The Clinical Utility of a Precision Medicine Blood Test Incorporating Age, Sex, and Gene Expression for Evaluating Women with Stable Symptoms Suggestive of Obstructive Coronary Artery Disease: Analysis from the PRESET Registry.

Background: Evaluating women with symptoms suggestive of coronary artery disease (CAD) remains challenging. A blood-based precision medicine test yielding an age/sex/gene expression score (ASGES) has shown clinical validity in the diagnosis of obstructive CAD. We assessed the effect of the ASGES on the management of women with suspected obstructive CAD in a community-based registry. Materials and Methods: The prospective PRESET (A Registry to Evaluate Patterns of Care Associated with the Use of Corus® CAD in Real World Clinical Care Settings) Registry (NCT01677156) enrolled 566 patients presenting with symptoms suggestive of stable obstructive CAD from 21 United States primary care practices from 2012 to 2014. Demographics, clinical characteristics, and referrals to cardiology or further functional and/or anatomical cardiac studies after ASGES testing were collected for this subgroup analysis of women from the PRESET Registry. Patients were followed for 1-year post-ASGES testing. Results: This study cohort included 288 women with a median age 57 years. The median body mass index was 29.2, with hyperlipidemia and hypertension present in 48% and 43% of patients, respectively. Median ASGES was 8.5 (range 1-40), with 218 (76%) patients having low (≤15) ASGES. Clinicians referred 9% (20/218) low ASGES versus 44% (31/70) elevated ASGES women for further cardiac evaluation (odds ratio 0.14, p < 0.0001, adjusted for patient demographics and clinical covariates). Across the score range, higher ASGES were associated with a higher likelihood of posttest cardiac referral. At 1-year follow-up, low ASGES women experienced fewer major adverse cardiac events than elevated ASGES women (1.3% vs. 4.2% respectively, p = 0.16). Conclusions: Incorporation of ASGES into the diagnostic workup demonstrated clinical utility by helping clinicians identify women less likely to benefit from further cardiac evaluation.

Economic Outcomes of a Precision Medicine Blood Test To Assess Obstructive Coronary Artery Disease: Results from the PRESET Registry.

PURPOSE: The evaluation of obstructive coronary artery disease (CAD) is inefficient and costly. Previous studies of an age/sex/gene expression score (ASGES) in this diagnostic workup have shown a 96% negative predictive value, as well as an 85% decreased likelihood of cardiac referral among low-score outpatients at 45 days. The objective was to explore the one-year cost implications of ASGES use among symptomatic outpatients. DESIGN: A prospective PRESET Registry (NCT01677156) enrolled stable, nonacute adult patients presenting with symptoms suggestive of obstructive CAD at 21 U.S. primary care practices. METHODOLOGY: Demographics, clinical factors, and ASGES (defined as low <=15 or elevated >15), as well as management plans post-ASGES, were collected. The economic endpoint analysis was based on the cost of cardiovascular-related tests, procedures, office visits, emergency room visits, and hospitalizations during one year after testing. RESULTS: The analysis included 566 patients, 51% of whom were women and the median age was 56. Forty-five percent had a low ASGES. The mean cost of cardiovascular care for patients in the year following ASGES was $1,647 for patients with a low ASGES versus $2,709 for those with an elevated score (39% reduction, P=.03 by Wilcoxon rank test). This relationship remained after multivariate analysis that adjusted for patient demographics and clinical covariates (P<.001). CONCLUSION: The ASGES helped identify patients with low current likelihood of obstructive CAD. These patients had lower costs of cardiovascular care during one year of follow-up. Early reductions in cardiac referrals at 45 days among these patients persisted at one year.

Utility of a Precision Medicine Test in Elderly Adults with Symptoms Suggestive of Coronary Artery Disease.

