Presented at the ACC Scientific Session 2015 by: Marc Sabatine (Brigham and Women's Hospital, Boston, MA, VS)

Background

PCKS9-antibodies have previously been shown to effectively lower LDL-c levels in various patient groups. Monoclonal antibodies directed at PCSK9, like evolocumab (AMG145), are safe and well tolerated in phase II and III studies. The effect of evolocumab on cardiovascular outcomes was unknown to date.
In the open-label OSLER extension study programme, patients enrolled in earlier phase II and III studies into the effect of evolocumab were included for comparison of the efficacy of evolocumab plus standard of care (n=2976) with standard of care alone (n=1489) in reducing death, myocardial infarction (MI) or stroke, and the need for hospitalisation or revascularisation, during a median follow-up period of 11.1 months (IQR: 11.0-12.8).

Belangrijkste resultaten

• 61% reduction (95%CI: 59-63%, P<0.0001) of median LDL-c levels were seen with evolocumab as compared with standard care (absolute reduction: 73 mg/dL, 95%CI: 71-76%). This decrease (from baseline in the parent study) was consistent throughout the OSLER follow-up of 48 weeks.
• 90.2% of patiënts on evolocumab met the LDL-c target of <100 mg/dL after 12 weeks, as compared with 26.0% of patients on standard care (P<0.001). The target of <70 mg/dL was achieved by 73.6% and 3.8% (P<0.001) respectively.
• Strongly significant differences were also seen in changes of levels of non-HDL-c, ApoB, Lp(a), triglyceriden, HDL-c and ApoA1.
• The composite endpoint was less frequent a year after randomisation in the evolocumab-treated group (0.95% vs. 2.18%, HR: 0.47, 95%CI: 0.28-0.78, P=0.003) as compared with patients who only received standard care.
• All components of the composite endpoint occurred less often in patients receiving evolocumab in addition to standard care, as compared with standard care only.
• No significant heterogeneity of the effect was seen in clinically relevant subgroups.
• No gradiënt was seen in the occurrence of adverse effects based on the LDL-c level reached, not even with LDL-c<25 mg/dL.

Conclusion

Treatment with PCSK9 inhibitor evolocumab halved the risk of mortality, myocardial infarction of stroke, and the need for hospitalisation or revascularisation as compared with patients who received only standard care. The robust LDL-c lowering obtained with inhibition of PCSK9 thus seems to be a safe and effective means to reduce major CV outcomes.

This study was simultaneously published in the New England Journal of Medicine.

3 minute education • 16-3-2015, ACC 2015, San Diego, Prof.dr. John Kastelein

OSLER 1 & 2: Long term efficacy and safety outcomes PCSK9 Inhibition

ACC 2015 Prof. John Kastelein, Amsterdam, comments on the results of the OSLER program with PCSK9 inhibitor evolocumab and provides a perspective on the potential of PCSK9 inhibitors.

- Our reports of the ACC Scientific Session are based on the information provided at the congress -