Angina Tops Ischemia as Predictor of Stable CAD Outcomes

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Among patients with stable coronary artery disease (CAD), angina with or without evidence of myocardial ischemia is associated with worse clinical outcomes, but silent ischemia is not, according to a study published online August 11, 2014, ahead of print in JAMA Internal Medicine. Most of the cardiovascular events, however, occur in the absence of either angina or ischemia.  

 Philippe Gabriel Steg, MD, of Hôpital Bichat (Paris, France), and colleagues looked at data from the prospective CLARIFY registry, which enrolled patients from 45 countries (not including the United States) from November 2009 to June 2010 and followed them for a median of 2 years. Patients were included if they met one of the following criteria:


  • Documented MI more than 3 months before enrollment
  • Angiographic evidence of coronary stenosis > 50%
  • Chest pain with evidence of MI on a stress electrocardiogram
  • CABG or PCI more than 3 months before enrollment


The new analysis included 20,291 patients who had undergone noninvasive testing for myocardial ischemia in the year before enrollment. They were divided into 4 groups, with angina determined by physician evaluation:

  • No angina or ischemia (65.1%) 
  • Myocardial ischemia without angina (silent ischemia, 14.9%)
  • Angina alone (9.1%)
  • Angina and ischemia (10.9%)


    Angina Matters Even Without Ischemia  

    There were 469 cardiovascular deaths or nonfatal MIs during follow-up. Most (58.2%) occurred in patients with neither angina nor ischemia; another 12.4% were associated with ischemia alone, 12.2% with angina alone, and 17.3% with both. 

    Compared with patients without symptoms or ischemia, there was an elevated risk of cardiovascular death or nonfatal MI among patients with angina alone and those with both angina and ischemia—but not among those with silent ischemia—after adjustment for age, sex, geographic region, smoking status, hypertension, diabetes, and dyslipidemia (table 1).

    Table 1. 2-Year Risk of Cardiovascular Death or MI


    Adjusted HR 
     vs No Angina/Ischemia  

    95% CI

    Ischemia Alone



    Angina Alone



    Angina and Ischemia




    The relationships were similar when looking at cardiovascular death and fatal or nonfatal MI as individual outcomes, and they were consistent across several sensitivity analyses.

    When angina was examined by severity, the risk of cardiovascular death or nonfatal MI was higher among patients with Canadian Cardiovascular Society class I symptoms (HR 1.85; 95% CI 1.36-2.53), class II symptoms (HR 1.47; 95% CI 1.11-1.95), and class III or IV symptoms (HR 1.76; 95% CI 1.15-2.69) compared with those without angina.

    Disconnect Between Angina and Ischemia   

    The fact that most of the events occurred in patients free from both angina and ischemia “[emphasizes] the importance of implementing optimal medical therapy and preventive measures regardless of symptoms or ischemia,” Dr. Steg and colleagues write.   

    But, they add, “our findings should not be interpreted as detracting from the value of treating ischemia because our patients were treated, and clear evidence suggests that the presence and severity of myocardial ischemia are important correlates of prognosis in stable CAD and possibly of the benefit of revascularization.”   

    John P. Erwin III, MD, of Baylor Scott & White Health (Temple, TX) told TCTMD in an email that the study supports current practice guidelines and appropriate use criteria. 

    “Many docs are still ordering ‘routine follow-up imaging studies to assess for ischemia’ in the absence of clinical symptoms under the guise of being ‘compulsive/thorough.’ This study should edify that there is no good rationale to continue such a practice…,” he said. “Even the finding of ischemia in the absence of symptoms did not portend a higher event rate than the patient with ischemic symptoms of angina.”

    He noted that the rate of silent ischemia identified in the registry (14.9%) was much lower than reported previously (25% to 45%), which “is probably attributable to our increasing use of revascularization and better adjuvant medical therapies than were available at the time of the older studies.” 

    Additionally, Dr. Erwin said it was surprising that silent ischemia was not associated with worse clinical outcomes since the Heart and Soul Study, which looked at psychosocial factors influencing the outcomes of patients with coronary heart disease, indicated that ischemia—not angina—determines outcome.


    Steg PG, Greenlaw N, Tendera M, et al. 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;Epub ahead of print. 

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    Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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    • The study was supported by research grants from Servier.
    • Dr. Steg reports relationships with multiple pharmaceutical companies.
    • Dr. Erwin reports no relevant conflicts of interest.