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Importance: Patients presenting to the emergency department with chest pain are routinely risk stratified for major adverse cardiac events using the HEART (History, Electrocardiogram, Age, Risk factors, and Troponin) score pathway, which incorporates clinical features, risk factors, electrocardiography findings, and initial serum troponin testing. A new HEART pathway incorporating high-sensitivity troponin level may improve risk stratification among patients with possible acute myocardial infarction (AMI)., Objective: To compare health outcomes and resource use among emergency department patients undergoing cardiac risk stratification with a HEART pathway using conventional vs high-sensitivity serum troponin., Design, Setting, and Participants: This multicenter pre-post cohort study was conducted between January 1 and September 6, 2021, at 16 Kaiser Permanente Southern California hospitals during uptake of a high-sensitivity serum troponin assay and included 17 384 adult patients who presented to an emergency department with chest pain and were risk stratified with a HEART pathway based on conventional troponin or high-sensitivity troponin., Exposures: A HEART pathway incorporating either conventional or high-sensitivity serum troponin was used to stratify study groups for risk of major adverse cardiac events within 30 days., Main Outcomes and Measures: The primary outcome was detection of AMI in the emergency department and within 30 days., Results: Of the 17 384 patients (median age, 58 years [IQR, 45-69 years]; 9767 women [56.2%]), 12 440 (71.6%) were risk stratified with a HEART pathway based on conventional troponin, and 4944 (28.4%) were risk stratified with a HEART pathway based on high-sensitivity troponin. Detection of AMI within 30 days was higher for the high-sensitivity troponin group than the conventional troponin group (288 [5.8%] vs 545 [4.4%]; P < .001), while the 30-day all-cause mortality rate was unchanged (16 [0.3%] vs 50 [0.4%]; P = .50). In the emergency department, 228 of 4944 patients (4.6%) in the high-sensitivity troponin group received a diagnosis of AMI compared with 251 of 12 440 patients (2.0%) in the conventional troponin group (P < .001). Among those who did not receive a diagnosis of AMI in the emergency department, an additional 60 patients (1.2%) in the high-sensitivity troponin group and 294 (2.4%) in the conventional troponin group (P < .001) received a diagnosis within 30 days. Patients in the high-sensitivity troponin group had lower rates of health care use compared with the conventional troponin group, including admission (605 [12.2%] vs 1862 [15.0%]; P < .001), stress testing within 7 days (506 [10.2%] vs 1591 [12.8%]; P < .001), and coronary revascularization within 30 days (51 [1.0%] vs 244 [2.0%]; P < .001)., Conclusions and Relevance: This multicenter pre-post cohort study suggests that a new HEART pathway incorporating high-sensitivity troponin may improve detection of AMI and decrease resource use among emergency department patients with chest pain.

