Potential Mediators for Treatment Effects of Novel Diabetes Medications on Cardiovascular and Renal Outcomes: A Meta-Regression Analysis.

BACKGROUND: Prior research suggests clinical effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are mediated by changes in glycated hemoglobin, body weight, systolic blood pressure, hematocrit, and urine albumin-creatinine ratio. We aimed to confirm these findings using a meta-analytic approach. METHODS AND RESULTS: We updated a systematic review of 9 GLP-1RA and 13 SGLT2i trials and summarized longitudinal mediator data. We obtained hazard ratios (HRs) for cardiovascular, renal, and mortality outcomes. We performed linear mixed-effects modeling of LogHRs versus changes in potential mediators and investigated differences in meta-regression associations among drug classes using interaction terms. HRs generally became more protective with greater glycated hemoglobin reduction among GLP-1RA trials, with average HR improvements of 20% to 30%, reaching statistical significance for major adverse cardiovascular events (ΔHR, 23%; P=0.02). Among SGLT2i trials, associations with HRs were not significant and differed from GLP1-RA trials for major adverse cardiovascular events (Pinteraction=0.04). HRs for major adverse cardiovascular events, myocardial infarction, and stroke became less efficacious (ΔHR, -15% to -34%), with more weight loss for SGLT2i but not for GLP-1RA trials (ΔHR, 4%-7%; Pinteraction<0.05). Among 5 SGLT2i trials with available data, HRs for stroke became less efficacious with larger increases in hematocrit (ΔHR, 123%; P=0.09). No changes in HRs by systolic blood pressure (ΔHR, -11% to 9%) and urine albumin-creatinine ratio (ΔHR, -1% to 4%) were found for any outcome. CONCLUSIONS: We confirmed increased efficacy findings for major adverse cardiovascular events with reduction in glycated hemoglobin for GLP1-RAs. Further research is needed on the potential loss of cardiovascular benefits with increased weight loss and hematocrit for SGLT2i.

Evaluation of premature ventricular complexes during in-hospital ECG monitoring as a predictor of ventricular tachycardia in an intensive care unit cohort.

In-hospital electrocardiographic (ECG) monitors are typically configured to alarm for premature ventricular complexes (PVCs) due to the potential association of PVCs with ventricular tachycardia (VT). However, no contemporary hospital-based studies have examined the association of PVCs with VT. Hence, the benefit of PVC monitoring in hospitalized patients is largely unknown. This secondary analysis used a large PVC alarm data set to determine whether PVCs identified during continuous ECG monitoring were associated with VT, in-hospital cardiac arrest (IHCA), and/or death in a cohort of adult intensive care unit patients. Six PVC types were examined (i.e., isolated, bigeminy, trigeminy, couplets, R-on-T, and run PVCs) and were compared between patients with and without VT, IHCA, and/or death. Of 445 patients, 48 (10.8%) had VT; 11 (2.5%) had IHCA; and 49 (11%) died. Isolated and run PVC counts were higher in the VT group (p = 0.03 both), but group differences were not seen for the other four PVC types. The regression models showed no significant associations between any of the six PVC types and VT or death, although confidence intervals were wide. Due to the small number of cases, we were unable to test for associations between PVCs and IHCA. Our findings suggest that we should question the clinical relevance of activating PVC alarms as a forewarning of VT, and more work should be done with larger sample sizes. A more precise characterization of clinically relevant PVCs that might be associated with VT is warranted.

Cardiovascular and Renal Benefits of Novel Diabetes Drugs by Baseline Cardiovascular Risk: A Systematic Review, Meta-analysis, and Meta-regression.

