For the former group, the panel notes that the combination of amlodipine with a renin-angiotensin aldosterone system blocker may be preferable to a diuretic combination, although either is acceptable.⁴¹

For patients with compelling indications, the ACCF/AHA panel recommends condition-based combination therapy with 2 or more of the therapies summarized in TABLE 2.^41,49 The panel’s algorithm for the management of hypertension in the elderly is depicted in FIGURE 2.⁴¹

FIGURE 2

ACCF/AHA algorithm for the management of hypertension in the elderly⁴¹

ACCF, American College of Cardiology Foundation; ACEI, angiotensin-converting enzyme inhibitor; AHA, American Heart Association; ALDO ANT, aldosterone antagonist; ARB, angiotensin II receptor blocker; BB, beta-blocker; BP, blood pressure; CA, calcium antagonist; CAD, coronary artery disease; CVD, cardiovascular disease; DBP, diastolic BP; MI, myocardial infarction; RAS, renin-angiotensin system; SBP, systolic BP; THIAZ, thiazide diuretic.
^aCombination therapy.
Source: Journal of the American College of Cardiology by American College of Cardiology. Reproduced with permission of Elsevier Inc. in the format Journal via Copyright Clearance Center.The National Institute for Health and Clinical Excellence (NICE), the United Kingdom-based clinical guideline development organization, recommends in its 2011 guidelines for the clinical management of primary hypertension in adults that patients less than 55 years of age, not of black African or Caribbean heritage, begin treatment with an ACEI or ARB.⁵⁰ The guidelines do not recommend beta-blockers for initial therapy, noting that they should be considered only in younger patients with intolerance or contraindications to ACEIs and ARBs, reproductive-aged women, and those with clinical evidence of increased sympathetic drive.⁵⁰

In contrast, patients 55 years and older, or blacks of African or Caribbean origin of any age, should begin treatment with a calcium channel blocker (CCB).⁵⁰ If they cannot tolerate a CCB, or for those with HF (or at high risk of HF), the guidelines recommend beginning therapy with a diuretic (preferably chlorthalidone or in-dapamide unless the patient’s hypertension is already controlled with bendroflumethiazide or HCTZ).

If initial treatment fails to lower BP adequately, step 2 of the NICE guidelines for all populations is treatment with an ACEI or ARB in combination with a calcium antagonist.⁵⁰ If further therapy is necessary (step 3), a thiazide diuretic (or thiazide-like) should be added to that combination. It is also recommended that patients with drug-resistant hypertension (ie, taking 3 agents at maximally tolerated doses, 1 of which should be a diuretic) should receive additional treatment with low-dose spironolactone (if their serum potassium level is ≤4.5 mmol/L) and higher-dose thiazide-type diuretics (if their serum potassium level is >4.5 mmol/L). If the diuretic is not tolerated or is ineffective, an alpha- or beta-blocker may be added. If patients continue to exhibit continued resistance, NICE recommends referral to a hypertension specialist. The NICE algorithm for the treatment of hypertension is shown in FIGURE 3.⁵⁰