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