BACKGROUND: Eligibility for glucagon-like peptide 1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) has been expanded to patients with diabetes at lower cardiovascular risk, but whether treatment benefits differ by risk levels is not clear. PURPOSE: To investigate whether patients with varying risks differ in cardiovascular and renal benefits from GLP-1RA and SGLT2i with use of meta-analysis and meta-regression. DATA SOURCES: We performed a systematic review using PubMed through 7 November 2022. STUDY SELECTION: We included reports of GLP-1RA and SGLT2i confirmatory randomized trials in adult patients with safety or efficacy end point data. DATA EXTRACTION: Hazard ratio (HR) and event rate data were extracted for mortality, cardiovascular, and renal outcomes. DATA SYNTHESIS: We analyzed 9 GLP-1RA and 13 SGLT2i trials comprising 154,649 patients. Summary HRs were significant for cardiovascular mortality (GLP-1RA 0.87 and SGLT2i 0.86), major adverse cardiovascular events (0.87 and 0.88), heart failure (0.89 and 0.70), and renal (0.84 and 0.65) outcomes. For stroke, efficacy was significant for GLP-1RA (0.84) but not for SGLT2i (0.92). Associations between control arm cardiovascular mortality rates and HRs were nonsignificant. Five-year absolute risk reductions (0.80-4.25%) increased to 11.6% for heart failure in SGLT2i trials in patients with high risk (Pslope < 0.001). For GLP1-RAs, associations were nonsignificant. LIMITATIONS: Analyses were limited by lack of patient-level data, consistency in end point definitions, and variation in cardiovascular mortality rates for GLP-1RA trials. CONCLUSIONS: Relative effects of novel diabetes drugs are preserved across baseline cardiovascular risk, whereas absolute benefits increase at higher risks, particularly regarding heart failure. Our findings suggest a need for baseline risk assessment tools to identify variation in absolute treatment benefits and improve decision-making.

Premature ventricular complexes during continuous electrocardiographic monitoring in the intensive care unit: Occurrence rates and associated patient characteristics.

AIMS AND OBJECTIVES: This study examined the occurrence rate of specific types of premature ventricular complex (PVC) alarms and whether patient demographic and/or clinical characteristics were associated with PVC occurrences. BACKGROUND: Because PVCs can signal myocardial irritability, in-hospital electrocardiographic (ECG) monitors are typically configured to alert nurses when they occur. However, PVC alarms are common and can contribute to alarm fatigue. A better understanding of occurrences of PVCs could help guide alarm management strategies. DESIGN: A secondary quantitative analysis from an alarm study. METHODS: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was followed. Seven PVC alarm types (vendor-specific) were described, and included isolated, couplet, bigeminy, trigeminy, run PVC (i.e. VT >2), R-on-T and PVCs/min. Negative binomial and hurdle regression analyses were computed to examine the association of patient demographic and clinical characteristics with each PVC type. RESULTS: A total of 797,072 PVC alarms (45,271 monitoring hours) occurred in 446 patients, including six who had disproportionately high PVC alarm counts (40% of the total alarms). Isolated PVCs were the most frequent type (81.13%) while R-on-T were the least common (0.29%). Significant predictors associated with higher alarms rates: older age (isolated PVCs, bigeminy and couplets); male sex and presence of PVCs on the 12-lead ECG (isolated PVCs). Hyperkalaemia at ICU admission was associated with a lower R-on-T type PVCs. CONCLUSIONS: Only a few distinct demographic and clinical characteristics were associated with the occurrence rate of PVC alarms. Further research is warranted to examine whether PVCs were associated with adverse outcomes, which could guide alarm management strategies to reduce unnecessary PVC alarms. RELEVANCE TO CLINICAL PRACTICE: Targeted alarm strategies, such as turning off certain PVC-type alarms and evaluating alarm trends in the first 24 h of admission in select patients, might add to the current practice of alarm management.

Lifetime Cardiovascular Disease Risk by Coronary Artery Calcium Score in Individuals With and Without Diabetes: An Analysis From the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: To assess lifetime cardiovascular disease (CVD) risk by coronary artery calcium (CAC) score in individuals with diabetes from the Multi-Ethnic Study of Atherosclerosis (MESA) and compare risk with that in individuals without diabetes. RESEARCH DESIGN AND METHODS: We developed a microsimulation model with well, diabetes, post-CVD, and death health states using multivariable time-dependent Cox regression with age as time scale. We initially used 10-year follow-up data of 6,769 MESA participants, including coronary heart disease (CHD) (n = 272), heart failure (n = 201), stroke (n = 186), and competing death (n = 619) and assessed predictive validity at 15 years. We externally validated the model in matched National Health and Nutrition Examination Survey (NHANES) participants. Subsequently, we predicted CVD risk until age 100 years by diabetes, 10-year pooled cohort equations risk, and CAC score category (0, 1-100, or 100+). RESULTS: The model showed good calibration and discriminative performance at 15 years, with discrimination indices 0.71-0.78 across outcomes. In the NHANES cohort, predicted 15-year mortality risk corresponded well with Kaplan-Meier risk, especially for those with diabetes: 29.6% (95% CI 24.9-34.8) vs. 32.4% (95% CI 27.2-37.2), respectively. Diabetes increased lifetime CVD risk, similar to shifting one CAC category upward (from 0 to 1-100 or from 1-100 to 100+). Patients with diabetes and CAC score of 0 had a lifetime CVD risk that overlapped with that of individuals without diabetes who were at low 10-year pooled cohort equations risk (<7.5%). CONCLUSIONS: Patients with diabetes carry a spectrum of CVD risk. CAC scoring may improve decisions for preventive interventions for patients with diabetes by better delineating lifetime CVD risk.

