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Evolocumab associated with durable lowering of LDL
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LDL lowering with evolocumab in patients with high cholesterol was sustained over a 4-year period, according to data published in JAMA Cardiology.
“These data suggest that evolocumab can help many patients who need additional lipid lowering beyond their existing therapy,” Michael J. Koren, MD, CEO for the Jacksonville Center for Clinical Research in Florida, and colleagues wrote. “Used with statins, PCSK9 antibodies reduce LDL to levels not previously achievable in routine clinical practice.”
The open-label OSLER-1 study, which was conducted from October 2011 to August 2016, included 1,324 eligible patients (mean age, 57 years; 52.9% women; median LDL, 133 mg/dL). Of these patients, 886 were also taking statins. Patients were randomly assigned a monthly dose of evolocumab (Repatha, Amgen; 420 mg) with standard of care (n = 882) or standard of care alone (n = 442). Those assigned to the standard of care only received evolocumab 1 year into the study.
The primary objective was to observe the changes among LDL levels, apolipoprotein B, non-HDL levels, lipoprotein(a), total cholesterol-to-HDL ratio and apolipoprotein B-to-apolipoprotein A-I ratio.
Positive results
At 52 weeks, the median LDL levels in patients who received evolocumab and standard of care decreased by 61% (53 mg/dL; 95% CI, –63 to –60) vs. 2% for those receiving standard of care alone (133 mg/dL; 95% CI, –5 to –0.2; P < .001), the researchers wrote. Decreases continued at weeks 100 (76.5 mg/dL), 160 (78.5 mg/dL) and 208 (75 mg/dL).
The median percentage decrease among the cohort, including those who were assigned evolocumab at 52 weeks after only receiving standard of care, were 60% at 64 weeks (95% CI, –61 to –59), 59% at 100 weeks (95% CI, –60 to –57), 59% at 160 weeks (95% CI, –61 to –58) and 57% at 208 weeks (95% CI, –59 to –55), according to the findings.
During follow-up, 157 patients (13%) lowered their statin intensity and 115 patients (9%) stopped taking them completely. At 208 weeks, patients who took unchanged statin therapy (n = 745) experienced an LDL decrease of 58%, the results showed.
Adverse events, which included the development of anti-evolocumab antibodies, new-onset diabetes, liver function test abnormalities, injection site reactions, adjudicated CV events and neurocognitive events, occurred in 79.3% of patients after 1 year of taking evolocumab and standard of care vs. 74% of those who received standard of care. The rate of new-onset diabetes among the evolocumab plus standard of care group was 2.8% vs. 4% for the standard of care only group, according to the researchers.
Neurocognitive events occurred in 0.4% of those in the evolocumab and standard care group, and there were no reports in the standard of care group. Muscle-related events transpired in 4.7% of patients in the evolocumab and standard of care group vs. 8.5% in the standard of care group.
At 1 year, 11 of 442 patients (2.5%) experienced adjudicated CV events in the standard of care group vs. 10 of 1,255 patients (0.8%) who received standard of care and evolocumab.
Study’s effect
Patients who were assigned evolocumab at the beginning of the study or after 1 year received the therapy for an average of 44 months, and their median LDL level reduction was 57%, according to the data.
“To our knowledge, these 4,641 patient-years of follow-up represent the longest and most extensive experience reported to date for evolocumab or any other PCSK9 inhibitor,” Koren and colleagues wrote.
“The adherence achieved in this open-label extension study is adequate, but it should be noted that participants were shielded from the current high cost of these drugs,” Neil J. Stone, MD, professor of medicine (cardiology) and preventive medicine at Northwestern University Feinberg School of Medicine, wrote in a related editorial. “It is hoped that if outcome trial data are shown to be beneficial, cost will not be a limiting factor for those who would have the largest incremental benefit.” – by Darlene Dobkowski
Disclosure: The study was funded by Amgen. Koren, an employee of Jacksonville Center for Clinical Research, reports receiving funding and consultant fees from Amgen, Pfizer, Regeneron and Sanofi. Stone reports no relevant financial disclosures. Please see the full study for the other researchers’ relevant financial disclosures.
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