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

Abstract

Abstract Introduction PCSK9 inhibitors have been used in statin intolerant patients to reduce low-density lipoprotein cholesterol (LDL-C) safely and effectively. However, evidence is lacking regarding the safety and clinical utility of PCSK9 inhibition in patients with markedly elevated creatine phosphokinase (CPK) levels. Methods We searched a large HMO database for patients with CPK levels above 1000 U/L, who were initiating PCSK9 inhibition therapy (Jan 2016–Dec 2019). The patients' treatment plans, adherence, CPK and LDL-C levels were analyzed. Results Of the1600 patients initiating PCSK9 inhibitors, 26 met study criteria, and all were previously treated by statins (in 18 patients ≥3 different statin types were prescribed). Myalgia was evident in most patients (n=24), and 5 were clinically diagnosed with rhabdomyolysis. Abnormal liver function tests were noted in 8 of the 26 patients. Most were very-high cardiovascular risk patients, with concurrent atherosclerotic cardiovascular disease (n=17) and baseline LDL-C levels >190 mg/dL (n=19). Peak CPK levels ranged from 1050–53540 U/L [median (IQR), 3687 (1876–8344)]. Concomitant secondary factors for CPK elevation included renal failure (n=5), inflammatory rheumatoid disorders (n=3), severe hypothyroidism (n=3), intensive exercise (n=2), nephrotic range proteinuria (n=1) and genetic muscular disease (n=1). The monoclonal antibodies, Alirocumab and Evolocumab, were initiated in 12 and 14 patients respectively. In 24 patients (92%) CPK reduction of >50% was noted and in 12 patients (46%) CPK levels returned to normal range (Figure). Under PCSK9 inhibition, 17 patients (65%) achieved LDL-C levels <70 mg/dL and in 12 patients (46%) LDL-C was <55 mg/dL. Only 2 patients discontinued PCSK9 inhibitors. Conclusions High-risk patients with markedly elevated CPK levels, can safely reduce LDL-C levels with PCSK9 inhibitors, and although statin intolerance is a major cause of elevated CPK, other predisposing and precipitating factors are common. Funding Acknowledgement Type of funding sources: None.