Wide Variance in Revascularization of Stable Myocardial Ischemia

Patrice Wendling

January 22, 2019

A new Canadian study shows wide variation in the use of revascularization in patients with asymptomatic stable ischemic heart disease (SIHD), highlighting the uncertainty over how to manage these patients.

Moreover, the study suggests startling benefits for revascularization over medical therapy alone — reducing the risks for myocardial infarction (MI) by 42% and all-cause death by 19% (hazard ratio [HR], 0.58; 95% CI, 0.46 - 0.73 and HR, 0.81; 95% CI, 0.69 - 0.96, respectively).

"There's no question that they are hypothesis-generating," lead author Andrew Czarnecki, MD, MSc, Sunnybrook Health Sciences Centre, Toronto, told theheart.org | Medscape Cardiology.

"It's very interesting that we were able to see such a big effect, and it makes you wonder how many patients are out there not getting revascularization purely on the basis of symptoms and perhaps in a situation where prognosis could have been changed," he said. "The answer isn't going to come from this study, but from good randomized controlled trials that will be able to account for all of the unmeasured confounders that were undoubtedly present in our analysis."

Rasha Al-Lamee, MD, Imperial College, London, and lead investigator of the sham-PCI ORBITA trial, said the observed benefits of revascularization are "far greater than what we've ever seen from any other published study."

She pointed out that patients treated with medical therapy alone were a "much, much more comorbid group," with higher rates of frailty, chronic obstructive pulmonary disease, anemia, renal disease, dialysis, diabetes, and previous coronary artery bypass grafting (CABG), stroke, and heart failure. In addition, there are likely to be other potential confounders that were not collected.

"It may well be that what they've actually shown is that medical therapy is predominantly selected for people who are sicker and therefore less likely to do as well because of other factors, not necessarily just that they weren't revascularized," she said.

The study was published online January 9 in the Journal of the American College of Cardiology Cardiovascular Interventions.

The last good randomized data in SIHD, the COURAGE trial, showed that percutaneous coronary intervention (PCI) was no better than optimal medical therapy for the prevention of MI or death in asymptomatic patients, but was criticized for potential selection bias, explained Czarnecki.

Appropriate-use criteria for revascularization in SIHD, last updated in 2017, are frequently used for clinical decision-making, but one of the key factors is whether symptoms are present, he said.

"My own feeling is that if you have high-risk disease, the presence or absence of symptoms may sway you to do it faster or slower, but the appropriateness of the intervention should be related to the prognostic importance of that intervention and the symptoms shouldn't really make a difference," Czarnecki said. "Not everyone has agreed with that kind of thinking, so I wanted to shed more light on this area."

Using a prospective clinical registry and administrative databases in Ontario, the investigators identified 9897 patients (mean age, 65.9 years; 78.4% male) who underwent a coronary angiogram for SIHD between October 2008 and October 2013. All patients had obstructive coronary artery disease and Canadian Cardiovascular Society class 0 angina at the time of angiography.

Initial treatment was medical therapy alone in 47% and revascularization in 53% (PCI, 32%; CABG, 21%). Within 1 year, 3.5% of the medical therapy group received PCI and 7.4% underwent CABG. A three-level hierarchal regression model was used to evaluate the influence of patient-, physician-, and hospital-level factors.

There was more than a twofold variation in revascularization practices between institutions that was not explained by measured patient-, physician-, or hospital-level factors (mean provincial revascularization ratio, 1.12), the authors report.

There was no difference between revascularization ratios at teaching and nonteaching centers (median, 1.09 vs 1.10).

Among patient factors, female sex was associated with a higher odds of revascularization 90 days after the index angiogram (odds ratio [OR], 1.16; 95% CI, 1.04 - 1.29), whereas older age was associated with lower odds (OR, 0.99; 95% CI, 0.98 -1.00).

Other significant negative predictors of revascularization were dialysis (OR, 0.71), previous stroke (OR, 0.66), peripheral vascular disease (OR, 0.80), and previous CABG (OR, 0.19).

High-risk ECG and functional imaging were not significantly associated with vascularization, whereas lesions in all coronary arteries were. The highest ORs were for left main (OR, 2.48), proximal left anterior descending (LAD) (OR, 2.11), and mid-LAD (OR, 1.62) disease.

Declining left ventricle (LV) function was strongly associated with medical management alone. Notably, the benefit of revascularization in terms of risk for MI and death was consistent in patients with and without LV dysfunction, the authors report.

Finally, angiography by an interventional cardiologist was significantly associated with higher odds of revascularization (OR, 1.46; 95% CI 1.33 -1.61), yet the average hospital angiogram annual volume was higher in the medical therapy group than in the revascularization group (3870 vs 3729; P < .001).

The median odds ratios (MOR) for the null model was 1.25, which was greater than most of the ORs that predict revascularization, with the exception of coronary anatomy, the authors note. "When patient-, physician-, and hospital-level factors were incorporated, the MOR did not reduce, suggesting that the between hospital variation was not accounted for by the factors in our model."

"What I found most interesting was that revascularization was less likely to be chosen for patients with poor LV function and high-risk stress testing and, perhaps as a result, didn't seem to be associated with any difference in the outcomes," said Al-Lamee. "That goes against what we would believe from previous datasets and what the guidelines tell us, which is that the efficacy of revascularization may be greatest in these patients."

In a related editorial, Stephen Ellis, MD, Cleveland Clinic, highlighted the potential for unmeasured confounders and lack of information on periprocedural MI. There is little agreement on the definition of these events among subspecialities, and rates can range from 3% to more than 15%, depending on the threshold used. This could "totally alter" the answer as to which treatment is associated with a lower risk fot death and MI, he said.

"Periprocedural infarction has become more controversial as to its prognostic significance," Czarnecki said. "But even if we assume that it does have prognostic significance, if anything, it would bias the results toward the null as opposed to showing an effect."

Ellis called on the authors to be more circumspect with their conclusions and said that the already somewhat controversial ISCHEMIA trial should provide insights into the management of silent ischemia. Results are expected this year from the trial, which is examining the role of revascularization in stable coronary disease and "will have 20% to 25% of patients with silent ischemia," he said.

The study was supported by a grant-in-aid from the Heart and Stroke Foundation of Canada ; coauthors Harindra Wijeysundera , MD , PhD, and Dennis T. Ko, MD, MSc, are supported by awards from the foundation. No other authors have relevant conflicts of interest. Al-Lamee has received speaker's honoraria from Philips Volcano. Ellis serves as a consultant for Abbott Vascular, Boston Scientific, and Medtronic.

JACC Cardiovasc Interv. Published online January 9, 2019. Abstract, Editorial

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