BACKGROUND: Diagnosing obstructive coronary artery disease (CAD) is challenging in elderly adults, and current diagnostic approaches for CAD expose these individuals to risks from contrast dye and invasive procedures. DESIGN: A Registry to Evaluate Patterns of Care Associated with the Use of Corus CAD in Real World Clinical Care Settings (PRESET; NCT01677156), pragmatic clinical trial. SETTING: Community, 21 primary care practices. PARTICIPANTS: Of 566 stable, nonacute outpatients presenting with symptoms suggestive of obstructive CAD, the 176 who were aged 65 and older (median age 70, 61% female) were the current study participants. INTERVENTION: Blood-based precision medicine test, incorporating age, sex, and gene expression score (ASGES) to improve clinical decision-making and quality of care. MEASUREMENTS: Information on demographic characteristics, clinical factors, ASGES results (range 1-40; low (≤15), high (>15)), referral patterns to cardiology and advanced cardiac testing, and major adverse cardiac events (MACEs) was collected in a subgroup analysis of elderly adults in the PRESET Registry. Follow-up was for 1 year after ASGES testing. RESULTS: Median ASGES was 25, and 40 (23%) participants had a low score. Clinicians referred 12.5% of participants with a low ASGES and 49.3% with a high ASGES to cardiology or advanced cardiac testing (odds ratio for referral = 0.12, P < .001, adjusted for participants demographics and clinical covariates). Higher scores were associated with greater likelihood of posttest cardiac referral. At 1-year follow-up, the incidence of a MACE or revascularization was 10% (13/136) in the high ASGES group and 0% (0/40) in the low ASGES group (P = .04). CONCLUSION: The ASGES test showed potential clinical utility in the evaluation of elderly outpatients with symptoms suggestive of obstructive CAD. Test use may reduce unnecessary referrals and the risk of procedure-related complications in individuals with low ASGES, who are unlikely to benefit from further testing, while also identifying individuals who may benefit from further cardiac evaluation and management.

Clinical Utility of a Precision Medicine Test Evaluating Outpatients with Suspected Obstructive Coronary Artery Disease.

BACKGROUND: Identifying patients with obstructive coronary artery disease can be challenging for primary care physicians. Advances in precision medicine may help augment clinical tools and redefine the paradigm for evaluating coronary artery disease in the outpatient setting. A blood-based age/sex/gene expression score (ASGES) incorporating key features of precision medicine has shown clinical validity with a 96% negative predictive value and 89% sensitivity in estimating a symptomatic patient's current likelihood of obstructive coronary artery disease. To better characterize the clinical utility of the ASGES and measure its impact on clinician decision-making, a community-based registry was established. METHODS: The prospective PRESET Registry (NCT01677156) enrolled stable, nonacute adult patients presenting with typical or atypical symptoms suggestive of obstructive coronary artery disease from 21 US primary care practices from August 2012 to August 2014. Demographics, clinical characteristics, and ASGES results (predefined as low [ASGES ≤15] or elevated [ASGES >15]) were collected, as were referrals to Cardiology or further functional/anatomic cardiac testing after ASGES testing. Patients were followed for 1 year post ASGES testing. RESULTS: Among the 566-patient cohort (median age 56 years), clinicians referred 26/252 (10%) of patients with low scores vs 137/314 (44%) of patients with elevated scores to Cardiology or advanced cardiac testing for further evaluation (unadjusted odds ratio 0.15, P <.0001; adjusted odds ratio after accounting for clinical covariates = 0.18, P <.0001). Data on 84 patients referred for advanced cardiac testing showed abnormal findings in 0 of 13 (0%) low ASGES and 10 of 71 (14%) elevated ASGES patients. Major adverse cardiovascular events and revascularization were noted in 3/252 (1.2%) patients with low ASGES and 14/314 (4.5%) patients with elevated ASGES score (P <.03). CONCLUSIONS: In this community-based cardiovascular registry, the ASGES demonstrated clinical utility in the evaluation of patients with suspected obstructive coronary artery disease. Low-score patients were less likely to undergo cardiac referral, were unlikely to have positive findings on further cardiac work-up, and had a low rate of adverse cardiovascular events in 1-year follow-up. Our work provides evidence supporting the value of using precision medicine in the delivery of cardiovascular care.