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Treatment of Hypertension in Persons with Coronary Artery Disease: What the Guidelines Recommend

Wilbert S. Aronow, MD, is a professor of medicine in the department of medicine and the divisions of cardiology, geriatrics, and pulmonary/critical care at New York Medical College in Valhalla, NY.

Volume 55 - Issue 10 - October 2015

ABSTRACT: Adults with coronary artery disease (CAD) should intensively treat their modifiable coronary risk factors, in particular hypertension, which is a major risk factor for sudden cardiac death and angina pectoris. Hypertension should be treated with beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers to lower blood pressure in patients with CAD. This article will review the 2003 to 2015 treatment guidelines for hypertension in patients with CAD.

Hypertension is a major risk factor for coronary artery disease (CAD).1-9 Guidelines, such as those from the American Heart Association (AHA), American College of Cardiology (ACC), and American Society of Hypertension (ASH), recommend lowering blood pressure (BP) to <140/90 mm Hg in patients age 80 and younger and to <150/90 mm Hg, if tolerated, in persons age 80 years and older.1-4,7-9 Hypertension is present in approximately 69% of patients with a first myocardial infarction (MI).10 Hypertension is also a major risk factor for sudden cardiac death and angina pectoris.3 This article will review the 2003 to 2015 treatment guidelines for hypertension in patients with CAD.

Coronary Artery Disease

Coronary risk factors should be controlled in patients with CAD, including smoking, hypertension, dyslipidemia, diabetes mellitus, obesity, and physical inactivity.9 Dietary sodium intake should be reduced in patients with CAD. 

Beta-blockers should be the initial antihypertensive treatment in patients with CAD and angina pectoris, in those who have had a MI, and in those who have left ventricular (LV) systolic dysfunction, unless they are contraindicated.9 Patients with previous MI and hypertension should be treated with beta-blockers and angiotensin-converting enzyme (ACE) inhibitors.1-4,8,9,11-25 If a third drug is needed, aldosterone antagonists may be used based on the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival study (EPHESUS).26 Patients receiving aldosterone antagonists should not have significant renal dysfunction or hyperkalemia.

Persons with LV systolic dysfunction should receive the beta-blockers carvedilol, metoprolol controlled release/extended release, or bisoprolol9,27-31 and ACE inhibitors or angiotensin receptor blockers (ARBs).9,27,32-39 Patients with hypertension and a reduced LV ejection fraction should avoid the use of verapamil, diltiazem, doxazosin, clonidine, moxonidine, hydralazine without a nitrate, and NSAIDs.9 Aliskiren is contraindicated in patients with diabetes who are receiving an ACE inhibitor or an ARB or who have an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and in persons with hyperkalemia. The combination of an ACE inhibitor and an ARB should be avoided.

Stable Angina Pectoris

Patients with hypertension and chronic stable angina pectoris should be treated with beta-blockers plus nitrates as antianginal drugs.9 In these patients, hypertension should be controlled with beta-blockers plus an ACE inhibitor or an ARB with the addition of a thiazide or thiazide-like diuretic if needed. If either angina pectoris or hypertension remains uncontrolled, a long-acting dihydropyridine calcium channel blocker (CCB) can be added to the therapeutic regimen. Nondihydropyridine CCBs, such as verapamil and diltiazem, cannot be used if LV systolic dysfunction is present. Combining a beta-blocker with either verapamil or diltiazem must be done with caution because of the increased risk for bradyarrhythmia and heart failure.9 Beta-blockers plus an ACE inhibitor or an ARB should be used initially in patients with hypertension and CAD who have chronic kidney disease.9 Patients with hypertension and vasospastic angina pectoris should be treated with nitrates plus CCBs.40

