Prevalence of anginal symptoms and myocardial ischemia and their effect on clinical outcomes in outpatients with stable coronary artery disease: data from the International Observational CLARIFY Registry

JAMA Intern Med. 2014 Oct;174(10):1651-9. doi: 10.1001/jamainternmed.2014.3773.


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: Identifier: ISRCTN43070564.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angina Pectoris / epidemiology*
  • Angina Pectoris / etiology
  • Angina Pectoris / mortality
  • Coronary Angiography
  • Coronary Artery Disease / complications*
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / mortality*
  • Death, Sudden, Cardiac / epidemiology*
  • Death, Sudden, Cardiac / etiology
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology*
  • Myocardial Infarction / etiology
  • Myocardial Infarction / mortality
  • Myocardial Ischemia / epidemiology*
  • Myocardial Ischemia / etiology
  • Myocardial Ischemia / mortality
  • Odds Ratio
  • Outpatients / statistics & numerical data*
  • Prevalence
  • Prospective Studies
  • Registries

Associated data

  • ISRCTN/ISRCTN43070564