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Causes of Cardiovascular and Non-Cardiovascular Death in the ISCHEMIA Trial

Sidhu, Mandeep S; Alexander, Karen P; Huang, Zhen; O'Brien, Sean M; Chaitman, Bernard R; Stone, Gregg W; Newman, Jonathan D; Boden, William E; Maggioni, Aldo P; Steg, Philippe Gabriel; Ferguson, Thomas B; Demkow, Marcin; Peteiro, Jesus; Wander, Gurpreet S; Phaneuf, Denis C; De Belder, Mark A; Doerr, Rolf; Alexanderson-Rosas, Erick; Polanczyk, Carisi A; Henriksen, Peter A; Conway, Dwayne S G; Miro, Vicente; Sharir, Tali; Lopes, Renato D; Min, James K; Berman, Daniel S; Rockhold, Frank W; Balter, Stephen; Borrego, David; Rosenberg, Yves D; Bangalore, Sripal; Reynolds, Harmony R; Hochman, Judith S; Maron, David J
BACKGROUND:The ISCHEMIA trial demonstrated no overall difference in the composite primary endpoint and the secondary endpoints of cardiovascular (CV) death/myocardial infarction or all-cause mortality between an initial invasive or conservative strategy among participants with chronic coronary disease and moderate or severe myocardial ischemia. Detailed cause-specific death analyses have not been reported. METHODS:We compared overall and cause-specific death rates by treatment group using Cox models with adjustment for pre-specified baseline covariates. Cause of death was adjudicated by an independent Clinical Events Committee as cardiovascular (CV), non-CV, and undetermined. We evaluated the association of risk factors and treatment strategy with cause of death. RESULTS:Four-year cumulative incidence rates for CV death were similar between invasive and conservative strategies [2.6% vs. 3.0%; hazard ratio (HR) 0.98; 95% CI (0.70 - 1.38)], but non-CV death rates were higher in the invasive strategy [3.3% vs. 2.1%; HR 1.45 (1.00 - 2.09)]. Overall, 13% of deaths were attributed to undetermined causes (38/289). Fewer undetermined deaths [0.6% vs. 1.3%; HR 0.48 (0.24 - 0.95)] and more malignancy deaths [2.0% vs. 0.8%; HR 2.11 (1.23 - 3.60)] occurred in the invasive strategy than in the conservative strategy. CONCLUSIONS:In ISCHEMIA, all-cause and CV death rates were similar between treatment strategies. The observation of fewer undetermined deaths and more malignancy deaths in the invasive strategy remains unexplained. These findings should be interpreted with caution in the context of prior studies and the overall trial results.
PMID: 35149037
ISSN: 1097-6744
CID: 5176162

Why Are We Still Prescribing Angiotensin-Converting Enzyme Inhibitors? [Comment]

Messerli, Franz H; Bavishi, Chirag; Bangalore, Sripal
PMID: 35130055
ISSN: 1524-4539
CID: 5156652

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Lawton, Jennifer S; Tamis-Holland, Jacqueline E; Bangalore, Sripal; Bates, Eric R; Beckie, Theresa M; Bischoff, James M; Bittl, John A; Cohen, Mauricio G; DiMaio, J Michael; Don, Creighton W; Fremes, Stephen E; Gaudino, Mario F; Goldberger, Zachary D; Grant, Michael C; Jaswal, Jang B; Kurlansky, Paul A; Mehran, Roxana; Metkus, Thomas S; Nnacheta, Lorraine C; Rao, Sunil V; Sellke, Frank W; Sharma, Garima; Yong, Celina M; Zwischenberger, Brittany A
AIM:The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use. METHODS:A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. Structure: Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline.
PMID: 34882436
ISSN: 1524-4539
CID: 5223192

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Lawton, Jennifer S; Tamis-Holland, Jacqueline E; Bangalore, Sripal; Bates, Eric R; Beckie, Theresa M; Bischoff, James M; Bittl, John A; Cohen, Mauricio G; DiMaio, J Michael; Don, Creighton W; Fremes, Stephen E; Gaudino, Mario F; Goldberger, Zachary D; Grant, Michael C; Jaswal, Jang B; Kurlansky, Paul A; Mehran, Roxana; Metkus, Thomas S; Nnacheta, Lorraine C; Rao, Sunil V; Sellke, Frank W; Sharma, Garima; Yong, Celina M; Zwischenberger, Brittany A
AIM:The guideline for coronary artery revascularization replaces the 2011 coronary artery bypass graft surgery and the 2011 and 2015 percutaneous coronary intervention guidelines, providing a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization as well as the supporting documentation to encourage their use. METHODS:A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. STRUCTURE:Coronary artery disease remains a leading cause of morbidity and mortality globally. Coronary revascularization is an important therapeutic option when managing patients with coronary artery disease. The 2021 coronary artery revascularization guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with coronary artery disease who are being considered for coronary revascularization, with the intent to improve quality of care and align with patients' interests.
PMID: 34895950
ISSN: 1558-3597
CID: 5223202

