By Michael H. Crawford, MD, Editor

SYNOPSIS: Patients with three-vessel or left main coronary artery disease randomized to coronary bypass surgery vs. percutaneous therapy on optimal medical therapy at five years with three or four of the recommended drugs recorded a lower 10-year all-cause mortality rate vs. those on ≤ 2 drugs.

SOURCE: Kawashima H, Serruys PW, Ono M, et al. Impact of optimal medical therapy on 10-year mortality after coronary revascularization. J Am Coll Cardiol 2021;78:27-38.

The SYNergy between percutaneous coronary intervention with TAXus (paclitaxel eluting stent) and cardiac surgery (SYNTAX) study demonstrated reduced mortality at five years in patients treated with optimal medical therapy following coronary artery revascularization.1 The SYNTAXES substudy extended the follow-up to 10 years. SYNTAXES was a multicenter, randomized, controlled trial of percutaneous coronary intervention (PCI) vs. coronary artery bypass surgery (CABG) in patients with left main or three-vessel disease with stable or unstable myocardial ischemia, but not myocardial infarction. It was conducted in 83 hospitals in 18 countries in North America and Europe.

Optimal medical therapy (OMT) consisted of an antiplatelet agent, a statin, an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), and a beta-blocker. The authors strongly encouraged prescribing all four drugs as part of OMT. However, the final decisions about which drugs to prescribe and how many were left to the treating physician. The primary outcome was all-cause mortality at 10 years. Patients were stratified by the number of OMT agents they were taking. Various covariates, such as age, sex, and clinical characteristics, were used to construct propensity-matched cohorts. At the five-year follow-up, there was drug information available for 1,472 patients, of whom 46% were on OMT and 54% were not.

Patients on OMT were more likely to have experienced a myocardial infarction and been diagnosed with three-vessel disease (36% vs. 28% and 64% vs. 57%, respectively; both P < 0.001). Otherwise, the two groups were well matched.

At 10 years, all-cause mortality in those on one or two of the four medications was 20% vs. 13% in those on three or four of the medications (adjusted HR, 0.47; 95% CI, 0.29-0.76; P = 0.002). An analysis of individual medications showed statistically significant differences in mortality if the patients were on antiplatelet drugs or statins, but not ACEI/ARB or beta-blockers. When the type of revascularization was considered, patients post-CABG benefitted more from OMT than those post-PCI. Again, this benefit was statistically significant only for antiplatelet drugs and statins. There was no effect of lesion characteristics and clinical presentation on the results. The authors concluded OMT at five years post-CABG or PCI for non-infarct-related three-vessel or left main coronary artery disease was associated with a significant reduction in all-cause mortality at 10 years vs. those not on OMT.

COMMENTARY

The main finding of this report is post-coronary artery revascularization patients on at least three of the four drugs considered OMT at five years have a better chance of survival at 10 years, with an absolute gain of 7%. Also, when individual drugs are considered, antiplatelet drugs and statins seem to be the most important, especially in post-CABG patients. Of course, this report is preaching to the choir. Antiplatelet drugs and statins are prescribed commonly to patients with coronary artery disease. In this study, antiplatelet usage was 87% and statin usage was 85%. Angiotensin-inhibiting agents and beta-blockers are used less and most often for specific indications, such as hypertension or post-myocardial infarction. The message here is that for at least five years after revascularization, patients should be on an antiplatelet drug, a statin, and at least one of the other two drugs. In the five-year follow-up of the SYNTAX trial, antiplatelet drugs, statins, and beta-blockers had HRs < 0.50 for survival. However, for angiotensin inhibitors, the HR was 0.70.1 Perhaps beta-blockers are the best choice for the third agent, unless there are specific reasons to use angiotensin inhibitors or contraindications to beta-blockers.

Although this was meticulously collected, randomized data, with a 10-year follow-up rate of 94%, it was a post hoc analysis of information collected for another purpose. There was no randomization of medication use, so there may be unmeasured confounders that biased drug selection. However, the biggest weakness of this study was the fact there was no assessment of drug adherence after five years. It was assumed drug use remained constant for the next five years. If a patient stuck with these drugs for five years after a procedure, would the patient remain compliant for another five years? We do not know this for sure. Another potential unmeasured confounder is a lack of information on lifestyle and other pharmacological interventions. Also, like any 10-year-old study, the current therapeutic milieu is markedly different. The stents used in the study were first generation. Now, there are more potent statins and other drugs for cholesterol-lowering. There are more potent antiplatelet drugs and new inhibitors of clotting (e.g., rivaroxaban). In addition, there are new diabetic drugs that also reduce mortality in coronary artery disease patients. Thus, these data, although encouraging, may be out of date.

REFERENCE

  1. Iqbal J, Zhang YJ, Holmes DR, et al. Optimal medical therapy improves clinical outcomes in patients undergoing revascularization with percutaneous coronary intervention or coronary artery bypass grafting: Insights from the Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) trial at the 5-year follow-up. Circulation 2015;131:1269-1277.