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

,

Medical Education Library

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

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

References

1. Hamdy RC. Hypertension: a turning point in the history of medicine…and mankind. South Med J. 2001;94(11):1045-1047.

2. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA. 1967;202(11):1028-1034.

3. 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.

4. Amery A, De Schaepdryver A. The European Working Party on High Blood Pressure in the Elderly. Am J Med. 1991;90(3A):1S-4S.

5. Medical Research Council Working Party. MRC trial of treatment of mild hypertension: principal results. Br Med J (Clin Res Ed). 1985;291(6488):97-104.

6. The Australian therapeutic trial in mild hypertension. Report by the Management Committee. Lancet. 1980;1(8181):1261-1267.

7. Wilhelmsen L, Berglund G, Elmfeldt D, et al. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. J Hypertens. 1987;5(5):561-572.

8. Wikstrand J, Berglund G, Tuomilehto J. Beta-blockade in the primary prevention of coronary heart disease in hypertensive patients. Review of present evidence. Circulation. 1991;84(6 Suppl):VI93-VI100.

9. Wikstrand J, Warnold I, Tuomilehto J, et al. Metoprolol versus thiazide diuretics in hypertension. Morbidity results from the MAPHY Study. Hypertension. 1991;17(4):579-588.

10. Olsson G, Tuomilehto J, Berglund G, et al. Primary prevention of sudden cardiovascular death in hypertensive patients. Mortality results from the MAPHY Study. Am J Hypertens. 1991;4(2 Pt 1):151-1511.

11. 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.

12. MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ. 1992;304(6824):405-412.

13. Dahlöf B, Lindholm LH, Hansson L, Scherstén B, Ekbom T, Wester PO. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet. 1991;338(8778):1281-1285.

14. 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.

15. Materson BJ, Reda DJ, Cushman WC, et al. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo [published correction appears in N Engl J Med. 1994;330(23):1689]. N Engl J Med. 1993;328(13):914-921.

16. Hansson L, Zanchetti A, Carruthers SG, et al. HOT Study Group. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998;351(9118):1755-1762.

17. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38 [published correction appears in BMJ. 1999;318(7175):29]. BMJ. 1998;317(7160):703-713.

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.

19. Staessen JA, Fagard R, Thijs L, et al. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet. 1997;350(9080):757-764.

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.

Other early notable clinical trials that evaluated treatment options for hypertension in the general public include the Hypertension Detection and Follow-up Program (HDFP),³ the Hypertension Optimal Treatment (HOT) study,¹⁶ and the United Kingdom Prospective Diabetes Study/Hypertension in Diabetes (UKPDS/HDS).^17,18 The key outcomes of these trials are shown in TABLE 1.^{3,4,11,12,16,20,22,25,39,40}

