Registry data of PCSK9i in patients with high CV risk and hypercholesterolemia
Safety and efficacy of alirocumab in a real-life setting: the ODYSSEY APPRISE study
Introduction and methods
In the 2019 ESC/EAS guidelines for management of dyslipidemia, addition of a PCSK9 inhibitor is recommended for patients with very-high CV risk who have not reached their risk-based LDL-c goal despite treatment with maximally tolerated statin and ezetimibe . In the recent American guidelines, similar treatment regime is recommended for adult patients with heterozygous FH and LDL-c ≥2.6 mmol/L . This is based on the observation that in clinical practice many patients do not reach their LDL-c treatment goals while on maximally tolerated statin, with or without ezetimibe [3-7].
ODYSSEY APPRISE was a European/Canadian prospective study to examine safety and efficacy of alirocumab in high CV risk patients with severe hypercholesterolemia who were insufficiently treated with maximally tolerated statin with or without other lipid-lowering therapy (not PCSK9 inhibitors). It was a single-arm, phase 3b, open-label study from June 2015 to April 2019. Patients received alirocumab every 2 weeks. Treatment period ranged from 12 weeks to 30 months (mean exposure was 72.4 [SD:42.5] weeks).
Eligible patients had HeFH or established CHD or a CHD risk equivalent, and hypercholesterolemia not adequately controlled with maximally tolerated statin with or without LLT. 994 Patients were enrolled.
Primary endpoint was assessment of safety parameters, including AEs, AEs of special interest, laboratory data, product complaints and vital signs. Main secondary endpoint was percent change in calculated LDL-c from baseline tot week 12.
- 71.6% Of patients (n=712) reported treatment-emergent adverse events (TEAEs).
- 4 Deaths were reported (two during TEAE period: death from cancer and death by suicide; two after the TEAE period: one death occurred from 5 serious AEs [acute myeloid leukemia, aplasia, sepsis, cardiac failure and malnutrition] and the other from 2 SAEs [pulmonary oedema and MI].
- 4.5% Of patients (n=45) discontinued treatment due to a TEAE (thrombocytopenia, myalgia, asthenia).
- Treatment-emergent SAEs were reported in 16.2% of patients (n=161). Nine patients (0.9%) had treatment-emergent SAEs considered to be related to alirocumab by the investigator (liver abscess, lung adenocarcinoma with bone metastasis, anemia, diabetes, seizure, chronic hepatitis, hepatocellular injury, maculopapular rash, increase in transaminases.
- TEAEs corresponding to AEs of special interest occurred in 34 patients (3.4%).
- Mean decrease in LDL-c from baseline to week 12 was 2.6 (SD:1.2) mmol/L (54.8%). And this decrease was maintained throughout the study duration.
- Percentage of patients that achieved LDL-c <2.59 mmol/L, LDL-c <1.81 mmol/L, and LDL-c <1.81 mmol/L and/or ≥50% reduction from baseline at week 12 was 74.6%, 50.2% and 69.1%, respectively.
Overall, addition of alirocumab to maximally tolerated statin with and without LLT was well tolerated in high-risk patients and resulted in a ~50% reduction after 12 weeks, that was sustained throughout the treatment duration.
The authors noted: ‘Although the current analysis provides valuable insights into the management of patients with high/very-high CV risk, future research should focus on the safety and efficacy of alirocumab in real-life populations, without the close monitoring used in controlled registries and clinical trials.’