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

Performance of Management Strategies with Class i Recommendations among Patients Hospitalized with ST-Segment Elevation Myocardial Infarction in China

Importance: Despite advances in the treatment of ST-segment elevation myocardial infarction (STEMI), little is known about how this evolving knowledge is applied in current clinical practice in China. Objective: To evaluate hospital performance and temporal trends in the management of STEMI. Design, Setting, and Participants: This study used data from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project, a nationwide quality improvement registry, in collaboration with the American Heart Association and the Chinese Society of Cardiology. Participants included patients with STEMI admitted to 143 tertiary hospitals across China from November 2014 to July 2019, and data were analyzed from November 2020 to December 2021. Main Outcomes and Measures: Levels, hospital-level variations, and trends for utilization rates of the 9 management strategies with Class I recommendations in Chinese and US guidelines. Results: A total of 57560 hospitalizations with STEMI were included. Overall, 20.0% of patients received all the care according to the 9 guideline-recommended strategies. The performance rate of quality measures was low for reperfusion therapy (61.0%, 35115/57560 patients), β-blocker at discharge (68.3%, 37750/55285 patients), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at discharge (55.1%, 2524/4578 patients), and smoking cessation counseling (36.5%, 9586/26265 patients) among those who were eligible. Of 25563 patients who underwent primary percutaneous coronary intervention (PCI), 66.8% underwent this procedure within 90 minutes of hospital arrival. Of 1128 patients who underwent fibrinolysis therapy, 253 (22.4%) underwent this treatment within 30 minutes of hospital arrival. Measures with high performance rates included receipt of dual antiplatelet therapy within 24 hours (95.5%, 54263/56848 patients) and at discharge (91.8%, 51452/56019 patients) and receipt of statin at discharge (93.0%, 52214/56141 patients) for those eligible. There was significant variation between hospitals in all-or-none score (ranging from 0 to 61.9%) and performance of individual measures. The quality of care improved during the study period, especially for reperfusion therapy, primary PCI within the first 90 minutes of hospital arrival, and smoking cessation counseling. Conclusions and Relevance: The quality of care for patients hospitalized with STEMI does not meet guideline-recommended strategies in China, with only 1 in 5 patients receiving all the care according to the 9 guideline-recommended strategies. Large disparities in the quality of care exist across hospitals

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

Postprocedure Anticoagulation in Patients With Acute ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Objectives: This study sought to assess the association between postprocedural anticoagulation (PPAC) use and several clinical outcomes. Background: PPAC after primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation myocardial infarction (STEMI) may prevent recurrent ischemic events but may increase the risk of bleeding. No consensus has been reached on PPAC use. Methods: Using data from the Improving Care for Cardiovascular Disease in China–Acute Coronary Syndrome registry, conducted between 2014 and 2019, we stratified all STEMI patients who underwent pPCI according to the use of PPAC or not. Inverse probability of treatment weighting and a Cox proportional hazards model with hospital as random effect were used to analyze differences in in-hospital clinical outcomes: the primary efficacy endpoint was mortality and the primary safety endpoint was major bleeding. Results: Of 34,826 evaluable patients, 26,272 (75.4%) were treated with PPAC and were on average younger, more stable at admission with lower bleeding risk score, more likely to have comorbidities and multivessel disease, and more often treated within 12 hours of symptom onset than those without PPAC. After inverse probability of treatment weighting adjustment for baseline differences, PPAC was associated with significantly reduced risk of in-hospital mortality (0.9% vs 1.8%; HR: 0.62; 95% CI: 0.43-0.89; P < 0.001) and a nonsignificant difference in risk of in-hospital major bleeding (2.5% vs 2.2%; HR: 1.05; 95% CI: 0.83-1.32; P = 0.14). Conclusions: PPAC in STEMI patients after pPCI was associated with reduced mortality without increasing major bleeding complications. Dedicated randomized trials with contemporary STEMI management are needed to confirm these findings

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

Risk Factors for In-Hospital Cardiac Arrest in Patients With ST-Segment Elevation Myocardial Infarction

Background: In-hospital cardiac arrest (IHCA) is one of the most deleterious complications of ST-segment elevation myocardial infarction (STEMI). Objectives: We systematically analyzed the clinical characteristics of STEMI patients with IHCA, as well as predictors and treatments associated with risk of IHCA, using a nationwide database. Methods: In the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project (2014-2019), we stratified patients presenting with STEMI within 24 hours after symptom onset according to IHCA or no IHCA during the index hospitalization. We analyzed patients’ clinical characteristics, mortality, and independent correlates of IHCA. Results: Of 40,670 STEMI patients, 2.2% (95% CI: 2.1%-2.4%) experienced IHCA. Among IHCA patients, the in-hospital mortality was 53.0% (95% CI: 49.7%-56.3%). IHCA represents 55.0% (95% CI: 51.6%-58.4%) of inpatient deaths. Age ≥75 years, female, nonsmoker, prior diabetes mellitus, prior renal failure, out-of-hospital cardiac arrest, heart rate >100 beats/min, systolic blood pressure <90 mm Hg, and Killip IV were identified as predictors of IHCA. IHCA patients were less likely to receive β-blockers and ticagrelor during the first 24 hours after first medical contact and were less likely to undergo primary percutaneous coronary intervention. After adjustment, primary percutaneous coronary intervention (adjusted HR: 0.82; 95% CI: 0.71-0.95), β-blockers (adjusted HR: 0.63; 95% CI: 0.47-0.86), and ticagrelor (adjusted HR: 0.57; 95% CI: 0.42-0.76) were associated with a reduced risk of IHCA. Conclusions: IHCA is rare in STEMI but is associated with high mortality. Multiple modifiable and unmodifiable factors are associated with its occurrence, suggesting that early intervention and rational drug treatment may improve its prognosis. (CCC Project- Acute Coronary Syndrome; NCT02306616

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