Real-world data PCSK9 inhibitors show same LDL-c reductions, but more side effects

Proprotein convertase subtilisin / Kexin 9 inhibition in patients with Familial Hypercholesterolemia: initial clinical experience

Literature - Galema-Boers JMH, Lenzen MJ, Sijbrands EJ and Roeters van Lennep JE - J Clin Lipidol 2017; 11(3):674-681

Main results

5% of patients was homozygous for FH and 60% had a history of CVD. Other cardiovascular risk factors were frequent (66% overweight, 40% hypertension, 15% diabetes mellitus), but only 5% smokers. 71% used statins combined with ezetimibe and 49% of statin users received high-intensity statins. At baseline, mean LDL-c was 6.9±2.3 mmol/L.
PCSK9 inhibition resulted in a mean LDL-c decrease of 55%±21%; in heFH 56%±20% and in hoFH 38%±32%. No difference in LDL-c reduction between evolocumab and alirocumab. Genetic heFH patients had less LDL-c decreased than those with clinical heFH (53% vs. 67%, P<0.001).
Three hoFH patients had at least 1 defective LDLR mutation and showed 50% LDL-c reduction, whereas 1 hoFH patient with a mutation of unknown effect on LDLR activity did not have any LDL-c reduction.
Statin-intolerant patients had less LDL-c decreased compared to patients who used PCSK9 inhibitors on top of statin therapy (47% vs. 58%, P=0.03).
Treatment goal of ≤2.5 mmol/L was achieved in 55% of patients without CVD and goal of ≤1.8 mmol/L was achieved in 60% of patients who were known with CVD. In total, 58% were on-target after PCSK9 therapy.
Fourteen patients (17%) reached very low LDL-c levels (<1.0 mmol/L). On the other hand, 11% were hypo- or non-responders.
None of the patients had problems using the auto-injector. All patients were adherent and 2 patients reported technical problems.
After 6 weeks on average, 39% of patients reported one or more side effects. Most were flu-like symptoms in the first days after administration, and abdominal symptoms. 10% reported neurological symptoms.
Statin-intolerant patients had significant less side effects (21 vs 46%, P=0.05) compared to patients who still used statins.
13% had one or more injection site-reaction and 8% discontinued treatment.

Conclusion

PCSK9 inhibitors in real-world setting showed similar LDL-c reductions as those observed in randomized clinical trials. However, side effects, especially flu-like symptoms, as well as injection site-reactions were reported more often compared to clinical trials. These findings emphasize the need to establish clinical registries to monitor the long-term efficacy and side effects of PCSK9 inhibitors outside randomized clinical trials.

References

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