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Lawton, Jennifer S; Tamis-Holland, Jacqueline E; Bangalore, Sripal; Bates, Eric R; Beckie, Theresa M; Bischoff, James M; Bittl, John A; Cohen, Mauricio G; DiMaio, J Michael; Don, Creighton W; Fremes, Stephen E; Gaudino, Mario F; Goldberger, Zachary D; Grant, Michael C; Jaswal, Jang B; Kurlansky, Paul A; Mehran, Roxana; Metkus, Thomas S; Nnacheta, Lorraine C; Rao, Sunil V; Sellke, Frank W; Sharma, Garima; Yong, Celina M; Zwischenberger, Brittany A
PMID: 34882435
ISSN: 1524-4539
CID: 5223182

2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines

Lawton, Jennifer S; Tamis-Holland, Jacqueline E; Bangalore, Sripal; Bates, Eric R; Beckie, Theresa M; Bischoff, James M; Bittl, John A; Cohen, Mauricio G; DiMaio, J Michael; Don, Creighton W; Fremes, Stephen E; Gaudino, Mario F; Goldberger, Zachary D; Grant, Michael C; Jaswal, Jang B; Kurlansky, Paul A; Mehran, Roxana; Metkus, Thomas S; Nnacheta, Lorraine C; Rao, Sunil V; Sellke, Frank W; Sharma, Garima; Yong, Celina M; Zwischenberger, Brittany A
AIM:The executive summary of the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions coronary artery revascularization guideline provides the top 10 items readers should know about the guideline. In the full guideline, the recommendations replace the 2011 coronary artery bypass graft surgery guideline and the 2011 and 2015 percutaneous coronary intervention guidelines. This summary offers a patient-centric approach to guide clinicians in the treatment of patients with significant coronary artery disease undergoing coronary revascularization, as well as the supporting documentation to encourage their use. METHODS:A comprehensive literature search was conducted from May 2019 to September 2019, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, CINHL Complete, and other relevant databases. Additional relevant studies, published through May 2021, were also considered. STRUCTURE:Recommendations from the earlier percutaneous coronary intervention and coronary artery bypass graft surgery guidelines have been updated with new evidence to guide clinicians in caring for patients undergoing coronary revascularization. This summary includes recommendations, tables, and figures from the full guideline that relate to the top 10 take-home messages. The reader is referred to the full guideline for graphical flow charts, supportive text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in the development of this guideline.
PMID: 34895951
ISSN: 1558-3597
CID: 5223212

Effects of initial invasive vs. initial conservative treatment strategies on recurrent and total cardiovascular events in the ISCHEMIA trial

Lopez-Sendon, Jose L; Cyr, Derek D; Mark, Daniel B; Bangalore, Sripal; Huang, Zhen; White, Harvey D; Alexander, Karen P; Li, Jianghao; Nair, Rajesh Goplan; Demkow, Marcin; Peteiro, Jesus; Wander, Gurpreet S; Demchenko, Elena A; Gamma, Reto; Gadkari, Milind; Poh, Kian Keong; Nageh, Thuraia; Stone, Peter H; Keltai, Matyas; Sidhu, Mandeep; Newman, Jonathan D; Boden, William E; Reynolds, Harmony R; Chaitman, Bernard R; Hochman, Judith S; Maron, David J; O'Brien, Sean M
AIMS/OBJECTIVE:The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial prespecified an analysis to determine whether accounting for recurrent cardiovascular events in addition to first events modified understanding of the treatment effects. METHODS AND RESULTS/RESULTS:Patients with stable coronary artery disease (CAD) and moderate or severe ischaemia on stress testing were randomized to either initial invasive (INV) or initial conservative (CON) management. The primary outcome was a composite of cardiovascular death, myocardial infarction (MI), and hospitalization for unstable angina, heart failure, or cardiac arrest. The Ghosh-Lin method was used to estimate mean cumulative incidence of total events with death as a competing risk. The 5179 ISCHEMIA patients experienced 670 index events (318 INV, 352 CON) and 203 recurrent events (102 INV, 101 CON). A single primary event was observed in 9.8% of INV and 10.8% of CON patients while ≥2 primary events were observed in 2.5% and 2.8%, respectively. Patients with recurrent events were older; had more frequent hypertension, diabetes, prior MI, or cerebrovascular disease; and had more multivessel CAD. The average number of primary endpoint events per 100 patients over 4 years was 18.2 in INV [95% confidence interval (CI) 15.8-20.9] and 19.7 in CON (95% CI 17.5-22.2), difference -1.5 (95% CI -5.0 to 2.0, P = 0.398). Comparable results were obtained when all-cause death was substituted for cardiovascular death and when stroke was added as an event. CONCLUSIONS:In stable CAD patients with moderate or severe myocardial ischaemia enrolled in ISCHEMIA, an initial INV treatment strategy did not prevent either net recurrent events or net total events more effectively than an initial CON strategy. CLINICAL TRIAL REGISTRATION/BACKGROUND:ISCHEMIA ClinicalTrials.gov number, NCT01471522, https://clinicaltrials.gov/ct2/show/NCT01471522.
PMID: 34514494
ISSN: 1522-9645
CID: 5166802

