Highlights
- •This is the first study that assess the intensive LDL cholesterol lowering effect of PCSK9 inhibition on tendon xanthomas.
- •Compared with standard lipid-lowering therapy, the combination with PCSK9 inhibitors showed greater tendon xanthoma regression.
- •Tendon xanthoma regression was observed with mean LDL cholesterol of 60 mg/dL.
- •Some patients developed asymptomatic calcifications inside the Achilles tendon.
- •These results suggest that PCSK9 inhibition is highly efficient regressing lipid deposits in heterozygous familial hypercholesterolemia.
Abstract
Background and aims
The effect of LDLc lowering with PCSK9 antibodies on tendon xanthomas (TX) is unknown.
Methods
TX was measured in 24 heterozygous familial hypercholesterolemia (HeFH) cases and
in 24 HeFH controls with or without PCSK9 inhibitors for at least one year.
Results
Exposure to PCSK9 inhibitors in cases was 2.96 ± 1.33 years. LDLc decreased 80.8 ± 7.66%
in cases and 56.9 ± 11.1% in controls. There was a decrease in maximum (−5.03%) and
mean (−5.32%) TX in cases but not in controls (+3.97%, +3.16, respectively, p = 0.01). PCSK9 inhibitor treatment was independently associated with TX reduction.
Conclusion
Addition of a PCSK9 inhibitor to statin and ezetimibe resulted in a greater decrease
in LDLc and TX after 3 years of treatment.
Keywords
Abbreviations:
AT (Achilles Tendon), TX (Tendon Xanthomas), HeFH (Heterozygous Familial hypercholesterolemia), HoFH (Homozygous Familial Hypercholesterolemia), CHD (Coronary Heart Disease), PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to AtherosclerosisAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Lipid deposition in human tendon xanthoma.M. J. Pathol. 1985; 121: 311-315
- Familial hypercholesterolemia.in: Scriver C.R. Baudet A.L. Sly W.S. Valle D. The Metabolic and Molecular Bases of Inherited Disease. McGraw-Hil, New York2001: 2863-2913
- Comparison of genetic versus clinical diagnosis in familial hypercholesterolemia.Am. J. Cardiol. 2008; 102: 1187-1193
- Coronary artery disease in heterozygous familial hipercolesterolemia patients with the same LDL receptor gene mutation.Circulation. 1995; 92: 290-295
- Overexpression of the CXCL3 gene in response to oxidized low-density lipoprotein is associated with the presence of tendon xanthomas in familial hypercholesterolemia.Biochem. Cell Biol. 2009; 87: 493-498
- 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: 2146-2157
- 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: 3478-3490
- 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: 1960-1965
- The lipid composition and localization of free and esterified cholesterol in different types of xanthomas.J. Invest. Dermatol. 1982; 78: 305-308
- 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: 311-317
- Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.N. Engl. J. Med. 2015; 372: 1489-1499
- Efficacy and safety of evolocumab in reducing lipids and cardiovascular events.N. Engl. J. Med. 2015; 372: 1500-1509
- 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
- PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial.Lancet. 2015; 385: 331-340
- Efficacy and safety of longer-term administration of evolocumab (AMG 145) in patients with hypercholesterolemia: 52-week results from the Open-Label Study of Long-Term Evaluation against LDL-C (OSLER) randomized trial.Circulation. 2014; 129: 234-243
- The use of Achilles tendon sonography to distinguish familial hypercholesterolemia from other genetic dyslipidemias.Arterioscler. Thromb. Vasc. Biol. 2005; 25: 2203-2208
- Molecular characterization of familial hypercholesterolemia in Spain.Atherosclerosis. 2012; 221: 137-142
- Rapid resolution of xanthelasmas after treatment with alirocumab.J. Clin. Lipidol. 2016; 10: 1259-1261
- Low-density lipoprotein apheresis in children with familial hypercholesterolemia: follow-up to 21 years.Ther. Apher. Dial. 2008; 12: 195-201
- Effect of evolocumab on progression of coronary disease in statin-treated patients: the GLAGOV randomized clinical trial.JAMA. 2016; 316: 2373-2384
- Interaction of collagen with the lipids of tendon xanthomata.J. Clin. Invest. 1978; 62: 836-846
- Stability and instability: two faces of coronary atherosclerosis.Circulation. 1996; 94: 2013-2020
- Regression of Achilles tendon thickness after statin treatment in patients with familial hypercholesterolemia: an ultrasonographic study.Atherosclerosis. 2009; 205: 151-155
- Long-term probucol treatment results in regression of xanthomas, but in progression of coronary atherosclerosis in a heterozygous patient with familial hypercholesterolemia.Atherosclerosis. 1996; 120: 181-187
- Factors underlying regression of coronary atheroma with potent statin therapy.Eur. Heart J. 2013; 34: 1818-1825
- Impact of statin therapy on coronary plaque composition: a systematic review and meta-analysis of virtual histology intravascular ultrasound studies.BMC Med. 2015; 13: 229
Article info
Publication history
Published online: June 08, 2017
Accepted:
June 2,
2017
Received in revised form:
June 1,
2017
Received:
March 31,
2017
Identification
Copyright
© 2017 Elsevier B.V. All rights reserved.