Acute Coronary Syndrome

In patients with acute coronary syndrome (ACS), the initial treatment of hypertension should include a short-acting beta1 selective blocker without intrinsic sympathomimetic activity, such as metoprolol tartrate or bisoprolol.9 Treatment with beta-blockers should be given initially within 24 hours of experiencing the symptoms of ACS. In persons with severe hypertension or ongoing ischemia, intravenous esmolol may be considered.9 In hemodynamically unstable patients or in those with decompensated heart failure, treatment with beta-blockers should be delayed until the patient is stabilized.9

In persons with ACS and hypertension, nitrates can be used to reduce BP, ongoing myocardial ischemia, or pulmonary congestion; however, nitrates should not be administered to patients with suspected right ventricular infarction or to those with hemodynamic instability.9 Intravenous or sublingual nitroglycerin is preferred initially.9

An Overview of Treatment Guidelines JNC 7 (2003)

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends that BP should be reduced to <140/90 mm Hg in patients with CAD.1 These JNC 7 guidelines recommend treating patients who have had an MI with a beta-blocker and an ACE inhibitor plus an aldosterone antagonist if a third drug is needed.1 In patients with hypertension and stable angina pectoris, the initial drug of choice is a beta-blocker. A long-acting CCB should be added if angina persists.1 In patients with an ACS, hypertension should be treated with a beta-blocker plus an ACE inhibitor, with the addition of other drugs (such as a diuretic and a CCB, if needed) to control BP.1

AHA Scientific Statement on Hypertension (2007) 

The AHA 2007 scientific statement on hypertension recommends that the BP be lowered to <130/80 mm Hg in persons with CAD, with consideration of decreasing BP to <120/80 mm Hg if LV systolic dysfunction is present.2 Patients with stable angina pectoris should be treated with a beta-blocker plus an ACE inhibitor or an ARB plus a long-acting nitrate and a thiazide diuretic. If angina pectoris or BP remain uncontrolled, a long-acting nondihydropyridine CCB can be added if there is no LV systolic dysfunction, or a long-acting dihydropyridine CCB can be added if there is LV systolic dysfunction.2 Patients with ACS should be treated with a beta-blocker plus an ACE inhibitor or with an ARB if the person is hemodynamically stable.2 If angina pectoris or BP is uncontrolled, a long-acting CCB (dihydropyridine if there is LV systolic dysfunction) can be added. A thiazide diuretic can also be added to control BP.2

However, clinical trial data does not support the AHA’s 2007 scientific statement on hypertension.41 The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE IT-TIMI) 22 trial enrolled 4162 adults with ACS (acute MI with or without ST-segment elevation or high-risk unstable angina pectoris).42 The lowest cardiovascular event rates occurred with a systolic BP (SBP) between 130 mm Hg and 140 mm Hg and a diastolic BP (DBP) between 80 mm Hg and 90 mm Hg with a nadir of 136/85 mm Hg with a J-shaped or U-shaped curve at low and high BP values.42 Randomized clinical trials of antihypertensive drugs provide evidence for a J-shaped relationship between SBP, DBP, and all-cause death, cardiovascular death, nonfatal and fatal stroke, and congestive heart failure.43

An observational subgroup analysis was performed in 6400 patients with CAD and diabetes mellitus in the International Verapamil SR Trandolapril Study (INVEST).44 Tight BP control was considered the maintenance of SBP at <130 mm Hg. Usual control of BP was considered the maintenance of SBP between 130 mm Hg and 139 mm Hg. Uncontrolled BP was considered the maintenance of SBP at ≥140 mm Hg. During the 16,893 patient-years of follow-up, uncontrolled SBP increased the primary outcome event of all-cause mortality, nonfatal MI, or nonfatal stroke by 46% (P<.001), and tight control of SBP insignificantly increased the primary outcome event by 11% compared with the usual control of SBP.44 The all-cause mortality rate was 11% in patients who had tight control of their SBP compared with 10.2% in patients who had usual control of their SBP (P=.06). With an extended follow-up to 5 years after the close of INVEST, the all-cause mortality rate increased 15% from 21.8% in the persons with usual control of SBP to 22.8% in persons with tight control of SBP (P=.04).44 

