Cost-Effectiveness of Vericiguat in Patients With Heart Failure With Reduced Ejection Fraction: The VICTORIA Randomized Clinical Trial.

BACKGROUND: The VICTORIA trial (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) demonstrated that, in patients with high-risk heart failure, vericiguat reduced the primary composite outcome of cardiovascular death or heart failure hospitalization relative to placebo. The hazard ratio for all-cause mortality was 0.95 (95% CI, 0.84-1.07). In a prespecified analysis, treatment effects varied substantially as a function of baseline NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, with survival benefit for vericiguat in the lower NT-proBNP quartiles (hazard ratio, 0.82 [95% CI, 0.69-0.97]) and no benefit in the highest NT-proBNP quartile (hazard ratio, 1.14 [95% CI, 0.95-1.38]). An economic analysis was a major secondary objective of the VICTORIA research program. METHODS: Medical resource use data were collected for all VICTORIA patients (N=5050). Costs were estimated by applying externally derived US cost weights to resource use counts. Life expectancy was projected from patient-level empirical trial survival results with the use of age-based survival modeling methods. Quality-of-life adjustments were based on prospectively collected EQ-5D-based utilities. The primary outcome was the incremental cost-effectiveness ratio, comparing vericiguat with placebo, assessed from the US health care sector perspective over a lifetime horizon. Cost-effectiveness was estimated using the total VICTORIA cohort, both with and without interaction between treatment and baseline NT-proBNP. RESULTS: Life expectancy modeling results varied according to whether the observed heterogeneity of treatment effect by baseline NT-proBNP values was incorporated into the modeling. Including the interaction term, the vericiguat arm had an estimated quality-adjusted life expectancy of 4.56 quality-adjusted life-years (QALYs) compared with 4.13 QALYs for placebo (incremental discounted QALY, 0.43). Without the treatment heterogeneity/interaction term, vericiguat had 4.50 QALYs compared with 4.33 QALYs for placebo (incremental discounted QALY, 0.17). Incremental discounted costs (vericiguat minus placebo) were $28 546 with the treatment interaction and $20 948 without it. Corresponding incremental cost-effectiveness ratios were $66 509 per QALY allowing for treatment heterogeneity and $124 512 without heterogeneity. CONCLUSIONS: Vericiguat use in the VICTORIA trial met criteria for intermediate value, but the incremental cost-effectiveness ratio estimates were sensitive to whether the analysis accounted for observed NT-proBNP treatment effect heterogeneity. The cost-effectiveness of vericiguat was driven by the projected incremental life expectancy among patients in the lowest 3 quartiles of NT-proBNP. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02861534.

Cost-Effectiveness of Coronary Artery Bypass Surgery Versus Medicine in Ischemic Cardiomyopathy: The STICH Randomized Clinical Trial.

BACKGROUND: The STICH Randomized Clinical Trial (Surgical Treatment for Ischemic Heart Failure) demonstrated that coronary artery bypass grafting (CABG) reduced all-cause mortality rates out to 10 years compared with medical therapy alone (MED) in patients with ischemic cardiomyopathy and reduced left ventricular function (ejection fraction ≤35%). We examined the economic implications of these results. METHODS: We used a decision-analytic patient-level simulation model to estimate the lifetime costs and benefits of CABG and MED using patient-level resource use and clinical data collected in the STICH trial. Patient-level costs were calculated by applying externally derived US cost weights to resource use counts during trial follow-up. A 3% discount rate was applied to both future costs and benefits. The primary outcome was the incremental cost-effectiveness ratio assessed from the US health care sector perspective. RESULTS: For the CABG arm, we estimated 6.53 quality-adjusted life-years (95% CI, 5.70-7.53) and a lifetime cost of $140 059 (95% CI, $106 401 to $180 992). For the MED arm, the corresponding estimates were 5.52 (95% CI, 5.06-6.09) quality-adjusted life-years and $74 894 lifetime cost (95% CI, $58 372 to $93 541). The incremental cost-effectiveness ratio for CABG compared with MED was $63 989 per quality-adjusted life-year gained. At a societal willingness-to-pay threshold of $100 000 per quality-adjusted life-year gained, CABG was found to be economically favorable compared with MED in 87% of microsimulations. CONCLUSIONS: In the STICH trial, in patients with ischemic cardiomyopathy and reduced left ventricular function, CABG was economically attractive relative to MED at current benchmarks for value in the United States. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00023595.

Cost-Effectiveness of Catheter Ablation Versus Antiarrhythmic Drug Therapy in Atrial Fibrillation: The CABANA Randomized Clinical Trial.

