Less Heart Attacks, More Survival: Coronary Surgery Proves It Once Again

A meta-analysis of major randomized clinical trials comparing coronary surgery (CABG) versus percutaneous intervention (PCI) that assesses the incidence of new myocardial infarctions during follow-up and their relationship with all-cause mortality.

The benefits of coronary artery bypass grafting (CABG) are indisputable in managing patients with ischemic heart disease. Numerous randomized studies have compared it to its strong competitor, percutaneous coronary intervention (PCI), resulting in piles of papers. For those who support CABG, each graft with optimal flow and pulsatility index—especially if arterial—represents a tangible benefit to the patient, enhancing both life expectancy and quality. However, it is important to remember that any treatment applied once coronary disease is established represents secondary protection, i.e., reducing the risk of future myocardial infarctions and shortening of survival relative to the absence of any therapeutic intervention. In other words, we continue to palliate. And while we may “play to win” with some patients, we may simply aim to “not lose” with others.

The continuous advancement of cardiac intervention and the struggle for shared indications with our specialty is a daily challenge, requiring constant updates and a drive for improvement. Studies like this one aim to strengthen the position of CABG. Recently, the outcomes of ISCHEMIA and REVIVED studies have impacted PCI in the revascularization of stable angina patients compared to optimal medical therapy. It has been suggested that this conclusion could also apply to revascularization with CABG. In fact, stable angina patients represent a large portion of our practice, with those stabilized after an acute coronary syndrome making up nearly the remaining volume. Stable angina indications remain pivotal for determining CABG or PCI assignment according to current clinical guidelines, paralleling stabilized acute coronary syndrome indications to cover most of the clinical spectrum of ischemic heart disease. Therefore, it is inappropriate to generalize PCI outcomes in stable angina treated with medical therapy to CABG, as it offers a treatment alternative with distinct principles and outcomes.

The meta-analysis by Gaudino et al. delves into the outcomes of principal randomized controlled trials (RCTs) published regarding secondary prevention, which is the core expected outcome of revascularization: improved survival and reduced incidence of new myocardial infarctions (MI). They reviewed 20 RCTs, including renowned trials such as BEST, EXCEL, FREEDOM, NOBLE, MASS-II, SYNTAX, PRECOMBAT, ARTS, etc., spanning from 1995 to 2015. Seven of these studies (35%: BEST, CARDia, EXCEL, FREEDOM, MASS-II, NOBLE, and SYNTAX) showed significant mortality reduction for patients undergoing CABG compared to PCI, while no significant differences were found in the remaining studies. Overall, considering all 20 trials, mortality reduction remained in favor of surgery and was independent of included studies according to the sensitivity analysis. In subgroup analysis, a significant association was observed between survival improvement provided by surgery and enhanced protection against new MIs in the surgical arm.

The authors conclude that in RCTs comparing CABG with PCI, the greater reduction in all-cause mortality in the surgical group correlates with CABG’s protective effect against new myocardial infarctions.

COMMENTARY:

Although this meta-analysis may not seem to offer new insights, it represents a crucial and benchmark work as the publication date of new myocardial revascularization indications approaches. First, it counters the results of a previous study by Bangalore et al., which included 14 RCTs (without distinguishing left main coronary artery disease from multivessel disease) and found no significant survival differences. A prior work by Head et al. already contradicted this outcome for multivessel disease. Gaudino et al.’s study confirms this benefit across any revascularization indication. Secondly, it is the first and only study to establish an association between the enhanced all-cause survival of patients undergoing CABG and the reduced incidence of new coronary events. This confirms two aspects: it provides causality to CABG’s previously assumed but unconfirmed survival benefit and validates the major flaw in the current trend of considering results in composite events instead of individually, as they are related events and cannot be evaluated together.

Focusing on causality, numerous factors may contribute to the survival benefit demonstrated by CABG in reducing new MIs and improving survival. Firstly, the technique’s intrinsic characteristics, as referenced in the editorial accompanying this study. CABG treats vessels with significant lesions in the mid-distal regions, with the anastomosis site selected away from diseased zones (typically progressing from proximal to distal, making it less vulnerable to disease progression), and utilizes one or more “substance-releasing” grafts that counteract endothelial dysfunction in the coronary bed (nitric oxide, neoangiogenic factors). Conversely, stents follow a treatment strategy at the disease site, susceptible to disease progression in the same or proximal areas, and as intravascular foreign bodies, they promote endothelial hyperplasia countered by cytotoxic agents coating the stent, which can flow downstream, impairing endothelial function in the distal bed and associated microcirculation. Secondly, the nature of stents makes them more reliant on patient adherence to dual antiplatelet therapy to reduce the risk of new MIs. CABG usually requires only single antiplatelet therapy, although dual therapy is recommended after an acute coronary syndrome, this recommendation is inconsistently followed in practice and in RCTs. Additionally, Head et al.’s meta-analysis showed that CABG benefits for three-vessel disease were independent of stent type (drug-eluting or metal). Lastly, CABG’s invasiveness has a transformative impact on patient lifestyle. Patients tend to adhere more strictly to healthy diets, physical activity, cessation of smoking, and therapeutic adherence post-surgery compared to PCI, often perceived as less invasive, hence a lesser health concern. Although it is a virtue of CABG that it drives patient behavior change, it remains a human technique performed on humans, where behavior is a major but challenging factor to influence in secondary prevention.

Every critically reviewed work has limitations worth mentioning. This analysis employs a traditional study-level meta-analysis instead of the newer patient-level methodology that aggregates each included study’s individual patient outcomes. Secondly, it spans a broad time range (20 years). Despite the minimal impact of stent type on CABG comparison outcomes, as shown in Head et al.’s study, surgical techniques and outcomes have evolved over time. Only in the most recent trials has CABG demonstrated survival benefits, as in older studies, nearly three-quarters of patients received PCI, and only 16% undergoing CABG received it as a primary treatment. Finally, while this meta-analysis includes all revascularization indications, a separate analysis for left main coronary artery disease treatment is needed (as previously done for multivessel disease by Head et al.). Despite potentially revealing a technical tie, further critical analysis is necessary. The tendency not to publish negative or non-significant results (except for interested non-inferiority designs) does not enhance evidence quality or meta-evidence like this.

In summary, let us continue to proudly defend our coronary surgery, one of the oldest and least varied surgical techniques. Let us practice sound surgical principles and, in Favaloro’s words, “in every medical act, respect for the patient and ethical and moral concepts must be present; then, science and conscience will always be on the same side.” This standard should guide evidence, clinical guidelines, and the beleaguered Heart-Team.

REFERENCE:
Gaudino M, Di Franco A, Spadaccio C, Rahouma M, Robinson NB, Demetres M, et al. Difference in spontaneous myocardial infarction and mortality in percutaneous versus surgical revascularization trials: A systematic review and meta-analysis. J Thorac Cardiovasc Surg. 2023 Feb;165(2):662-669.e14. doi: 10.1016/j.jtcvs.2021.04.062.

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