After acute myocardial infarction (AMI), a high proportion of Canadian patients do not achieve the threshold low-density lipoprotein cholesterol (LDL-C) levels (<1.8 mmol/L) recommended by the Canadian Cardiovascular Society in 2021, which increases the risk of subsequent atherosclerotic cardiovascular disease (ASCVD) events such as myocardial infarction, ischemic stroke, peripheral artery disease, and cardiovascular mortality (1,2).

As part of a larger real-world evidence study examining ASCVD outcomes across Alberta, Canada, Medlior and Amgen Canada, in collaboration with expert clinical advisors, examined the LDL-C levels and threshold achievement among patients dispensed lipid-lowering therapies (LLT) post-AMI. The study examined three LDL-C thresholds of <1.8, <1.4, and <1.0 mmol/L recommended by recent Canadian, American, and European guidelines for therapeutic intensification from statins among patients with ASCVD and very high-risk subgroups (3-5). Findings were published recently in the journal Cardiology and Therapy (6).

What the study examined

A retrospective cohort study of patients identified with AMI between April 1, 2015 and March 31, 2019 was conducted using administrative health databases in Alberta. Patients were grouped by their highest-intensity LLT dispensed post-AMI; LLTs were mutually exclusive and categorized based on the following hierarchy:

• Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) + another LLT
• PCSK9i alone
• Ezetimibe + statin
• Statins at high, moderate, or low intensity
• Ezetimibe alone

Available LDL-C levels were examined in the year before and the year after the LLT dispense date, for each treatment group.

Study highlights

• The time between AMI event and the highest-intensity LLT was markedly longer for patients receiving PSCK9i. The median (IQR) times were:
  • PCSK9i + LLT = 324.0 (127.0-454.0) days
  • PCSK9i alone = 387.5 (179.0-710.0) days
  • Ezetimibe + statin group = 121.0 (26.0-458.0) days
  • High-intensity statin group = 0.0 (0.0-7.0) days
  • Ezetimibe alone group = 18.0 (0.0-65.0) days
• The greatest reduction in LDL-C levels was seen when patients were on PCSK9i + LLT.
  • Median (95% confidence interval) LDL-C levels decreased from 2.7 (2.3-3.4) mmol/L before to 0.9 (0.5-1.2) mmol/L after treatment.
• The proportion of patients below the 1.8 mmol/L threshold increased by 77.7% in the PSCK9i + LLT group after treatment. Similar changes were observed for the other two thresholds.

What do the results mean?

This study presents further evidence that in a real-world Canadian population of high-risk patients with AMI, PCSK9i therapy in combination with other LLTs or alone is associated with better LDL-C reduction and higher proportions of patients meeting guideline thresholds; however, there was a longer time between the AMI event and PCSK9i treatments.

Future research in this discipline could focus on quantifying the economic burden from the gap in time between ASCVD events and PCSK9i treatment initiation, which could lead to subsequent CV events, and how earlier treatment intensification may benefit high-risk subgroups of patients with ASCVD.

This study was sponsored by Amgen Canada and in collaboration with expert clinical advisors Dr. Todd Anderson, Dr. Bryan Har, and Medlior. The published article describing this study is freely available from the journal Cardiology and Therapy: https://link.springer.com/article/10.1007/s40119-022-00300-7.

Sources:

1. Sarak B, Savu A, Kaul P, et al. Lipid Testing, Lipid-Modifying Therapy, and PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) Inhibitor Eligibility in 27 979 Patients With Incident Acute Coronary Syndrome. Circ Cardiovasc Qual Outcomes 2021; 14(4): e006646.
2. Sud M, Han L, Koh M, et al. Low-Density Lipoprotein Cholesterol and Adverse Cardiovascular Events After Percutaneous Coronary Intervention. Journal of the American College of Cardiology 2020; 76(12): 1440-50.
3. Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of atherosclerotic Cardiovascular Disease Risk. Journal of the American College of Cardiology 2022; 80(14): 1366-418.
4. Pearson GJ, Thanassoulis G, Anderson TJ, et al. 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults. Canadian Journal of Cardiology 2021; 37(8): 1129-50.
5. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). European Heart Journal 2019; 41(1): 111-88.
6. Mackinnon ES, Har B, Champsi S, et al. Guideline LDL-C Threshold Achievement in Acute Myocardial Infarction Patients: A Real-World Evidence Study Demonstrating the Impact of Treatment Intensification with PCSK9i. Cardiology and Therapy 2023; doi: 10.1007/s40119-022-00300-7