Faculty Bibliography

We hypothesized that the insensitivity of the electrocardiogram in identifying acute circumflex occlusion would result in differences in the distribution of the infarct-related artery (IRA) between patients with non-ST-segment elevation myocardial infarction (NSTEMI) and STEMI enrolled in the Occluded Artery Trial. We also sought to evaluate the effect of percutaneous coronary intervention to the IRA on the clinical outcomes for patients with NSTEMI. Overall, those with NSTEMI constituted 13% (n = 283) of the trial population. The circumflex IRA was overrepresented in the NSTEMI group compared to the STEMI group (42.5 vs 11.2%; p <0.0001). The 7-year clinical outcomes for the patients with NSTEMI randomized to percutaneous coronary intervention and optimal medical therapy versus optimal medical therapy alone were similar for the primary composite of death, myocardial infarction, and class IV congestive heart failure (22.3% vs 20.2%, hazard ratio 1.20, 99% confidence interval 0.60 to 2.40; p = 0.51) and the individual end points of death (13.8% vs 17.0%, hazard ratio 0.82, 99% confidence interval 0.37 to 1.84; p = 0.53), myocardial infarction (6.1 vs 5.1%, hazard ratio 1.11, 99% confidence interval 0.28 to 4.41; p = 0.84), and class IV congestive heart failure (6.7% vs 6.0%, hazard ratio 1.50, 99% confidence interval 0.37 to 6.02; p = 0.45). No interaction was seen between the electrocardiographically determined myocardial infarction type and treatment effect (p = NS). In conclusion, the occluded circumflex IRA is overrepresented in the NSTEMI population. Consistent with the overall trial results, stable patients with NSTEMI and a totally occluded IRA did not benefit from randomization to percutaneous coronary intervention.

OPINION STATEMENT: Coronary artery disease is the leading cause of death and disability worldwide. While an invasive strategy of early revascularization reduces cardiovascular morbidity and mortality in patients with acute coronary syndromes, there is no convincing evidence that this strategy leads to an incremental survival advantage for patients with stable ischemic heart disease (SIHD) beyond that achieved by optimal medical therapy. Two landmark trials, COURAGE and BARI 2D, suggest that a strategy of aggressive medical therapy is a reasonable initial approach to such patients. However, there remain certain groups of patients, those with at least moderate ischemia on baseline stress testing, where there is still clinical equipoise. Major society guidelines favor revascularization based on observational data and trials of CABG conducted decades ago, yet data from modern randomized trials are lacking. Ongoing trials such as ISCHEMIA should provide clinicians with evidence to guide selection of the appropriate initial management strategy for patients with SIHD.

Summary. Background: The CYP2C19 genotype is a predictor of adverse cardiovascular events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) treated with clopidogrel. Objectives: We aimed to evaluate the cost-effectiveness of a CYP2C19*2 genotype-guided strategy of antiplatelet therapy in ACS patients undergoing PCI, compared with two 'no testing' strategies (empiric clopidogrel or prasugrel). Methods: We developed a Markov model to compare three strategies. The model captured adverse cardiovascular events and antiplatelet-related complications. Costs were expressed in 2010 US dollars and estimated using diagnosis-related group codes and Medicare reimbursement rates. The net wholesale price for prasugrel was estimated as $5.45 per day. A generic estimate for clopidogrel of $1.00 per day was used and genetic testing was assumed to cost $500. Results: Base case analyses demonstrated little difference between treatment strategies. The genetic testing-guided strategy yielded the most QALYs and was the least costly. Over 15 months, total costs were $18 lower with a gain of 0.004 QALY in the genotype-guided strategy compared with empiric clopidogrel, and $899 lower with a gain of 0.0005 QALY compared with empiric prasugrel. The strongest predictor of the preferred strategy was the relative risk of thrombotic events in carriers compared with wild-type individuals treated with clopidogrel. Above a 47% increased risk, a genotype-guided strategy was the dominant strategy. Above a clopidogrel cost of $3.96 per day, genetic testing was no longer dominant but remained cost-effective. Conclusions: Among ACS patients undergoing PCI, a genotype-guided strategy yields similar outcomes to empiric approaches to treatment, but is marginally less costly and more effective.