PCSK9 Inhibitor Decreases LDL Cholesterol in Statin Intolerant Patients


Statin-intolerant patients with muscle-related side effects had a greater reduction in low-density lipoprotein cholesterol from treatment with Repatha.

Amgen recently announced the release of data from the phase 3 GAUSS-3 trial that evaluated the PCSK9 inhibitor evolocumab (Repatha) in high cholesterol patients who are statin intolerant.

The results of the study, published in the Journal of the American Medical Association (JAMA), showed that statin-intolerant patients with muscle-related side effects (MRSE) had a greater reduction in low-density lipoprotein cholesterol (LDL-C) after 24 weeks compared with ezetimibe.

Patients entering the active-controlled part of the study had a mean LDL-C level of 219.9 mg/dL at baseline.

Data from prespecified co-primary endpoints showed the mean LDL-C reduction from baseline at weeks 22 and 24 was 54% for Repatha compared with 16.7% for ezetimibe (p<0.001). At week 24, LDL-C reduction was 52.8% for Repatha compared with 16.7% for ezetimibe (p<0.001).

Muscle-related side effects were reported in 20.7% of Repatha patients and 28.8% of ezetimibe patients.

“Statin-associated muscle symptoms represent a major unresolved challenge in the care of patients with cardiovascular disease,” said Sean E. Harper, MD, executive vice president of Research and Development at Amgen. “These findings are promising, demonstrating safety and efficacy results consistent with the other GAUSS studies.”

The most common adverse events were nasopharyngitis, muscle spasms, arthralgia, pain in extremity, fatigue, headache, and back pain. GAUSS-3 took on a rigorous active statin rechallenge in patients with a history of intolerance to 2 or more statins to determine a patient population that developed MRSE on statin therapy, but not on the placebo.

The rechallenge lasted 10 weeks and resulted in more than 40% of the rechallenged patients developed intolerable MRSE to atorvastatin and not the placebo.

“By employing a unique crossover design, these study results provide insights into our understanding of statin intolerance, which can be difficult to define from patient-reported symptoms alone,” said co-lead author Erik S.G. Stroes, MD, PhD. “This rigorously-designed trial clearly shows that in carefully selected patients, statin intolerance withstands the placebo-controlled test. These often high-risk patients truly experience muscle-related side effects while on statin therapy and may therefore benefit from an alternative treatment like evolocumab to lower their LDL cholesterol.”

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