Review
Medical Therapy Versus Myocardial Revascularization in Chronic Coronary Syndrome and Stable Angina

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Abstract

Coronary artery disease is a leading cause of death in the United States. Angina is encountered frequently in clinical practice. Effective management of patients with coronary artery disease and stable angina should consist of therapy aimed at symptom control and reduction of adverse clinical outcomes. Therapeutic options for angina include antianginal drugs: nitrates, beta-blockers, calcium channel blockers, ranolazine, and myocardial revascularization. Recent trials have shown that although revascularization is slightly better in controlling symptoms, optimal medical therapy that includes aggressive risk factor modification is equally effective in reducing the risk of future coronary events and death. On the basis of the available data, it seems appropriate to prescribe optimal medical therapy in most patients with coronary artery disease and stable angina, and reserve myocardial revascularization for selected patients with disabling symptoms despite optimal medical therapy.

Section snippets

Current Therapeutic Approaches for Stable Angina

The available therapeutic modalities for treatment of patients with angina include antianginal drugs and myocardial revascularization. Although until recently the antianginal therapy primarily consisted of nitrates, beta-blockers, and calcium channel blockers, newer drugs (ranolazine, ivabradine) with unique mechanisms have now become available. Despite the efficacy of antianginal drugs, many patients are referred for revascularization, mainly because of a misguided belief and bias that these

Antianginal Drug Therapy

Nitrates, beta-blockers, and calcium channel blockers (Table 2) traditionally have been used for angina relief.1, 2, 5, 6, 7, 8, 9, 10 Although these drugs are effective antianginal agents, data are lacking on the effect of such therapies on clinical outcomes, including myocardial infarction and death in patients with coronary artery disease and stable angina.1, 5, 6 Table 3 shows some of the important side effects and limitations of antianginal agents in the treatment of stable angina.

Nitrates

Nitrates work primarily by venodilatation resulting in venous pooling of blood, which reduces ventricular volume, cardiac work, and chamber size (Table 2). Nitrates are systemic and coronary arterial vasodilators; however, to what extent these effects account for their antianginal efficacy is not well established (except in patients with coronary artery spasm). Sublingual nitroglycerine is the most effective therapy for relief of anginal episodes. Often, long-acting nitrates are prescribed as

Beta-blockers

Beta-blockers are recommended as first-line therapy in coronary artery disease and stable angina. Treatment with beta-blockers has been associated with improved exercise tolerance and reduced frequency and severity of angina.1, 2, 5, 6, 8 Beta-blockers work by reducing myocardial oxygen demand by decreasing ventricular inotropy, heart rate, and maximal velocity of myocardial fiber shortening. Beta-blockers reduce risk of death (sudden and non-sudden) and myocardial infarction, primarily in

Calcium Channel Blockers

Calcium channel blockers are potent coronary and systemic arterial vasodilators that are highly effective in patients with coronary artery spasm (Table 2). Calcium channel blockers have become popular for treatment of angina primarily because of the lower incidence of side effects (Table 3). However, their impact on cardiovascular outcomes in coronary artery disease and stable angina has not been systematically evaluated in randomized controlled trials.

Newer Antianginal Drugs

Although there has been a lack of development of newer antianginal drugs during the past 25 years, new drugs with a unique mechanism of action have been introduced for treatment of stable angina. Of these, ranolazine and ivabradine have undergone the most extensive evaluations and are discussed next.

