Highlights on the most recent real-world data on the use of PCSK9 inhibitors, including those from the SWEDEHEART and AIFA registries.
Key Takeaway
SWEDEHEART study
- In a real-world setting, early and larger reductions in LDL-C levels were associated with an improvement in CV outcomes after an MI.
- LDL-C goals as recommended in the current EAS/ESC guidelines were more likely to be achieved using a higher-intensity LLT, requiring a combination of statin with ezetimibe and/or PCSK9.
- Prior statin-treated patients with MI have the greatest risk and may benefit the most from larger LDL-C reductions, which would benefit from a prioritized PCSK9 inhibitor use.
- CR visits allow better treatment intensification and reinforce adherence to LLT.
AIFA study
- Patients initiating PCSK9 inhibitors showed markedly elevated LDL-C, although >40% of the patients were receiving maximal LLT.
- Half of these patients were considered statin-intolerant, as per the definitions recommended in the Italian guidelines.
- Persistence with PCSK9 inhibitor treatment after 2 years was very high (>82%); adherence during persistent use of PCSK9 inhibitors was also very high (>90%).
- Overall, mean LDL-C reduction during PCSK9 inhibitor treatment was 59%, consistent with the findings in clinical trials.
- The proportion of very high-risk patients with ASCVD reaching the recommended LDL-C target (<55 mg/dL) was approximately 58%, higher than that reported in the real-world setting.
- Alirocumab and evolocumab showed comparable LDL-C efficacy, although a large proportion of patients with ASCVD required up-titration to alirocumab 150 mg Q2W.
Why This Matters
Key Highlights
SWEDEHEART study
- Several studies have demonstrated that after an MI, it is very important
to initiate LLT to reduce LDL-C; this hypothesis has been broadly
supported by data from the SWEDEHEART registry.
- Between the index event and the CR visit, 56% of patients were treated with low- or medium-intensity statin, 33% with high-intensity statins, and 10% with no statins.
- Larger LDL-C reduction and more intensive statin therapy after an MI were associated with the lowest recurrence of MACE, major CV events, and all-cause mortality.
- Greater reductions in LDL-C between admission and 6–10 weeks after MI translated into lower rates of CV events.
- Another analysis of the SWEDEHEART study demonstrated that:
- Around 50% of patients who survived the MI and started LLT needed intensification of LDL-C-lowering treatment at 6–10 weeks.
- This can be achieved using high-intensity statins, addition of ezetimibe, and eventually using PCSK9 inhibitors to reach to the target recommended by the ESC/EAS guidelines.
AIFA study
- This study aimed to describe the clinical characteristics of high-risk patients who received alirocumab (75 or 150 mg Q2W) or evolocumab (140 mg Q2W).
- Overall, 10,737 patients (mean age, 62.7 years; CVD manifestation, 81.6%) were included and randomized to alirocumab (n = 4,736) or evolocumab (n = 6,001).
- Approximately 50% entered into prescription because they were classified as a statin-intolerant.
Persistence and adherence to PCSK9 inhibitor treatment
- At 6-, 12-, and 24-month follow-ups, persistence was very high. At the end of the follow-up, it was above 80%.
- Adherence among those who were persistent to PCSK9 inhibitors after 24 months of follow-up was approximately 90%.
LDL-C reduction
- At baseline, the mean LDL-C was very high (>160 mg/dL). After 6 months, this level was markedly reduced and remained consistent up to the 24-month follow-up.
- At the end of this period, the absolute reduction of LDL-C was 95 mg/dL, and this translated into a percent reduction of approximately 60%.
- At 6, 12, and 20 months of follow-up, attainment of LDL-C target during PCSK9 inhibitor treatment remained very high at approximately 60%.
ABBREVIATIONS:
ASCVD, atherosclerotic cardiovascular disease; CR, cardiac rehabilitation; CV, cardiovascular; EAS, European Atherosclerosis Society; ESC, European Society of Cardiology; LDL-C, low-density lipoprotein cholesterol; LLT, lipid-lowering therapy; LMT, lipid-modifying therapy; MACE, major adverse cardiovascular events; MI, myocardial infarction; PCSK9, proprotein convertase subtilisin/kexin-9; Q2W, once every 2 weeks.
MAT-BH-2200056/v2/Jan 2024