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international Heart and Vascular Disease Journal Volume 3, Number 8, December 2015
Journal of the Cardioprogress Foundation
LEADING ARTICLE
Treatment of Hypertension in Patients
With Coronary Artery Disease
Aronow W.S.
Westchester Medical Center/New York Medical College, Valhalla, New York, USA Autor
Wilbert S. Aronow, MD, FACC, FAHA, Cardiology Division, Department of Medicine
Abstract
Patients with coronary artery disease should have their modifiable coronary risk factors intensively treated. Dietary sodium should be reduced. Hypertension should be treated with beta blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Long-acting nitrates are effective antianginal and antiisch-emic drugs. Calcium channel blockers may be added if angina persists despite beta blockers and long-acting nitrates... The American Heart Association/American Society of Cardiology 2015 guidelines recommend that the target blood pressure should be less than 140/90 mm Hg in patients with coronary artery disease and with an acute coronary syndrome if they are aged 80 years and younger but less than 150 mm Hg if they are older than 80 years of age. Octogenarians should be checked for orthostatic changes with standing, and a a systolic blood pressure less than 130 mm Hg and a diastolic blood pressure less than 65 mm Hg should be avoided. Caution is advised in causing a diastolic blood pressure less than 60 mm Hg in patients with diabetes mellitus or in patients older than 60 years of age. In addition to the beta blockers carvedilol, metoprolol CR/XL, and bisoprolol, patients with hypertension and congestive heart failure should be treated with diuretics and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and patients with persistent severe symptoms with aldosterone antagonists if not contraindicated.
Key Words
Myocardial infarction; coronary artery disease; hypertension; beta blockers; angiotensin-converting enzyme inhibitors; aldosterone antagonists; calcium channel blockers; nitrates.
Introduction
Hypertension is a major risk factor for cardiovascular disease [1-9 ]. These guidelines recommend lowering the blood pressure to less than 140/90 mm Hg in patients younger than age 80 years and to less than 150/90 mm Hg in patients aged 80 years and older if
tolerated [1-4, 7-9]. Hypertension is present in approximately 69% of patients with a first myocardial infarction [10], in approximately 77% of patients with a first stroke [10], in approximately 74% of patients with congestive heart failure [10], and in 60% of patients with peripheral arterial disease [11]. Hypertension is
* Corresponding author. Tel. (914) 493-531 1. Fax: (914) 235-6274 E-mail: [email protected]
also a major risk factor for a dissecting aortic aneurysm, sudden cardiac death, angina pectoris, atrial fibrillation, diabetes mellitus, the metabolic syndrome, chronic kidney disease, thoracic and abdominal aortic aneurysms, left ventricular hypertrophy, vascular dementia, Alzheimer's disease, and ophthalmologic disorders [3]. This paper will discuss the management of patients with coronary artery disease recommended by the 2015 American Heart Association/ American College of Cardiology/American Society of Hypertension guidelines on treatment of hypertension in patients with coronary artery disease [9].
Coronary Risk Factor Reduction
Modifiable coronary risk factors should be treated. Smokers should be strongly encouraged to stop smoking because it will reduce cardiovascular mortality and all-cause mortality in patients with coronary artery disease. A smoking cessation program should be recommended to smokers [12]. Nicotine replacement therapy [13], bupropion [14], and vareni-cline [15] are approved pharmacologic treatments for promoting smoking cessation.
Hypertension should be treated with sodium restriction to not exceed 1.5 grams daily, weight reduction if necessary, discontinuation of drugs that increase blood pressure, avoidance of caffeine and tobacco, limiting alcohol intake to no more than two drinks per day in men and one drink per day in women and light weight men, an increase in physical activity, a decrease of dietary saturated fat and cholesterol, and maintenance of adequate dietary potassium, calcium, and magnesium intake [3].
Patients with coronary artery disease should consume a Step II American Heart Association (AHA) diet. Numerous double-blind, randomized, placebo-controlled trials have demonstrated that patients with coronary artery disease treated with statins have a reduction in cardiovascular events and in mortality [16-20]. High-dose statins (rosuvastatin 20-40 mg daily and atorvastatin (40-80 mg daily) lower serum low-density lipoprotein cholesterol 50% or more and should be administered to patients with coronary artery disease [21]. Addition of ezetimibe to high-dose statin therapy has been demonstrated to further reduce serum lipo-protein cholesterol and reduce coronary events in patients after an acute coronary syndrome [22].
