PCSK9 inhibition is associated with regression of tendon xanthomas in FH

20/06/2017

In a case-control study on HeFH patients treated with potent statins, the addition of a PCSK9 antibody resulted in a greater decrease of tendon xanthomas thickness after 3 years of treatment.

Effect of intensive LDL cholesterol lowering with PCSK9 monoclonal antibodies on tendon xanthoma regression in familial hypercholesterolemia
Literature - Bea AM, Perez-Calahorra S, Marco-Benedi V, et al. - Atherosclerosis 2017 Jun 8;263:92-96.

Background

Tendon xanthomas (TX) begin to appear after the third decade of life in 20% to 50% of patients with heterozygous familial hypercholesterolemia (HeFH). The presence of TX is a major criterion for the clinical diagnosis of HeFH, and it is associated with higher LDL-C levels, more intense subclinical atherosclerosis and higher risk of CHD [1-4].

PCSK9 inhibition with monoclonal antibodies leads to additional significant reductions of LDL-C levels on top of high-dose statins with or without ezetimibe [5,6]. However, its effect on TX in HeFH patients is not known.

In this prospective case-control study, the effect of prolonged PCSK9 inhibition on TX regression compared with high dose statin therapy was evaluated in HeFH patients. Cases were HeFH patients who were enrolled in open-label clinical trials and/or were assigned to active treatment in the double-blinded phase (treated for at least 12 months with alirocumab 75 mg or 150 mg biweekly, evolocumab 140 mg every two weeks or evolocumab 420 mg every four weeks). Age-matched controls were genetically defined HeFH with TX. All subjects were receiving high doses of potent statins with or without ezetimibe.

TX was measured in 24 HeFH cases and in 24 HeFH controls. Mean exposure to PCSK9 inhibitors in cases was 2.96±1.33 years. Mean and maximum Achilles tendon thickness were measured bilaterally using high-resolution sonography before PCSK9 inhibition in cases, and the measurements were repeated in both groups in a follow-up visit.

Main results

  • LDL-C levels decreased from 326±60.4 mg/dL to 61.0±20.2 mg/dL (-80.8±7.66%; P<0.001) in HeFH subjects receiving PCSK9 inhibitors and from 314±65.0 mg/dL to 131±26.9 mg/dL (-56.9±11.1%; P <0.001) in the control group. The mean percentage reduction in LDL-C was higher with PCSK9 inhibitors (P <0.001).
  • Similar differences between groups were observed in total-C, non-HDL-C and Apo-B. No differences were found between cases and controls in triglycerides, HDL-C and Apo-A1.
  • The mean percentage change in maximum and mean TX thickness in cases was -5.03% and -5.32%, respectively. There was a non-significant increase in controls (+3.97% and +3.16, respectively), with significant differences between groups (P=0.01).
  • In the regression analysis, the PCSK9 inhibitor treatment was independently associated with percentage reduction of TX thickness after adjustment for age, gender, baseline TX thickness and baseline LDL-C (Beta: -6.081; 95% CI: -10.431 to -1.730; P = 0.007).

Conclusion

In a prospective case-control study with HeFH patients treated with potent statins, addition of a PCSK9 antibody resulted in a greater decrease in LDL-c and TX thickness after on average 3 years of treatment.

References

1. Cuchel M, Bruckert E, Ginsberg HN, et al. European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J. 2014;35:2146-57.

2. Nordestgaard BG, Chapman MJ, Humphries SE, et al. European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34:3478-90.

3. Civeira F, Castillo S, Alonso R, et al. Spanish Familial Hypercholesterolemia Group. Tendon xanthomas in familial hypercholesterolemia are associated with cardiovascular risk independently of the low-density lipoprotein receptor gene mutation. Arterioscler Thromb Vasc Biol. 2005;25:1960-5.

4. Oosterveer DM, Versmissen J, Yazdanpanah M, et al. Differences in characteristics and risk of cardiovascular disease in familial hypercholesterolemia patients with and without tendon xanthomas: a systematic review and meta-analysis. Atherosclerosis. 2009;207:311-7.

5. Sabatine MS, Giugliano RP, Wiviott SD, et al; Open-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators.. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1500-9.

6. Kastelein JJ, Ginsberg HN, Langslet G, et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart

J. 2015;36:2996-3003.

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