Guideline LDL-C Threshold Achievement in Acute Myocardial Infarction Patients: A Real-World Evidence Study Demonstrating the Impact of Treatment Intensification with PCSK9i.

INTRODUCTION: A high proportion of Canadian patients with acute myocardial infarction (AMI) do not achieve the threshold low-density lipoprotein cholesterol (LDL-C) levels recommended by the Canadian Cardiovascular Society in 2021. This increases the risk of subsequent atherosclerotic cardiovascular disease (ASCVD) events. Here, we assess LDL-C levels and threshold achievement among patients by lipid-lowering therapies (LLT) received post-AMI. METHODS: A retrospective cohort study of patients identified with AMI between 2015 and 2019 was conducted using administrative health databases in Alberta, Canada. Patients were grouped by their highest-intensity LLT post-AMI (proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) + another LLT; PCSK9i alone; ezetimibe + statin; statins (high, moderate, low intensity); or ezetimibe alone), and available LDL-C levels were examined in the year before and after LLT dispense date. RESULTS: The cohort included 15,283 patients. In patients on PCSK9i + LLT, the median [95% confidence interval (CI)] LDL-C levels decreased from 2.7 (2.3-3.4) before to 0.9 (0.5-1.2) mmol/l after treatment, the largest decrease among treatment groups. In the ezetimibe + statin and high-intensity statin groups, median (95% CI) values after treatment were 1.5 (1.5-1.6) and 1.4 (1.4-1.4) mmol/l, respectively. The proportion of patients below the 1.8 mmol/l threshold increased by 77.7% in the PSCK9i + LLT group after treatment, compared to 45.4 and 32.4% in the ezetimibe + statin and high-intensity statin groups, respectively. CONCLUSIONS: Intensification with PCSK9i in AMI patients results in a greater proportion of patients achieving below the recommended LDL-C threshold versus statins and or ezetimibe alone. Increased focus on achieving below the LDL-C thresholds with additional LLT as required may benefit patient cardiovascular outcomes.

Cost-Effectiveness Analysis of Evolocumab in Adult Patients with Atherosclerotic Cardiovascular Disease in Canada.

INTRODUCTION: To evaluate the cost-effectiveness of evolocumab when added to standard of care lipid-lowering treatment (LLT) for patients with atherosclerotic cardiovascular disease (ASCVD) who cannot adequately control their low-density lipoprotein cholesterol (LDL-C) despite optimized LLT in Canada. METHODS: An incremental cost-utility analysis was conducted using a Markov cohort state transition model adapted to the Canadian setting. Analyses were conducted from a public health and societal perspective using a lifetime time horizon for Canada. Scenario analyses were conducted on the basis of recommendations from the 2021 Canadian Cardiovascular Society (CCS) dyslipidemia guidelines. RESULTS: In ASCVD patients with prior myocardial infarction (MI) and baseline LDL-C ≥ 1.8 mmol/L, adding evolocumab to optimized statin therapy with or without ezetimibe is associated with an incremental cost per quality-adjusted life year (QALY) gained of $66,453 CAD. Furthermore, for every 100 patients treated with evolocumab for lifetime, adding evolocumab to optimized LLT will prevent approximately 52 cardiovascular (CV) events, of which seven would be fatal. The results are generally robust using univariate and simultaneous variation in model input parameters. Scenario analyses for patient populations as per the CCS guidelines suggest that evolocumab added to optimized LLT may be considered cost-effective, given an incremental cost-effectiveness ratio (ICER) threshold of CAD$100,000 per QALY gained. Limitations associated with this analysis should be interpreted in the context of data and modeling assumptions used. CONCLUSION: Overall, this analysis supports reimbursement of evolocumab by payers in patients with ASCVD who cannot reach LDL-C thresholds despite optimized LLT to reduce unnecessary fatal and non-fatal CV events.

Prevalence of atherosclerotic cardiovascular disease and subsequent major adverse cardiovascular events in Alberta, Canada: A real-world evidence study.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality worldwide. Data from Canadian populations regarding the burden of ASCVD are limited. Therefore, we describe the 5-year period prevalence of ASCVD and subsequent major adverse cardiovascular event (MACE) outcomes among patients with ASCVD in Alberta, Canada. METHODS: A retrospective, observational study was conducted by linking provincial health services data, vital statistics, and pharmaceutical dispenses data. Five-year period prevalence of clinical ASCVD was captured between 2011 and 2016, and a cohort of adult patients with an initial clinical ASCVD event were identified between 2012 and 2016. One-year incidence rates (IRs) of subsequent MACE outcomes were calculated as composite and individual measures. A subgroup of patients with acute myocardial infarction (AMI) as their index event was examined. RESULTS: There were 198 573 patients (mean [standard deviation] age: 63.9 [15.6] years; 56.6% males) identified with clinical ASCVD between 2012 and 2016. Overall, the 5-year period prevalence of ASCVD in Alberta was 89.9 per 1000 persons and the 1-year IR for a primary MACE outcome was 6.15 (95% confidence interval [CI]: 6.03-6.26) per 100 person-years. Among the ASCVD cohort, 9465 had an AMI as their index event and the IR for a primary MACE outcome was 14.30 (95% CI: 13.45-15.20) per 100 person-years. CONCLUSIONS: This study found that the prevalence of ASCVD and the rate of subsequent MACE outcomes 1 year following the initial ASCVD event are substantial, particularly among patients with an AMI. Secondary prevention strategies aimed at lowering this risk are needed for patients with ASCVD.