The Journal of American College of Cardiology shall publish the 5 years follow up of the PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty using Sirolimus Stents in Patients With Left Main Coronary Artery Disease) trial data presented in the recent American College of Cardiology 2015 Scientific Sessions. The PRECOMBAT trial randomized 600 patients with unprotected left main artery stenosis in 13 Korean sites to PCI with a sirolimus eluting stent (SES) or CABG (300); these patients had angina, non ST-segment elevation myocardial infarction or silent ischemia. Their mean age was 62 years, one third had diabetes and half had unstable angina. The SYNTAX score was about 25 in both groups. More than 70% had left main with 2 or 3 vessel disease.
At 5 years 90% of the patients were on aspirin and 50% were receiving a statin. The PCI group got 2.7 stents on an average and intravascular ultrasound (IVUS) was used in more than 90% of patients. About 2.7 grafts were attached in the CABG cohort and almost two-thirds had off pump surgery. In CABG the internal mammary artery was preferred for grafting the left anterior descending artery.
At the end of 5 years there was no significant difference in the primary end point of MACCE (a composite of death from any cause, myocardial infarction, stroke or ischemia driven target vessel revascularization (TVR), but patients who underwent PCI were more likely to have TVR than surgical patients. In 2011 PRECOMBAT had reported non-inferiority of PCI versus CABG after follow up of 1 year. At 5 years the composite end point of death, myocardial infarction or stroke was 8.4% in the group and 9.6% in the CABG patients (p=0.66).
The last 2 decades have witnessed tremendous improvement in stent technology accompanied by better adjunctive drug treatment. Left main disease considered only for CABG surgery is now being offered the alternative of PCI if there is suitable anatomy. The SYNTAX trial (employing paclitaxel eluting stents) 5 year follow-up had also reported that PCI was a viable alternative to CABG in patients with SYNTAX score less than 32; clinical outcomes were similar in PCI as compared to CABG. The PRECOMBAT trial differed from the SYNTAX study in using sirolimus stents and IVUS in almost all patients in the PCI group.
The PCI patients had significantly greater repeat procedures but this did not translate into increased hard endpoints such as death, myocardial infarction or stroke. It is plausible that results of PRECOMBAT were in variance with SYNTAX due to being underpowered and having patients of East Asian ethnicity. Both PRECOMBAT and SYNTAX have demonstrated better clinical outcomes with PCI in left main disease then in multi-vessel disease; it almost appears that these 2 entities are separate animals with different destinations; completely 2 different diseases. The reasons for different clinical outcomes could be that in left main disease we have a larger vessel to deal with and there is less tortuosity. More information will be provided by the ongoing EXCEL study (Evaluation of Xience Prime or Xience V Versus CABG for Effectiveness of Left Main Revascularization) that compares 3-year composite end point of death, myocardial infarction or stroke in patients treated with the second generation Xience stent versus CABG. It is important to note that all cause mortality was lower with PCI than with CABG in patients with scores <33 (7.9% vs. 15.1%; p=0.02), in the SYNTAX 5 year follow up. The SYNTAX trial had randomly assigned 1800 patients with left main or 3 vessel disease to PCI or CABG; of these there were 705 patients with left main disease. PCI treated patients had a lower risk of stroke but higher revascularization rate versus CABG. Major cardiac and cerebrovascualar events were similar between both arms in patients with low/intyermediate SYNTAX scores but significantly increased in PCI patients with higher scores >33.
The PRECOMBAT 5 year follow up trial has strikingly reported that results of PCI were non-inferior to CABG even in patients with the highest baseline SYNTAX scores (>33), but the study as has been admitted by the authors is underpowered to compare hard endpoints and the conclusions drawn can be at best considered hypothesis generating. We have to wait for more adequately powered trials to make firm conclusions on the feasibility of PCI in patients with left main (low or intermediate –complexity) disease, but in the mean time PCI for left main disease appears both safe and effective with similar outcomes to CABG up to 5 years.
The ‘ASAN MAIN’ registry from Korea (published in Circulation : Cardiovascular Interventions in March 2015) Interventions reported that results in left main stenting have steadily improved over the last 15 years starting from bare metal stenting in 1995 to second generation DES in 2010. Their data reveals PCI increased form 35% in the BMS era to 52% in the late DES era; there was increased usage of IVUS from 80% to 87% and left main bifurcations were more frequently treated with a single stent crossover than with 2-stent technique (60% vs. 25%; p < 0.001). The incidence of MACCE ( composite of death,MI,stroke or repeat revascularisation also fell. There are another 2 large randomised trials of PCI versus CABG in left main disease (EXCEL and NOBLE) underway and their results should be out in 2016. The EXCEL trial recommends but does not mandate employment of IVUS or FFR during PCI of left main lesions.