Treating Angina Pectoris in Hypertension
It is estimated that 13.5 million people in the United States have ischemic heart disease (IHD), and 1.5 million new cases are diagnosed each year. IHD remains the leading cause of mortality, resulting in approx 500,000 deaths annually. Many studies have identified specific risk factors for coronary artery disease. These include a family history, diabetes mellitus, hypertension, hyperlipidemia, and smoking. The incidence of cardiovascular events increases with the number of risk factors present and is greater than would be predicted by their combined presence. Primary and secondary prevention including effective blood pressure control and lowering of serum cholesterol levels, together with significant strides in the treatment of IHD, have resulted in significant reductions in morbidity and mortality. In this chapter, we review the management of the hypertensive patient with IHD.
Medical therapy
Medical therapy for the hypertensive patient with IHD is aimed at lowering blood pressure, reducing myocardial ischemia, alleviating anginal symptoms, and preventing recurrent cardiovascular events.
Antiplatelet agents and anticoagulant therapy
Aspirin has been shown to reduce the risk of major cardiovascular events in patients with IHD. The risk of death and myocardial infarction (myocardial infarction) is reduced in patients presenting with an acute coronary syndrome (unstable angina [UA] or non-Q wave myocardial infarction [NQWMI]). Similarly, the addition of aspirin to thrombolytic therapy for the treatment of acute myocardial infarction resulted in an additive benefit, reducing the incidence of death and nonfatal reinfarction. Therefore, aspirin should be administered to every patient with IHD in the absence of contraindications.
Patients allergic to or intolerant of aspirin may be treated with ticlopidine or clopidogrel, which are antiplatelet agents that inhibit adenosine diphosphate-dependent platelet aggregation. However, clopidogrel appears to have a better safety profile than ticlopidine with a lower incidence of thrombocytopenia, neutropenia, and gastrointestinal side effects.
The use of heparin in addition to aspirin is currently recommended for the acute treatment of moderate- to high-risk patients. However, unstable anginal symptoms recur after heparin is discontinued, owing to reactivation of the coagulation system, and it appears that concomitant treatment with aspirin may prevent this withdrawal phenomenon. This suggests that the culprit lesion is still active after 1 wk of therapy. Furthermore, a significant number of patients continue to have recurrent cardiac events for months after discharge. In fact, activation of the coagulation mechanism has been shown to persist for up to 6 months after the acute event. Nevertheless, even prolonged treatment with a low molecular weight heparin, which has been shown to be superior to unfractionated heparin (UFH) for the acute management of UA/ NQWMI, did not result in a further decrease in events beyond that seen in the acute treatment phase.
Newer, more potent antiplatelet agents that block the glycoprotein (Gp) Ilb/IIIa receptor are now available. These agents compete with fibrinogen for binding to the Gp Ilb/IIIa receptor, and thereby inhibit the common final pathway of platelet aggregation. Because of the positive results from several clinical trials, tirofiban and eptifibatide are now widely utilized for the management of UA/NQWMI patients, in addition to standard medical therapy, especially in those patients deemed to be at high risk. This includes patients with unstable anginal symptoms associated with ST segment depression, new significant T wave inversions or an elevated cardiac troponin. Appropriate therapy for this subgroup of acute coronary syndrome patients includes early cardiac catheterization and percutaneous transluminal coronary angioplasty (PTCA) if feasible. In fact, the greatest benefit of these agents was realized in the subgroup of patients who underwent an early coronary interventional procedure and in whom the Gp Ilb/IIIa infusion was continued for 12-24 h after the procedure.
To date, clinical trials involving abciximab, a monoclonal antibody directed at the platelet Gp Ilb/IIIa receptor complex, have included only patients undergoing coronary angioplasty, although the agent remains under study for use outside the catheterization laboratory. In the Evaluation of Platelet Ilb/IIIa Inhibition for Prevention of Ischemic Complications (EPIC) trial, the administration of abciximab resulted in a 35% reduction in the risk of major adverse cardiac events at 30 d. This benefit was sustained after 3 yr of follow-up, and it is explained in part by the ability of abciximab to provide rapid, profound, and sustained inhibition of platelet function for up to 15 d as it continuously redistributes among circulating platelets.
