28th April 2020, Dr Chee L Khoo
The incidence and mortality from coronary artery disease in Australia continue to decline. Coronary revascularisation consisting of percutaneous coronary intervention and coronary artery bypass graft (CABG) is rapidly increasing as the standard of care for coronary artery disease. There have been numerous trials comparing CABG with percutaneous coronary intervention (PCI) and so far, no studies have convincingly shown any overall difference between the two revascularisation strategies. There are even fewer studies comparing revascularisation procedures with optimal medical therapy (OMT).
The evidence comparing the prognosis of patients undergoing optimal medical treatment with patients undergoing revascularisation has been conflicting. Observational studies suggested
that, compared to medical treatment, coronary revascularisation improved prognosis in patients with extensive myocardial ischemia. However, most of the previous trials comparing revascularisation by coronary artery bypass graft (CABG) with medical therapy did not include pharmacological agents that are currently known to improve clinical outcomes in these patients, i.e. aspirin, statins, beta blockers, and renin angiotensin-aldosterone system inhibitors.
The ISCHEMIA (International Study of Comparative Effectiveness with Medical and Invasive Approaches) trial was one of the most anticipated late breaking trials presented at the American Heart Association Scientific Sessions held in Philadelphia, November 16–18, 2019. The rationale for the ISCHEMIA trial was to ascertain if – added to optimal medical therapy (OMT) – a strategy involving routine cardiac catheterization and myocardial revascularization improves prognosis in higher-risk patients with moderate to severe ischaemia.
5179 patients with evidence of moderate to severe ischaemia based on non-invasive imaging were randomised to either invasive or conservative treatment. The primary end-point was composite cardiovascular death, myocardial infarction (MI), resuscitated cardiac arrest and hospitalisation for unstable angina or heart failure. Secondary endpoints included time to death or MI, the individual major adverse cardiovascular events (MACE) events, and quality of life.
The average follow-up period was 3.3 years. Primary endpoint occurred in 13.3% of the patients in the invasive strategy arm vs. 15.5% of those in the conservative arm (adjusted hazard ratio = 0.93 (0.80, 1.08); p-value = 0.34). The major secondary endpoint of cardiovascular death or myocardial infarction occurred in 11.7% of the patients in the invasive strategy arm vs. 13.9% of those in the conservative arm (adjusted hazard ratio = 0.90 (0.77, 1.06); p value=0.21). In other words, invasive strategy as compared with an initial conservative strategy did not confer a reduced risk over a median of 3.3 years.
Optimal medical treatment was what they aimed for but only 41% of both arms achieved guideline directed lipid and blood pressure goals.
In a parallel study in patients with end-stage renal disease on dialysis or estimated glomerular filtration rate <30 mL/min/1.73 m2, ISCHEMIA-CKD, patients in the invasive arm fared worse because stroke, and death or new dialysis, were increased in the invasive group, compared to optimal medical treatment alone. This is not surprising.
The invasive arm did fare better in improving angina symptoms and quality of life compared with the conservative arm but only 34.3% and 36.6% of invasive and conservative patients, respectively, had no angina at baseline and only 44.1% and 44.5% had angina several times per month.
What ISCHEMIA illustrated that for asymptomatic patients with moderate to severe coronary artery disease as determined by non-invasive imaging (e.g. coronary artery calcium score), intensive medical treatment does just as well as revascularisation (CABG or PCI). If more patients achieved lipid and BP targets, medical treatment may actually be superior.
Camici PG, Merz NG, Beltrame J, et al. The ISCHEMIA Trial. International J of Cardiology 4 Feb 2020. doi.org/10.1016/j.ijcard.2020.02.011