Response by Bangalore et al to Letter Regarding Article, "Routine Revascularization Versus Initial Medical Therapy for Stable Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Randomized Trials".

Abstract

HomeCirculationVol. 143, No. 14Response by Bangalore et al to Letter 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 InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse by Bangalore et al to Letter Regarding Article, “Routine Revascularization Versus Initial Medical Therapy for Stable Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Randomized Trials” Sripal Bangalore, David J. Maron, Gregg W. Stone and Judith S. Hochman Sripal BangaloreSripal Bangalore https://orcid.org/0000-0001-9485-0652 Division of Cardiology, New York University Grossman School of Medicine (S.B., J.S.H.). Search for more papers by this author , David J. MaronDavid J. Maron Department of Medicine, Stanford University School of Medicine, CA (D.J.M.). Search for more papers by this author , Gregg W. StoneGregg W. Stone https://orcid.org/0000-0002-3416-8210 Division of Cardiology, The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (G.W.S.). Cardiovascular Research Foundation, New York (G.W.S.). Search for more papers by this author and Judith S. HochmanJudith S. Hochman https://orcid.org/0000-0002-5889-5981 Division of Cardiology, New York University Grossman School of Medicine (S.B., J.S.H.). Search for more papers by this author Originally published5 Apr 2021https://doi.org/10.1161/CIRCULATIONAHA.120.052370Circulation. 2021;143:e809–e810In Response:Shah contends that the greater freedom from angina with routine revascularization when compared with initial medical therapy in our meta-analysis1 is confounded because there was no sham-controlled group in the included trials and that the greater relief of angina in the revascularization group is likely attributable to a “placebo” effect. Although it is possible that there is a placebo effect with invasive therapies in unblinded trials, it is unlikely that the placebo effect would be long lasting over a mean of 4.5 years. Moreover, the mean effect sizes (a difference of 4.4 points [95% CI, −3.3 to 12.0]) in the Seattle Angina Questionnaire angina frequency score at 6 weeks in the sham-controlled ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trial was similar to that in the unblinded ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial.2,3 In addition, percutaneous coronary intervention resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47 [95% CI, 1.30–4.72]; P=0.006) in ORBITA.4 As such, the results are concordant. Finally, we excluded older coronary artery bypass grafting versus “medical therapy” trials because patients in the control arms in those trials had very limited medical therapy administered.Zadeh et al state that the difference in nonprocedural myocardial infarction (MI) favoring the routine revascularization group over initial medical therapy is likely attributable to differences in dual antiplatelet therapy (DAPT) use between the groups. Although prolonged DAPT administration in the invasive compared with the conservative strategy may in part have contributed to the lower rate of late spontaneous MI in the ISCHEMIA trial, the difference in DAPT use was principally present within 12 months of randomization.5 There was low use of DAPT beyond 12 months, with <10% difference in DAPT use between the 2 arms. Despite this, the benefit of invasive management in reducing nonprocedural MI primarily accrued beyond 12 months of follow-up, suggesting that it was the revascularization, per se, that was responsible for reducing the late MI risk (similar to that observed in the FAME-2 [Fractional Flow Reserve Versus Angiography for Multivessel Evaluation-2] trial).5 Moreover, the relative reduction in nonprocedural MI in ISCHEMIA was similar to that in the COMPLETE trial (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) of culprit only versus complete revascularization in patients with ST-segment–elevation MI, where there was no significant difference in DAPT usage between the arms.6Disclosures None.Footnoteshttps://www.ahajournals.org/journal/circ