Cost-Effectiveness of LDL-C Lowering With Evolocumab in Patients With High Cardiovascular Risk in the United States

Randomized trials have shown marked reductions in low-density lipoprotein cholesterol (LDL-C), a risk factor for cardiovascular disease (CVD), when evolocumab is administered. We hypothesized that evolocumab added to standard of care (SOC) vs SOC alone is cost-effective in the treatment of patients with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic CVD (ASCVD) with or without statin intolerance and LDL-C >100 mg/dL. Using a Markov cohort state transition model, primary and recurrent CVD event rates were predicted considering population-specific trial-based mean risk factors and calibrated against observed rates in the real world. The LDL-C–lowering effect from population-specific phase 3 randomized studies for evolocumab was used together with estimated LDL-C–lowering effect on CVD event rates per 38.67-mg/dL LDL-C lowering from a statin-trial meta-analysis. Costs and utilities were included from published sources. Evolocumab treatment was associated with both increased cost and improved quality-adjusted life-years (QALY): HeFH (incremental cost: US$153 289, incremental QALY: 2.02, incremental cost-effectiveness ratio: US$75 863/QALY); ASCVD (US$158 307, 1.12, US$141 699/QALY); and ASCVD with statin intolerance (US$136 903, 1.36, US$100 309/QALY). Evolocumab met both the American College of Cardiology/American Heart Association (ACC/AHA) and World Health Organization (WHO) thresholds in each population evaluated. Sensitivity and scenario analyses confirmed that model results were robust to changes in model parameters. Among patients with HeFH and ASCVD with or without statin intolerance, evolocumab added to SOC may provide a cost-effective treatment option for lowering LDL-C using ACC/AHA intermediate/high value and WHO cost-effectiveness thresholds. More definitive information on the clinical and economic value of evolocumab will be available from the forthcoming CVD outcomes study

Prognosis, characteristics, and provision of care for patients with the unspecified heart failure electronic health record phenotype: a population-based linked cohort study of 95262 individuals

Background Whether the accuracy of the phenotype ascribed to patients in electronic health records (EHRs) is associated with variation in prognosis and care provision is unknown. We investigated this for heart failure (HF, characterised as HF with preserved ejection fraction [HFpEF], HF with reduced ejection fraction [HFrEF] and unspecified HF). Methods We included individuals aged 16 years and older with a new diagnosis of HF between January 2, 1998 and February 28, 2022 from linked primary and secondary care records in the Clinical Practice Research Datalink in England. We investigated the provision of guideline-recommended diagnostic investigations and pharmacological treatments. The primary outcome was a composite of HF hospitalisation or all-cause death, and secondary outcomes were time to HF hospitalisation, all-cause death and death from cardiovascular causes. We used Kaplan–Meier curves and log rank tests to compare survival across HF phenotypes and adjusted for potential confounders in Cox proportional hazards regression analyses. Findings Of a cohort of 95,262 individuals, 1271 (1.3%) were recorded as having HFpEF, 10,793 (11.3%) as HFrEF and 83,198 (87.3%) as unspecified HF. Individuals recorded as unspecified HF were older with a higher prevalence of dementia. Unspecified HF, compared to patients with a recorded HF phenotype, were less likely to receive specialist assessment, echocardiography or natriuretic peptide testing in the peri-diagnostic period, or receive angiotensin-converting enzyme inhibitors, beta blockers or mineralocorticoid receptor antagonists up to 12 months after diagnosis (risk ratios compared to HFrEF, 0.64, 95% CI 0.63–0.64; 0.59, 0.58–0.60; 0.57, 0.55–0.59; respectively) and had significantly worse outcomes (adjusted hazard ratios compared to HFrEF, HF hospitalisation and death 1.66, 95% CI 1.59–1.74; all-cause mortality 2.00, 1.90–2.10; cardiovascular death 1.77, 1.65–1.90). Interpretation Our findings suggested that absence of specification of HF phenotype in routine EHRs is inversely associated with clinical investigations, treatments and survival, representing an actionable target to mitigate prognostic and health resource burden

Cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab in patients with a history of myocardial infarction in Sweden

Aims To assess the cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab added to standard-of-care lipid-lowering treatment [maximum tolerated dose (MTD) of statin and ezetimibe] in Swedish patients with a history of myocardial infarction (MI). Methods and results Cost-effectiveness was evaluated using a Markov model based on Swedish observational data on cardiovascular event rates and efficacy from the FOURIER trial. Three risk profiles were considered: recent MI in the previous year; history of MI with a risk factor; and history of MI with a second event within 2 years. For each population, three minimum baseline low-density lipoprotein cholesterol (LDL-C) levels were considered: 2.5 mmol/L (≈100 mg/dL), based on the current reimbursement recommendation in Sweden; 1.8 mmol/L (≈70 mg/dL), based on 2016 ESC/EAS guidelines; and 1.4 mmol/L (≈55 mg/dL), or 1.0 mmol/L (≈40 mg/dL) for MI with a second event, based on 2019 ESC/EAS guidelines. Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab was associated with increased quality-adjusted life-years and costs vs. standard-of-care therapy. Incremental cost-effectiveness ratios (ICERs) were below SEK700 000 (∼€66 500), the generally accepted willingness-to-pay threshold in Sweden, for minimum LDL-C levels of 2.3 (recent MI), 1.7 (MI with a risk factor), and 1.7 mmol/L (MI with a second event). Sensitivity analyses demonstrated that base-case results were robust to changes in model parameters. Conclusion Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab added to MTD of statin and ezetimibe may be considered cost-effective at its list price for minimum LDL-C levels of 1.7–2.3 mmol/L, depending on risk profile, with ICERs below the accepted willingness-to-pay threshold in Sweden

