Management of Stable Angina

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Abstract

Stable angina pectoris is a common disorder, and its prevalence increases with age. Patients with stable angina pectoris experience a pressure or a choking sensation in the chest and adjacent areas, or shortness of breath (angina equivalent), associated with physical or emotional stress. Most patients with stable angina pectoris have severe obstructive atherosclerotic lesions of complex morphology in one or more than one coronary artery and multiple non-obstructive lesions.
Obstructive lesions limit the increase of blood flow needed during periods of increased myocardial oxygen demand, such as exercise. The endothelium overlying the lesions is dysfunctional and is responsible for paradoxical constriction of the stenotic site during exercise resulting in further reduction of blood flow distal to the lesion. The resultant imbalance between myocardial oxygen supply and demand produces reversible myocardial ischaemia and its clinical consequences, such as anginal pain and/or shortness of breath.

Non-obstructive lesions are lipid-rich and soft in consistency and the endothelium overlying these lesions is prone to fissuring and disruption. The exact mechanism of plaque-endothelial surface disruption remains elusive. Several mechanisms, including an active inflammatory process, have been implicated. The fissured endothelium exposes the atheromatous material inside the vessel wall to the circulating blood. This results in platelet aggregation and deposition, which may be followed by additional intraluminal thrombosis. The clinical presentation may remain silent or manifest as acute coronary syndrome (myocardial infarction, unstable angina) or sudden ischaemic death.

The annual death rate of patients with stable angina is 1.6% to 3.2%. The most important determinant of prognosis is underlying left ventricular systolic function at rest, co-morbid conditions, and the severity and extent of coronary artery disease (CAD). Treatment goals are:

  • abolition or reduction of the frequency of angina attacks;
  • prolongation of angina-free walking duration;
  • abolition or reduction of other consequences of reversible myocardial ischaemia, such as dyspnoea; and
  • prevention or reduction of serious adverse outcomes (myocardial infarction, unstable angina and ischaemic sudden death) due to plaqueendothelial surface disruption.

The treatment must be applicable to a large segment of the population with stable angina. Pharmacological therapy should be devoid of intolerable adverse effects and drug interactions. Newer therapy should be either superior to, or as effective as, already proven therapy and should show additional beneficial effects when used in addition to currently proven and effective treatment of stable angina pectoris.

Currently available anti-anginal drugs (long-acting nitrates, beta blockers and calcium channel blockers) and revascularisation procedures alleviate or prevent anginal symptoms but have not been shown to improve survival or reduce the incidence of myocardial infarction in patients with stable angina pectoris. On the other hand, the strategies that reduce the incidence of adverse outcomes have few anti-anginal effects. Therefore, treatment of stable angina must include the use of anti-anginal drugs and/or revascularisation procedures plus strategies that reduce adverse clinical outcomes.

Treatment Aimed at Decreasing the Frequency and Severity of Anginal Symptoms and Myocardial Ischaemia
Several strategies are available to achieve this goal. Anti-anginal drugs (nitrates, beta-blockers and calcium channel blockers) are usually the first option. Revascularisation procedures, percutaneous balloon dilation of the coronary artery (PTCA), with or without stent placement, are being increasingly used, especially in the US, and coronary bypass surgery is now being offered only to selected patients with stable angina pectoris.
 

Devices and Coronary Bypass Surgery

Revascularisation Procedures
Percutaneous interventions to dilate stenotic coronary arteries and coronary bypass surgery increase blood flow to the ischaemic myocardium. Both modalities relieve angina and reduce or abolish exercise-induced ischaemia. The treatment effects are obvious soon after the procedure, but neither procedure reduces mortality or the incidence of myocardial infarction compared with anti-anginal drug therapy.

Percutaneous Coronary Revascularisation
Balloon dilation of stenotic coronary lesions with or without stent placement abolishes or reduces the frequency of anginal symptoms, increases angina-free walking duration and reduces exercise-induced ischaemia. Compared with medical therapy, symptom relief is immediate and of greater magnitude, but restenosis of the dilated lesions occurs in 20% to 40% of patients, necessitating a repeat procedure or bypass surgery. Restenosis rates are even higher in diabetic patients. Recently, drug-coated stents were approved. Initially, it was claimed that drug-coated stents have 0% restenosis, but recent reports suggest a restenosis rate of 8% to 11%. Subacute thrombosis, which may be fatal, remains a concern following stent placement, including drug-coated stents, and has been reported in 0.5% to 1% of patients. Serious adverse outcomes at six months following drug-coated stents were reported in 9% compared with 14% following bare stents in the same institution.