Diagnostic and prognostic significance of premature ventricular complexes in community and hospital-based participants: A scoping review.

BACKGROUND: While there are published studies that have examined premature ventricular complexes (PVCs) among patients with and without cardiac disease, there has not been a comprehensive review of the literature examining the diagnostic and prognostic significance of PVCs. This could help guide both community and hospital-based research and clinical practice. METHODS: Scoping review frameworks by Arksey and O'Malley and the Joanna Briggs Institute (JBI) were used. A systematic search of the literature using four databases (CINAHL, Embase, PubMed, and Web of Science) was conducted. The review was prepared adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Review (PRISMA-ScR). RESULTS: A total of 71 relevant articles were identified, 66 (93%) were observational, and five (7%) were secondary analyses from randomized clinical trials. Three studies (4%) examined the diagnostic importance of PVC origin (left/right ventricle) and QRS morphology in the diagnosis of acute myocardial ischemia (MI). The majority of the studies examined prognostic outcomes including left ventricular dysfunction, heart failure, arrhythmias, ischemic heart diseases, and mortality by PVCs frequency, burden, and QRS morphology. CONCLUSIONS: Very few studies have evaluated the diagnostic significance of PVCs and all are decades old. No hospital setting only studies were identified. Community-based longitudinal studies, which make up most of the literature, show that PVCs are associated with structural and coronary heart disease, lethal arrhythmias, atrial fibrillation, stroke, all-cause and cardiac mortality. However, a causal association between PVCs and these outcomes cannot be established due to the purely observational study designs employed.

Long-term Predictions of Incident Coronary Artery Calcium to 85 Years of Age for Asymptomatic Individuals With and Without Type 2 Diabetes.

OBJECTIVE: To examine the utility of repeated computed tomography (CT) coronary artery calcium (CAC) testing, we assessed risks of detectable CAC and its cardiovascular consequences in individuals with and without type 2 diabetes ages 45-85 years. RESEARCH DESIGN AND METHODS: We included 5,836 individuals (618 with type 2 diabetes, 2,972 without baseline CAC) from the Multi-Ethnic Study of Atherosclerosis. With logistic and Cox regression we evaluated the impact of type 2 diabetes, diabetes treatment duration, and other predictors on prevalent and incident CAC. We used time-dependent Cox modeling of follow-up data (median 15.9 years) for two repeat CT exams and cardiovascular events to assess the association of CAC at follow-up CT with cardiovascular events. RESULTS: For 45 year olds with type 2 diabetes, the likelihood of CAC at baseline was 23% vs. 17% for those without. Median age at incident CAC was 52.2 vs. 62.3 years for those with and without diabetes, respectively. Each 5 years of diabetes treatment increased the odds and hazard rate of CAC by 19% (95% CI 8-33) and 22% (95% CI 6-41). Male sex, White ethnicity/race, hypertension, hypercholesterolemia, obesity, and low serum creatinine also increased CAC. CAC at follow-up CT independently increased coronary heart disease rates. CONCLUSIONS: We estimated cumulative CAC incidence to age 85 years. Patients with type 2 diabetes develop CAC at a younger age than those without diabetes. Because incident CAC is associated with increased coronary heart disease risk, the value of periodic CAC-based risk assessment in type 2 diabetes should be evaluated.

Estimating Long-Term Health Utility Scores and Expenditures for Cardiovascular Disease From the Medical Expenditure Panel Survey.

