Purpose: Better methods are needed to assess patients presenting with symptoms suggestive of obstructive coronary artery disease (CAD). We hypothesized that the use of a gene expression score (GES) would lead to a change in the diagnostic evaluation.Methods: The Primary Care Providers Use of a Gene Expression Test in Coronary Artery Disease Diagnosis (IMPACT-PCP) trial (clinical trial identifier NCT01594411, clinicaltrials.gov) was a prospective study of stable, nonacute, nondiabetic patients presenting with chest pain and related symptoms at 4 primary care practices. All patients underwent GES testing, with clinicians documenting their planned diagnostic strategy both before and after GES. The GES was derived from a peripheral blood draw measuring expression of 23 genes and has been shown to have a 96% negative predictive value for excluding the diagnosis of obstructive CAD.Results: Of the 251 study patients, 140 were women (56%); the participants had a mean age of 56 years (standard deviation, 13.0) and a mean body mass index of 30 mg/kg 2 (standard deviation, 6.7). The mean GES was 16 (range, 1-38), and 127 patients (51%) had a low GES ([ltqeu]15). A change in the diagnostic testing pattern before and after GES testing was noted in 145 of 251 patients (58% observed vs. 10% predefined expected change; P < .001).Conclusions

Introduction: Chest pain is the chief complaint in ~10,000 visits/day in the primary care provider (PCP) office and results in approximately $5 billion/yr in testing costs. Better methods are needed to more accurately assess the CAD risk of patients (pts) in an office-based, non-invasive fashion and to optimize referrals to advanced non-invasive testing for further evaluation and care planning. Hypothesis: We hypothesized that gene expression score (GES) results would lead to a change in the PCP’s diagnostic evaluation of stable pts presenting in the ambulatory setting with symptoms suggestive of obstructive CAD. Methods: The IMPACT-PCP Trial was a multi-center, prospective study which enrolled 251 consecutive pts with no history of CAD seen by nine clinicians for evaluation of chest pain and related symptoms. All patients underwent GES testing: the clinician’s diagnostic strategy was evaluated before and after the GES result was known. The GES is a blood-based molecular diagnostic test with a 96% NPV for excluding the diagnosis of obstructive CAD (defined as at least one vessel with ≥50% coronary artery stenosis by quantitative coronary angiography or core-lab CT-angiography) in symptomatic patients. The primary outcome of interest was the decision change in the diagnostic testing pattern pre/post GES testing as measured by McNemar’s test and logistic regression modeling. Results: Characteristics of the 251 pts eligible for primary endpoint analysis included 140 (56%) women, mean age of 56.2 years (SD± 13.0), average BMI of 29.7 (SD± 6.7), and mean GES of 16 (SD± 10). Following GES, a decision change in treatment plan (e.g. MPI, CTA, and cardiac catheterization) was noted in 145 pts (58% observed vs 10% expected change, p<0.001). More patients had a decreased (n=93, 37%) versus increased (n=52, 21%) intensity of testing (p<0.001). In particular, among the 127 low GES pts (51% of study pts), 60% (76/127) had decreased testing and only 2% (3/127) had increased testing. Follow-up is ongoing, with 233 (93%) pts having completed 30-day follow-up. There has been one MACE event (stroke) reported. Conclusion: The GES was associated with a statistically significant and clinically relevant change in clinical decision making among pts evaluated for suspected symptomatic CAD. In conclusion, the addition of the GES showed clinical utility above and beyond conventional decision-making by optimizing the pt’s diagnostic evaluation, particularly around the reduction in the intensity of diagnostic testing among low GES patients.