Choice of Revascularization Strategy for Patients With Coronary Artery Disease

Surgical coronary artery bypass grafting (CABG) was first performed in 1967 and percutaneous transluminal coronary artery angioplasty (PTCA) in 1977. Initially the 2 revascularization methods appeared complementary: the less invasive PTCA seemed suited for patients with limited lesions, and CABG for those with diffuse disease. The Duke University group, in a large prospective study, first established that PTCA achieved the greatest survival benefit in patients with a single-vessel disease other than proximal left anterior descending (LAD) artery stenosis, and CABG in those with multivessel disease or proximal LAD artery stenosis. Patients with 2-vessel disease or an isolated proximal LAD artery stenosis had similar results with either therapy.^{1 - 2} However, individual clinical variables, such as the characteristics of the stenosis, the patient's ventricular function, and associated comorbidities, are often factored into the final decision about the method of revascularization. In the 1990s, a number of randomized trials attempted to refine the indications for PTCA vs CABG in patients who could concurrently be approached by both methods.

At least 9 prospective, randomized trials have compared the benefits of CABG vs PTCA among patients with coronary artery disease (CAD) suitable to either method.^{3 - 11} Despite differences in patient populations and entry criteria, the trials have consistently found that both methods produce similar rates of early and late irreversible events (death or myocardial infarction) during an average follow-up of 5 years. In the Bypass Angioplasty Revascularization Investigation (BARI) trial, the cumulative survival rates at 5 years were 89% and 86% for patients assigned to CABG and PTCA, respectively, and the corresponding rates of freedom from myocardial infarction were 80% and 79%.³ An initial approach with CABG, however, was superior in terms of some intermediate variables (eg, relief of angina, avoidance of additional revascularization, and improvement in exercise capacity) and inferior in terms of others (eg, greater postprocedural pain and discomfort, duration of hospitalization and rehabilitation).^{4 - 12}

In all the trials and throughout follow-up, there was an excess of angina (21% vs 11% after 1 year) and requirement for additional revascularization procedures (38% vs 3% after 3 years) for patients who received initial PTCA.^{2 ,5} Incomplete revascularization and restenosis of the dilated vessel generally accounted for residual or recurrent angina. Complete revascularization was achieved in 57% of patients after PTCA and in 91% after CABG in the BARI trial (which included only patients with multivessel disease).³ Although the follow-up periods were long enough to measure the full effect of postangioplasty restenosis, they were too short to account for venous bypass attrition, as the half-life of venous grafts is estimated at 10 years.¹³

Although PTCA offers the advantages of lower initial hospital costs and an earlier return-to-work date, the differences in total cost appear to decrease over time as patients who undergo PTCA are more likely to require additional revascularization. For instance, the initial cost of CABG was originally twice that of PTCA in the Randomized Intervention Treatment of Angina (RITA) trial, but after 5 years the difference was less than 5%.⁴ Other trials^{9 ,14} have found similar results.

Quality of life was assessed by the RITA trial, using the Nottingham Health Profile¹⁵ to evaluate emotional, social, and physical distress as well as daily life achievements (eg, work, social life, sex life, and hobbies).¹⁶ Both interventions produced marked improvement in every aspect of life quality. Only complete eradication of angina, however, was able to produce scores similar to the population norms. Residual or recurrent angina, even if mild or medically treatable, had a negative impact, especially on emotional reactions and daily life achievements.

The impact of revascularization on cognitive function remains unclear. The BARI trial evaluated memory, concentration, and speed of information processing 5 years after randomization in 125 patients scheduled for cardiac evaluation.¹⁷ The scores obtained were similar between both revascularization strategies, and also between patients who received operations and those who did not. However, the study could not completely exclude the possibility of cognitive deterioration following CABG, as baseline and early postoperative assessments were not performed. The study was also considerably underpowered to detect a difference in this variable, and the evaluated population was relatively young. The risk of neurological or neuropsychological damage after bypass graft surgery is closely related to age and extent of atherosclerosis, with a steep increase of risk among patients aged 75 years or older.^{18 - 20}

Although these trials illuminate some of the costs and benefits of CABG vs PTCA, they have limited relevance for clinical practice because the samples may not have been representative of all patients with CAD. For instance, generally fewer than 10% of the patients who were screened for these trials were eligible to participate. Furthermore, the trials did not address several emerging techniques and refinements of PTCA and CABG.