BACKGROUND: In the CABANA trial (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation), catheter ablation did not significantly reduce the primary end point of death, disabling stroke, serious bleeding, or cardiac arrest compared with drug therapy by intention-to-treat, but did improve the quality of life and freedom from atrial fibrillation recurrence. In the heart failure subgroup, ablation improved both survival and quality of life. Cost-effectiveness was a prespecified CABANA secondary end point. METHODS: Medical resource use data were collected for all CABANA patients (N=2204). Costs for hospital-based care were assigned using prospectively collected bills from US patients (n=1171); physician and medication costs were assigned using the Medicare Fee Schedule and National Average Drug Acquisition Costs, respectively. Extrapolated life expectancies were estimated using age-based survival models. Quality-of-life adjustments were based on EQ-5D-based utilities measured during the trial. The primary outcome was the incremental cost-effectiveness ratio, comparing ablation with drug therapy on the basis of intention-to-treat, and assessed from the US health care sector perspective. RESULTS: Costs in the first 3 months averaged $20 794±SD 1069 higher with ablation compared with drug therapy. The cumulative within-trial 5-year cost difference was $19 245 (95% CI, $11 360-$27 170) and the lifetime mean cost difference was $15 516 (95% CI, -$2963 to $35,512) higher with ablation than with drug therapy. The drug therapy arm accrued an average of 12.5 life-years (LYs) and 10.7 quality-adjusted life-years (QALYs). For the ablation arm, the corresponding estimates were 12.6 LYs and 11.0 QALYs. The incremental cost-effectiveness ratio was $57 893 per QALY gained, with 75% of bootstrap replications yielding an incremental cost-effectiveness ratio <$100 000 per QALY gained. With no quality-of-life/utility adjustments, the incremental cost-effectiveness ratio was $183 318 per LY gained. CONCLUSIONS: Catheter ablation of atrial fibrillation was economically attractive compared with drug therapy in the CABANA Trial overall at present benchmarks for health care value in the United States on the basis of projected incremental QALYs but not LYs alone.

Index and follow-up costs of endovascular abdominal aortic aneurysm repair from the Endurant Stent Graft System Post Approval Study (ENGAGE PAS).

OBJECTIVE: Trials for endovascular aneurysm repair (EVAR) report lower perioperative mortality and morbidity, but also higher costs compared with open repair. However, few studies have examined the subsequent cost of follow-up evaluations and interventions. Therefore, we present the index and 5-year follow-up costs of EVAR from the Endurant Stent Graft System Post Approval Study. METHODS: From August 2011 to June 2012, 178 patients were enrolled in the Endurant Stent Graft System Post Approval Study de novo cohort and treated with the Medtronic Endurant stent graft system (Medtronic Vascular, Santa Rosa, Calif), of whom 171 (96%) consented for inclusion in the economic analysis and 177 participated in the quality-of-life (QOL) assessment over a 5-year follow-up period. Cost data for the index and follow-up hospitalizations were tabulated directly from hospital bills and categorized by Uniform Billing codes. Surgeon costs were calculated by Current Procedural Terminology codes for each intervention. Current Procedural Terminology codes were also used to calculate imaging and clinic follow-up reimbursement as surrogate to cost based on year-specific Medicare payment rates. Additionally, we compared aneurysm-related versus nonaneurysm-related subsequent hospitalization costs and report EuroQol 5D QOL dimensions. RESULTS: The mean hospital cost per person for the index EVAR was $45,304 (interquartile range [IQR], $25,932-$44,784). The largest contributor to the overall cost was operating room supplies, which accounted for 50% of the total cost at a mean of $22,849 per person. One hundred patients had 233 additional post index admission inpatient admissions; however, only 32 readmissions (14%) were aneurysm related, with a median cost of $13,119 (IQR, $4570-$24,153) compared with a nonaneurysm-related median cost of $6609 (IQR, $1244-$26,466). Additionally, 32 patients were admitted a total of 37 times for additional procedures after index admission, of which 14 (38%) were aneurysm-related. The median cost of hospitalization for aneurysm-related subsequent intervention was $22,023 (IQR, $13,177-$47,752), compared with a median nonaneurysm-related subsequent intervention cost of $19,007 (IQR, $8708-$33,301). After the initial 30-day visit, outpatient follow-up imaging reimbursement averaged $550 per person per year ($475 for computed tomography scans, $75 for the abdomen), whereas annual office visits averaged $107 per person per year, for a total follow-up reimbursement of $657 per person per year. There were no significant differences in the five EuroQol 5D QOL dimensions at each follow-up compared with baseline. CONCLUSIONS: Costs associated with index EVAR are driven primarily by cost of operating room supplies, including graft components. Subsequent admissions are largely not aneurysm related; however, cost of aneurysm-related hospitalizations is higher than for nonaneurysm admissions. These data will serve as a baseline for comparison with open repair and other devices.