A meta-analysis of 147 randomized trials of 464,000 patients treated with antihypertensive drugs showed that, except for the extra protective effect of beta-blockers given after MI and a minor additional effect of CCBs in the prevention of stroke, beta-blockers, ACE inhibitors, ARBs, diuretics, and CCBs cause similar reductions in coronary events and stroke for a given reduction in BP.11 The proportionate decrease in cardiovascular events was the same or similar regardless of the pretreatment BP and the presence or absence of cardiovascular events.15 If beta-blockers are used for the treatment of hypertension, atenolol should not be used.45-47

ACCF/AHA Expert Consensus on Hypertension (2011)

The American College of Cardiology Foundation (ACCF)/AHA 2011 expert consensus on hypertension in the elderly recommends that BP be decreased to <140/90 mm Hg in patients with CAD who are age 80 and older.3 Based on data from the Hypertension in the Very Elderly Trial,48 these guidelines recommended lowering SBP in patients with CAD who are age 80 years and older to between 140 mm Hg and 145 mm Hg, if tolerated, in the standing position.3

The ACCF/AHA 2011 expert consensus on hypertension in the elderly recommends the use of a beta-blocker and an ACE inhibitor plus an aldosterone antagonist, if needed, as initial antihypertensive drug therapy in elderly persons who have had an MI.3 Patients with angina pectoris should receive a beta-blocker plus a CCB, and patients with CAD should receive a beta-blocker plus an ACE inhibitor with the addition of a thiazide diuretic and a CCB, if needed, to control BP.3

European Society of Hypertension/European Society of Cardiology (2013)

The 2013 European Society of Hypertension/European Society of Cardiology guidelines on the treatment of hypertension recommend that SBP be lowered to <140 mm Hg in patients with CAD.4 In persons with hypertension and a recent MI, beta-blockers are the drug of choice.4 In other patients with CAD, any antihypertensive drug can be used, but beta-blockers and CCBs are preferred in patients with angina pectoris.4

Canadian Hypertension Education Program (2013)

The 2013 Canadian Hypertension Education Program guidelines recommend lowering SBP to <140 mm Hg in persons with CAD who are age 80 and younger and to <150 mm Hg in those age 80 and older.7 

aSH/International Society of Hypertension (2014) 

The ASH/International Society of Hypertension 2014 guidelines for the management of hypertension recommend lowering BP to <140/90 mm Hg in persons with CAD.8 Furthermore, patients with CAD are recommended to be initially treated with a beta-blocker plus an ACE inhibitor or an ARB to lower the BP to <140/90 mm Hg.8 If an additional drug is needed to control BP, a thiazide diuretic or CCB should be added.8 If a fourth antihypertensive drug is needed, it should be the alternative third antihypertensive drug (ie, a thiazide diuretic or a CCB).8

AHA/American Society of Cardiology (2015) 

The AHA/American Society of Cardiology 2015 guidelines recommend that the target BP should be <140/90 mm Hg in persons with CAD and with ACS if they are age 80 and younger, but <150 mm Hg if they are age 80 and older.9 Consideration can be given to lower BP to <130/80 mm Hg in patients with a class IIb C indication for ACS.9 Octogenarians should be checked for orthostatic changes that occur with standing, and SBP of <130 mm Hg and DBP of <65 mm Hg should be avoided.9 Caution is advised in decreasing DBP to <60 mm Hg in persons with diabetes or in patients older than age 60.9

An ACE inhibitor or ARB should be administered to patients with ACS, especially in persons with an anterior MI, if hypertension persists, if there is a reduced LV ejection fraction, or if diabetes is present.9 If hypertension persists after the use of a beta-blocker plus an ACE inhibitor or an ARB, a long-acting dihydropyridine CCB may be added.9 