Ranolazine

Recently, ranolazine was approved by the Food and Drug Administration (FDA) for treatment of angina.11, 12 Although the precise mechanism of action of ranolazine is not established, it is thought to be related to selective late sodium channel blockade. The findings from several clinical trials suggest that antianginal effect of ranolazine is different than that of conventional antianginal medications because it is not a coronary vasodilator and does not reduce myocardial oxygen demand (no

Ivabradine

Ivabradine is a newer drug that has been evaluated in patients with coronary artery disease and stable angina.16, 17, 18 Ivabradine is a specific inhibitor of the I-f channels in the sinoatrial node and considered as a pure heart rate-lowering agent in patients with sinus rhythm. Ivabradine does not have an effect on blood pressure, myocardial inotropy, intracardiac conduction, or ventricular repolarization.16, 17, 18 Ivabradine is effective in reducing myocardial ischemia and controlling

Combination Therapy

Combination therapy is often necessary to achieve adequate symptom control in many patients with stable angina. Ideal combination therapy should provide maximum symptom relief with few adverse effects. Current guidelines recommend that combination therapy should use a beta-blocker with nitrate or a calcium channel blocker on the basis of a patient's underlying comorbid conditions. Such a combination may allow the clinician to use lower doses of each agent to achieve symptom control with minimal

Other Drugs in Patients with Stable Angina and Chronic Coronary Artery Disease

On the basis of the results of several randomized controlled trials demonstrating vasculoprotective effects of renin-angiotensin-aldosterone system blockers and statins, these drugs also are routinely recommended for patients with coronary artery disease and stable angina in an effort to reduce the risk of myocardial infarction and death. The following section provides a brief overview in this regard.

Angiotensin-Converting Enzyme Inhibitors

On the basis of the well-demonstrated vasculoprotective effects of angiotensin-converting enzyme inhibitor in 2 randomized controlled trials, the Heart Outcomes Prevention Evaluation (HOPE) trial21 and the European trial on reduction of cardiac events with perindopril in stable coronary artery disease (EUROPA),22 angiotensin-converting enzyme inhibitors are recommended for most patients with stable coronary artery disease. In the HOPE trial,21 compared with placebo, treatment with ramipril was

Lipid-Lowering Therapy

A number of studies during the last 2 decades have shown that lipid-lowering therapy with statins reduces not only the risk of major acute cardiac events but also the need for revascularization and decreases signs and symptoms of myocardial ischemia.24, 25, 26, 27, 28 Several randomized controlled trials have specifically evaluated the role of lipid-lowering therapy with statin as anti-ischemic therapy in patients with stable coronary artery disease and have shown that lipid-lowering therapy is

Role of Myocardial Revascularization

Myocardial revascularization has been evaluated and compared with medical therapy in patients with coronary artery disease and stable angina. Revascularization includes coronary artery bypass grafting and percutaneous coronary intervention with or without stent deployment. Although revascularization provides relief of anginal symptoms, it only abolishes anginal episodes in a minority of patients. A significant proportion of patients continue to experience anginal symptoms after

Comparison of Revascularization with Medical Therapy

During the past 4 decades, several studies32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 have compared the impact of pharmacologic therapy versus revascularization in patients with coronary artery disease and stable angina. In general, these studies have shown that revascularization is usually more effective in symptom control compared with conventional antianginal drug therapy. However, it is important to note that since the earlier time when

Strategies Comparing Invasive versus Optimum Medical Therapy

Several studies have evaluated the role of coronary artery bypass grafting, percutaneous coronary intervention, and medical therapy in patients with stable coronary artery disease. These include the Asymptomatic Cardiac Ischemia Pilot,35, 36 the Medicine, Angioplasty, or Surgery Study trials,51, 52, 55 the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation trial,32 and the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial.56 Overall, the results of

Conclusions

There are many therapeutic options available for the treatment of anginal symptoms in patients with stable coronary artery disease. These options include antianginal drugs: nitrates, beta-blockers, calcium channel blockers, and ranolazine, as well as myocardial revascularization procedures. Although combination therapy is often necessary for symptomatic relief, there has been no evaluation of the effects of combination antianginal therapy on hard clinical end points. Recent trials have shown

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    Funding: None.

    Conflict of Interest: Dr Deedwania is a consultant/speaker for Novartis, Gilead, Servier, and Pfizer. Dr Carbajal has no conflicts of interest associated with the work presented in this manuscript.

    Authorship: Both authors had access to the data and played a role in writing this manuscript.

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