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Background: Ezetimibe, when added to simvastatin therapy, reduces cardiovascular events after recent acute coronary syndrome. However, the impact of ezetimibe on cardiovascular-related hospitalizations and associated costs is unknown.Methods and Results: We used patient-level data from the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) to examine the impact of simvastatin-ezetimibe versus simvastatin-placebo on cardiovascular-related hospitalizations and related costs (excluding drug costs) over 7 years follow-up. Medicare Severity-Diagnosis Related Groups were assigned to all cardiovascular hospitalizations. Hospital costs were estimated using Medicare reimbursement rates for 2013. Associated physician costs were estimated as a percentage of hospital costs. The impact of treatment assignment on hospitalization rates and costs was estimated using Poisson and linear regression, respectively. There was a significantly lower cardiovascular hospitalization rate with ezetimibe compared with placebo (risk ratio, 0.95; 95% confidence interval, 0.90-0.99; P=0.031), mainly attributable to fewer hospitalizations for percutaneous coronary intervention, angina, and stroke. Consequently, cardiovascular-related hospitalization costs over 7 years were $453 per patient lower with ezetimibe (95% confidence interval, -$38 to -$869; P=0.030). Although all prespecified subgroups had lower cost with ezetimibe therapy, patients with diabetes mellitus, patients aged ≥75 years, and patients at higher predicted risk for recurrent ischemic events had even greater cost offsets.Conclusions: Addition of ezetimibe to statin therapy in patients with a recent acute coronary syndrome leads to reductions in cardiovascular-related hospitalizations and associated costs, with the greatest cost offsets in high-risk patients. These cost reductions may completely offset the cost of the drug once ezetimibe becomes generic, and may lead to cost savings from the perspective of the healthcare system, if treatment with ezetimibe is targeted to high-risk patients.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique Identifier: NCT00202878. [ABSTRACT FROM AUTHOR]

Background: Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) improves clinical outcomes and quality of life. Optimizing GDMT in the hospital is associated with greater long-term use in HFrEF. This study aimed to describe the efficacy of a multidisciplinary virtual HF intervention on GDMT optimization among patients with HFrEF admitted for any cause. Methods: In this pilot randomized, controlled study, consecutive patients with HFrEF admitted to noncardiology medicine services for any cause were identified at a large academic tertiary care hospital between May to September 2021. Major exclusions were end-stage renal disease, hemodynamic instability, concurrent COVID-19 infection, and current enrollment in hospice care. Patients were randomized to a clinician-level virtual peer-to-peer consult intervention providing GDMT recommendations and information on medication costs versus usual care. Primary end points included (1) proportion of patients with new GDMT initiation or use and (2) changes to HF optimal medical therapy scores which included target dosing (range, 0–9). Results: Of 242 patients identified, 91 (38%) were eligible and randomized to intervention (N=52) or usual care (N=39). Baseline characteristics were similar between intervention and usual care (mean age 63 versus 67 years, 23% versus 26% female, 46% versus 49% Black, mean ejection fraction 33% versus 31%). GDMT use on admission was also similar. There were greater proportions of patients with GDMT initiation or continuation with the intervention compared with usual care. After adjusting for optimal medical therapy score on admission, changes to optimal medical therapy score at discharge were higher for the intervention group compared with usual care (+0.44 versus −0.31, absolute difference +0.75, adjusted estimate 0.86±0.42; P =0.041). Conclusions: Among eligible patients with HFrEF hospitalized for any cause on noncardiology services, a multidisciplinary pilot virtual HF consultation increased new GDMT initiation and dose optimization at discharge. [ABSTRACT FROM AUTHOR]