Effects of Ranolazine on Angina and Quality of Life After Percutaneous Coronary Intervention With Incomplete Revascularization: Results From the Ranolazine for Incomplete Vessel Revascularization (RIVER-PCI) Trial.

BACKGROUND: Angina often persists or returns in populations following percutaneous coronary intervention (PCI). We hypothesized that ranolazine would be effective in reducing angina and improving quality of life (QOL) in incomplete revascularization (ICR) post-PCI patients. METHODS AND RESULTS: In RIVER-PCI, 2604 patients with a history of chronic angina who had ICR post-PCI were randomized 1:1 to oral ranolazine versus placebo; QOL analyses included 2389 randomized subjects. Angina and QOL questionnaires were collected at baseline and months 1, 6, and 12. Ranolazine patients were more likely than placebo to discontinue study drug by month 6 (20.4% versus 14.1%, P<0.001) and 12 (27.2% versus 21.3%, P<0.001). Following qualifying index PCI, the primary QOL outcome (Seattle Angina Questionnaire [SAQ] angina frequency score) improved markedly, but similarly, in the ranolazine and placebo groups, respectively, from baseline (67.3±24.5 versus 69.7±24.0, P=0.01) to month 1 (86.6±18.1 versus 85.8±18.5, P=0.27) and month 12 (88.4±17.8 versus 88.5±17.8, P=0.94). SAQ angina frequency repeated measures did not differ in adjusted analysis between groups post baseline (mean difference 1.0; 95% CI -0.2, 2.2; P=0.11). Improvement in SAQ angina frequency was observed with ranolazine at month 6 among diabetics (mean difference 3.3; 95% CI 0.6, 6.1; P=0.02) and those with more angina (baseline SAQ angina frequency ≤60; mean difference 3.4; 95% CI 0.6, 6.2; P=0.02), but was not maintained at month 12. CONCLUSIONS: Despite ICR following PCI, there was no incremental benefit in angina or QOL measures by adding ranolazine in this angiographically-identified population. These measures markedly improved within 1 month of PCI and persisted up to 1 year in both treatment arms. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442038.

Economic Outcomes With Anatomical Versus Functional Diagnostic Testing for Coronary Artery Disease.

BACKGROUND: PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain) found that initial use of at least 64-slice multidetector computed tomography angiography (CTA) versus functional diagnostic testing strategies did not improve clinical outcomes in stable symptomatic patients with suspected coronary artery disease (CAD) requiring noninvasive testing. OBJECTIVE: To conduct an economic analysis for PROMISE (a major secondary aim of the study). DESIGN: Prospective economic study from the U.S. perspective. Comparisons were made according to the intention-to-treat principle, and CIs were calculated using bootstrap methods. (ClinicalTrials.gov: NCT01174550). SETTING: 190 U.S. centers. PATIENTS: 9649 U.S. patients enrolled in PROMISE between July 2010 and September 2013. Median follow-up was 25 months. MEASUREMENTS: Technical costs of the initial (outpatient) testing strategy were estimated from Premier Research Database data. Hospital-based costs were estimated using hospital bills and Medicare cost-charge ratios. Physician fees were taken from the Medicare Physician Fee Schedule. Costs were expressed in 2014 U.S. dollars, discounted at 3% annually, and estimated out to 3 years using inverse probability weighting methods. RESULTS: The mean initial testing costs were $174 for exercise electrocardiography; $404 for CTA; $501 to $514 for pharmacologic and exercise stress echocardiography, respectively; and $946 to $1132 for exercise and pharmacologic stress nuclear testing, respectively. Mean costs at 90 days were $2494 for the CTA strategy versus $2240 for the functional strategy (mean difference, $254 [95% CI, -$634 to $906]). The difference was associated with more revascularizations and catheterizations (4.25 per 100 patients) with CTA use. After 90 days, the mean cost difference between the groups out to 3 years remained small. LIMITATION: Cost weights for test strategies were obtained from sources outside PROMISE. CONCLUSION: Computed tomography angiography and functional diagnostic testing strategies in patients with suspected CAD have similar costs through 3 years of follow-up. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Rationale and design of the Affordability and Real-world Antiplatelet Treatment Effectiveness after Myocardial Infarction Study (ARTEMIS): A multicenter, cluster-randomized trial of P2Y12 receptor inhibitor copayment reduction after myocardial infarction.