Diabetics with coronary artery disease should be treated with dietary therapy, weight reduction if necessary, and appropriate drugs if needed to control hyperglycemia. Other coronary risk factors should
be controlled.. Metformin should be the initial drug to treat hyperglycemia in most patients [23, 24]. The hemoglobin A1c level should be reduced to <7% in patients with diabetes mellitus [23].
Obese patients with coronary artery disease must undergo weight reduction [12]. Weight reduction is also a first approach to controlling hyperglycemia, mild hypertension, and dyslipidemia. Regular aerobic exercise should be added to diet in treating obesity. The body mass index should be reduced to 18.5 to 24.9 kg/m2 [12]. Exercise training programs have been found to improve endurance and functional capacity in patients with coronary artery disease [25,26]. The goal to be achieved is at least 30 minutes of exercise daily for 7 days per week with a minimum of 5 days of physical exercise per week [12].
Target Blood Pressure
The American Heart Association/American Society of Cardiology 2015 guidelines recommend that the target blood pressure should be less than 140/90 mm Hg in patients with coronary artery disease and with an acute coronary syndrome if they are aged 80 years and younger but less than 150 mm Hg if they are older than 80 years of age [9]. Consideration can be given to reduce the blood pressure to less than 130/80 mm Hg with a class lib C indication [9]. Octogenarians should be checked for orthostatic changes with standing, and a a systolic blood pressure less than 130 mm Hg and a diastolic blood pressure less than 65 mm Hg should be avoided [9]. Caution is advised in causing a diastolic blood pressure less than 60 mm Hg in patients with diabetes mellitus or in patients older than 60 years of age [9].
The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE IT-TIMI) 22 trial included 4,162 patients with an acute coronary syndrome (acute myocardial infarction with or without ST-segment elevation or high-risk unstable angina pectoris) [27]. The lowest cardiovascular events rates occurred with a systolic blood pressure between 130 to 140 mm Hg and a diastolic blood pressure between 80 to 90 mm Hg with a nadir of 136/85 mm [27].
Among 8,354 adults aged 60 years and older with coronary artery disease in the International VErapamil SR Trandolapril (INVEST) study, a baseline systolic blood pressure of 150 mm Hg and higher, and 22,308 patient years of follow-up, 57% had a systolic blood pressure less than 140 mm Hg, 21% had a systolic blood pressure of 140 to 149 mm Hg, and 22% had a
systolic blood pressure of 150 mm Hg and higher [6]. The primary outcome of all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke occurred in 9.36% of adults with a systolic blood pressure of less than 140 mm Hg, in 12.71% of adults with a systolic blood pressure of 140-149 mm Hg, and in 21.3% of adults with a systolic blood pressure of 150 mm Hg and higher (p<0.0001) [6]. Using propensity score analyses, compared with a systolic blood pressure of less than 140 mm Hg, a systolic blood pressure of 140 to 149 mm Hg increased cardiovascular mortality by 34% (p =0.04), total stroke by 89% (p = 0.002), and nonfatal stroke by 70% (p = 0.03) [6]. Compared with a systolic blood pressure of less than 140 mm Hg, a systolic blood pressure of 150 mm Hg and higher increased the primary outcome by 82% (p <0.0001), all-cause mortality by 60% (p<0.0001), cardiovascular mortality by 218% (p<0.0001), and total stroke by 283% (p<0.0001) [6].
Antihypertensive Therapy
A meta-analysis of 147 randomized trials of 464,000 adults with hypertension reported that except for the extra protective effect of beta blockers given after myocardial infarction and a minor additional effect of calcium channel blockers in preventing stroke, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, and calcium channel blockers caused a similar decrease in coronary events and stroke for a given reduction in blood pressure [28]. The proportionate reduction in cardiovascular events was the same or similar regardless of pretreatment blood pressure and the presence or absence of cardiovascular events [28]. If beta blockers are used to treat adults with hypertension, atenolol should not be used [29-31].
Coronary Artery Disease
Coronary risk factors should be controlled including smoking, hypertension, dyslipidemia, diabetes melli-tus, obesity, and physical inactivity [9]. Dietary sodium should be reduced.