β-Blockers
β-blockers without intrinsic sympathomimetic activity are an important class of drugs for the treatment of patients with IHD. They exert their beneficial effects by decreasing blood pressure, heart rate, and myocardial contractility with a net effect of decreasing myocardial oxygen demand. The ability of β-blockers to improve survival after a transmural myocardial infarction, limit infarct size, and reduce the risk of a recurrent infarction or myocar-dial rupture has been well documented. In fact, β-blockers are the only drugs that have been shown to reduce the risk of sudden cardiac death and intracerebral hemorrhage after an myocardial infarction. However, there are no large-scale clinical trials on UA or NQWMI. For the treatment of stable anginal symptoms, β-blockers offer similar reductions in death, myocardial infarction, and relief from angina as compared to calcium channel blockers, but with fewer adverse events.
More recently, β-blockers have been shown to improve symptoms and exercise capacity, as well as decrease mortality in patients with congestive heart failure (congestive heart failure) secondary to systolic dysfunction. Because β-blockers have a tendency to exacerbate heart failure symptoms, concomitant treatment with diuretics and an angiotensin-converting enzyme inhibitor is necessary.
Calcium channel blockers
Calcium channel blockers may be used for the management of anginal symptoms and blood pressure if adequately controlled with a β-blocker. Despite reports suggesting that short-acting calcium channel blockers can increase overall mortality in patients with coronary artery disease, recent studies with long-acting calcium channel blockers have failed to support this claim. In fact, blood pressure control is more persistent and stable and therefore results in less activation of the sympathetic nervous system. Long-acting calcium channel blockers have also been shown to decrease the incidence of silent and symptomatic ischemic episodes. In patients with a NQWMI, diltiazem reduces the incidence of postinfarction angina, early reinfarction, and death. However, the use of diltiazem, verapamil, and procardia should be avoided in patients with an acute myocardial infarction in the presence of congestive heart failure and severe left ventricular dysfunction.
Second-generation dihydropyridines such as amplodipine and felodi-pine are now available for the treatment of hypertension and angina. Because they exert no significant negative inotropic or chronotropic effects on the heart, they can be used safely in patients with severe heart failure and severely reduced systolic function.
Combination therapy utilizing a β-blocker and calcium channel blocker is generally well tolerated. However, bradycardia, hypotension, and heart block have been reported to occur in 10-15% of patients on verapamil and a β-blocker. Therefore, caution should be exercised when using this combination.
Angiotensin-converting enzyme inhibitors
Based on the results of several, large clinical trials, angiotensin-converting enzyme inhibitors should be part of the medical regimen for the hypertensive patient with IHD who has congestive heart failure and/or a large myocardial infarction with severely reduced systolic function. More recently, the angiotensin-converting enzyme inhibitor ramipril was shown to reduce the incidence of myocardial infarction, stroke or death from cardiovascular causes in a broad range of high-risk patients with a normal ejection fraction and no heart failure.
Nitrates
Nitrates remain a mainstay of therapy for the management of patients with symptomatic coronary artery disease because they reduce the number of ischemic events. However, nitrates do not affect mortality or the incidence of myocardial infarction in these patients. To avoid the development of tolerance, patients should have a daily nitrate-free interval.
Revascularization
PTCA remains the method of choice for the revascularization of patients with single- and double-vessel coronary artery disease and preserved systolic function. Compared to medical therapy, PTCA offers improved exercise capacity and the need for fewer antianginal medications with no impact on mortality or subsequent myocardial infarction. In a study of nondiabetic patients with triple-vessel disease and no significant systolic dysfunction, it was shown that PTCA and coronary artery bypass graft (CABG) surgery resulted in equivalent survival and freedom from myocardial infarction. However, patients initially treated with CABG had fewer episodes of angina, were on less antianginal medication, and required fewer repeat revascularization procedures. Diabetic patients with triple-vessel coronary artery disease appear to have a higher mortality with PTCA and should therefore be referred for CABG.
CABG confers a survival advantage in patients with significant left main disease, triple-vessel coronary artery disease with reduced systolic function, double-vessel coronary artery disease with a proximal left anterior descending artery stenosis, and left ventricular aneurysm with heart failure symptoms or sustained ventricular arrhythmias. Therefore, CABG is the treatment of choice for these patients. In patients with anatomy unfavorable for PTCA, CABG is utilized for relief of symptoms and offers little or no survival advantage.
Secondary prevention
Modification of the known risk factors for coronary artery disease including hypertension, hyperlipidemia, diabetes mellitus, and smoking reduces cardiovascular morbidity and mortality. In addition, family history, obesity, physical inactivity, homocysteinemia, alcohol consumption, and psychologic factors are important risk factors for cardiovascular disease. Instituting an aggressive treatment strategy aimed at slowing the progression of coronary artery disease and preventing recurrent cardiovascular events is the goal of secondary prevention.
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