Implantation of stents in coronary arteries to stabilize the freshly dilated stenosis has become an important adjunct to conventional PTCA. As a result, the need for rescue CABG decreased from 5%³ to less than 1% in patients undergoing PTCA,²¹ despite the fact that more complex lesions are being approached by this route. Randomized trials further established the value of stents in reducing the rates of death, myocardial infarction, early restenosis, and recurrent angina.^{21 - 24}

A randomized study showed similar results between systematic placement of stents in all target lesions vs a strategy of provisional stenting only for lesions that appeared to be unstable within 30 minutes of balloon angioplasty. The angiographic restenosis rates at 6 months were 19% and 16%, respectively, and the event-free survival rates were 81% and 83%.²⁵ The overall cost of the provisional strategy, however, was significantly less. Between 30% and 50% of patients may achieve an optimal result with balloon angioplasty alone.²⁶ Further improvement after percutaneous coronary intervention can be expected with the addition of inhibitors of platelet glycoprotein IIb/IIIa receptors. In prospective randomized trials, the rates of acute and subacute thrombosis of the dilated or stented vessels were significantly reduced with these agents.²²

CABG can now be performed without extracorporeal circulation. The elimination of the heart-lung bypass pump results in lower morbidity and reduced hospitalization and rehabilitation stay compared with traditional CABG.²⁷ Complete revascularization can be achieved in many patients with 1-vessel or 2-vessel disease, and in some with 3-vessel disease.^{27 - 28} The method may also be useful as a palliative measure in patients with increased surgical risk or reduced life expectancy. It is also advantageous in patients with severe atherosclerosis of the ascending aorta or aortic arch, as it avoids the risks of systemic and cerebral embolization following manipulation of the ascending aorta during cannulation, cross-clamping, and implantation of venous grafts. Off-pump surgery, which maintains a normal perfusion pressure and pulsatility (in contrast to the flow generated by the heart-lung machine), further reduces the risk of postoperative neuropsychological disturbance in elderly patients, who are likely to have obstructed cerebral arteries and impaired cerebral autoregulation.²⁹ Although long-term results are not available, the immediate results of off-pump surgery compare favorably with those of conventional CABG in as many as 25% of patients with CAD.^{27 - 28 ,30} The method, however, is technically more demanding, and its optimal clinical indications need to be better defined. Off-pump surgery has been combined with PTCA to revascularize surgically less accessible coronary arteries.³¹ This hybrid approach may be attractive in high-risk situations like some "redo" coronary bypass operations.

Another major advance is the wide use of arterial grafts.³² The most common approach involves grafting the left internal thoracic artery to the LAD. A second arterial conduit (such as the right internal thoracic artery or the radial artery of the nondominant hand) is also frequently used. The outstanding longevity of arterial conduits combined with appropriate control of risk factors for atherosclerosis may obviate the need for later revascularization procedures in most patients.³³ A study from the Cleveland Clinic found a cumulative survival rate of 79% at 12 years after double arterial bypass graft, and 77% of subjects had not required subsequent revascularization during that time.³²

A PTCA is probably optimal for revascularization of a limited myocardial mass or single-vessel disease, and surgery more suited for a large mass or multiple-vessel disease. Both methods are appropriate to treat patients with an intermediate disease. Other clinical variables, such as the patient's preference and motivation, often dictate the optimal approach. For instance, the Emory Angioplasty versus Surgery Trial (EAST) found that eligible patients who refused enrollment had a better outcome than those who accepted it, suggesting that these variables (whose effects are blunted in a randomized process) can influence the decision about the most appropriate therapy.³⁴

Whichever method is chosen, the long-term relief of angina will only be attained if dedicated attention to risk factors and efficient lipid-lowering therapy are implemented. Statin drugs, for instance, appear to have significant benefit in patients with CAD, both by reducing lipid levels and by inhibiting vascular smooth muscle proliferation.^{35 - 36} If the effect, observed on primary and secondary prevention of atherosclerosis are sustainable, therapy with such agents could in the end prove as decisive as the choice of myocardial revascularization.