BACKGROUND: Long-term health utility scores and costs used in cost-effectiveness analyses of cardiovascular disease prevention and management can be inconsistent, outdated, or invalid for the diverse population of the United States. Our aim was to develop a user friendly, standardized, publicly available code and catalog to derive more valid long-term values for health utility and expenditures following cardiovascular disease events. METHODS: Individual-level Short Form-12 version 2 health-related quality of life and expenditure data were obtained from the pooled 2011 to 2016 Medical Expenditure Panel Surveys. We developed code using the R programming language to estimate preference-weighted Short Form-6D utility scores from the Short Form-12 for quality-adjusted life year calculations and predict annual health care expenditures. Result predictors included cardiovascular disease diagnosis (myocardial infarction, ischemic stroke, heart failure, cardiac dysrhythmias, angina pectoris, and peripheral artery disease), sociodemographic factors, and comorbidity variables. RESULTS: The cardiovascular disease diagnoses with the lowest utility scores were heart failure (0.635 [95% CI, 0.615-0.655]), angina pectoris (0.649 [95% CI, 0.630-0.667]), and ischemic stroke (0.649 [95% CI, 0.635-0.663]). The highest annual expenditures were for heart failure ($20 764 [95% CI, $17 500-$24 027]), angina pectoris ($18 428 [95% CI, $16 102-$20 754]), and ischemic stroke ($16 925 [95% CI, $15 672-$20 616]). CONCLUSIONS: The developed code and catalog may improve the quality and comparability of cost-effectiveness analyses by providing standardized methods for extracting long-term health utility scores and expenditures from Medical Expenditure Panel Survey data, which are more current and representative of the US population than previous sources.

The Association Between Secondhand Smoke Exposure and Survival for Patients With Heart Failure.

BACKGROUND: The effect of secondhand tobacco smoke (SHS) exposure on patients with heart failure (HF) is uncertain. We investigated the association of mortality with SHS exposure for patients with HF. METHODS: Nonsmokers with clinical HF were enrolled from 2003 to 2008 in a single-center longitudinal cohort study. The effect of SHS exposure determined by high-sensitivity urinary cotinine on mortality was estimated by multivariable proportional hazards modeling. RESULTS: Mortality was assessed after median 4.3 years. Of 202 patients, enrollment urinary cotinine levels were below the limit of detection for 106 (52%) considered unexposed to SHS. The median detectable cotinine was 0.47 ng/mL (interquartile range: [0.28, 1.28]). Participants were 41% female, 65 ± 17 years old, and 57% white race. Elevated cotinine was associated with increased mortality after multivariate adjustment: hazard ratio (HR) per 1 ng/mL increase in urinary cotinine: 1.15, 95% confidence interval (CI): 1.08-1.23, P < .001. Higher age (HR per 5-year increase: 1.32, 95% CI: 1.22-1.43, P < .001), male sex (HR vs female: 1.52, 95% CI: 1.02-2.28, P = .040), and New York Heart Association class (HR for class III vs I: 2.91, 95% CI: 1.71-4.99, P < .001) were also associated with mortality. CONCLUSIONS: SHS exposure is associated with a dose-dependent increase in mortality for patients with HF.

Fully Automated Echocardiogram Interpretation in Clinical Practice.

BACKGROUND: Automated cardiac image interpretation has the potential to transform clinical practice in multiple ways, including enabling serial assessment of cardiac function by nonexperts in primary care and rural settings. We hypothesized that advances in computer vision could enable building a fully automated, scalable analysis pipeline for echocardiogram interpretation, including (1) view identification, (2) image segmentation, (3) quantification of structure and function, and (4) disease detection. METHODS: Using 14 035 echocardiograms spanning a 10-year period, we trained and evaluated convolutional neural network models for multiple tasks, including automated identification of 23 viewpoints and segmentation of cardiac chambers across 5 common views. The segmentation output was used to quantify chamber volumes and left ventricular mass, determine ejection fraction, and facilitate automated determination of longitudinal strain through speckle tracking. Results were evaluated through comparison to manual segmentation and measurements from 8666 echocardiograms obtained during the routine clinical workflow. Finally, we developed models to detect 3 diseases: hypertrophic cardiomyopathy, cardiac amyloid, and pulmonary arterial hypertension. RESULTS: Convolutional neural networks accurately identified views (eg, 96% for parasternal long axis), including flagging partially obscured cardiac chambers, and enabled the segmentation of individual cardiac chambers. The resulting cardiac structure measurements agreed with study report values (eg, median absolute deviations of 15% to 17% of observed values for left ventricular mass, left ventricular diastolic volume, and left atrial volume). In terms of function, we computed automated ejection fraction and longitudinal strain measurements (within 2 cohorts), which agreed with commercial software-derived values (for ejection fraction, median absolute deviation=9.7% of observed, N=6407 studies; for strain, median absolute deviation=7.5%, n=419, and 9.0%, n=110) and demonstrated applicability to serial monitoring of patients with breast cancer for trastuzumab cardiotoxicity. Overall, we found automated measurements to be comparable or superior to manual measurements across 11 internal consistency metrics (eg, the correlation of left atrial and ventricular volumes). Finally, we trained convolutional neural networks to detect hypertrophic cardiomyopathy, cardiac amyloidosis, and pulmonary arterial hypertension with C statistics of 0.93, 0.87, and 0.85, respectively. CONCLUSIONS: Our pipeline lays the groundwork for using automated interpretation to support serial patient tracking and scalable analysis of millions of echocardiograms archived within healthcare systems.

