STOCKHOLM — The prognosis of nonobstructive coronary artery disease may be far less benign than generally assumed, according to two studies presented at the annual congress of the European Society of Cardiology.

Patients with less than 50% luminal stenosis upon diagnostic coronary angiography aren't considered candidates for percutaneous intervention; they are typically told they have “mild” CAD with a very good prognosis. For this reason, critical pathways for risk assessment and treatment of such patients have never been developed, according to Raffaele Bugiardini, M.D., of the University of Bologna, Italy.

The assumption that nonobstructive CAD carries a good prognosis is not based on hard data and had not been examined in a large study until recently. And now that it has, the assumption turns out to be incorrect, he said.

Dr. Bugiardini presented a secondary analysis of three published randomized clinical trials from the Thrombolysis in Myocardial Infarction (TIMI) program involving 10,915 patients with acute coronary syndromes (ACS) for whom angiographic data were available. The studies were the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT-TIMI 22), Orbofiban in Patients With Unstable Coronary Syndromes (OPUS-TIMI 16), and TIMI II-B studies.

The prevalence of nonobstructive CAD in this ACS population was 8.3%. Slightly more than half of the 910 affected patients had mild CAD as defined by a stenosis of less than 50%, whereas the remainder had angiographically normal, smooth coronary arteries.

The primary outcome measure in Dr. Bugiardini's analysis was the combined 1-year rate of death, MI, stroke, coronary revascularization, and/or unstable angina requiring rehospitalization. It occurred in 11.2% of patients with nonobstructive CAD. The incidence was 8.8% in ACS patients with angiographically normal arteries and 13.5% in those with less than 50% stenosis.

Those rates will strike most physicians as surprisingly high. Even more disturbing was the unexpectedly high rate of the most serious outcomes—death or nonfatal MI—in this supposedly low-risk population. The overall incidence was 2% at 1 year, with a 2.8% rate of death or nonfatal MI among patients with mild CAD and 1.3% in those with angiographically normal coronary arteries, Dr. Bugiardini said.

ACS patients with nonobstructive CAD with and without a primary study end point were evenly matched in terms of baseline demographic characteristics, as well as treatment.

Now that the prevailing assumption—that mild CAD carries a good prognosis—has been discredited, it becomes important for physicians to risk-stratify patients with nonobstructive CAD as to their likelihood of developing future coronary events so that their management can be tailored appropriately, he said. The validated and widely used TIMI risk score for patients with unstable angina/non-ST-segment elevation MI can play a useful role here, he added.

When he applied the TIMI risk score to the 665 eligible patients, the associated 1-year risk of death or MI climbed from 0% in those with a TIMI score of 0 to 4.1% in those with a score of 4 or more. (See box above.)

“The 0.6% death or MI rate seen with a TIMI score of 1 is the expected rate in the general population of asymptomatic subjects. But when you go to a score of 3 points, you see a completely unacceptable 2.8% rate of death or MI. That's unbelievable. So patients with a score of 3 or 4 are really at great risk,” said Dr. Bugiardini.

Separately, Sylvie Swales, M.D., presented data from the World Health Organization's Monitoring Trends and Determinants in Cardiovascular Disease project (MONICA) Belgian substudy. This prospective survey of the 130,000 residents of the Belgian province of Luxembourg identified all those who underwent coronary angiography for the first time in any Belgian hospital during 1985–1996.

The subsequent 5-year incidence of coronary death among 274 subjects with mild CAD as defined by a less than 50% stenosis was 7.8%, similar to the 8.1% rate among 377 others with angiographically significant single-vessel disease not treated with angioplasty or bypass surgery. The 5-year rate of coronary death or nonfatal MI was 10.3% in the group with mild CAD and 14.8% in those with significant single-vessel CAD as defined by a 50% or greater stenosis.

The prognosis was far better for the 763 individuals whose angiogram showed smooth vessels. Their 5-year rate of coronary death was just 0.7%, while their rate of coronary death or nonfatal MI was 1.2%, noted Dr. Swales of the Catholic University of Leuven (Belgium).

Dr. Bugiardini said that although it's possible some cases that are labeled as “nonobstructive” CAD represent misclassification of the angiogram, it has been his clinical observation that poor patient compliance with secondary prevention measures is a much bigger factor.

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'Mild' Nonobstructive CAD Is Often Anything But