The risk of stent thrombosis of dual antithrombotic therapy for patients who require oral anticoagulant undergoing percutaneous coronary intervention: insights of a meta-analysis of randomized trials

Kuno, Toshiki; Ueyama, Hiroki; Takagi, Hisato; Bangalore, Sripal
Recent meta-analyses investigating dual antithrombotic therapy (DAT) versus triple antithrombotic therapy (TAT) among patients who require oral anticoagulants especially with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) raised the concern of stent thrombosis (ST) and myocardial infarction (MI), however, these meta-analyses did not include all randomized trials who require oral anticoagulants. We aimed to investigate the efficacy of DAT versus TAT in these patients undergoing PCI. Our data showed the risk of ST was not significantly different in DAT vs. TAT (HR [95%CI]: 1.50 [0.97-2.34], p = .07; I
PMID: 35001785
ISSN: 1651-2006
CID: 5118302

Putting the 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization Into Practice: A Case Series [Case Report]

Bittl, John A; Bangalore, Sripal; DiMaio, J Michael; Grant, Michael C; Lawton, Jennifer S; Tamis Holland, Jacqueline E
This case series shows how the 2021 ACC/AHA/SCAI guideline for coronary artery revascularization can be used to decide between revascularization or optimal medical therapy to reduce mortality or cardiovascular events in selected subsets of patients with stable ischemic heart disease and complex coronary disease with or without left ventricular dysfunction. (Level of Difficulty: Advanced.).
PMCID:8743811
PMID: 35036940
ISSN: 2666-0849
CID: 5131332

Predictors of outcome in the ISCHEMIA-CKD trial: Anatomy versus ischemia

Bainey, Kevin R; Fleg, Jerome L; Hochman, Judith S; Kunichoff, Dennis F; Anthopolos, Rebecca; Chernyavskiy, Alexander M; Demkow, Marcin; Lopez-Quijano, Juan-Manuel; Escobedo, Jorge; Poh, Kian Keong; Ramos, Ruben B; Lima, Eduardo G; Schuchlenz, Herwig; Ali, Ziad A; Stone, Gregg W; Maron, David J; O'Brien, Sean M; Spertus, John A; Bangalore, Sripal
BACKGROUND:The ISCHEMIA-CKD (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches-Chronic Kidney Disease) trial found no advantage to an invasive strategy compared to conservative management in reducing all-cause death or myocardial infarction (D/MI). However, the prognostic influence of angiographic coronary artery disease (CAD) burden and ischemia severity remains unknown in this population. We compared the relative impact of CAD extent and severity of myocardial ischemia on D/MI in patients with advanced chronic kidney disease (CKD). METHODS:Participants randomized to invasive management with available data on coronary angiography and stress testing were included. Extent of CAD was defined by the number of major epicardial vessels with ≥50% diameter stenosis by quantitative coronary angiography. Ischemia severity was assessed by site investigators as moderate or severe using trial definitions. The primary endpoint was D/MI. RESULTS:Of the 388 participants, 307 (79.1%) had complete coronary angiography and stress testing data. D/MI occurred in 104/307 participants (33.9%). Extent of CAD was associated with an increased risk of D/MI (P < .001), while ischemia severity was not (P = .249). These relationships persisted following multivariable adjustment. Using 0-vessel disease (VD) as reference, the adjusted hazard ratio (HR) for 1VD was 1.86, 95% confidence interval (CI) 0.94 to 3.68, P = .073; 2VD: HR 2.13, 95% CI 1.10 to 4.12, P = .025; 3VD: HR 4.00, 95% CI 2.06 to 7.76, P < .001. Using moderate ischemia as the reference, the HR for severe ischemia was 0.84, 95% CI 0.54 to 1.30, P = .427. CONCLUSION/CONCLUSIONS:Among ISCHEMIA-CKD participants randomized to the invasive strategy, extent of CAD predicted D/MI whereas severity of ischemia did not.
PMID: 34582775
ISSN: 1097-6744
CID: 5147072