An 8-week, open-label, dose-finding study of nimodipine for the treatment of progranulin insufficiency from GRN gene mutations.

INTRODUCTION: Frontotemporal lobar degeneration-causing mutations in the progranulin (GRN) gene reduce progranulin protein (PGRN) levels, suggesting that restoring PGRN in mutation carriers may be therapeutic. Nimodipine, a Food and Drug Administration-approved blood-brain barrier-penetrant calcium channel blocker, increased PGRN levels in PGRN-deficient murine models. We sought to assess safety and tolerability of oral nimodipine in human GRN mutation carriers. METHODS: We performed an open-label, 8-week, dose-finding, phase 1 clinical trial in eight GRN mutation carriers to assess the safety and tolerability of nimodipine and assayed fluid and radiologic markers to investigate therapeutic endpoints. RESULTS: There were no serious adverse events; however, PGRN concentrations (cerebrospinal fluid and plasma) did not change significantly following treatment (percent changes of -5.2 ± 10.9% in plasma and -10.2 ± 7.8% in cerebrospinal fluid). Measurable atrophy within the left middle frontal gyrus was observed over an 8-week period. DISCUSSION: While well tolerated, nimodipine treatment did not alter PGRN concentrations or secondary outcomes.

Appropriate Reconciliation of Cardiovascular Medications After Elective Surgery and Postdischarge Acute Hospital and Ambulatory Visits.

OBJECTIVE: To describe appropriate discharge reconciliation of cardiovascular medications and assess associations with postdischarge healthcare utilization in surgical patients. DESIGN: Retrospective cohort study from January 2007 to December 2011. SETTING: An academic medical center. PATIENTS: Seven hundred and fifty-two adults undergoing elective noncardiac surgery and taking antiplatelet agents, beta-blockers, renin-angiotensin system inhibitors, or statin lipid-lowering agents before surgery. MEASUREMENTS: Primary predictor: appropriate discharge reconciliation of preoperative cardiovascular medications (continuation without documented contraindications). Primary outcomes: acute hospital visits (emergency department visits or hospitalizations) and unplanned ambulatory visits (primary care or surgical) at 30 days after surgery. RESULTS: Preoperative medications were appropriately reconciled in 436 (58.0%) patients. For individual medications, appropriate discharge reconciliation occurred for 156 of the 327 patients on antiplatelet agents (47.7%), 507 of the 624 patients on beta-blockers (81.3%), 259 of the 361 patients on renin-angiotensin system inhibitors (71.8%), and 302 of the 406 patients on statins (74.4%). In multivariable analyses, appropriate reconciliation of all preoperative medications was not associated with acute hospital (adjusted odds ratio [AOR], 0.94; 95% confidence interval [CI], 0.63-1.41) or unplanned ambulatory visits (AOR, 1.48; 95% CI, 0.94-2.35). Appropriate reconciliation of statin therapy was associated with lower odds of acute hospital visits (AOR, 0.47; 95% CI, 0.26-0.85). There were no other statistically significant associations between appropriate reconciliation of individual medications and either outcome. CONCLUSIONS: Although large gaps in appropriate discharge reconciliation of chronic cardiovascular medications were common in patients undergoing elective surgery, these gaps were not consistently associated with postdischarge acute hospital or ambulatory visits.

Cost-effectiveness of the polypill versus risk assessment for prevention of cardiovascular disease.