The majority of patients who undergo PTCA/stenting are maintained on anti-anginal drugs and it is difficult to evaluate the true beneficial effects of PTCA/stenting in the absence of concomitant anti-anginal drug therapy. In a recent study in CCS class II angina, optimal medical therapy, which also included high doses of the lipid-lowering agent atorvastatin, was more effective at reducing adverse clinical outcomes than PTCA/stenting, although symptom relief initially occurred more often with PTCA/stenting.

Trials have shown that PTCA/stenting is equally as effective as coronary bypass surgery with the exception that symptoms recur more often following PTCA/stenting and a repeat revascularisation procedure is needed in 20% to 30% of patients.

PTCA/stenting does not reduce the incidence of death or myocardial infarction in patients with stable angina. On the contrary, the reported incidence of peri-procedural biochemical myocardial infarction is 4% to 7%.

Coronary Artery Bypass Surgery
Coronary artery bypass surgery is highly effective at relieving angina and myocardial ischaemia. However, many patients subsequently develop obstructive lesions in the venous conduits necessitating further risky interventions. Arterial conduits are preferred as late occlusion in the arterial conduits occurs less frequently.

Coronary bypass surgery, although effective, is associated with 1% to 3% mortality and significant morbidity. Published randomised trials have failed to show that coronary bypass surgery either reduces mortality or the incidence of myocardial infarction compared with medical treatment or PTCA/ stenting. Subgroup analysis of the published data showed beneficial effects of coronary bypass surgery in patients with left main stenosis and in those with three-vessel disease in one study and three-vessel disease with diminished left ventricular function in another study. Therefore, it should be reserved for patients with left main stenosis or those with multivessel disease and reduced left ventricle systolic function and for patients who do not respond adequately to pharmacologic therapy and or PTCA/stenting procedures.

Given the evidence that neither percutaneous interventions nor coronary artery bypass surgery improves survival or reduces serious adverse outcomes compared with medical therapy, it is preferable to try medical therapy first and consider percutaneous intervention or bypass surgery if medical therapy has failed.

Enhanced external counterpulsation (EECP) improves exercise performance with reduction in myocardial ischaemia in patients with stable angina pectoris. However, reported trials are rather small and at present EECP is reserved for patients who do not respond to conventional anti-anginal therapy and are not candidates for a revascularisation procedure.

At present, direct laser revascularisation procedures are only being used in patients who are not candidates for a revascularisation procedure and are refractory to medical therapy. Percutaneous transmyocardial revascularisation is not superior to a Sham procedure in patients with stable angina.

Spinal cord stimulation and transcutaneous nerve stimulation are reserved for those patients who are not candidates for a revascularisation procedures and remain very symptomatic despite optimal drug therapy. Anti-anginal drugs, PTCA with or without stents, bypass surgery and other devices do not improve survival or reduce the incidence of myocardial infarction in patients with stable angina. The following strategies are therefore needed to improve outcome.

Treatment Aimed at Reducing Adverse Outcomes
Smoking cessation reduces the risk of CAD mortality by 50% in one year. After five to 10 years, the coronary mortality rate in the ex-smokers matches that of non-smokers. Stopping smoking may increase exercise performance in patients with stable angina pectoris.

Aspirin reduces the incidence of death and acute myocardial infarction in patients with stable angina pectoris. Therefore, all patients with stable angina pectoris should be treated with daily aspirin (81├óÔé¼ÔÇ£320mg) provided they do not have a history of an allergic reaction to aspirin and do not experience intolerable gastrointestinal side effects.

There are no data to indicate that newer anti-platelet agents clopidogrel and ticlopidine are superior to aspirin in patients with stable angina pectoris. Largescale trials comparing aspirin with clopidogrel in patients with stable angina pectoris are lacking. Lipid-lowering therapy, especially with statins, reduces coronary morbidity and mortality in patients with established CAD. In a small study, aggressive lowering of low-density lipoprotein (LDL) cholesterol with atorvastatin plus anti-anginal therapy was superior to percutaneous interventions plus antianginal therapy in patients with stable angina pectoris. Gemfibrozil reduced the incidence of serious adverse outcome in male patients with stable angina and low high-density lipoprotein (HDL) levels (<35mg per dl) in the VA-HIT trial.

Available data supports aggressive treatment of lipid abnormalities in addition to daily use of aspirin and smoking cessation in patients with stable angina pectoris.

Beta-blockers reduce adverse outcomes in patients with reduced systolic left ventricular function (ejection fraction <40%). Bisoprolol or metoprolol XL or carvedilol should be used in patients with stable angina who have evidence of low ejection fraction.

ACE Inhibitors
Routine use of ACE I is recommended by US and European guidelines on the basis of published data showing improvement in cardiovascular modality and morbidity in patients with CAD who have reduced left ventricular systolic function (ejection fraction <40%), and in patients with stable CAD.