Chronic stable angina coronary artery bypass grafting versus medical therapy


 * Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S.

Overview
It is well established that revascularization with CABG has shown to provide better symptomatic relief and improved survival rates in comparison to medical therapy in some patients with stable angina. However, the long term benefit of CABG is limited by the progression of atherosclerosis in other unbypassed vessels and stenosis of the graft itself.

Symptomatic Benefit
One of the earliest study that compared the benefit of CABG versus medical therapy in the management of stable angina was the Coronary Artery Surgery Study (CASS) (1990). This study demonstrated that more patients were angina-free after CABG as observed during one year (66% in the CABG group versus 30% in the medically treated group) and five-year follow-up (63% versus 38%). However, at ten-year follow-up these advantages were much less apparent and almost similar in both the groups (47% versus 42%) secondary to the recurrence of symptoms in the CABG group and also a large portion of medically treated patients underwent CABG at a later date, rendering them asymptomatic.

Effect of Severity of Angina
Non-randomized observational study from the CASS registry involving 4,209 patients with similar angiographic findings was performed to evaluate the effect of angina severity on the clinical outcome of medical therapy. At 5-year follow-up, the survival rate was found to be significantly higher in the surgically treated group, in patients with Class III or IV angina and triple-vessel disease with either normal left ventricular function (? 92% in the surgically treated group versus 74% in the medically treated group; P=less than 0.0001) or reduced LV function (82% in the surgically treated group versus 52% in the medically treated group; P=less than 0.0001). Thus, the study confirmed the importance of clinical as well as anatomic factors in determining the prognosis of patients with ischemic heart disease and indicated that CABG improved the late-survival in patients with triple vessel disease and severe angina pectoris.

No Survival Benefit Observed
Studies done in the early 1970's-1980's demonstrated no significant survival benefit observed with CABG in comparison to medical therapy alone.

Selected patients who may Benefit from CABG

 * CABG has shown to offer significant survival benefits in patients with high-risk CAD. This includes patients with:
 * Left main stenosis or left main equivalent disease. Based on the CASS registry, patients with three-vessel disease and significant left main obstruction, the 4-year survival decreased from 70% to 60%. Thus, indicating the presence of left main coronary artery disease significantly decreased survival and hence poor prognosis.


 * Severe proximal LAD stenosis. Proximal LAD stenosis with concurrent RCA obstruction has shown to be associated with worst outcomes in comparison to a lesion present in the distal LAD.


 * Triple-vessel disease with severe LV dysfunction.


 * The 2004 ACC/AHA guidelines on CABG, recommended CABG would benefit patients with:
 * One- or two-vessel CAD without significant proximal LAD stenosis but with a large area of viable myocardium and high-risk criteria on noninvasive testing.
 * Disabling angina despite maximal noninvasive therapy.

Effect of Positive Exercise Stress Test

 * Based on the exercise tolerance and duration to ST segment depression during exercise, patients with symptomatic coronary artery disease who received medical therapy are classified into high-risk subgroup with an annual mortality of greater than 5% per year and a low-risk subgroup with an annual mortality of 1% per year.


 * According to the Duke treadmill score (DTS) for exercise testing, low-risk patients with a score of greater than or equal to (+5), had no coronary stenosis greater than 75% (60% patients) or single-vessel disease (16% patients). By comparison, high-risk patients with a score lower than (-11) reported to have triple-vessel or left main coronary disease (74% patients). However, the 5-year mortality was found to be 3%, 10%, and 35% for low-, moderate-, and high-risk DTS groups (P<0.0001).


 * In patients with suspected CAD, the ability of exercise-induced myocardial hypoperfusion on thallium scintigraphy may be used to determine which patients could more likely have an increased survival benefit from revascularization as opposed to medical therapy. In a retrospective evaluation, 10,627 consecutive patients without prior MI or revascularization underwent exercise or adenosine perfusion scintigraphy. Of these, 671 patients underwent revascularization (2.8% mortality) and 9956 patients received medical therapy (1.3% mortality; P=0.0004) within 60 days after myocardial perfusion scintigraphy. At 2-year follow-up, medical therapy group demonstrated a significant survival advantage over patients undergoing revascularization in the setting of no or mild ischemia with an inducible ischemia of lower than 10% of total myocardium (0.9% versus 3.3%), whereas patients undergoing revascularization demonstrated an increasing survival benefit in the presence of moderate to severe ischemia with an inducible ischemia of greater than 10% of total myocardium (2.6% versus 5.4%).