OBJECTIVE: There is an international trend towards recommending medication to prevent cardiovascular disease (CVD) in individuals at increasingly lower cardiovascular risk. We assessed the cost-effectiveness of a population approach with a polypill including a statin (simvastatin 20 mg) and three antihypertensive agents (amlodipine 2.5 mg, losartan 25 mg and hydrochlorothiazide 12.5 mg) and periodic risk assessment with different risk thresholds. METHODS: We developed a microsimulation model for lifetime predictions of CVD events, diabetes, and death in 259 146 asymptomatic UK Biobank participants aged 40-69 years. We assessed incremental costs and quality-adjusted life-years (QALYs) for polypill scenarios with the same combination of agents and doses but differing for starting age, and periodic risk assessment with 10-year CVD risk thresholds of 10% and 20%. RESULTS: Restrictive risk assessment, in which statins and antihypertensives were prescribed when risk exceeded 20%, was the optimal strategy gaining 123 QALYs (95% credible interval (CI) -173 to 387) per 10 000 individuals at an extra cost of £1.45 million (95% CI 0.89 to 1.94) as compared with current practice. Although less restrictive risk assessment and polypill scenarios prevented more CVD events and attained larger survival gains, these benefits were offset by the additional costs and disutility of daily medication use. Lowering the risk threshold for prescription of statins to 10% was economically unattractive, costing £40 000 per QALY gained. Starting the polypill from age 60 onwards became the most cost-effective scenario when annual drug prices were reduced below £240. All polypill scenarios would save costs at prices below £50. CONCLUSIONS: Periodic risk assessment using lower risk thresholds is unlikely to be cost-effective. The polypill would become cost-effective if drug prices were reduced.

Comparing the cost-effectiveness of four novel risk markers for screening asymptomatic individuals to prevent cardiovascular disease (CVD) in the US population.

BACKGROUND: High sensitivity CRP (hsCRP), coronary artery calcification on CT (CT calcium), carotid artery intima media thickness on ultrasound (cIMT) and ankle-brachial index (ABI) improve prediction of cardiovascular disease (CVD) risk, but the benefit of screening with these novel risk markers in the U.S. population is unclear. METHODS AND RESULTS: A microsimulation model evaluating lifelong cost-effectiveness for individuals aged 40-85 at intermediate risk of CVD, using 2003-2004 NHANES-III (N=3736), Framingham Heart Study, U.S. Vital Statistics, meta-analyses of independent predictive effects of the four novel risk markers and treatment effects was constructed. Using both an intention-to-treat (assumes adherence <100% and incorporates disutility from taking daily medications) and an as-treated (100% adherence and no disutility) analysis, quality adjusted life years (QALYs), lifetime costs (2014 US $), and incremental cost-effectiveness ratios (ICER in $/QALY gained) of screening with hsCRP, CT coronary calcium, cIMT and ABI were established compared with current practice, full adherence to current guidelines, and ubiquitous statin therapy. In the intention-to-treat analysis in men, screening with CT calcium was cost effective ($32,900/QALY) compared with current practice. In women, screening with hsCRP was cost effective ($32,467/QALY). In the as-treated analysis, statin therapy was both more effective and less costly than all other strategies for both men and women. CONCLUSIONS: When a substantial disutility from taking daily medication is assumed, screening men with CT coronary calcium is likely to be cost-effective whereas screening with hsCRP has value in women. The individual perceived disutility for taking daily medication should play a key role in the decision.

Comparative cost-effectiveness of non-invasive imaging tests in patients presenting with chronic stable chest pain with suspected coronary artery disease: a systematic review.

