BackgroundLow-density lipoprotein cholesterol (LDL-C) lowering is key to reduce atherosclerotic disease progression and recurrent events for patients after acute coronary syndrome (ACS). However,... Show moreBackgroundLow-density lipoprotein cholesterol (LDL-C) lowering is key to reduce atherosclerotic disease progression and recurrent events for patients after acute coronary syndrome (ACS). However, LDL-C management for post-ACS patients remains challenging in clinical practice.HypothesisThe ACS EuroPath III project was designed to optimize LDL-C management in post-ACS patients by promoting guideline implementation and translating existing evidence into effective actions.MethodsThree surveys targeting cardiologists (n = 555), general practitioners (GPs; n = 445), and patients (n = 662) were conducted in Europe, with the aim of capturing information on patient characteristics and treatment during acute phase, discharge and follow-up. GPs’ and patients’ opinions on key treatment aspects were also collected. Based on survey results, international experts and clinicians identified areas of improvement and generated prototype solutions. Participants voted to select the most feasible and replicable proposals for co-development and implementation.ResultsFive key areas of improvement were identified: (1) inappropriate treatment prescribed at discharge; (2) lack of lipid guidance in the discharge letter; (3) inadequate lipid-lowering therapy (LLT) optimization; (4) gaps in guideline knowledge and lack of referral practices for GPs; (5) patients’ concerns about lipid management. Proposed solutions for these focus areas included development of a treatment algorithm for the acute phase, a standardized GP discharge letter, an assessment tool for LLT efficacy at follow-up, an education plan for GPs/patients and a patient engagement discharge kit. The standardized GP discharge letter and treatment algorithm have been selected as the highest priority solutions for development.ConclusionThese initiatives have the potential to improve adherence to guidelines and patient management after ACS. Show less
Elevated red blood cell distribution width (RDW) is associated with increased risk for major adverse cardiovascular events (MACE) and death in patients with cardiovascular disease. The ODYSSEY OUT... Show moreElevated red blood cell distribution width (RDW) is associated with increased risk for major adverse cardiovascular events (MACE) and death in patients with cardiovascular disease. The ODYSSEY OUT-COMES trial compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome (ACS) and elevated atherogenic lipoproteins despite optimized statin treatment. This post hoc analysis determined whether RDW independently predicts risk of MACE and death in patients after recent ACS, whether RDW influences MACE reduction with alirocumab, and whether alirocumab treatment affects RDW. Associations of baseline RDW with risk of MACE and death were analyzed in the placebo group in adjusted proportional hazards models. Interactions of RDW and treatment on the risk of MACE and death were evaluated. An increasing quartile of RDW was associated with characteristics that predicted risk of MACE and death including age, hypertension, diabetes, atherosclerotic conditions and events, revascularizations, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. After ad-justing for baseline characteristics associated with the risk of MACE or death, baseline RDW remained independently associated with the risk of MACE and death in the placebo group (hazard ratios [95% confidence intervals] 1.08 [1.02-1.15] and 1.13 [1.03-1.24] per 1% increase of RDW, respectively, both p < 0.001). There was no interaction of RDW and treatment on MACE or death, nor did alirocumab affect RDW. RDW was associated with an increased risk of MACE and death, independent of established risk factors.(c) 2022 National Lipid Association. Published by Elsevier Inc.This is an open access article under the CC BY-NC-ND license( http://creativecommons.org/licenses/by-nc-nd/4.0/ ) Show less
BACKGROUND Cholesterol reduction with proprotein convertase subtitisin-kexin type 9 inhibitors reduces ischemic events; however, the cost-effectiveness in statin-treated patients with recent acute... Show moreBACKGROUND Cholesterol reduction with proprotein convertase subtitisin-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 atirocumab 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 Atirocumab) 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 tow-density lipoprotein cholesterol (LDL-C) level >= 70 mg/l, non-high-density lipoprotein cholesterol >= 100 mg/dl, or apotipoprotein B >= 80 mg/l. Atirocumab 75 mg or placebo was administered subcutaneously every 2 weeks. Atirocumab 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 atirocumab versus placebo and, based on clinical efficacy findings from the trial, was stratified by baseline LDL-C levels -100 mg/dt 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 a100 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, atirocumab improves cardiovascular outcomes at costs considered intermediate value, with good value in patients with baseline LDL-C mg/dt but less economic value with LDL-C >= 100 mg/dl. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Atirocumab [ODYSSEY OUTCOMES]; NCT01663402) (J Am Colt Cardiol 2020;75:2297-308) (C) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. Show less
BACKGROUND Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density... Show moreBACKGROUND Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C).OBJECTIVES A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE).METHODS One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina.RESULTS Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081).CONCLUSIONS Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402) (C) 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. Show less