Cost-effectiveness of Evolocumab therapy for reducing cardiovascular events in patients with atherosclerotic cardiovascular disease

Importance: The proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab has been demonstrated to reduce the composite of myocardial infarction, stroke, or cardiovascular death in patients with established atherosclerotic cardiovascular disease. To our knowledge, long-term cost-effectiveness of this therapy has not been evaluated using clinical trial efficacy data. Objective: To evaluate the cost-effectiveness of evolocumab in patients with atherosclerotic cardiovascular disease when added to standard background therapy. Design, Setting, and Participants: A Markov cohort state-transition model was used, integrating US population-specific demographics, risk factors, background therapy, and event rates along with trial-based event risk reduction. Costs, including price of drug, utilities, and transitional probabilities, were included from published sources. Exposures: Addition of evolocumab to standard background therapy including statins. Main Outcomes and Measures: Cardiovascular events including myocardial infarction, ischemic stroke and cardiovascular death, quality-adjusted life-year (QALY), incremental cost-effectiveness ratio (ICER), and net value-based price. Results: In the base case, using US clinical practice patients with atherosclerotic cardiovascular disease with low-density lipoprotein cholesterol levels of at least 70 mg/dL (to convert to millimoles per liter, multiply by 0.0259) and an annual events rate of 6.4 per 100 patient-years, evolocumab was associated with increased cost and improved QALY: incremental cost, $105 398; incremental QALY, 0.39, with an ICER of$268 637 per QALY gained ($165 689 with discounted price of$10 311 based on mean rebate of 29% for branded pharmaceuticals). Sensitivity and scenario analyses demonstrated ICERs ranging from $100 193 to$488 642 per QALY, with ICER of $413 579 per QALY for trial patient characteristics and event rate of 4.2 per 100 patient-years ($270 192 with discounted price of $10 311) and$483 800 if no cardiovascular mortality reduction emerges. Evolocumab treatment exceeded $150 000 per QALY in most scenarios but would meet this threshold at an annual net price of$9669 ($6780 for the trial participants) or with the discounted net price of$10 311 in patients with low-density lipoprotein cholesterol levels of at least 80 mg/dL. Conclusions and Relevance: At its current list price of $14 523, the addition of evolocumab to standard background therapy in patients with atherosclerotic cardiovascular disease exceeds generally accepted cost-effectiveness thresholds. To achieve an ICER of$150 000 per QALY, the annual net price would need to be substantially lower ($9669 for US clinical practice and$6780 for trial participants), or a higher-risk population would need to be treated

Association between early oral β-blocker therapy and risk for in-hospital major bleeding after percutaneous coronary intervention for acute coronary syndrome: findings from CCC-ACS project

Aims: Information regarding β-blocker use and bleeding risk in patients on antithrombotic therapy in contemporary practice is limited. We examined the association between early (within the first 24 hours) oral β-blocker therapy and major in-hospital bleeds among acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI). Methods and results: In the Improving Care for Cardiovascular Disease in China-ACS project, among patients without contraindications to β-blocker, we examined the association between early oral β-blocker exposure [users/non-users, dosing, and type (metoprolol vs. bisoprolol)] and major in-hospital bleeds. Of the 43 640 eligible patients, 36.0% patients received early oral β-blocker and 637 major bleeds were recorded. Compared with non-users, early oral β-blocker was associated reduced risks for major bleeds [odds ratio (OR): 0.48; 95% confidence interval (CI): 0.38-0.61] and in-hospital mortality (OR: 0.47; 95% CI: 0.34-0.64) in multivariable-adjusted logistic regression models. Early oral β-blocker use associated reduction in major bleeding was evident both in high-dose (defined by metoprolol-equivalent dose &ge;50 mg/day) users (OR: 0.47; 95% CI: 0.33-0.68) and in low-dose users (metoprolol-equivalent dose <50 mg/day; OR: 0.61; 95% CI: 0.47-0.79). No significant difference was observed between metoprolol and bisoprolol in terms of reductions in major bleeding and mortality. Analyses based on inverse-probability-of-treatment-weighted regression adjustment and propensity-score matching yielded consistent findings. Conclusion: In this retrospective study based on the nationwide ACS registry, among patients treated by PCI, in addition to a reduction in in-hospital mortality, oral β-blocker therapy initiated within the first 24 hours was associated with a reduced risk for major in-hospital bleeds. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT0230661

A Risk Stratification Scheme for In-Hospital Cardiogenic Shock in Patients With Acute Myocardial Infarction

