Cost-Effectiveness of Alirocumab in Patients With Acute Coronary Syndromes: The ODYSSEY OUTCOMES Trial.

BACKGROUND: Cholesterol reduction with proprotein convertase subtilisin-kexin type 9 inhibitors reduces ischemic events; however, the cost-effectiveness in statin-treated patients with recent acute coronary syndrome remains uncertain. OBJECTIVES: This study sought to determine whether further cholesterol reduction with alirocumab would be cost-effective in patients with a recent acute coronary syndrome on optimal statin therapy. METHODS: A cost-effectiveness model leveraging patient-level data from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was developed to estimate costs and outcomes over a lifetime horizon. Patients (n = 18,924) had a recent acute coronary syndrome and were on high-intensity or maximum-tolerated statin therapy, with a baseline low-density lipoprotein cholesterol (LDL-C) level ≥70 mg/dl, non-high-density lipoprotein cholesterol ≥100 mg/dl, or apolipoprotein B ≥80 mg/l. Alirocumab 75 mg or placebo was administered subcutaneously every 2 weeks. Alirocumab was blindly titrated to 150 mg if LDL-C remained ≥50 mg/dl or switched to placebo if 2 consecutive LDL-C levels were <15 mg/dl. Incremental cost per quality-adjusted life-year (QALY) was determined with the addition of alirocumab versus placebo and, based on clinical efficacy findings from the trial, was stratified by baseline LDL-C levels ≥100 mg/dl and <100 mg/dl. RESULTS: Across the overall population recruited to the ODYSSEY OUTCOMES trial, using an annual treatment cost of US$5,850, the mean overall incremental cost-effectiveness ratio was US$92,200 per QALY (base case). The cost was US$41,800 per QALY in patients with baseline LDL-C ≥100 mg/dl, whereas in those with LDL-C <100 mg/dl the cost per QALY was US$299,400. Among patients with LDL-C ≥100 mg/dl, incremental cost-effectiveness ratios remained below US$100,000 per QALY across a wide variety of sensitivity analyses. CONCLUSIONS: In patients with a recent acute coronary syndrome on optimal statin therapy, alirocumab improves cardiovascular outcomes at costs considered intermediate value, with good value in patients with baseline LDL-C ≥100 mg/dl but less economic value with LDL-C <100 mg/dl. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402).

Addressing Social Determinants of Health in the Care of Patients With Heart Failure: A Scientific Statement From the American Heart Association.

Heart failure is a clinical syndrome that affects >6.5 million Americans, with an estimated 550 000 new cases diagnosed each year. The complexity of heart failure management is compounded by the number of patients who experience adverse downstream effects of the social determinants of health (SDOH). These patients are less able to access care and more likely to experience poor heart failure outcomes over time. Many patients face additional challenges associated with the cost of complex, chronic illness management and must make difficult decisions about their own health, particularly when the costs of medications and healthcare appointments are at odds with basic food and housing needs. This scientific statement summarizes the SDOH and the current state of knowledge important to understanding their impact on patients with heart failure. Specifically, this document includes a definition of SDOH, provider competencies, and SDOH assessment tools and addresses the following questions: (1) What models or frameworks guide healthcare providers to address SDOH? (2) What are the SDOH affecting the delivery of care and the interventions addressing them that affect the care and outcomes of patients with heart failure? (3) What are the opportunities for healthcare providers to address the SDOH affecting the care of patients with heart failure? We also include a case study (Data Supplement) that highlights an interprofessional team effort to address and mitigate the effects of SDOH in an underserved patient with heart failure.

Risk of Major Adverse Cardiovascular Events and Major Hemorrhage Among White and Black Patients Undergoing Percutaneous Coronary Intervention.

Background Data on racial disparities in major adverse cardiovascular events (MACE) and major hemorrhage (HEM) after percutaneous coronary intervention are limited. Factors contributing to these disparities are unknown. Methods and Results PRiME-GGAT (Pharmacogenomic Resource to Improve Medication Effectiveness-Genotype-Guided Antiplatelet Therapy) is a prospective cohort. Patients aged ≥18 years undergoing percutaneous coronary intervention were enrolled and followed for up to 1 year. Racial disparities in risk of MACE and HEM were assessed using an incident rate ratio. Sequential cumulative adjustment analyses were performed to identify factors contributing to these disparities. Data from 919 patients were included in the analysis. Compared with white patients, black patients (n=203; 22.1% of the cohort) were younger and were more likely to be female, to be a smoker, and to have higher body mass index, lower socioeconomic status, higher prevalence of diabetes mellitus and moderate to severe chronic kidney disease, and presentation with acute coronary syndrome and to undergo urgent percutaneous coronary intervention. The incident rates of MACE (34.1% versus 18.2% per 100 person-years, P<0.001) and HEM (17.7% versus 10.3% per 100 person-years, P=0.02) were higher in black patients. The incident rate ratio was 1.9 (95% CI, 1.3-2.6; P<0.001) for MACE and 1.7 (95% CI, 1.1-2. 7; P=0.02) for HEM. After adjustment for nonclinical and clinical factors, black race was not significantly associated with outcomes. Rather, differences in socioeconomic status, comorbidities, and coronary heart disease severity were attributed to racial disparities in outcomes. Conclusions Despite receiving similar treatment, racial disparities in MACE and HEM still exist. Opportunities exist to narrow these disparities by mitigating the identified contributors.