Coronary artery disease (CAD) remains one of the leading causes of morbidity and mortality globally. The most cost-effective imaging strategy to diagnose CAD in patients with stable chest pain is however uncertain. To review the evidence on comparative cost-effectiveness of different imaging strategies for patients presenting with stable chest pain symptoms suggestive for CAD. Systematic review. Studies performing a formal economic evaluation or decision analysis in the English language published between January 1995 and December 2015 were identified using PubMed, Medline (OvidSP), Embase, Web of Science, Cochrane economic evaluations library, and EconLit. Reviews and meta-analyses were excluded. Two independent reviewers assessed titles and abstracts. Of the 4498 titles identified, 70 met our selection criteria. One reviewer used a modified version of the CHEERS checklist to assess study quality. One reviewer extracted data on study details, which were checked by a second reviewer. There is a major heterogeneity between the available cost-effectiveness studies included in this study. The included studies compared very different testing strategies in very different ways and provided mostly short-term results. Strategies of no-testing and xECG were underrepresented. Nonetheless, the findings from this systematic review suggest that for patients with a low to intermediate prior probability of having obstructive CAD, computed tomography coronary angiography (CTCA) may be cost-effective as an initial diagnostic imaging test in comparison with CAG or other non-invasive diagnostic tests. If functional testing is required, stress echocardiography (SE) or single-photon emission computed tomography (SPECT) are suggested to be cost-effective initial strategies in patients with intermediate prior probability of CAD. Yet, other functional testing strategies such as xECG and positron-emission tomography (PET) scanning have not been studied as intensely. Immediate CAG is suggested to be a cost-effective strategy for patients at a high prior probability of having obstructive CAD whom may benefit from revascularization. The study emphasizes the inextricable link between clinical effectiveness and economic efficiency. Evidence suggests that the optimal diagnostic imaging strategy for individuals suspected of having CAD is CTCA for low and intermediate disease probability, followed by SE or SPECT as necessary, and invasive CAG for high disease probability. Further studies are needed to evaluate the cost-effectiveness of alternative non-invasive tests, including a no-testing strategy.

The optimal imaging strategy for patients with stable chest pain: a cost-effectiveness analysis.

BACKGROUND: The optimal imaging strategy for patients with stable chest pain is uncertain. OBJECTIVE: To determine the cost-effectiveness of different imaging strategies for patients with stable chest pain. DESIGN: Microsimulation state-transition model. DATA SOURCES: Published literature. TARGET POPULATION: 60-year-old patients with a low to intermediate probability of coronary artery disease (CAD). TIME HORIZON: Lifetime. PERSPECTIVE: The United States, the United Kingdom, and the Netherlands. INTERVENTION: Coronary computed tomography (CT) angiography, cardiac stress magnetic resonance imaging, stress single-photon emission CT, and stress echocardiography. OUTCOME MEASURES: Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: The strategy that maximized QALYs and was cost-effective in the United States and the Netherlands began with coronary CT angiography, continued with cardiac stress imaging if angiography found at least 50% stenosis in at least 1 coronary artery, and ended with catheter-based coronary angiography if stress imaging induced ischemia of any severity. For U.K. men, the preferred strategy was optimal medical therapy without catheter-based coronary angiography if coronary CT angiography found only moderate CAD or stress imaging induced only mild ischemia. In these strategies, stress echocardiography was consistently more effective and less expensive than other stress imaging tests. For U.K. women, the optimal strategy was stress echocardiography followed by catheter-based coronary angiography if echocardiography induced mild or moderate ischemia. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to changes in the probability of CAD and assumptions about false-positive results. LIMITATIONS: All cardiac stress imaging tests were assumed to be available. Exercise electrocardiography was included only in a sensitivity analysis. Differences in QALYs among strategies were small. CONCLUSION: Coronary CT angiography is a cost-effective triage test for 60-year-old patients who have nonacute chest pain and a low to intermediate probability of CAD. PRIMARY FUNDING SOURCE: Erasmus University Medical Center.

The new lipid guidelines: what do primary care clinicians think?

BACKGROUND: Little is known about the opinions of primary care clinicians regarding the newly released 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for the Prevention of Primary and Secondary Atherosclerotic Disease. This survey was created to assess the awareness, attitudes, and practices of primary care clinicians on adoption of the new guidelines and to explore obstacles to implementation and suggestions for improving shared decision-making. METHODS: Six hundred practicing clinicians within the San Francisco Bay Area Collaborative Research Network were invited to participate in this cross-sectional, Internet-based pilot survey of primary care clinicians. These survey data were collected in March 2014, approximately 4 months after the release of the new guidelines and 1 month after the release of the ACC/AHA risk estimator application. RESULTS: One hundred eighty-three clinicians responded to the survey. Of those respondents, 176 (96%) were aware of the guidelines. The majority (64%) reported implementing the new guidelines with at least some of their patients, while a minority (25%) reported adopting the guidelines for many of their patients. Disagreeing with the guidelines was the main hindrance to adoption. CONCLUSIONS: While many primary care clinicians are aware of the new guidelines, a substantial proportion has yet to implement them into their clinical practice, and obstacles remain for full adoption. Further understanding of clinicians' views, opinions, and needs is necessary to optimize the approach to lipid management and ensure integration into current practice.