Effect of Left ventricular dysfunction

 * Left ventricular dysfunction is a more important predictor of survival than the number of diseased vessels and hence remains a strong indication for revascularization.


 * Based on the CASS registry,


 * Patients with significant coronary artery disease who had an ejection fraction of 50-100%, 35-49%, and 0-34% had a 4-year survival of 92%, 83% and 58%, respectively.


 * The systolic contraction pattern was assessed in five selected segments and given a score of 1-6, with a score of 1 for normal function, increasing to 6 if an aneurysm was present. In a patient with normal LV contraction in all five segments of the LV ventricular angiogram, the LV score would equal 5. Patients with an LV score of 5-11, 12-16 and 17-30 had 4-year survivals of 90%, 71% and 53%, respectively.


 * Patients with good LV function (a score of 5-11) had a 4-year survival of 94%, 91% and 79% for one-, two- and three-vessel disease, respectively. Patients with poor left ventricular function (score of 17-30) had a 4-year survival rate of 67%, 61% and 42% in one-, two- and three-vessel disease, respectively.


 * Patients with triple-vessel disease and ejection fraction higher than 34% and lower than 50%, have demonstrated a significant improvement in the seven-year survival with elective CABG (88% patients in the surgical group versus 65% in medically treated group; P=0.009). However, no survival benefit from CABG was observed in patients with single-vessel or double-vessel disease and was shown to be similar in both the surgical and medically treated groups.


 * Based on a study that analyzed 135 consecutive patients with LV dysfunction (EF 10-30%, mean 23.6%) who underwent isolated CABG over an 8-year. Preoperatively, 63% of patients had angina, 61% had heart failure (23% with pulmonary edema), and 24% manifested severe ventricular arrhythmia. The in-hospital mortality rate was 5.2%. At 1, 3, and 4.5 year follow-up respectively, all-cause survival was 87%, 81%, and 71%, and freedom from cardiac death was 90%, 85%, and 80%. LVEF (assessed in 104 of 128 hospital survivors) demonstrated a significant improvement from 24% pre-operatively to 34% post-operatively (P<0.0001). This partial reversibility of left ventricular dysfunction after revascularization may reflect a hibernating myocardium.

Limitations for Long-term Symptomatic Benefit
With the exception of left main disease, the long-term survival benefit from CABG is limited and tends to be affected with the presence of severe LV dysfunction, increased rate of development of saphenous vein graft disease and/or atherosclerosis progression in other coronary vessels.


 * In the CASS registry, 6-8% patients per year underwent repeat surgery for recurrent symptoms and the approximate five-year mortality rate with CABG was 1% per year.


 * Another study done in the late 1980's demonstrated that immediate post-CABG approximately 77% patients were free from all ischemic events at 5-years and reported improved survival rates in approximately 80% patients as observed at ten-year follow-up. However, 50% had recurrence of angina and only 15% remained angina-free at 15-year follow-up.

Limitations for Long-term Survival Benefit

 * The benefits of CABG on survival and post-infarction mortality tends to be diminished with long-term follow-up even in high-risk patients, and considered to be secondary to the progression of coronary artery disease which could be minimized with the current aggressive risk-factor modification.


 * Several studies have shown that CABG may be beneficial in prolonging survival in patients with left ventricular dysfunction; however, the same does not apply to patients with a non-viable scarred myocardium. Thus, suggesting the need for myocardial viability assessment prior to the consideration of CABG.


 * Meta-analysis that assessed 24 myocardial viability studies involving 3,088 patients with a ejection fraction between 32-40%, demonstrated a strong association between myocardial viability on non-invasive testing and improved survival after revascularization in patients with chronic CAD and LV dysfunction. Patients with viable myocardium, revascularization was associated with 79.6% reduction in annual mortality (16% versus 3.2%, chi-square=147, P<0.0001) compared with medical treatment. Patients without viability had intermediate mortality, trending to higher rates with revascularization versus medical therapy (7.7% versus 6.2%, P=NS). Thus, the absence of viable myocardium has been associated with no significant difference in prognostic outcomes, irrespective of treatment strategy.

Surgical Recovery
Recovery is slow even in patients with successful surgery. The most powerful factor in determining post-operative employment is the presence or absence of post-operative angina. Randomized studies that assessed the quality of life and return to normal function, reported a initial superior benefit with CABG; however, no significant difference was observed among the two groups- medically treated and surgically treated at two-, five- and ten-year follow-up.