Aldosterone antagonists are indicated in patients receiving beta-blockers plus ACE inhibitors or ARBs after having an MI who have LV systolic dysfunction and either heart failure or diabetes mellitus.9,15,16,49 However, they should be avoided if the serum potassium is ≥5.0 mEq/L or if the serum creatinine is ≥2.5 mg/dL in men or ≥2.0 mg/dL in women.9,16 Loop diuretics are preferred to thiazide and thiazide-type diuretics in patients with heart failure or in those with chronic kidney disease and an eGFR <30 mL/min.9 People with uncontrolled hypertension may need additional antihypertensive drugs, despite the use of beta-blockers, ACE inhibitors, ARBs, CCBs, diuretics, or aldosterone antagonists.50 

References:

 

  1. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The JNC 7 Report. JAMA. 2003;289(19):2560-2572.
  2. Rosendorff C, Black HR, Cannon CP, et al. Treatment of hypertension in the prevention and management of ischemic heart disease. A scientific statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. Circulation. 2007;115(21):2761-2788.
  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. J Am Coll Cardiol. 2011;57(20):2037-2114.
  4. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34(28):2159-2219.  
  5. Banach M, Bromfield S, Howard G, et al. Association of systolic blood pressure levels with cardiovascular events and all-cause mortality among older adults taking antihypertensive medication. Int J Cardiol. 2014;176(1):219-226.
  6. Bangalore S, Gong Y, Cooper-DeHoff RM, et al. 2014 Eighth Joint National Committee Panel recommendation for blood pressure targets revisited: results from the INVEST study. J Am Coll Cardiol. 2014;64:784-793. 
  7. Hackam DG, Quinn RR, Ravani P, et al. The 2013 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol. 2013;29(5):528-542. 
  8. Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hyptertens (Greenwich). 2014;16(1):14-26.
  9. Rosendorff C, Lackland DT, Allison M, Aronow WS, et al. AHA/ACC/ASH scientific statement. Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. J Am Coll Cardiol. 2015;65(18):1998-2038.
  10. Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics-2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009;119(3):e21-e181.
  11. Law MR, Morris JK, Wald NJ. Use of BP lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665.
  12. Teo KK, Yusuf S, Furberg CD. Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction. An overview of results from randomized controlled trials. JAMA. 1993;270(13):1589-1595.
  13. Hansteen V. Beta blockade after myocardial infarction: The Norwegian Propranolol Study in high-risk patients. Circulation.1983;67(suppl I):I-57-I-60.
  14. Hjalmarson A, Elmfeldt D, Herlitz J, et al. Effect on mortality of metoprolol in acute myocardial infarction. Lancet.1981;2(8251):823-827.
  15. Gundersen T, Abrahamsen AM, Kjekshus J, et al. Timolol-related reduction in mortality and reinfarction in patients ages 65-75 years surviving acute myocardial infarction. Circulation. 1982;66(6):1179-1184.
  16. Pedersen TR for the Norwegian Multicentre Study Group. Six-year follow-up of the Norwegian Multicentre Study on Timolol after acute myocardial infarction. N Engl J Med. 1985;313(17):1055-1058.
  17. Beta-Blocker Heart Attack Trial Research Group. A randomized trial of propranolol in patients with acute myocardial infarction. JAMA. 1982;247(12):1707-1714.
  18. The CAPRICORN Investigators. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001;357:1385-1390.
  19. Park KC, Forman DE, Wei JY. Utility of beta-blockade treatment for older postinfarction patients. J Am Geriatr Soc. 1995;43:751-755.
  20. Chadda K, Goldstein S, Byington R, Curb JD. Effect of propranolol after acute myocardial infarction in patients with congestive heart failure. Circulation. 1986;73(3):503-510.
  21. The Beta-Blocker Pooling Project Research Group. The Beta-Blocker Pooling Project (BBPP): subgroup findings from randomised trials in post-infarction patients. Eur Heart J. 1988;9(1):8-16.
  22. HOPE (Heart Outcomes Prevention Evaluation) Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145-153.