Importance: A 2016 review for the US Preventive Services Task Force (USPSTF) found use of statins for primary prevention of cardiovascular disease (CVD) was associated with reduced mortality and cardiovascular outcomes., Objective: To update the 2016 review on statins for primary prevention of CVD to inform the USPSTF., Data Sources: Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (to November 2021); surveillance through May 20, 2022., Study Selection: Randomized clinical trials on statins vs placebo or no statin and statin intensity in adults without prior cardiovascular events; large cohort studies on harms., Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality., Main Outcomes and Measures: All-cause and cardiovascular mortality, myocardial infarction, stroke, composite cardiovascular outcomes, and adverse events., Results: Twenty-six studies were included: 22 trials (N = 90 624) with 6 months to 6 years of follow-up compared statins vs placebo or no statin, 1 trial (n = 5144) compared statin intensities, and 3 observational studies (n = 417 523) reported harms. Statins were significantly associated with decreased risk of all-cause mortality (risk ratio [RR], 0.92 [95% CI, 0.87 to 0.98]; absolute risk difference [ARD], -0.35% [95% CI, -0.57% to -0.14%]), stroke (RR, 0.78 [95% CI, 0.68 to 0.90]; ARD, -0.39% [95% CI, -0.54% to -0.25%]), myocardial infarction (RR, 0.67 [95% CI, 0.60 to 0.75]; ARD, -0.85% [95% CI, -1.22% to -0.47%]), and composite cardiovascular outcomes (RR, 0.72 [95% CI, 0.64 to 0.81]; ARD, -1.28% [95% CI, -1.61% to -0.95%]); the association with cardiovascular mortality was not statistically significant (RR, 0.91 [95% CI, 0.81 to 1.02]; ARD, -0.13%). Relative benefits were consistent in groups defined by demographic and clinical characteristics, although data for persons older than 75 years were sparse. Statin therapy was not significantly associated with increased risk of serious adverse events (RR, 0.97 [95% CI, 0.93 to 1.01]), myalgias (RR, 0.98 [95% CI, 0.86 to 1.11]), or elevated alanine aminotransferase level (RR, 0.94 [95% CI, 0.78 to 1.13]). Statin therapy was not significantly associated with increased diabetes risk overall (RR, 1.04 [95% CI, 0.92 to 1.19]), although 1 trial found high-intensity statin therapy was significantly associated with increased risk (RR, 1.25 [95% CI, 1.05 to 1.49]). Otherwise, there were no clear differences in outcomes based on statin intensity., Conclusions and Relevance: In adults at increased CVD risk but without prior CVD events, statin therapy for primary prevention of CVD was associated with reduced risk of all-cause mortality and CVD events. Benefits of statin therapy appear to be present across diverse demographic and clinical populations, with consistent relative benefits in groups defined by demographic and clinical characteristics.

Importance: Race and ethnicity have been studied as risk factors in cardiovascular disease. How risk factors, epicardial coronary artery disease, and cardiac events differ between Black and White individuals undergoing noninvasive testing for coronary artery disease is not known., Objective: To assess differences in cardiovascular risk burden, coronary plaque, and major adverse cardiac events between Black and White individuals assigned to receive coronary computed tomography angiography (CCTA) or functional testing for stable chest pain., Design, Setting, and Participants: A nested observational cohort study within the PROMISE trial was conducted at 193 outpatient sites in North America. A total of 1071 non-Hispanic Black (hereafter Black) and 7693 non-Hispanic White (hereafter White) participants with stable chest pain undergoing noninvasive cardiovascular testing were included. This analysis was conducted from February 13, 2015, to November 2, 2021., Main Outcomes and Measures: The primary end point was the composite of death, myocardial infarction, or hospitalization for unstable angina over a median follow-up of 24.4 months., Results: Among 1071 Black individuals (12.2%) (women, 646 [60.3%]; mean [SD] age, 59 [8] years) and 7693 White individuals (87.8%) (women, 4029 [52.4%]; mean [SD] age, 61.1 [8.4] years), Black participants had a higher cardiovascular risk burden (more hypertension and diabetes), yet there was a similarly low major adverse cardiovascular events rate over a median 2-year follow-up (32 [3.0%] vs 243 [3.2%]; P = .84). Sensitivity analyses restricted to the 79.8% (6993 of 8764) individuals with a normal or mildly abnormal noninvasive testing result and the 54.3% (4559 of 8396) not receiving statin therapy yielded similar findings. In comparison of Black and White individuals in the CCTA group (n = 3323), significant coronary stenosis (hazard ratio [HR], 7.21; 95% CI, 1.94-26.76 vs HR, 4.30; 95% CI, 2.62-7.04) and high-risk plaque (HR, 3.47; 95% CI, 1.00-12.06 vs HR, 2.21; 95% CI, 1.37-3.57) were associated with major adverse cardiovascular events in both Black and White patients. However, with respect to epicardial coronary artery disease burden, Black individuals had a less-prevalent coronary artery calcium score greater than 0 (45.1% vs 63.2%; P < .001), coronary stenosis greater than or equal to 50% (32 [8.7%] vs 430 [14.6%]; P = .001), and high-risk plaque (139 [37.6%] vs 1547 [52.4%]; P < .001)., Conclusions and Relevance: The findings of this study suggest that, despite a greater cardiovascular risk burden in Black persons, rates of coronary artery calcium, stenosis, and high-risk plaque observed via CCTA were lower in Black persons than White persons. This result suggests differences in cardiovascular risk burden and coronary plaque in Black and White individuals with stable chest pain.

