Key result
The reported benefit of routine revascularization over conservative therapy for stable ischemic heart disease may be confounded by unequal dual antiplatelet therapy use and restrictive MI definitions.
Absolute Event Rate: 15.4% vs 12.7%
This letter highlights that the apparent benefit of routine revascularization on nonprocedural MI in stable ischemic heart disease may be driven by confounding from unequal dual antiplatelet therapy use rather than the procedure itself.
Bangalore et al 1 reported a lower risk of nonprocedural myocardial infarction with a routine revascularization versus an early conservative strategy in their meta-analysis of patients with stable coronary heart disease, but they do not acknowledge 2 major factors that may, in part or even entirely, explain this difference.Foremost, patients assigned to revascularization using percutaneous coronary intervention (PCI) routinely receive dual antiplatelet therapy (DAPT), whereas this is less common in patients assigned to the conservative arm.Throughout the trial period, fewer patients assigned to the conservative versus the invasive strategy in the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial received DAPT, at times approaching a 2:1 ratio among participants.Similar large differences in the administration of DAPT were noted in the FAME-2 (Fractional Flow Reserve Versus Angiography for Multi-Vessel Evaluation-2) study.Given a 22% risk reduction of nonprocedural myocardial infarction in pooled data and 53% in high-risk patients, 2 disparate allocation of DAPT unequivocally favors the invasive arm.Thus, differences should be interpreted considering this bias.Revascularization with coronary artery bypass grafting, as opposed to PCI, is associated with lower risk of spontaneous myocardial infarction in selected patients. 3Although an analysis of ISCHEMIA suggested similar risk reduction for coronary artery bypass grafting and PCI, the association is confounded by the disproportional use of DAPT in the PCI group.The results should be presented separately for coronary artery bypass grafting and PCI while acknowledging the confounding relationship of DAPT use in the PCI arm.It should be also noted that procedure-related myocardial infarctions were restrictively defined in many of the included studies, for example, ISCHEMIA and FAME-2.When an alternative definition was applied in ISCHEMIA, a lower 5-year cumulative overall myocardial infarction rate was observed with the conservative strategy versus invasive (12.7% versus 15.4% [95% CI for difference, 0.3%-5.1%])-despite the unequal allocation of DAPT favoring the invasive arm.The authors emphasize lower "unstable" angina presentations with an invasive strategy, but unstable angina is a controversial concept-even considered obsolete by leaders in the field 4 -and thus should be avoided as a study end point.Furthermore, unblinded allocation of treatment adds another well-established bias against a conservative approach in this context. 5e believe that, without acknowledging these important considerations, the authors' report remains unbalanced.We are concerned that a subjective analysis of clinical trial data may result in exposing patients to potentially unwarranted procedures.
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Ferraro et al. (2021) conducted a letter in Stable coronary heart disease. Routine revascularization (invasive strategy) vs. Early conservative strategy (initial medical therapy) was evaluated on 5-year cumulative overall myocardial infarction (using alternative definition in ISCHEMIA) (95% CI 0.3-5.1). The reported benefit of routine revascularization over conservative therapy for stable ischemic heart disease may be confounded by unequal dual antiplatelet therapy use and restrictive MI definitions.
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