Background: Although cholesterol-lowering medications can reduce the risk of recurrent cardiovascular events, premature discontinuation limits effectiveness. Discontinuation rates have not been systematically reported for lipid-lowering trials.Methods and Results: We evaluated medication discontinuation in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), which evaluated placebo+simvastatin versus ezetimibe+simvastatin in patients hospitalized with the acute coronary syndrome and followed longitudinally postdischarge. Reasons for discontinuation were evaluated from randomization through study end (median 71.9 [interquartile range 51.8-85.8] months). Kaplan-Meier (KM) discontinuation rates were evaluated at 30 days, 1 year, and through year 7, and compared by treatment arm and region, with Cox proportional hazards modeling used to evaluate predictors of discontinuation. Overall, 46.7% of subjects discontinued study medication (KM rate by study end 50.9% [95% CI, 50.1%-51.7%]). The risk of discontinuation was highest early in the trial but decreased with increasing time, with a terminal KM rate per 100 person-years of 8.4 (8.2-8.6) from years 1 to 7. Discontinuation was higher in the placebo+simvastatin versus ezetimibe+simvastatin arm (KM rate 52.0% versus 49.8%, P=0.049) and was highest in the United States (7-year KM rate 57.4%). In multivariable modeling, smoking, prior revascularization, hypertension, unstable angina, female sex, nonwhite race, and US location were associated with higher discontinuation rates.Conclusions: Although discontinuation was highest early and stabilized to 8% per year, because of prolonged follow-up, most discontinuation occurred after year 1. Adding ezetimibe to statin therapy did not increase discontinuation risk. Geographic differences and patient-level factors should be considered in trial design and analysis.Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00202878. [ABSTRACT FROM AUTHOR]

Introduction: IMPROVE-IT enrolled 18,144 patients post ACS with an LDL-C ≤ 125 mg/dL. The trial assessed effects on major cardiovascular (CV) outcomes of adding the non-statin LDL-C lowering drug ezetimibe (EZ) vs placebo to 40 mg/day of simvastatin (S). The S was uptitrated to 80 mg/day if the LDL-C was confirmed < 7 9 mg/dL during follow-up. Treatment duration averaged 5.2 + 2.2 years. The long trial duration, ongoing controversy around EZ and label changes related to S 80mg led to higher than anticipated premature treatment discontinuation. The targeted LDL-C for S-alone was <70 mg/dL and addition of EZ was anticipated to lower LDL-C by~15 mg/dL. In addition to the intention to treat (ITT) analysis (presented earlier at this meeting) we prespecified an on-treatment (OT) analysis to provide additional understanding of the effect of further LDL-C lowering with EZ on CV outcomes. Methods: The OT analyses will include patients who took at least one dose of study drug and will evaluate time while on drug through 30 days after permanent discontinuation or end-of-study whichever came first. Events will be assessed on the prespecified primary endpoint (CV death, Ml, stroke, hospitalization for unstable angina and coronary revascularization) and its components using the Cox proportional hazards model with multivariate adjustments. Results: As of May 30th 2104, the median LDL-C at entry was 95 mg/dL, for both populations and 59 mg/dL for the ITT population but 57 mg/dL for the OT population at 1 year. Follow-up time for the ITT and OT populations were 94,363 and 71,526 patient-years respectively. Table 1 compares key baseline characteristics of patients who did and did not prematurely stop drug before end-of-trial or within 30 days of dying. Unblinded data will be available in late Sept/Oct2014 to evaluate effects on treatment benefit. Conclusions: The results of the OT analysis will enhance the understanding of the effects of LDL-C lowering with EZ [ABSTRACT FROM AUTHOR]

