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Optimal Medical Therapy and 10-Year Mortality After Revascularization
Quick Takes
- A post hoc subgroup analysis of the SYNTAXES trials showed that patients with three-vessel/left main disease undergoing PCI or CABG receiving optimal medical therapy at 5-year follow-up had a survival benefit at 10 years.
- Only 46% of those enrolled were on optimal medical therapy at 5 years.
- Patients with three-vessel or left main disease undergoing PCI or CABG on antiplatelet agents and statins at 5 years had a lower 10-year all-cause mortality compared to those not on them.
Study Questions:
What is the clinical benefit of optimal medical therapy (OMT) on 10-year mortality in patients with three-vessel and/or left main (3VD/LM) coronary artery disease (CAD)?
Methods:
This was a post hoc subanalysis of the SYNTAXES trial; a 10-year follow-up, multicenter trial that randomized patients with 3VD/LM disease to either percutaneous coronary intervention (PCI) (n = 903) or coronary artery bypass grafting (CABG) (n = 897). Detailed drug history was collected at regular intervals for 5 years. OMT was defined as a combination of an antiplatelet, statin, angiotensin-converting enzyme (ACE) inhibitor, and beta-blocker. Medication use was encouraged but not mandated and was at the discretion of the managing clinician. The primary outcome was all-cause mortality at 10 years.
Results:
Of 1,800 randomized patients, medication history at 5 years was available in 1,472. Of these, 678 patients (46.1%) took OMT. Patients on OMT were more likely to have had a myocardial infarction with a higher prevalence of 3VD and total occlusion. The total number of lesions were more in the OMT group with a higher SYNTAX score. Residual SYNTAX score was higher in the OMT group.
After adjusting for confounding factors, patients on OMT at 5 years had a lower mortality at 10 years than those on ≤2 classes of medications that constitute OMT (13.1% vs. 19.9%; adjusted hazard ratio [aHR], 0.47 with 95% confidence interval [CI], 0.29-0.76). In multivariate analyses, the hazard for mortality was lower in patients on antiplatelet agents (13.2% vs. 22.6%; aHR, 0.48; 95% CI, 0.29-0.82) and statins (13.1% vs. 20.3%; aHR, 0.56; 95% CI, 0.35-0.91). When stratified by type of revascularization, patients in the CABG arm prescribed antiplatelet drugs and statins had a lower mortality compared to those not.
Conclusions:
In a post hoc subanalysis of the SYNTAXES trial, patients with 3VD/LM disease undergoing CABG or PCI receiving OMT at 5-year follow-up had a mortality benefit at very late follow-up at 10 years compared to those not receiving OMT. Patients receiving ≥3 components of OMT (antiplatelet, statins, ACE inhibitors, beta-blockers) at 5 years had a survival benefit. Individual components of OMT at 5 years that conferred a mortality benefit on additional analysis included antiplatelet agents and statins. This benefit with antiplatelets and statins was emphasized in patients receiving a CABG.
Perspective:
OMT in patients with obstructive coronary artery disease has been extensively established. However, most trials have focused on short- or medium-term outcomes. Important takeaways from this study include that despite being enrolled in a randomized trial, only 46% of patients with LM/3VD were on evidence-based OMT at 5 years after a PCI/CABG. In a real-world cohort, this number is likely to be smaller despite this being a substantially high-risk population. Second, receiving ≥3 components of OMT were associated with a 7% absolute difference in all-cause mortality at 10 years. The hazard of mortality was lowered by nearly 50% in patients receiving antiplatelet agents and statins.
Since this trial was conducted over a decade ago, additional agents have proven mortality benefits in addition to antiplatelets, statins, ACE inhibitors, and beta-blockers in patients with CAD—such as SGLT-2 inhibitors and PCSK9 inhibitors—further highlighting the importance of OMT. It is important to focus not only on prescribing appropriate medications in patients with obstructive CAD, but also to focus on measures to ensure that patients are adherent in the long-term to these medications despite the polypharmacy, and to improve their affordability.
Clinical Topics: Cardiac Surgery, Cardiovascular Care Team, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Prevention, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Cardiac Surgery and Arrhythmias, Nonstatins, Novel Agents, Statins, Interventions and Coronary Artery Disease
Keywords: Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, Cardiac Surgical Procedures, Coronary Artery Bypass, Coronary Artery Disease, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization, Percutaneous Coronary Intervention, Pharmaceutical Preparations, Platelet Aggregation Inhibitors, Polypharmacy, Secondary Prevention