BACKGROUND: The use of oral P2Y12 receptor inhibitors after acute myocardial infarction (MI) can reduce risks of subsequent major adverse cardiovascular events (composite of all-cause death, recurrent MI, and stroke), yet medication persistence is suboptimal. Although copayment cost has been implicated as a factor influencing medication persistence, it remains unclear whether reducing or eliminating these costs can improve medication persistence and/or downstream clinical outcomes. DESIGN: ARTEMIS is a multicenter, cluster-randomized clinical trial designed to examine whether eliminating patient copayment for P2Y12 receptor inhibitor therapy affects medication persistence and clinical outcomes. We will enroll approximately 11,000 patients hospitalized for acute ST-elevation and non-ST-elevation MI at 300 hospitals. Choice and duration of treatment with a P2Y12 receptor inhibitor will be determined by the treating physician. Hospitals randomized to the copayment intervention will provide vouchers to cover patients' copayments for their P2Y12 receptor inhibitor for up to 1 year after discharge. The coprimary end points are 1-year P2Y12 receptor inhibitor persistence and major adverse cardiovascular events. Secondary end points include choice of P2Y12 receptor inhibitor, patient-reported outcomes, and postdischarge cost of care. CONCLUSION: ARTEMIS will be the largest randomized assessment of a medication copayment reduction intervention on medication persistence, clinical outcomes, treatment selection, and cost of care after acute MI.

Health-related quality of life outcomes with prasugrel among medically managed non-ST-segment elevation acute coronary syndrome patients: Insights from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial.

BACKGROUND: Few studies have assessed treatment effects on health-related quality of life (HRQoL) in patients with acute coronary syndrome (ACS) treated without revascularization. The TRILOGY ACS trial randomized patients with ACS to either prasugrel or clopidogrel therapy plus aspirin. Outcomes showed a complex pattern suggestive of late benefits with respect to repeat clinical events and benefits confined to patients who underwent angiography. Here, we examine the HRQoL correlates of these patterns. METHODS: HRQoL was measured at baseline and 3, 12, and 24 months or end of study (EOS) in 7243 patients aged <75 years using the EuroQol 3-level, group 5-dimension index (EQ-5D). Linear mixed effects models for repeated measures were used to examine treatment differences in HRQoL overall, stratified by angiography status, and among patients who did and did not have non-fatal events. RESULTS: No baseline differences in HRQoL were seen between patients randomized to prasugrel (n=3620) or clopidogrel (n=3623). At 24 months, remaining patients assigned to prasugrel (n=1450) vs. clopidogrel (n=1443) had higher EQ-5D index scores (86.4 vs. 84.9, P=.01). Mixed effects models found no difference in EQ-5D scores among prasugrel and clopidogrel patients overall across subgroups stratified by angiography status. However, among patients with non-fatal clinical events, patients on clopidogrel reported a larger decrement in HRQoL than patients on prasugrel (79.5±18.1 vs. 80.6±18.0; P=.02). CONCLUSIONS: Overall, there was no difference in HRQoL outcomes among patients receiving prasugrel vs. clopidogrel. However, the differential effects of the treatments among patients with non-fatal events require further investigation.

Medical resource use, costs, and quality of life in patients with acute decompensated heart failure: findings from ASCEND-HF.

BACKGROUND: The Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) randomly assigned 7,141 participants to nesiritide or placebo. Dyspnea improvement was more often reported in the nesiritide group, but there were no differences in 30-day all-cause mortality or heart failure readmission rates. We compared medical resource use, costs, and health utilities between the treatment groups. METHODS AND RESULTS: There were no significant differences in inpatient days, procedures, and emergency department visits reported for the first 30 days or for readmissions to day 180. EQ-5D health utilities and visual analog scale ratings were similar at 24 hours, discharge, and 30 days. Billing data and regression models were used to generate inpatient costs. Mean length of stay from randomization to discharge was 8.5 days in the nesiritide group and 8.6 days in the placebo group (P = .33). Cumulative mean costs at 30 days were $16,922 (SD $16,191) for nesiritide and $16,063 (SD $15,572) for placebo (P = .03). At 180 days, cumulative costs were $25,590 (SD $30,344) for nesiritide and $25,339 (SD $29,613) for placebo (P = .58). CONCLUSIONS: The addition of nesiritide contributed to higher short-term costs and did not significantly influence medical resource use or health utilities compared with standard care alone.