Variation in Lipid-Lowering Therapy Use in Patients With Low-Density Lipoprotein Cholesterol ≥190 mg/dL: Insights From the National Cardiovascular Data Registry-Practice Innovation and Clinical Excellence Registry.

BACKGROUND: Patients with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL are at high risk of atherosclerotic cardiovascular disease events. Treatment guidelines recommend intensive treatment in these patients. Variation in the use of lipid-lowering therapies (LLTs) in these patients in a national sample of cardiology practices is not known. METHODS AND RESULTS: Using data from the American College of Cardiology National Cardiovascular Data Registry-Practice Innovation and Clinical Excellence registry, we assessed the proportion of patients with LDL-C ≥190 mg/dL (n=49 447) receiving statin, high-intensity statin, LLT associated with ≥50% LDL-C lowering, ezetimibe, or a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor between January 2013 and December 2016. We assessed practice-level rates and variation in LLT use using median rate ratio (MRR) adjusted for patient and practice characteristics. MRRs represent the likelihood that 2 random practices would differ in treatment of identical patients with LDL-C ≥190 mg/dL. The proportion of patients receiving a statin, high-intensity statin, LLT associated with ≥50% LDL-C reduction, ezetimibe, or PCSK9 inhibitor were 58.5%, 31.9%, 34.6%, 8.5%, and 1.5%, respectively. Median practice-level rates and adjusted MRR for statin (56% [interquartile range, 47.3%-64.8%]; MRR, 1.20 [95% confidence interval [CI], 1.17-1.23]), high-intensity statin (30.2% [interquartile range, 12.1%-41.1%]; MRR, 2.31 [95% CI, 2.12-2.51]), LLT with ≥50% LDL-C lowering (31.8% [interquartile range, 15.3%-45.5%]; MRR, 2.12 [95% CI, 1.95-2.28]), ezetimibe (5.8% [interquartile range, 2.8%-9.8%]; MRR, 2.42 [95% CI, 2.21-2.63]), and PCSK9 inhibitors (0.16% [interquartile range, 0%-1.9%]; MRR, 2.38 [95% CI, 2.04-2.72]) indicated significant gaps and >200% variation in receipt of several of these medications for patients across practices. Among those without concomitant atherosclerotic cardiovascular disease, even larger treatment gaps were noted (proportion of patients on a statin, high-intensity statin, LLT with ≥50% LDL-C reduction, ezetimibe, or PCSK9 inhibitor were 50.8%, 25.25%, 26.8%, 4.9%, and 0.74%, respectively). CONCLUSIONS: Evidence-based LLT use remains low among patients with elevated LDL-C with significant variation in care. System-level interventions are needed to address these gaps and reduce variation in care of these high-risk patients.

Association of race and sex with risk of incident acute coronary heart disease events.

CONTEXT: It is unknown whether long-standing disparities in incidence of coronary heart disease (CHD) among US blacks and whites persist. OBJECTIVE: To examine incident CHD by black and white race and by sex. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 24,443 participants without CHD at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, who resided in the continental United States and were enrolled between 2003 and 2007 with follow-up through December 31, 2009. MAIN OUTCOME MEASURE: Expert-adjudicated total (fatal and nonfatal) CHD, fatal CHD, and nonfatal CHD (definite or probable myocardial infarction [MI]; very small non-ST-elevation MI [NSTEMI] had peak troponin level <0.5 µg/L). RESULTS: Over a mean (SD) of 4.2 (1.5) years of follow-up, 659 incident CHD events occurred (153 in black men, 138 in black women, 254 in white men, and 114 in white women). Among men, the age-standardized incidence rate per 1000 person-years for total CHD was 9.0 (95% CI, 7.5-10.8) for blacks vs 8.1 (95% CI, 6.9-9.4) for whites; fatal CHD: 4.0 (95% CI, 2.9-5.3) vs 1.9 (95% CI, 1.4-2.6), respectively; and nonfatal CHD: 4.9 (95% CI, 3.8-6.2) vs 6.2 (95% CI, 5.2-7.4). Among women, the age-standardized incidence rate per 1000 person-years for total CHD was 5.0 (95% CI, 4.2-6.1) for blacks vs 3.4 (95% CI, 2.8-4.2) for whites; fatal CHD: 2.0 (95% CI, 1.5-2.7) vs 1.0 (95% CI, 0.7-1.5), respectively; and nonfatal CHD: 2.8 (95% CI, 2.2-3.7) vs 2.2 (95% CI, 1.7-2.9). Age- and region-adjusted hazard ratios for fatal CHD among blacks vs whites was near 2.0 for both men and women and became statistically nonsignificant after multivariable adjustment. The multivariable-adjusted hazard ratio for incident nonfatal CHD for blacks vs whites was 0.68 (95% CI, 0.51-0.91) for men and 0.81 (95% CI, 0.58-1.15) for women. Of the 444 nonfatal CHD events, 139 participants (31.3%) had very small NSTEMIs. CONCLUSIONS: The higher risk of fatal CHD among blacks compared with whites was associated with cardiovascular disease risk factor burden. These relationships may differ by sex.