Objective: To examine the contributions of chest pain, anxiety, and pain catastrophizing to disability in 97 patients with noncardiac chest pain (NCCP) and to test whether chest pain and anxiety were related indirectly to greater disability via pain catastrophizing., Methods: Participants completed daily diaries measuring chest pain for 7 days before completing measures of pain catastrophizing, trait anxiety, and disability. Linear path model analyses examined the contributions of chest pain, trait anxiety, and catastrophizing to physical disability, psychosocial disability, and disability in work, home, and recreational activities., Results: Path models accounted for a significant amount of the variability in disability scales (R(2) = 0.35 to 0.52). Chest pain and anxiety accounted for 46% of the variance in pain catastrophizing. Both chest pain (beta = 0.18, Sobel test Z = 2.58, p < .01) and trait anxiety (beta = 0.14, Sobel test Z = 2.11, p < .05) demonstrated significant indirect relationships with physical disability via pain catastrophizing. Chest pain demonstrated a significant indirect relationship with psychosocial disability via pain catastrophizing (beta = 0.12, Sobel test Z = 1.96, p = .05). After controlling for the effects of chest pain and anxiety, pain catastrophizing was no longer related to disability in work, home, and recreational activities., Conclusions: Chest pain and anxiety were directly related to greater disability and indirectly related to physical and psychosocial disability via pain catastrophizing. Efforts to improve functioning in patients with NCCP should consider addressing pain catastrophizing.

Background: Elevated levels of high-sensitivity C-reactive protein (hsCRP) are associated with higher risk of adverse outcomes in patients at risk for or with established coronary artery disease. Retrospective analyses suggest that this risk may be modified with statin therapy. However, a role for hsCRP in monitoring the success of therapy remains uncertain., Methods and Results: We measured the serum concentration of hsCRP at 30 days (n=3813) and 4 months in patients with non-ST-elevation or ST-elevation acute coronary syndrome randomly assigned to an early intensive versus delayed conservative simvastatin strategy in the Aggrastat-to-Zocor Trial. Patients with hsCRP >3 mg/L at 30 days had significantly higher 2-year mortality rates than those with hsCRP 1 to 3 mg/L or hsCRP <1 mg/L (6.1% versus 3.7% versus 1.6%, P<0.0001). Results were similar with hsCRP measured at 4 months. After adjusting for age, gender, diabetes, smoking, cardiovascular history, index event, lipid levels, and randomly assigned treatment, patients with hsCRP >3 mg/L were at more than 3-fold higher risk of death (HR, 3.7; 95% CI, 1.9 to 7.2) compared with those with hsCRP <1 mg/L. "Average" levels of hsCRP (1 to 3 mg/L) were also associated with increased risk compared with those with hsCRP <1 mg/L (HR, 2.3; 95% CI, 1.2 to 4.6). Patients allocated to early intensive statin therapy were more likely to achieve hsCRP levels <1 mg/L at 30 days (P=0.028) and 4 months (P<0.0001)., Conclusions: Achieved levels of hsCRP at 30 days and 4 months after acute coronary syndrome are independently associated with long-term survival. Patients treated with more aggressive statin therapy are more likely to achieve lower levels of hsCRP.

Background: Anxiety is often present with depression and may be one of its manifestations. Although the adverse effects of depression in patients with chronic heart failure (CHF) have been well studied, the relation between anxiety and CHF prognosis has not been addressed. In a secondary analysis of data collected for a published study of depression and prognosis in patients with CHF, we examined the relations among anxiety, depression, and prognosis., Methods and Results: We measured symptoms of anxiety with the Spielberger State-Trait Anxiety Inventory (STAI) scale and symptoms of depression with the Beck Depression Inventory (BDI) scale in 291 patients with CHF hospitalized as a result of cardiac events. We followed up these patients for all-cause mortality over 1 year. The mean scores for state anxiety (State-A) and trait anxiety (Trait-A) were identical at 33.5; the mean BDI score was 8.7+/-7.6. State-A and Trait-A scores correlated highly with each other (r=0.85; P<0.01) and with BDI score (State-A, r=0.52; Trait-A, r=0.59; P<0.01). Cox proportional-hazards model with and without confounding variables showed no relation between State-A or Trait-A and 1-year mortality. BDI scores, however, significantly predicted increased mortality during 1-year follow-up (hazard ratio, 1.04 for each 1-unit increase; P<0.01)., Conclusions: Although anxiety and depression are highly correlated in CHF patients, depression alone predicts a significantly worse prognosis for these patients.