Adverse Outcomes for Nonobstructive Coronary Artery Disease

Results of a retrospective, cohort study showed a significantly greater 1-year risk of myocardial infarction (MI) and all-cause mortality in patients with nonobstructive coronary artery disease (CAD) compared with patients who had no apparent CAD [JAMA. 2014;312(17):1754-1763].

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Little is known about the adverse outcomes of patients with nonobstructive CAD, despite its high prevalence. To fill this void, researchers used data from the national Veterans Affairs (VA) Clinical Assessment, Reporting, and Tracking (CART) program to evaluate the hypothesis of an association between increasing CAD across the continuum of nonobstructive and obstructive CAD with increasing rates of MI and all-cause mortality.

The study included 37,674 patients from 79 VA cardiac catheterization laboratories who underwent elective coronary angiography for CAD indications between October 2007 and September 2012. Patients with known prior CAD events were excluded from the study.

The primary outcome of the study was 1-year hospitalization for nonfatal MI after index angiography. Secondary outcomes included 1-year all-cause mortality and combined mortality and 1-year MI.

Of the 37,674 patients, 8384 (22.3%) had nonobstructive CAD and 20,899 (55.4%) had obstructive CAD. Nonobstructive CAD was defined as coronary artery stenosis ≥20% but <50% in the left main coronary artery or stenosis ≥20% but <70% in any other epicardial coronary artery.

The study found that the risk of 1-year MI increased progressively by extent of CAD. The 1-year MI rate among patients with no apparent CAD was 0.11% (95% confidence interval [CI], 0.1-0.2), 0.24% for patients with 1-vessel nonobstructive CAD (95% CI, 0.1-0.4), 0.56% for patients with 2-vessel nonobstructive CAD (95% CI, 0.3-1), and 0.59% for patients with 3-vessel nonobstructive CAD (95% CI, 0.3-1.3).

For patients with obstructive CAD, the risk of 1-year MI was 1.18% for patients with 1-vessel obstructive CAD (95% CI, 1-1.4), 2.18% for patients with 2-vessel obstructive CAD (95% CI, 1.8-2.6), and 2.47% for patients with 3-vessel or left main obstructive CAD (95% CI, 2.1-2.9).

Relative to patients with no apparent CAD, the hazard ratio (HR) for 1-year MI for patients with 1-vessel nonobstructive CAD was 2 (95% CI, 0.85-5.1), 4.6 for 2-vessel nonobstructive CAD (95% CI, 2-10.5), and 4.5 for 3-vessel nonobstructive CAD (95% CI, 1.6-12.5).

For patients with obstructive CAD, relative to patients with no apparent CAD, the HR for 1 year MI was 9 for 1-vessel obstructive CAD (95% CI, 4.2-19), 16.5 for 2-vessel obstructive CAD (95% CI, 8.1-33.7), and 19.5 for 3-vessel obstructive CAD (95% CI, 9.9-38.2).

For secondary outcomes, the study found an association between 1-year mortality rates and increasing extent of CAD that ranged from 1.38% in patients with no apparent CAD to 4.3% in patients with 3-vessel or left main obstructive CAD.

No significant relationship was found between mortality and patients with 1- or 2-vessel nonobstructive CAD, but a significant association with mortality was seen in patients with 3-vessel or left main nonobstructive CAD (HR, 1.6; 95% CI, 1.1-2.5), as well as in patients with 1-vessel obstructive CAD (HR, 1.9; 95% CI, 1.4-2.6), 2-vessel obstructive CAD (HR, 2.8; 95% CI, 2.1-3.7), and 3-vessel or left main obstructive CAD (HR, 3.4; 95% CI, 2.6-4.4).

According to the study’s lead author, Thomas M. Maddox, MD, MSc, FACC, FAHA, associate professor, department of medicine, University of Colorado School of Medicine, Aurora, Colorado, these findings confirm that the presence of any CAD is risky and worthy of action and attention.

“Nonobstructive CAD is not insignificant or benign, but instead confers significant risk for [MI] and mortality,” he said in an interview with First Report Managed Care, adding that clinicians should consider talking to patients with nonobstructive CAD about preventive strategies that include aspirin, statins, and lifestyle modifications such as smoking cessation.

“Trials testing the effectiveness of these therapies in patients with nonobstructive CAD should also occur,” Dr. Maddox said.

Among the limitations of the study cited by the authors include the potential for misclassification of the degree of CAD severity, the potential that the association between CAD extent and MI mortality rates could have been confounded by factors other than CAD extent, and lack of ability to assess cardiac-specific mortality.—Mary Beth Nierengarten