Importance: Chest pain is among the most common reasons for emergency department (ED) presentations. However, most patients are at low risk for acute coronary syndrome (ACS), with low cardiac adverse outcomes rates. Biomarker testing with troponin levels is key in the initial assessment for ACS. Although serial troponin testing can improve the diagnosis of ACS in clinical practice, some patients deemed to be low risk are discharged after a single negative troponin test result., Objective: To report the clinical outcomes of patients discharged after a single negative troponin test result compared with patients discharged after serial troponin measurements., Design, Setting, and Participants: This is a retrospective cohort study of ED encounters from May 5, 2016, to December 1, 2017, across 15 community EDs within an integrated health care system in southern California. The study cohort includes 27 918 adult ED encounters in which patients were evaluated for suspected ACS with a HEART (history, electrocardiogram, age, risk factors, and troponin) score and an initial conventional troponin-I measurement below the level of detection (<0.02 ng/mL). Statistical analysis was performed from December 1, 2019, to December 1, 2020., Exposure: Single troponin test vs multiple troponin tests., Main Outcomes and Measures: The primary outcome was acute myocardial infarction or cardiac mortality; secondary outcomes included coronary artery bypass graft, percutaneous coronary intervention, invasive coronary angiography, and unstable angina within 30 days of discharge. A multivariable logistic regression model was performed to evaluate the association between testing strategies and clinical outcomes., Results: A total of 27 918 patient encounters (16 212 women [58.1%]; mean [SD] age, 58.7 [15.2] years) were included in the study. Of patients with an initial troponin measurement below the level of detection, 14 459 (51.8%) were discharged after a single troponin measurement, and 13 459 (48.2%) underwent serial troponin tests. After adjustment for cardiac risk factors and comorbidities, there was no statistically significant difference in the primary outcome of acute myocardial infarction or cardiac mortality within 30 days between the 2 groups (single troponin, 56 [0.4%] vs serial troponin, 52 [0.4%]; adjusted odds ratio, 1.41 [95% CI, 0.96-2.07]). Patients discharged after a single troponin test had lower rates of coronary artery bypass graft (adjusted odds ratio, 0.24 [95% CI, 0.11-0.48]) and invasive coronary angiography (adjusted odds ratio, 0.46 [95% CI, 0.38-0.56])., Conclusions and Relevance: This study suggests that patients are routinely discharged from the ED after a single negative troponin test result, and when compared with serial troponin testing, a single troponin test appears safe based on current physician decision-making, with no difference in rates of 30-day cardiac mortality and acute myocardial infarction, which are low in both groups.