Objective: Cardiogenic shock (CS) is the leading cause of death in patients with acute myocardial infarction (AMI) despite advances in care. This study aims to derive and validate a risk score for in-hospital development of CS in patients with AMI. Methods: In this study, we used the Improving Care for Cardiovascular Disease in China–Acute Coronary Syndrome (CCC–ACS) registry of 76,807 patients for model development and internal validation. These patients came from 158 tertiary hospitals and 82 secondary hospitals between 2014 and 2019, presenting AMI without CS upon admission. The eligible patients with AMI were randomly assigned to derivation (n = 53,790) and internal validation (n = 23,017) cohorts. Another cohort of 2,205 patients with AMI between 2014 and 2016 was used for external validation. Based on the identified predictors for in-hospital CS, a new point-based CS risk scheme, referred to as the CCC–ACS CS score, was developed and validated. Results: A total of 866 (1.1%) and 39 (1.8%) patients subsequently developed in-hospital CS in the CCC–ACS project and external validation cohort, respectively. The CCC–ACS CS score consists of seven variables, including age, acute heart failure upon admission, systolic blood pressure upon admission, heart rate, initial serum creatine kinase-MB level, estimated glomerular filtration rate, and mechanical complications. The area under the curve for in-hospital development of CS was 0.73, 0.71, and 0.85 in the derivation, internal validation and external validation cohorts, respectively. Conclusion: This newly developed CCC–ACS CS score can quantify the risk of in-hospital CS for patients with AMI, which may help in clinical decision making. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02306616

Malnutrition as assessed by nutritional risk index is associated with worse outcome in patients admitted with acute decompensated heart failure: an ACAP-HF data analysis

Malnutrition is common at hospital admission and tends to worsen during hospitalization. This controlled population study aimed to determine if serum albumin or moderate and severe nutritional depletion by Nutritional Risk Index (NRI) at hospital admission are associated with increased length of hospital stay (LOS) in patients admitted with acute decompensated heart failure (ADHF). Serum albumin levels and lymphocyte counts were retrospectively determined at hospital admission in 1740 consecutive patients admitted with primary and secondary diagnosis of ADHF. The Nutrition Risk Score (NRI) developed originally in AIDS and cancer populations was derived from the serum albumin concentration and the ratio of actual to usual weight, as follows: NRI = (1.519 × serum albumin, g/dL) + {41.7 × present weight (kg)/ideal body weight(kg)}. Patients were classified into four groups as no, mild, moderate or severe risk by NRI. Multiple logistic regressions were used to determine the association between nutritional risk category and LOS

Asymptomatic atrial fibrillation among hospitalized patients: clinical correlates and in-hospital outcomes in Improving Care for Cardiovascular Disease in China-Atrial Fibrillation

AIMS: The clinical correlates and outcomes of asymptomatic atrial fibrillation (AF) in hospitalized patients are largely unknown. We aimed to investigate the clinical correlates and in-hospital outcomes of asymptomatic AF in hospitalized Chinese patients. METHODS AND RESULTS: We conducted a cross-sectional registry study of inpatients with AF enrolled in the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation Project between February 2015 and December 2019. We investigated the clinical characteristics of asymptomatic AF and the association between the clinical correlates and the in-hospital outcomes of asymptomatic AF. Asymptomatic and symptomatic AF were defined according to the European Heart Rhythm Association score. Asymptomatic patients were more commonly males (56.3%) and had more comorbidities such as hypertension (57.4%), diabetes mellitus (18.6%), peripheral artery disease (PAD; 2.3%), coronary artery disease (55.5%), previous history of stroke/transient ischaemic attack (TIA; 17.9%), and myocardial infarction (MI; 5.4%); however, they had less prevalent heart failure (9.6%) or left ventricular ejection fractions ≤40% (7.3%). Asymptomatic patients were more often hospitalized with a non-AF diagnosis as the main diagnosis and were more commonly first diagnosed with AF (23.9%) and long-standing persistent/permanent AF (17.0%). The independent determinants of asymptomatic presentation were male sex, long-standing persistent AF/permanent AF, previous history of stroke/TIA, MI, PAD, and previous treatment with anti-platelet drugs. The incidence of in-hospital clinical events such as all-cause death, ischaemic stroke/TIA, and acute coronary syndrome (ACS) was higher in asymptomatic patients than in symptomatic patients, and asymptomatic clinical status was an independent risk factor for in-hospital all-cause death, ischaemic stroke/TIA, and ACS. CONCLUSION: Asymptomatic AF is common among hospitalized patients with AF. Asymptomatic clinical status is associated with male sex, comorbidities, and a higher risk of in-hospital outcomes. The adoption of effective management strategies for patients with AF should not be solely based on clinical symptoms

Effect of nesiritide in patients with acute decompensated heart failure

Background Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. Methods We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. Results Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P = 0.03) and 24 hours (68.2% vs. 66.1%, P = 0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, −0.7 percentage points; 95% confidence interval [CI], −2.1 to 0.7; P = 0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, −0.4 percentage points; 95% CI, −1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P = 0.11). Conclusions Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.