Economic analysis of endovascular repair versus surveillance for patients with small abdominal aortic aneurysms.

BACKGROUND: The Positive Impact of EndoVascular Options for Treating Aneurysms Early (PIVOTAL) trial enrolled individuals with small (4.0- to 5.0-cm diameter) abdominal aortic aneurysms (AAA) and reported no difference in rupture or aneurysm-related death for patients who received early endovascular repair (EVAR) vs surveillance with serial imaging studies. We evaluated resource use, medical cost, and quality of life outcomes associated with the PIVOTAL treatment strategies. METHODS: This prospective economic and quality of life study was conducted within a randomized trial, with PIVOTAL sites participating in the quality of life (n = 67) and economic (n = 63) studies. The PIVOTAL trial randomized 728 patients (366 early EVAR and 362 surveillance). We used information from 701 quality of life (351 early EVAR and 350 surveillance) and 614 economic (314 early EVAR and 300 surveillance) study participants enrolled in the PIVOTAL trial. The main outcome measures were total medical costs and the aneurysm repair rate at 48 months. RESULTS: After 6 months, the rate of aneurysm repair was 96 vs 10 per 100 patients in the early EVAR and surveillance groups, respectively (difference, 86; 95% confidence interval [CI], 82-90; P < .0001), and total medical costs were greater in the early EVAR group ($33,471 vs $5520; difference, $27,951; 95% CI, $25,156-$30,746; P < .0001). In months 7 through 48, however, the rate of aneurysm repair was 54 per 100 patients in the surveillance group, and total medical costs were higher for patients in the surveillance vs the early EVAR group ($40,592 vs $15,197; difference, $25,394; 95% CI, $15,184-$35,605; P < .0001). At 48 months' follow-up, early EVAR patients had greater cumulative use of AAA repair (97 vs 64 per 100 patients; difference, 34; 95% CI, 21-46; P < .0001), but there was no difference in total medical costs ($48,669 vs $46,112; difference, $2557; 95% CI, -$8043 to $13,156; P = .64). After discounting at 3% per annum, total medical costs for early EVAR and surveillance patients remained similar ($47,765 vs $43,532; difference, 4232; 95% CI, -$5561 to $14,025; P = .40). There were no treatment-related differences in quality of life at 24 months. CONCLUSIONS: A treatment strategy involving early repair of smaller AAA with EVAR is associated with no difference in total medical costs at 48 months vs surveillance with serial imaging studies. Longer follow-up is required to determine whether the late medical cost increases observed for surveillance will persist beyond 48 months.

Quality of life after late invasive therapy for occluded arteries.

BACKGROUND: The open-artery hypothesis postulates that late opening of an infarct-related artery after myocardial infarction will improve clinical outcomes. We evaluated the quality-of-life and economic outcomes associated with the use of this strategy. METHODS: We compared percutaneous coronary intervention (PCI) plus stenting with medical therapy alone in high-risk patients in stable condition who had a totally occluded infarct-related artery 3 to 28 days after myocardial infarction. In 951 patients (44% of those eligible), we assessed quality of life by means of a battery of tests that included two principal outcome measures, the Duke Activity Status Index (DASI) (which measures cardiac physical function on a scale from 0 to 58, with higher scores indicating better function) and the Medical Outcomes Study 36-Item Short-Form Mental Health Inventory 5 (which measures psychological well-being). Structured quality-of-life interviews were performed at baseline and at 4, 12, and 24 months. Costs of treatment were assessed for 458 of 469 patients in the United States (98%), and 2-year cost-effectiveness was estimated. RESULTS: At 4 months, the medical-therapy group, as compared with the PCI group, had a clinically marginal decrease of 3.4 points in the DASI score (P=0.007). At 1 and 2 years, the differences were smaller. No significant differences in psychological well-being were observed. For the 469 patients in the United States, cumulative 2-year costs were approximately $7,000 higher in the PCI group (P<0.001), and the quality-adjusted survival was marginally longer in the medical-therapy group. CONCLUSIONS: PCI was associated with a marginal advantage in cardiac physical function at 4 months but not thereafter. At 2 years, medical therapy remained significantly less expensive than routine PCI and was associated with marginally longer quality-adjusted survival. (ClinicalTrials.gov number, NCT00004562.)

Cangrelor Use Patterns and Transition to Oral P2Y12 Inhibitors Among Patients With Myocardial Infarction: Initial Results From the CAMEO Registry.