Importance: Both noninvasive anatomic and functional testing strategies are now routinely used as initial workup in patients with low-risk stable chest pain (SCP)., Objective: To determine whether anatomic approaches (ie, coronary computed tomography angiography [CTA] and coronary CTA supplemented with noninvasive fractional flow reserve [FFRCT], performed in patients with 30% to 69% stenosis) are cost-effective compared with functional testing for the assessment of low-risk SCP., Design, Setting, and Participants: This cost-effectiveness analysis used an individual-based Markov microsimulation model for low-risk SCP. The model was developed using patient data from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. The model was validated by comparing model outcomes with outcomes observed in the PROMISE trial for anatomic (coronary CTA) and functional (stress testing) strategies, including diagnostic test results, referral to invasive coronary angiography (ICA), coronary revascularization, incident major adverse cardiovascular event (MACE), and costs during 60 days and 2 years. The validated model was used to determine whether anatomic approaches are cost-effective over a lifetime compared with functional testing., Exposure: Choice of index test for evaluation of low-risk SCP., Main Outcomes and Measures: Downstream ICA and coronary revascularization, MACE (death, nonfatal myocardial infarction), cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) of competing strategies., Results: The model cohort included 10 003 individual patients (median [interquartile range] age, 60.0 [54.4-65.9] years; 5270 [52.7%] women; 7693 [77.4%] White individuals), who entered the model 100 times. The Markov model accurately estimated the test assignment, results of anatomic and functional index testing, referral to ICA, revascularization, MACE, and costs at 60 days and 2 years compared with observed data in PROMISE (eg, coronary CTA: ICA, 12.2% [95% CI, 10.9%-13.5%] vs 12.3% [95% CI, 12.2%-12.4%]; revascularization, 6.2% [95% CI, 5.5%-6.9%] vs 6.4% [95% CI, 6.3%-6.5%]; functional strategy: ICA, 8.1% [95% CI, 7.4%-8.9%] vs 8.2% [95% CI, 8.1%-8.3%]; revascularization, 3.2% [95% CI, 2.7%-3.7%] vs 3.3% [95% CI, 3.2%-3.4%]; 2-year MACE rates: coronary CTA, 2.1% [95% CI, 1.7%-2.5%] vs 2.3% [95% CI, 2.2%-2.4%]; functional strategy, 2.2% [95% CI, 1.8%-2.6%] vs 2.4% [95% CI, 2.3%-2.4%]). Anatomic approaches led to higher ICA and revascularization rates at 60 days, 2 years, and 5 years compared with functional testing but were more effective in patient selection for ICA (eg, 60-day revascularization-to-ICA ratio, CTA: 53.7% [95% CI, 53.3%-54.0%]; CTA with FFRCT: 59.5% [95% CI, 59.2%-59.8%]; functional testing: 40.7% [95% CI, 40.4%-50.0%]). Over a lifetime, anatomic approaches gained an additional 6 months in perfect health compared with functional testing (CTA, 25.16 [95% CI, 25.14-25.19] QALYs; CTA with FFRCT, 25.14 [95% CI, 25.12-25.17] QALYs; functional testing, 24.68 [95% CI, 24.66-24.70] QALYs). Anatomic strategies were less costly and more effective; thus, CTA with FFRCT dominated and CTA alone was cost-effective (ICERs ranged from $1912/QALY for women and $3,559/QALY for men) compared with functional testing. In probabilistic sensitivity analyses, anatomic approaches were cost-effective in more than 65% of scenarios, assuming a willingness-to-pay threshold of $100 000/QALY., Conclusions and Relevance: The results of this study suggest that anatomic strategies may present a more favorable initial diagnostic option in the evaluation of low-risk SCP compared with functional testing.

Importance: Professional guidelines recommend noninvasive cardiac testing (NIT) within 72 hours of an emergency department (ED) evaluation for suspected acute coronary syndrome. However, there is inexact evidence that this strategy reduces the risk of future death or acute myocardial infarction (MI)., Objective: To evaluate the effectiveness of early NIT in reducing the risk of death or acute MI within 30 days., Design, Setting, and Participants: This retrospective, multicenter cohort study within the Kaiser Permanente Southern California integrated health care delivery system compared the effectiveness of early noninvasive cardiac testing vs no testing in patients with chest pain and in whom acute MI was ruled out who presented to an ED from January 2015 to December 2017. Patients were followed up for up to 30 days after emergency department discharge., Exposures: Noninvasive cardiac testing performed within 3 days of an ED evaluation for suspected acute coronary syndrome., Main Outcomes and Measures: The primary outcome was composite risk of death or acute MI, within 30 days of an ED discharge., Results: A total of 79 040 patients were evaluated in this study, of whom 57.7% were female. The mean (SD) age of the cohort was 57 (16) years, and 16 164 patients (21%) had completed early NIT. The absolute risk of death or MI within 30 days was low (<1%). Early NIT had the minor benefit of reducing the absolute composite risk of death or MI (0.4% [95% CI, -0.6% to -0.3%]), and, separately, of death (0.2% [95% CI, -0.2% to -0.1%]), MI (-0.3% [95% CI, -0.5% to -0.1%]), and major adverse cardiac event (-0.5% [95% CI, -0.7% to -0.3%]). The number needed to treat was 250 to avoid 1 death or MI, 500 to avoid 1 death, 333 to avoid 1 MI, and 200 to avoid 1 major adverse cardiovascular event within 30 days. Subgroup analysis revealed a number needed to treat of 14 to avoid 1 death or MI in the subset of patients with elevated troponin., Conclusions and Relevance: Early NIT was associated with a small decrease in the risk of death or MI in patients admitted to the ED with suspected acute coronary syndrome, but this clinical strategy may not be optimal for most patients given the large number needed to treat.

