Philippe Gabriel Steg1, Nicola Greenlaw2, Michal Tendera3, Jean-Claude Tardif4, Roberto Ferrari5, Muayed Al-Zaibag6, Paul Dorian7, Dayi Hu8, Svetlana Shalnova9, Fernando José Sokn10, Ian Ford2, Kim M Fox11. 1. Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France2Unit 1148, Institut National de la Santé et de la Recherche Médicale, Paris, France3Département Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and Remodeling), Department of Cardiology, Hô 2. Robertson Centre for Biostatistics, University of Glasgow, Glasgow, Scotland. 3. Third Division of Cardiology, Medical University of Silesia, Katowice, Poland. 4. Department of Medicine, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada. 5. Department of Cardiology and Laboratory for Technologies of Advanced Therapies Centre, University Hospital of Ferrara and Maria Cecilia Hospital, Ferrara, Italy9Maria Cecili Hospital, Gruppo Villa Maria Care & Research, Ettore Sansavini Health Science Fou. 6. King Abdul-Aziz Cardiac Center, National Guard Health Affairs, Riyadh, Saudi Arabia. 7. Division of Cardiology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. 8. Heart Institute, Peking University People's Hospital, Beijing, China. 9. State Research Centre for Preventive Medicine, Moscow, Russia. 10. Department of Cardiology, Institute Adrogue, Buenos Aires, Argentina15Department of Cardiology, University Buenos Aires, Buenos Aires, Argentina. 11. National Heart and Lung Institute, Imperial College, Institute of Cardiovascular Medicine and Sciences, Royal Brompton Hospital, London, England.
Abstract
IMPORTANCE: In the era of widespread revascularization and effective antianginals, the prevalence and prognostic effect of anginal symptoms and myocardial ischemia among patients with stable coronary artery disease (CAD) are unknown. OBJECTIVE: To describe the current clinical patterns among patients with stable CAD and the association of anginal symptoms or myocardial ischemia with clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: The Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease (CLARIFY) registry enrolled outpatients in 45 countries with stable CAD in 2009 to 2010 with 2-year follow-up (median, 24.1 months; range, 1 day to 3 years). Enrollees included 32 105 outpatients with prior myocardial infarction, chest pain, and evidence of myocardial ischemia, evidence of CAD on angiography, or prior revascularization. Of these, 20 291 (63.2%) had undergone a noninvasive test for myocardial ischemia within 12 months of enrollment and were categorized into one of the following 4 groups: no angina or ischemia (n = 13 207 [65.1%]); evidence of myocardial ischemia without angina (silent ischemia) (n = 3028 [14.9%]); anginal symptoms alone (n = 1842 [9.1%]); and angina and ischemia (n = 2214 [10.9%]). EXPOSURES: Stable CAD. MAIN OUTCOME AND MEASURE: The composite of cardiovascular (CV)-related death or nonfatal myocardial infarction. RESULTS: Overall, 4056 patients (20.0%) had anginal symptoms and 5242 (25.8%) had evidence of myocardial ischemia on results of noninvasive testing. Of 469 CV-related deaths or myocardial infarctions, 58.2% occurred in patients without angina or ischemia, 12.4% in patients with ischemia alone, 12.2% in patients with angina alone, and 17.3% in patients with both. The hazard ratios for the primary outcome relative to patients without angina or ischemia and adjusted for age, sex, geographic region, smoking status, hypertension, diabetes mellitus, and dyslipidemia were 0.90 (95% CI, 0.68-1.20; P = .47) for ischemia alone, 1.45 (95% CI, 1.08-1.95; P = .01) for angina alone, and 1.75 (95% CI, 1.34-2.29; P < .001) for both. Similar findings were observed for CV-related death and for fatal or nonfatal myocardial infarction. CONCLUSIONS AND RELEVANCE: In outpatients with stable CAD, anginal symptoms (with or without ischemia on noninvasive testing) but not silent ischemia appear to be associated with an increased risk for adverse CV outcomes. Most CV events occurred in patients without angina or ischemia. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN43070564.
IMPORTANCE: In the era of widespread revascularization and effective antianginals, the prevalence and prognostic effect of anginal symptoms and myocardial ischemia among patients with stable coronary artery disease (CAD) are unknown. OBJECTIVE: To describe the current clinical patterns among patients with stable CAD and the association of anginal symptoms or myocardial ischemia with clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: The Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease (CLARIFY) registry enrolled outpatients in 45 countries with stable CAD in 2009 to 2010 with 2-year follow-up (median, 24.1 months; range, 1 day to 3 years). Enrollees included 32 105 outpatients with prior myocardial infarction, chest pain, and evidence of myocardial ischemia, evidence of CAD on angiography, or prior revascularization. Of these, 20 291 (63.2%) had undergone a noninvasive test for myocardial ischemia within 12 months of enrollment and were categorized into one of the following 4 groups: no angina or ischemia (n = 13 207 [65.1%]); evidence of myocardial ischemia without angina (silent ischemia) (n = 3028 [14.9%]); anginal symptoms alone (n = 1842 [9.1%]); and angina and ischemia (n = 2214 [10.9%]). EXPOSURES: Stable CAD. MAIN OUTCOME AND MEASURE: The composite of cardiovascular (CV)-related death or nonfatal myocardial infarction. RESULTS: Overall, 4056 patients (20.0%) had anginal symptoms and 5242 (25.8%) had evidence of myocardial ischemia on results of noninvasive testing. Of 469 CV-related deaths or myocardial infarctions, 58.2% occurred in patients without angina or ischemia, 12.4% in patients with ischemia alone, 12.2% in patients with angina alone, and 17.3% in patients with both. The hazard ratios for the primary outcome relative to patients without angina or ischemia and adjusted for age, sex, geographic region, smoking status, hypertension, diabetes mellitus, and dyslipidemia were 0.90 (95% CI, 0.68-1.20; P = .47) for ischemia alone, 1.45 (95% CI, 1.08-1.95; P = .01) for angina alone, and 1.75 (95% CI, 1.34-2.29; P < .001) for both. Similar findings were observed for CV-related death and for fatal or nonfatal myocardial infarction. CONCLUSIONS AND RELEVANCE: In outpatients with stable CAD, anginal symptoms (with or without ischemia on noninvasive testing) but not silent ischemia appear to be associated with an increased risk for adverse CV outcomes. Most CV events occurred in patients without angina or ischemia. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN43070564.
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