Background In clinical trials, cangrelor has been shown to reduce percutaneous coronary intervention-related ischemic complications without increasing major bleeding. This study was performed to examine cangrelor use and transition to oral P2Y12 inhibitors in routine clinical practice. Methods and Results The CAMEO (Cangrelor in Acute Myocardial Infarction: Effectiveness and Outcomes) registry is a multicenter, retrospective observational study of platelet inhibition strategies for patients with myocardial infarction undergoing percutaneous coronary intervention. In phase 1, data were collected on consecutive patients with myocardial infarction (n=482) treated with any P2Y12 inhibitor to understand cangrelor use by hospital. In phase 2, data were collected in a 2:1 (cangrelor-: non-cangrelor-treated) ratio of patients with myocardial infarction (n=873). In phase 1, cangrelor use varied across hospitals (overall, 50.4% [range, 6.0%-100%]). Of patients receiving cangrelor in both phases (n=819), 3.3% received either the bolus or infusion only. Cangrelor was infused for a median of 121 (76-196) minutes; and 38.3% received an infusion for <2 hours. Most patients transitioned from cangrelor to ticagrelor (ticagrelor, 85.3%; clopidogrel, 9.5%; prasugrel, 5.2%). Many patients (16.4%) had a >1-hour gap between cangrelor cessation and oral P2Y12 inhibitor initiation; this was highest among those transitioned to clopidogrel (56.6% versus 34.5% prasugrel versus 10.8% ticagrelor; P<0.001). Only 27.3% were dosed with cangrelor and transitioned to an oral P2Y12 inhibitor in a fashion consistent with the pivotal trials and US Food and Drug Administration label. Conclusions This multicenter registry demonstrated interhospital variability in how cangrelor was administered and transitioned to an oral P2Y12 inhibitor. These findings highlight opportunities for optimization of cangrelor dosing, infusion duration, and transition of care from the catheterization laboratory to the ward setting.

Disparities in Loss to Follow-Up Among Adults With Congenital Heart Disease in North Carolina.

BACKGROUND: The AHA/ACC Adult Congenital Heart Disease guidelines recommend that most adults with congenital heart disease (CHD) follow-up with CHD cardiologists every 1 to 2 years because longer gaps in care are associated with adverse outcomes. This study aimed to determine the proportion of patients in North Carolina who did not have recommended follow-up and to explore predictors of loss to follow-up. METHODS: Patients ages ≥18 years with a healthcare encounter from 2008 to 2013 in a statewide North Carolina database with an ICD-9 code for CHD were assessed. The proportion with cardiology follow-up within 24 months following index encounter was assessed with Kaplan-Meier estimates. Cox regression was utilized to identify demographic factors associated with differences in follow-up. RESULTS: 2822 patients were identified. Median age was 35 years; 55% were female. 70% were white, 22% black, and 3% Hispanic; 36% had severe CHD. The proportion with 2-year cardiology follow-up was 61%. Those with severe CHD were more likely to have timely follow-up than those with less severe CHD (72% vs 55%, P < .01). Black patients had a lower likelihood of follow-up than white patients (56% vs 64%, P = .01). Multivariable Cox regression identified younger age, non-severe CHD, and non-white race as risk factors for a lower likelihood of follow-up by 2 years. CONCLUSION: 39% of adults with CHD in North Carolina are not meeting AHA/ACC recommendations for follow-up. Younger and minority patients and those with non-severe CHD were particularly vulnerable to inadequate follow-up; targeted efforts to retain these patients in care may be helpful.

Home use of automated external defibrillators for sudden cardiac arrest.

BACKGROUND: The most common location of out-of-hospital sudden cardiac arrest is the home, a situation in which emergency medical services are challenged to provide timely care. Consequently, home use of an automated external defibrillator (AED) might offer an opportunity to improve survival for patients at risk. METHODS: We randomly assigned 7001 patients with previous anterior-wall myocardial infarction who were not candidates for an implantable cardioverter-defibrillator to receive one of two responses to sudden cardiac arrest occurring at home: either the control response (calling emergency medical services and performing cardiopulmonary resuscitation [CPR]) or the use of an AED, followed by calling emergency medical services and performing CPR. The primary outcome was death from any cause. RESULTS: The median age of the patients was 62 years; 17% were women. The median follow-up was 37.3 months. Overall, 450 patients died: 228 of 3506 patients (6.5%) in the control group and 222 of 3495 patients (6.4%) in the AED group (hazard ratio, 0.97; 95% confidence interval, 0.81 to 1.17; P=0.77). Mortality did not differ significantly in major prespecified subgroups. Only 160 deaths (35.6%) were considered to be from sudden cardiac arrest from tachyarrhythmia. Of these deaths, 117 occurred at home; 58 at-home events were witnessed. AEDs were used in 32 patients. Of these patients, 14 received an appropriate shock, and 4 survived to hospital discharge. There were no documented inappropriate shocks. CONCLUSIONS: For survivors of anterior-wall myocardial infarction who were not candidates for implantation of a cardioverter-defibrillator, access to a home AED did not significantly improve overall survival, as compared with reliance on conventional resuscitation methods. (ClinicalTrials.gov number, NCT00047411 [ClinicalTrials.gov].).

