Secondary Prevention after Coronary Artery Bypass Grafting: Anti-coagulation and anti-platelet therapy is only one factor

In this issue of the Journal of Cardiac Surgery, Sembi et al (1) nicely summarize the data regarding the use of anti-coagulation and anti-platelet therapy after coronary artery bypass grafting (CABG). In summary, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel/ticagrelor/prasugrel does not lead to improved graft patency rates or clinical outcomes after on pump CABG over aspirin monotherapy, despite a rational that it should. The protective effects of DAPT tended to be observed to be greater extent in patients undergoing off pump CABG, likely because cardiopulmonary bypass partially activates or “beats up” the platelets and makes them less effective. In general, the addition of the potent thienopyridines increased the risk of major bleeding, although the incidence of major bleeding is relatively low after either on pump or off pump surgical revascularization. There is a lack of evidence for anticoagulation post-CABG, with some trials showing that warfarin or rivaroxaban provide no protection against graft failure, but decrease the incidence of major adverse cardiovascular events. These findings are inconsistent. Indeed, even in patients with postoperative atrial fibrillation, the use of warfarin has recently been associated with increased mortality and major bleeding compared to anti-platelet therapy alone (2). This in part lead to the initiation of a large scale multicenter trial sponsored by the Cardiothoracic Surgery Network of the National Heart Lung and Blood Institute to address anticoagulation after CABG in the setting of postoperative atrial fibrillation.

The paper by Sembi (1) has a running title of “Secondary prevention post-CABG.” I decided to reverse the title and running title when naming this review, because I believe anti-platelet therapy is only one, albeit, a major component of secondary prevention after CABG. As surgeons, we tend to concentrate on the technical aspect of an operation. This can be the use of the on pump vs off pump method for CABG, valve repair or replacement for ischemic mitral regurgitation, how much aorta to resect for a dissection repair or the use of multiple vs one arterial graft for CABG. For CABG, the long-term outcome is dependent to a major degree on lifestyle change, smoking cessation and serum lipid and glucose management. (3) These issues tend to be relegated to a minor component of the discussion.

A comprehensive strategy for risk factor management improves survival, reduces recurrent ischemic events including the need for repeat revascularization procedures, and has been associated with improved quality of life. Even enrollment in an outpatient rehabilitation program has been associated with improved outcome long-term. After a successful CABG operation, the surgeon generally relegates the long-term management of the patient to the primary care physician or cardiologist. This is appropriate. Otherwise, we surgeons would see dozens of post CABG patients each week in our office and have no time to do anything else. However, it is important not only that physicians or surgeons implement these recommendations in appropriate CABG patients, but also that the healthcare systems help implementation these measures of secondary prevention to maximize the long-term outcome and cost effectiveness to the patient. (3) It is amazing how poor secondary prevention is after CABG (4,5). In fact, 5 randomized controlled trials reporting medical therapy after PCI with drug-eluding stents or CABG was recently published (5). In this analysis, compliance with any antiplatelet therapy plus beta-blocker plus statin was an abysmal 67% at one year and 53% after 5 years. Worse yet, compliance with the above plus an angiotensin converting enzyme therapy was 40% at one year and 38% at 5 years. This does not even take into consideration weight loss, exercise or smoking cessation, and the compliance tended to be worse for patients undergoing CABG vs PCI. It has been estimated that just over two thirds of patients quit smoking for at least one year after CABG (6), which much better than it was 20 years ago. Interestingly, it was recently reported that preoperative smoking has little or no effect on mortality after CABG. However, patients had a 33% increased relative risk of death from all causes and a 75% increased relative risk of cardiac death if they did not quit smoking for at least one year after CABG. The mortality benefit of smoking cessation was 3% at 5 years and 14% at 15 years and the benefit with regard to need for repeat revascularization was 41% (7).

In the recently published Arterial Revascularization Trial (ART) (8), Taggart and colleagues reported no difference in mortality (20.3% vs 21.9) or the secondary composite outcome of death, myocardial infarction or stroke (24.9% vs 27.3%) if bilateral vs single mammary artery conduits were used for CABG, respectively. While this trial retrospectively has been criticized as being fatally flawed due to poor design, excessive crossover, use of the radial artery in the single IMA arm and differences in technical skills between investigators, one factor at play may be the good compliance with medical therapy after CABG that was present in the trial. Perhaps bilateral mammary artery grafts are relatively better in non-compliant patients, but if the patient adheres to strict guideline directed medical therapy, sheds a few pounds and takes up a hobby other than smoking cigarettes, the difference in outcome between a CABG using a single mammary artery or 2 mammary arteries may be small. The same can be said for the use of a radial artery or other multiple arterial approaches. The ROMA trial (9) supposedly has fixed all of the problems with the ART trial. The title of this reference is “The ROMA trial: why it is needed.” The ROMA trial is needed because of the discordance in the results of retrospective trials and the one randomized trial (ART). I was an early adopter of the use of bilateral mammary arteries in the early 1990’s, and was asked by my then senior, more experienced colleagues “why I am doing that?” I responded that “If one IMA is good, 2 must be better.” I suspect the ROMA trial will demonstrate an improved survival in patients undergoing CABG with multiple arterial grafts, but that is what I presented about the 5 year results of the ART trial at the American Heart Association Scientific Sessions during my discussion of Dr Taggart’s presentation. We need to keep an open mind on clinical research. Galen’s theories of medicine and physiology were held to be the irrefutable truth from the second century of the common era to the late 1800’s. George Washington’s death was most likely hastened by the excessive bloodletting and other questionable practices he endured prior to his death of a throat infection (10). We also need to be mindful of factors that affect the benefit of CABG, other than the use of multiple arterial grafts and an off pump approach. Secondary preventative measures, including anti-platelet therapy have a major role in optimizing long-term outcomes. I would go out on a limb and say these factors are just as important or more important than the use of multiple arterial grafts.