A safety and clinical efficacy analysis of PCSK9 monoclonal antibodies in patients with markedly elevated creatine phosphokinase levels.

American journal of blood research Pub Date : 2021-08-15 eCollection Date: 2021-01-01
Ina Volis, Eric Hislop, Walid Saliba, Barak Zafrir
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引用次数: 0

Abstract

Introduction: PCSK9 inhibitors (PCSK9i) are often used in statin-intolerant patients, aiming to reduce low-density lipoprotein cholesterol (LDL-C). Along with the growing experience with their use, there is a lack of evidence regarding the safety, tolerability, and clinical utility of PCSK9i in patients with markedly elevated creatine phosphokinase (CPK) levels.

Methods: We screened a comprehensive HMO database for patients treated with PCSK9i (Jan 2016-Dec 2019), in whom elevated CPK levels (>1,000 U/L) were documented prior to the initiation of therapy. Treatment plans, adherence, and the levels of CPK and LDL-C were analyzed.

Results: Of the 1,600 patients initiating treatment with PCSK9i, 26 had prior CPK values >1,000 U/L [median (IQR): 3,687 (1,876-8,344) U/L]. All 26 patients were previously treated with statins, which presumably resulted in adverse effects (myalgia in 24, and rhabdomyolysis in 5 patients) therefore mandating their discontinuation. Concomitant secondary factors for CPK elevation were present in 11 patients, and included renal failure, rheumatoid disorders, hypothyroidism, intensive exercise, proteinuria and genetic muscular disease. Of the 26 patients treated with PCSK9i, alirocumab was administered to 12 patients, and evolocumab to 14. Following the initiation of treatment with either drug, 24 patients (92%) demonstrated a reduction in CPK of >50%, and in 12 (46%) CPK levels have returned to normal values. With regard to treatment goals, 17 patients (65%) have achieved an LDL-C level of <70 mg/dL, and 12 (46%) have reached a level of <55 mg/dL. No serious adverse reactions were documented, and only 2 patients discontinued the treatment (not due to muscle symptoms or CPK elevation).

Conclusions: PCSK9i constitute a safe, tolerable, and effective treatment for hyperlipidemia in patients with markedly elevated CPK. While statin intolerance is a major cause for CPK elevation, concomitant etiologies for increased CPK values were rather common.

Abstract Image

PCSK9单克隆抗体在肌酸磷酸激酶水平明显升高患者中的安全性和临床疗效分析。
PCSK9抑制剂(PCSK9i)常用于他汀类药物不耐受患者,旨在降低低密度脂蛋白胆固醇(LDL-C)。随着使用经验的增加,缺乏关于PCSK9i在肌酸磷酸激酶(CPK)水平明显升高的患者中的安全性、耐受性和临床应用的证据。方法:我们筛选了一个综合的HMO数据库,其中包括2016年1月至2019年12月接受PCSK9i治疗的患者,这些患者在开始治疗前记录的CPK水平升高(>1,000 U/L)。分析治疗方案、依从性、CPK和LDL-C水平。结果:在开始使用PCSK9i治疗的1,600例患者中,26例患者的既往CPK值>1,000 U/L[中位数(IQR): 3,687 (1,876-8,344) U/L]。所有26例患者之前都接受过他汀类药物治疗,这可能导致了不良反应(24例肌痛,5例横纹肌溶解),因此必须停药。11例患者存在CPK升高的伴随继发因素,包括肾衰竭、类风湿疾病、甲状腺功能减退、剧烈运动、蛋白尿和遗传性肌肉疾病。在26例接受PCSK9i治疗的患者中,12例患者使用alirocumab, 14例患者使用evolocumab。在开始使用任何一种药物治疗后,24名患者(92%)表现出CPK降低>50%,12名患者(46%)CPK水平恢复到正常值。在治疗目标方面,17例(65%)患者LDL-C水平达到。结论:PCSK9i对CPK显著升高的高脂血症患者是一种安全、耐受、有效的治疗方法。虽然他汀类药物不耐受是CPK升高的主要原因,但伴随CPK值升高的病因相当普遍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
American journal of blood research
American journal of blood research MEDICINE, RESEARCH & EXPERIMENTAL-
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