Beta blockers are the initial antihypertensive drugs to use in patients with coronary artery disease who have angina pectoris, who have had a myocardial infarction, and in those who have left ventricular systolic dysfunction unless contraindicated [9]. Patients with prior myocardial infarction and hypertension should be treated with beta blockers and angioten-sin-converting enzyme inhibitors.[2-4, 8, 9,28, 32-45]. Atenolol should be avoided [29-31]. If a third drug is
needed, aldosterone antagonists may be used based on the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival (EPHESUS) trial [46]. Patients treated with aldosterone antagonists should not have significant renal dysfunction or hy-perkalemia.
In addition to the beta blockers carvedilol, meto-prolol CR/XL, and bisoprolol, [9, 47-51], patients with hypertension and congestive heart failure should be treated with diuretics and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers [9, 47, 52-60], and patients with persistent severe symptoms with aldosterone antagonists [9, 46, 47, 61]. Angiotensin-converting enzyme inhibitors or angio-tensin receptor blockers should also be administered to patients with diabetes mellitus or chronic kidney disease [ 3, 4, 8, 62, 63].
Hydralazine plus isosorbide dinitrate should be added to African-American patients with New York Heart Association class III or IV heart failure with a reduced left ventricular ejection fraction already receiving diuretics, beta blockers, and an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker [9, 47, 64]. Drugs to avoid in patients with hypertension and heart failure with a reduced left ventricular ejection fraction include verapamil, diltiazem, doxazosin, clonidine, moxonidine, hydralazine without a nitrate, and nonsteroidal anti-inflammatory drugs [9].
In patients with hypertension and heart failure with a preserved left ventricular ejection fraction, class I theraputic indications include control of systolic and diastolic hypertension, control of the ventricular rate in patients with atrial fibrillation, and reduction of pulmonary congestion and peripheral edema with diuretics [9, 47]. Class IIb therapeutic indications include use of beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or calcium channel blockers [9].
Stable Angina Pectoris
Patients with hypertension and chronic stable angina pectoris should be treated with beta blockers plus nitrates as antianginal agents [9]. The hypertension in these patients should be controlled with beta blockers plus an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker with addition of a thi-azide or thiazide-like diuretic if needed. If either the angina pectoris or the hypertension remains uncontrolled, a long-acting dihydropyridine calcium channel blocker can be added to the therapeutic regimen. Nondihydropyridine calcium channel blockers such
as verapamil and diltiazem cannot be used if there is left ventricular systolic dysfunction. Combining a beta blocker with either verapamil or diltiazem must be used with caution because of the increased risk of bradyarrhythmias and heart failure [9].
Acute Coronary Syndromes
In patients with an acute coronary syndrome, initial therapy of hypertension should include a short-acting beta1 selective beta blocker without intrinsic sympathomimetic activity such as metoprolol tartrate or bi-soprolol [9]. Treatment with beta blockers should be started initially within 24 hours of symptoms. In patients with severe hypertension or ongoing ischemia, intravenous esmolol may be considered [9]. In hemo-dynamically unstable patients or those with decompensated heart failure, treatment with beta blockers should be delayed until the patient is stabilized [9].
In patients with acute coronary syndromes with hypertension, nitrates can be used to reduce blood pressure or to reduce ongoing myocardial ischemia or pulmonary congestion [9]. However, nitrates should not be given to patients with suspected right ventricular infarction or in those with hemodynamic instability. Intravenous or sublingual nitroglycerin is preferred initially [9].
An angiotensin-converting ernzyme inhibitor or angiotensin receptor blocker should be given to patients with an acute coronary syndrome , especially in patients with an anterior myocardial infarction, if hypertension persists, if there is a reduced left ventricular ejection fraction, or if diabetes mellitus is present [9]. If hypertension persists after use of a beta blocker plus an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, a long-acting dihydropyridine calcium channel blocker may be added [9]. Aldosterone antagonists are indicated in patients receiving beta blockers plus angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after myocardial infarction who have left ventricular systolic dysfunction and either heart failure or diabetes mellitus [9]. However, they should be avoided if the serum potassium is s 5.0 mEq/L or if the serum creatinine is s 2.5 mg/dL in men or s2.0 mg/dL in women [9]. Loop diuretics are preferred to thiazide and thiazide-type diuretics in patients with heart failure or in patients with chronic kidney disease and an estimated glomerular filtration rate less than 30 mL/minute [9].
Conflict of interest: None declared.
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