Letter by Ferraro and Arbab-Zadeh Regarding Article, "Routine Revascularization Versus Initial Medical Therapy for Stable Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Randomized Trials".

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HomeCirculationVol. 143, No. 14Letter by Ferraro and Arbab-Zadeh Regarding Article, “Routine Revascularization Versus Initial Medical Therapy for Stable Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Randomized Trials” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBLetter by Ferraro and Arbab-Zadeh Regarding Article, “Routine Revascularization Versus Initial Medical Therapy for Stable Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Randomized Trials” Richard Ferraro, MD Armin Arbab-ZadehMD, PhD, MPH Richard FerraroRichard Ferraro https://orcid.org/0000-0002-0660-2753 Johns Hopkins University Medicine/Cardiology, Baltimore, MD. Search for more papers by this author , Armin Arbab-ZadehArmin Arbab-Zadeh Johns Hopkins University Medicine/Cardiology, Baltimore, MD. Search for more papers by this author Originally published5 Apr 2021https://doi.org/10.1161/CIRCULATIONAHA.120.050595Circulation. 2021;143:e805–e806To the Editor:Bangalore et al1 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.3 Although 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 field4—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.5We 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.Disclosures None.Footnoteshttps://www.ahajournals.org/journal/circ