Physicians' Academy for Cardiovascular Education

PCSK9 antibody 150 mg once a month works well for patients not on statin therapy

Stroes E, JAHA, 2016

Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study


Stroes E, Guyton JR, Lepor N, et al.  
J Am Heart Assoc. 2016;5:e003421.
 

Background

Statin therapy reduces LDL-c levels and CVD risk, but can lead to muscle adverse events (MAE) [1,2]. As a consequence, the dose is often reduced in these patients which often leads to undertreatment and thus elevated LDL-c levels and high CVD risk [3]. Alirocumab, a PCSK9 inhibitor, can also reduce LDL-c levels either as monotherapy, or on top of statin therapy [4].
 
In this phase 3, placebo-controlled multinational study (ODYSSEY CHOICE II), the efficacy and safety of alirocumab 150 mg every 4 weeks was evaluated as a therapeutic option for 233 patients with hypercholesterolemia but not on statin therapy, for a duration of 24 weeks. Patients were randomly assigned to placebo Q2W, alirocumab 150 mg every 4 weeks (150 Q4W) or 75 mg every 2 weeks (75 Q2W). When predefined LDL-c target levels were not met at week 8, in both arms dose were adjusted (blinded) to 150 mg every 2 weeks at week 12 (150 Q2W)
 

Main results

  • The mean baseline LDL-c levels were 163.9 mg/dL for the 150 Q4W group, 154.5 mg/dL for the 75 Q2W group and 158.5 mg/dL for the placebo group.
  • At week 12, the mean percentage changes in LDL-c from baseline were -52.3% for the 150 Q4W group, -53.6% in the 75 Q2W group and -3.2% in the placebo group.
  • 49.1% of 150 Q4W patients switched to 150 Q2W at week 12, which was 36.0% of 75 Q2W patients. In general, these patients had higher LDL-c levels at baseline.
  • At week 24, the mean LDL-c changes from baseline were -51.7% in the 150 Q4W group (63.9% achieved LDL-c targets), -53.5% in the 75 Q2W group (70.3% achieved LDL-c targets) and +4.7% in the placebo group (for both groups P<0.0001 versus placebo).
  • Safety: alirocumab was generally well tolerated at any dose regimen. The percentages of patients with at least 1 adverse event were 77.6% in the 150 Q4W group, 63.8% in the placebo group, and 73.0% in the 75 Q2W group. Injection-site reactions were the most common treatment-emergent adverse events.

Conclusion

Alirocumab 150 mg every 4 weeks (150 Q4W) reduces LDL-c levels and may provide an additional treatment option for patients with muscle adverse events not receiving statin treatment, with the additional option of a dose adjustment to 150 mg every 2 weeks (150 Q2W).  
 
Find this article online at JAHA
 

References

1. Reiner Z, Catapano AL, De Backer G, et al. ESC/EAS guidelines for the management of dyslipidaemias: the Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32:1769–1818.
2. Kashani A, Phillips CO, Foody JM, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation. 2006;114:2788–2797.
3. Stroes ES, Thompson PD, Corsini A, et al. Statin associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015;36:1012–1022.
4. Kereiakes DJ, Robinson JG, Cannon CP, et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: the ODYSSEY COMBO I study. Am Heart J. 2015;169:906–915.