  23. Aronow WS, Ahn C, Kronzon I. Effect of beta blockers alone, of angiotensin-converting enzyme inhibitors alone, and of beta blockers plus angiotensin-converting enzyme inhibitors on new coronary events and on congestive heart failure in older persons with healed myocardial infarcts and asymptomatic left ventricular systolic dysfunction. Am J Cardiol. 2001;88(11):1298-1300.
  24. Aronow WS, Ahn C. Incidence of new coronary events in older persons with prior myocardial infarction and systemic hypertension treated with beta blockers, angiotensin-converting enzyme inhibitors, diuretics, calcium antagonists, and alpha blockers. Am J Cardiol. 2002;89(10):1207-1209.
  25. Aronow WS. Current role of beta blockers in the treatment of hypertension. Expert Opin PharmacotheR. 2010;11(16):2599-2607.
  26. Pitt B, White H, Nicolau J, et al. Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am Coll Cardiol. 2005;46(3):425-431.
  27. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guidelines for the management of heart failure: executive summary. A report of the American College of Cardiology Foundation /American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):1495-1539.
  28. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med. 1996;334(21):1349-1355.
  29. CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet. 1999;353(9146):9-13.
  30. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353(9169):2001-2007.
  31. Packer M, Coats AJS, Fowler MB, et al. Effect of carvedilol on survival in chronic failure. N Engl J Med. 2001;344:651-658.
  32. Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA. 1995;273(18):1450-1456.
  33. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the Survival and Ventricular Enlargement Trial. The SAVE investigators. N Engl J Med. 1992;327(10):669-677.
  34. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet. 1993;342(8875):821-828.
  35. Ambrosioni E, Borghi C, Magnani B. The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators N Engl J Med. 1995;332(2):80-85.
  36. Kober L, Torp-Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1995;333(25):1670-1676.
  37. Fox KM,The European trial on reduction of cardiac events with perindopril in stable coronary artery disease investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362(9368):782-788. 
  38. Pfeffer MA, McMurray JJV, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349(20):1893-1906.
  39. Granger CB, McMurray JJV, Yusuf S, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet. 2003;362(9386):772-776.
  40. Aronow WS, Frishman WH. Angina in the elderly. In: Aronow WS, Fleg J, Rich MW, eds. Tresch and Aronow’s Cardiovascular Disease in the Elderly. 5th ed. Boca Raton, FL: CRC Press; 2013:191-212.
  41. Aronow WS. Hypertension guidelines. Hypertension. 2011;58(3):347-348.
  42. Bangalore S, Qin J, Sloan S, et al. What is the optimal blood pressure in patients after acute coronary syndromes? Relationship of blood pressure and cardiovascular events in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE IT-TIMI) 22 trial. Circulation. 2010;122(21):2142-2151. 
  43. Banach M, Aronow WS. Blood pressure J-curve. Curr Hypertens rep. 2012;14(6):556-566.
  44. Cooper-DeHoff RM, Gong Y, Handberg EM, et al. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA. 2010;304(1):61-68.
  45. Aronow WS. Might losartan reduce sudden cardiac death in diabetic patients with hypertension? Lancet. 2003;362(9384):591-592.
  46. Carlberg B, Samuelson O, Lindholm LH. Atenolol in hypertension: is it a wise choice? Lancet. 2004;364(9946):1684-1689.
  47. Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against losartan. Lancet. 2002;359(9311):995-1003. 
  48. Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Eng J Med. 2008;358:1887-1898.
  49. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341(10):709-717.
  50. Aronow WS, Frishman WH. Systemic hypertension in the elderly. In: Aronow WS, Fleg J, Rich MW, eds. Tresch and Aronow’s Cardiovascular Disease in the Elderly, 5th ed. Boca Raton, FL: CRC Press; 2013:104-120.