In a post-hoc analysis of the ISCHEMIA trial, initial revascularization with PCI or CABG was associated with increased early risk of CV events, particularly procedural MI, but a lower late risk compared with medical therapy only in patients with stable coronary artery disease (CAD).

This summary is based on the publication of Redfors B, Stone GW, Alexander JH, et al. - Outcomes According to Coronary Revascularization Modality in the ISCHEMIA Trial. J Am Coll Cardiol. 2024 Feb 6;83(5):549-558. doi: 10.1016/j.jacc.2023.11.002

Introduction and methods

Background

The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial among patients with stable coronary artery disease (CAD) showed there was no difference in the risk of ischemic events between an invasive (INV) strategy of coronary angiography and revascularization if feasible, in addition to medical therapy, and a conservative (CON) strategy of medical therapy only [1]. In the INV study arm, the type of revascularization (PCI or CABG) was not randomized and the decision was deferred to the local heart team. As these coronary revascularization modalities have different mechanisms and different periprocedural and long-term outcomes, they may compare differently to medical therapy alone [2,3].

Aim of the study

In a post-hoc analysis of the ISCHEMIA trial, the authors examined the accrual of CV events over time among CAD patients separately for revascularization with PCI or CABG.

Methods

The ISCHEMIA trial was a multicenter open-label RCT in which 5179 patients with chronic CAD and moderate or severe ischemia on noninvasive testing and acceptable or absent levels of angina were randomized (in a 1:1 ratio) to an initial INV strategy (coronary angiography and coronary revascularization if appropriate) plus medical therapy or to an initial CON strategy with medical therapy only and angiography/revascularization if medical therapy failed (in case of refractory angina or primary endpoint event). In the INV group, patients with no preceding primary endpoint events were categorized as INV-PCI (n=1500) or INV-CABG (n=512) from the time of revascularization; 576 patients did not undergo revascularization before experiencing a primary endpoint event. The CON group comprised 2591 patients.

Outcomes

The primary endpoint of the ISCHEMIA trial was a composite outcome of CV death, protocol-defined MI, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest.

Main results

• In the INV-CABG group, the primary endpoint occurred in 84 patients (16.4%) over a median follow-up time of 2.85 years (Q1-Q3: 1.77–3.97). Of these events, 48 (57.1%) took place within 30 days after CABG, of which 40 (83.3%) were procedural MIs.
• Among INV-PCI patients, 147 (9.8%) experienced a primary endpoint event over a median follow-up time of 2.94 years (Q1-Q3: 1.89–4.10). Of these events, 31 (21.1%) occurred within 30 days after PCI, including 24 (77.4%) procedural MIs.
• In the CON group, 352 (13.6%) had primary outcome events over a median follow-up time of 3.2 years (Q1-Q3: 2.2–4.2). Of these events, 22 (6.3%) occurred within 30 days of randomization.
• When a more sensitive definition of procedural MI was used, the contribution of procedural MI to the primary composite endpoint was even higher after CABG or PCI.
• When looking at the distribution of the different types of primary endpoint events, the most common event in the INV-CABG group was procedural MI (34/84; 40.5%), whereas spontaneous MI was the most common in the INV-PCI group (58/147; 39.5%) and CON group (180/352; 51.1%). In the INV-PCI group, 24 patients (16.3%) had a procedural MI and no other primary endpoint event.
• Both INV-CABG and INV-PCI were associated with a higher early (within 30 days) risk of the primary endpoint compared with CON (adjusted HR: 16.25; 95%CI: 11.44–23.07 and 2.99; 95%CI: 1.97–4.53, respectively) and a lower late risk (adjusted HR: 0.63; 95%CI: 0.44–0.89 and 0.66; 95%CI: 0.53–0.82, respectively).

Conclusion

This post-hoc analysis of the ISCHEMIA trial demonstrated that an initial strategy of revascularization with PCI or CABG was associated with a higher risk of early CV events but a lower long-term CV event risk compared with CON in patients with stable CAD. The early risk was greatest after CABG, due to a higher number of procedural MIs.

The authors conclude “[t]his observation emphasizes the importance of considering the definition and clinical relevance of the individual events that constitute a composite outcome when interpreting trial results. [...] more research is required to refine the optimal definition for procedural MI after revascularization and to determine whether the criteria should be similar or different after PCI and CABG.”

Find this article online at J Am Coll Cardiol.

References

1. Maron DJ, Hochman JS, Reynolds HR, et al. Initial invasive or conservative strategy for stable coronary disease. N Engl J Med. 2020;382:1395–1407.

2. Fortier JH, Ferrari G, Glineur D, et al. Implications of coronary artery bypass grafting and percutaneous coronary intervention on disease progression and the resulting changes to the physiology and pathology of the native coronary arteries. Eur J Cardiothorac Surg. 2018;54:809–816.

3. Doenst T, Haverich A, Serruys P, et al. PCI and CABG for treating stable coronary artery disease: JACC review topic of the week. J Am Coll Cardiol. 2019;73:964–976.