Quality of life with defibrillator therapy or amiodarone in heart failure.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy significantly prolongs life in patients at increased risk for sudden death from depressed left ventricular function. However, whether this increased longevity is accompanied by deterioration in the quality of life is unclear. METHODS: In a randomized trial, we compared ICD therapy or amiodarone with state-of-the-art medical therapy alone in 2521 patients who had stable heart failure with depressed left ventricular function. We prospectively measured quality of life at baseline and at months 3, 12, and 30; data collection was 93 to 98% complete. The Duke Activity Status Index (which measures cardiac physical functioning) and the Medical Outcomes Study 36-Item Short-Form Mental Health Inventory 5 (which measures psychological well-being) were prespecified primary outcomes. Multiple additional quality-of-life outcomes were also examined. RESULTS: Psychological well-being in the ICD group, as compared with medical therapy alone, was significantly improved at 3 months (P=0.01) and at 12 months (P=0.003) but not at 30 months. No clinically or statistically significant differences in physical functioning among the study groups were observed. Additional quality-of-life measures were improved in the ICD group at 3 months, 12 months, or both, but there was no significant difference at 30 months. ICD shocks in the month preceding a scheduled assessment were associated with a decreased quality of life in multiple domains. The use of amiodarone had no significant effects on the primary quality-of-life outcomes. CONCLUSIONS: In a large primary-prevention population with moderately symptomatic heart failure, single-lead ICD therapy was not associated with any detectable adverse quality-of-life effects during 30 months of follow-up.

Treatment with adenosine diphosphate receptor inhibitors-longitudinal assessment of treatment patterns and events after acute coronary syndrome (TRANSLATE-ACS) study design: expanding the paradigm of longitudinal observational research.

BACKGROUND: Platelet inhibition is critical in reducing both short- and long-term atherothrombotic risks after acute myocardial infarction (MI), especially among patients managed with percutaneous coronary intervention (PCI). Currently available antiplatelet medications, including adenosine diphosphate (ADP) receptor inhibitors, have demonstrated variability in efficacy and safety in clinical trials, yet few studies have examined contemporary "real-world" approaches to platelet inhibition and associated outcomes. METHODS: TRANSLATE-ACS is a prospective observational study that will track up to 17,000 MI patients managed with PCI, from the inhospital to outpatient settings for up to 12 months postdischarge to provide a comprehensive picture of current treatment patterns and outcomes in routine clinical practice. TRANSLATE-ACS exemplifies a collaborative study design that efficiently builds upon a well-established PCI registry platform, and yet, through a systematic telephone interview follow-up process, provides important longitudinal clinical and economic follow-up capacity through 15 months after initial MI hospitalization. Furthermore, TRANSLATE-ACS incorporates a hospital-level, clustered, randomized substudy to investigate the impact of point-of-care platelet inhibition testing on subsequent patient management. Finally, TRANSLATE-ACS provides feedback through quarterly reports to participating sites on their care practices benchmarked to peer performance to support and promote longitudinal quality of cardiovascular care delivery. CONCLUSION: TRANSLATE-ACS not only addresses important clinical and scientific questions but also includes pioneering design features that will assist in the evolution of clinical registries.

Erythritol, an Artificial Sweetener, Is Acaricidal Against Pest Mites and Minimally Harmful to a Predatory Mite.

