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

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

Conclusions: High-risk patients with markedly elevated CPK levels can safely reduce LDL-C levels with PCSK9 monoclonal antibodies, and although statin intolerance is a major cause of elevated CPK, other predisposing and precipitating factors are common.