TABLE 1

Findings from the early clinical trials in hypertension

Clinical Trial	Intervention	Primary Outcome	Result
HDFP^3,39	Patients randomized to systemic antihypertensive treatment or community medical therapy (referral)	5-year mortality	5-year mortality reduced by 17% in treatment group (P < 0.01); after 12 years, BP still higher in treatment than in stepped-care treatment group
HOT¹⁶	Patients all began on felodipine, with an ACEI or a BB added as necessary If BP goal was still not reached, HCTZ could be added Patients in each group also randomized to low-dose aspirin or placebo Subjects were randomly assigned to reach 1 of 3 DBP goals: ≤90 mm Hg; ≤85 mm Hg; or ≤80 mm Hg	Major CV events with 3 target DBPs reached during therapy and with low-dose aspirin therapy	Lowest incidence of major CV events achieved at mean BP of 138.5/82.6 mm Hg; lowest risk of CV mortality achieved at mean BP of 138.8/86.5 mm Hg Low-dose aspirin reduced major CV events by 15% and all MI by 36%, although nonfatal major bleeding was twice as common with low-dose aspirin than with placebo
UKPDS/HDS^17,18	Patients with T2DM randomized to atenolol or captopril, with additional antihypertensive agents (other than ACEIs or BBs) allowed	Effect of tight BP control on diabetes-related complications, morbidity, and mortality	Tight BP control (<150/85 mm Hg) with either atenolol or captopril significantly reduced the risk of all endpoints, including risk of diabetes-related death or complication, stroke, MI, and heart failure
EWPHPE⁴	Patients ≥60 years of age randomized to HCTZ + triamterene + methyldopa or placebo	CV and MI mortality; nonfatal CV events	Significant reduction in CV and MI mortality (P < .05) but not nonfatal CV events in treatment group vs placebo Found U-shaped relationship between mortality and SBP in treated group vs mortality and DBP in placebo group
MRC-2¹²	Patients 65-74 years of age randomized to atenolol + HCTZ or amiloride	Reduction in mortality and morbidity due to stroke and CHD and reduction in mortality due to all causes	Only the HCTZ group demonstrated a significant reduction in stroke, coronary events, and all CV events (P=.4, P=.0009, and P=.0005, respectively)
STOP-2²²	Patients 70-84 years of age randomized to atenolol + HCTZ or amiloride; or to metoprolol or prinodolol	Incidence of fatal stroke, MI, or other CVD mortality	Similar reductions in BP, mortality, and major events in all treatment groups
SCOPE²⁵	Patients 70-89 years of age randomized to candesartan or placebo (open-label antihypertensive therapy added as needed and extensively used in control group)	Major CV events; secondary measures included CV death, nonfatal and fatal stroke and MI, cognitive function	Greater BP decreases in candesartan group but no significant risk reduction in major CV events between the 2 groups Significant reduction in nonfatal stroke (P=.04) and all stroke (P=.06) in the treatment group No other significant differences between the groups, although a post-hoc analysis found less cognitive decline among those with only mild cognitive impairment at baseline in the candesartan-treated group (P=.04)⁴⁰
SHEP¹¹	Patients ≥60 years of age randomized to chlorthalidone with or without atenolol or reserpine, with nifedipine as third-line therapy, or to placebo	Stroke; nonfatal MI, coronary death, major CV events, death due to all causes	Significant reduction in 5-year incidence of total stroke in active treatment group (P=.0003) and significant reduction in all secondary endpoints
Syst-Eur¹⁹	Patients >60 years of age randomized to nitrendipine with possible addition of enalapril, HCTZ, or both, or to placebo	Fatal and nonfatal stroke, fatal and nonfatal cardiac events including sudden death, all-cause mortality	Significant reductions in all endpoints except all-cause mortality in treatment group; study halted early because of the 42% total stroke reduction in treatment arm (P < .003)
Syst-China²⁰	Patients ≥60 years of age randomized to nitrendipine with captopril or HCTZ, or both if needed; or matching placebo	Nonfatal stroke; all-cause, CV, and stroke mortality; and all fatal and nonfatal CV events	Significant reductions in all endpoints
ACEI, angiotensin-converting enzyme inhibitor; BB, beta-blocker; BP, blood pressure; CV, cardiovascular; CHD, coronary heart disease; CVD, CV disease; DBP, diastolic BP; EWPHE, European Working Party on High Blood Pressure in the Elderly study; HDFP, Hypertension Detection and Follow-up Program; HCTZ, hydrochlorothiazide; HOT, Hypertension Optimal Treatment study; MI, myocardial infarction; MRC-2, Medical Research Council trial of treatment of hypertension in older adults; SBP, systolic BP; SCOPE, Study on Cognition and Prognosis in the Elderly; SHEP, Systolic Hypertension in the Elderly Program; STOP-2, Swedish Trial in Old Patients with Hypertension-2; Syst-Eur, Systolic Hypertension in Europe trial; Syst-China, Systolic Hypertension in China trial; T2DM, type 2 diabetes mellitus; UKPDS/HDS, United Kingdom Prospective Diabetes Study/Hypertension in Diabetes.