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No Muscle-Related Adverse Effects Seen With High-Dose Atorvastatin: Presented at DALM

By Chris Berrie

VENICE, ITALY -- October 27, 2004 -- There appears to be no relationship between use of atorvastatin at high doses and the development of muscle-related adverse effects in patients with dyslipidaemia and hypertension, according to research presented here October 26th at the XV International Symposium on Drugs Affecting Lipid Metabolism.

Connie Newman, MD, medical director advisor and senior medical director, cardiovascular division, Worldwide Medical Group, Pfizer, New York, New York, United States, detailed results of an 8-week, multinational, prospective, randomised, double-blind, placebo-controlled study that described the incidence of creatine phosphokinase (CPK) elevations, myalgia, and myopathy in the RESPOND trial.

The study population of 1660 dyslipidaemic patients with hypertension aged 18 to 75 years were evaluated for the effects on lipid parameters and systolic blood pressure of the statin atorvastatin and the calcium channel blocker amlodipine at fixed doses. Patients were randomised in equal numbers to receive one of 15 combinations of placebo, amlodipine, and/or atorvastatin.

To evaluate specifically the safety of atorvastatin across the dose range used (0, 10, 20, 40, and 80 mg), the researchers combined the data from each amlodipine dose (0, 5, 10 mg) within each fixed atorvastatin dose. Thus, Dr. Newman reported the data according to the atorvastatin dose (n = 332 for each), irrespective of the amlodipine dose used. All of the treated subjects were included in the safety analysis

Using a definition of increases in serum CPK activity of more than 2 times the upper limit of normal (ULN), there was a lower than 3% incidence of CPK elevations both in the zero atorvastatin group (2.8%), and across the atorvastatin treatments, without showing increases over the statin dose range (10 mg, 2.9%; 20 mg, 1.9%; 40 mg, 1.3%; 80 mg, 2.2%).

Similarly, myalgia development was minimal and unrelated to treatment with atorvastatin (0 mg, 1.5%; 10 mg, 2.9%; 20 mg, 1.9%; 40 mg, 1.3%; 80 mg, 2.2%). Only 2 of these patients had elevated CPK levels (between 2 and 5 times ULN), 1 each in the atorvastatin 10-mg and 20-mg groups. No cases of myopathy were seen.

In addition to myalgia, other muscle-pain-related adverse events were back pain and arthralgia, and although these led to the discontinuation in less than 1% of patients, they were not related to the atorvastatin dose used.

Thus, despite the common perception that increases in statin dose can lead to increases in muscle-related adverse events, Dr. Newman stressed that, "The incidence of CPK elevations was low and comparable to [zero atorvastatin] irrespective of dosage, the incidence of myalgia was low, and the muscle-related adverse events did not increase in this study with the dose of atorvastatin."


[Presentation title: Muscle-Related Adverse Effects Are Comparable With Atorvastatin Versus Placebo in 1660 Patients. Poster 124]

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