Should high creatine kinase discourage the initiation or continuance of statins for the treatment of hypercholesterolemia?

Charles J. Glueck, Bishal Rawal, Naseer Ahmed Khan, Samrat Yeramaneni, Naila Goldenberg, Ping Wang
Cholesterol Center, Jewish Hospital, Cincinnati, OH 45229, USA

Metabolism 2009;58:290-295

Overall Summary:

When some patients take statin medications, the may develop mild to moderate muscle pain, tenderness, cramps, and, more rarely, weakness. These symptoms may be associated with a high level of a muscle enzyme, creatine kinase (CK), in the blood. However, there are many patients on statins who have no symptoms, but have high CK in their blood. Often, this high CK leads the physician to stop the statins, despite the fact that the patient is asymptomatic. Our study has shown that in asymptomatic patients with high CK (250 to 2500 IU/L), statins can be given safely, with excellent LDL cholesterol lowering, and without muscle pain or damage.

Scientific Summary

Patients with high low-density lipoprotein cholesterol (LDLC) and asymptomatic high creatine kinase (CK) (≥250 but <2500 IU/L, 10× the laboratory upper normal limit [UNL]) are often not started on statins or have statins stopped because of concern about myositis or rhabdomyolysis. In the current report, we prospectively examined the hypothesis that asymptomatic patients with high CK (≥250 but <2500 IU/L) tolerate statins well at doses reducing LDLC to target, less than 100 mg/dL, without development of myalgia-myositis. We assessed outcomes of 3 groups of patients referred to us because of asymptomatic high CK (≥250 but <2500 IU/L)—1 group (n = 29) on statins at referral and continued on statins, 1 group (n = 20) not on statins and started on statins, and 1 group (n = 19) not on statins and not given statins—all restudied 1 month after entry and then every 3 months. Of the 68 patients, 59 (87%) had CK greater than 1 to 3 times the UNL, 7 (10%) had CK greater than 3 to 5 times the UNL, and 2 (3%) had CK greater than 5 to 10 times the UNL. After 1.2 months of follow-up in 29 statin→statin patients, median CK fell from 353 to 301 (P = .0018) and was 287 (P = .015) after 4 months. After 1.3 months of follow-up in 20 no statin→statin patients, median CK fell from 397 to 292 (P = .0094) and was 419 after 4.1 months. After 1.1 months of follow-up in 19 no statin→no statin patients, median CK fell from 392 to 323 (P = .14) and was 271 (P = .029) after 4.2 months. By repeated-measures analysis, there were no differences in entry CK among the 3 treatment groups; CK fell (P = .04) in the no statin→no statin patients. Despite high baseline CK (48 patients with CK 1-5× the UNL, 1 with CK 5-10× UNL), no patients during followup on statins developed CK greater than 10 times the UNL (2500 IU/L), none discontinued statins or reduced statin dose because of myalgia-myositis, and there was no rhabdomyolysis. High pretreatment CK, particularly 1 to 5 times the UNL, should not be an impediment to start or continue statins to lower LDLC.