Importance: Coronary computed tomographic angiography (coronary CTA) can characterize coronary artery disease, including high-risk plaque. A noninvasive method of identifying high-risk plaque before major adverse cardiovascular events (MACE) could provide practice-changing optimizations in coronary artery disease care., Objective: To determine whether high-risk plaque detected by coronary CTA was associated with incident MACE independently of significant stenosis (SS) and cardiovascular risk factors., Design, Setting, and Participants: This prespecified nested observational cohort study was part of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. All stable, symptomatic outpatients in this trial who required noninvasive cardiovascular testing and received coronary CTA were included and followed up for a median of 25 months., Exposures: Core laboratory assessment of coronary CTA for SS and high-risk plaque (eg, positive remodeling, low computed tomographic attenuation, or napkin-ring sign)., Main Outcomes and Measures: The primary end point was an adjudicated composite of MACE (defined as death, myocardial infarction, or unstable angina)., Results: The study included 4415 patients, of whom 2296 (52%) were women, with a mean age of 60.5 years, a median atherosclerotic cardiovascular disease (ASCVD) risk score of 11, and a MACE rate of 3% (131 events). A total of 676 patients (15.3%) had high-risk plaques, and 276 (6.3%) had SS. The presence of high-risk plaque was associated with a higher MACE rate (6.4% vs 2.4%; hazard ratio, 2.73; 95% CI, 1.89-3.93). This association persisted after adjustment for ASCVD risk score and SS (adjusted hazard ratio [aHR], 1.72; 95% CI, 1.13-2.62). Adding high-risk plaque to the ASCVD risk score and SS assessment led to a significant continuous net reclassification improvement (0.34; 95% CI, 0.02-0.51). Presence of high-risk plaque increased MACE risk among patients with nonobstructive coronary artery disease relative to patients without high-risk plaque (aHR, 4.31 vs 2.64; 95% CI, 2.25-8.26 vs 1.49-4.69). There were no significant differences in MACE in patients with SS and high-risk plaque as opposed to those with SS but not high-risk plaque (aHR, 8.68 vs. 9.31; 95% CI, 4.25-17.73 vs 4.21-20.61). High-risk plaque was a stronger predictor of MACE in women (aHR, 2.41; 95% CI, 1.25-4.64) vs men (aHR, 1.40; 95% CI, 0.81-2.39) and younger patients (aHR, 2.33; 95% CI, 1.20-4.51) vs older ones (aHR, 1.36; 95% CI, 0.77-2.39)., Conclusions and Relevance: High-risk plaque found by coronary CTA was associated with a future MACE in a large US population of outpatients with stable chest pain. High-risk plaque may be an additional risk stratification tool, especially in patients with nonobstructive coronary artery disease, younger patients, and women. The importance of findings is limited by low absolute MACE rates and low positive predictive value of high-risk plaque., Trial Registration: clinicaltrials.gov Indentifier: NCT01174550.