Erythritol, an artificial sweetener, has shown promise as an organic, human-safe insecticide. Recently, erythritol applications were shown to be successful at controlling pear psylla (Cacopsylla pyricola (Förster)) (Hempitera: Psyllidae), the most important pest of pear in the Pacific Northwest, USA. Twospotted spider mite (Tetranychus urticae Koch) (Trombidiformes: Tetranychidae) and pear rust mite (Epitrimerus pyri (Nalepa)) (Trombidiformes: Eriophyidae) can also be highly damaging pear pests. Their common natural enemy, Galendromus occidentalis (Nesbitt) (Mesostigmata: Phytoseiidae), can provide biological control if selective pesticides are used for managing other pests. Through a series of bioassays, we sought to determine whether erythritol could also be used for controlling either species of pest mite. We also examined whether erythritol had acute or sublethal impacts on G. occidentalis, through a variety of exposure methods. Effects examined included mortality, fecundity, prey consumption, and locomotion. We determined that a high concentration of erythritol (30%) had efficacy against both pest mite species and caused arresting behavior in twospotted spider mite. Erythritol caused little acute mortality in G. occidentalis, but did reduce fecundity and prey consumption through some exposure methods. Through motion-capture software, we determined that this is primarily due to reduced movement, likely caused by difficulty walking on residues and excessive grooming behavior. Because the predatory mite non-target effects were less acute than those for the two pest mites, we concluded that erythritol could likely be integrated into pear IPM with little or no disruption of mite biological control.

Ascertaining Nonfatal Endpoints in Clinical Trials: Central Adjudication Versus Patient Insurance Claims.

BACKGROUND: The 21st Century Cures Act allows the US Food and Drug Administration (FDA) to utilize real-world data (RWD) to create real-world evidence (RWE) for new indications or post approval study requirements. We compared central adjudication with two insurance claims data sources to understand how endpoint accuracy differences impact RWE results. METHODS: We developed a decision analytic model to compare differences in efficacy (all-cause death, stroke and myocardial infarction) and safety (bleeding requiring transfusion) results for a simulated acute coronary syndrome antiplatelet therapy clinical trial. Endpoint accuracy metrics were derived from previous studies that compared centrally-adjudicated and insurance claims-based clinical trial endpoints. RESULTS: Efficacy endpoint results per 100 patients were similar for the central adjudication model (intervention event rate, 11.3; control, 13.7; difference, 2.4) and the prospective claims data collection model (intervention event rate, 11.2; control 13.6; difference, 2.3). However, the retrospective claims linking model's efficacy results were larger (intervention event rate, 14.6; control, 18.0; difference, 3.4). True positive event rate results (intervention, control and difference) for both insurance claims-based models were less than the central adjudication model due to false negative events. Differences in false positive event rates were responsible for differences in efficacy results for the two insurance claims-based models. CONCLUSION: Efficacy endpoint results differed by data source. Investigators need guidance to determine which data sources produce regulatory-grade RWE.

Outcomes for patients with anterior myocardial infarction and prior cardiac arrest in the home automated external defibrillator trial (HAT).

BACKGROUND: Patients with sudden cardiac arrest occurring in the acute phase of myocardial infarction (MI-SCA) are believed to be at similar risk of death after revascularization compared with MI patients without SCA (MI-no SCA). Among patients with anterior MI, we examined whether those with MI-SCA were at greater risk of all-cause mortality or sudden cardiac death (SCD) than MI-no SCA patients. METHODS: The Home Automated External Defibrillator Trial enrolled patients with anterior MI who had not received or were candidates for an implantable cardioverter defibrillator (ICD). Our cohort included patients with a reported SCA event, in the acute phase of an MI, prior to HAT trial enrollment. Cox proportional hazards models examined the adjusted association between MI-SCA versus MI-no SCA patients and all-cause mortality and sudden cardiac death (SCD). We also determined whether the relationship between prior SCA and outcomes changed with subsequent events (syncope, revascularization, and recurrent MI) during follow-up. RESULTS: Of 6849 patients, 650 (9.5%) had MI-SCA before trial enrollment. Approximately 48% of patients had the MI-SCA event ≤1 year prior to enrollment; 71% of SCA events were in-hospital. MI-SCA patients were younger, more frequently white, and had higher rates of prior PCI versus MI-no SCA patients. There were no differences in adjusted all-cause mortality (hazard ratio [HR 0.95; 95% CI 0.65-1.38]) or SCD (HR 1.12; 95% CI 0.68-1.83) for MI-SCA vs. MI-no SCA. After ICD implantation, MI-SCA patients experienced higher all-cause mortality risk (HR 5.01, 95% CI 1.05-23.79) versus MI-no SCA patients; there was no mortality difference between MI-SCA and MI-no SCA patients without ICD implantation (HR 0.89, 95% CI 0.60-1.31), [interaction p = 0.035]. CONCLUSIONS: Patients with MI-SCA had similar adjusted risk of all-cause mortality and SCD compared with MI-no SCA. After ICD implantation, MI-SCA patients had higher mortality compared with MI-no SCA patients.