New data from Evolocumab ( Repatha ) cardiovascular outcomes trial ( FOURIER ) were presented at the 2017 National Lipid Association Scientific Sessions, which showed that Evolocumab consistently and safely has reduced cardiovascular events in patients with established cardiovascular disease regardless of baseline low-density lipoprotein cholesterol ( LDL-C ) level below or above 70 mg/dL.
A separate analysis also demonstrated Evolocumab has reduced cardiovascular events in patients being treated with maximum-intensity statin therapy.
The two analyses compared clinical outcomes in patients stratified by baseline LDL-C above and below 70 mg/dL and in patients on maximum-intensity statin therapy, defined as Atorvastatin 80 mg or Rosuvastatin 40 mg daily, versus patients on less intense statin therapy.
Previously, physicians have debated the benefit of treating high-risk cardiovascular patients with baseline LDL-C levels below 70 mg/dL.
The Evolocumab cardiovascular outcomes trial showed that even patients already at lower levels of baseline LDL-C are still at risk for a cardiovascular event, and the addition of Evolocumab can continue to safely lower these patients' cardiovascular risk by reducing their LDL-C levels beyond current targets.
In patients with a baseline LDL-C below 70 mg/dL ( n=2,034 ), Evolocumab has reduced the median baseline LDL-C from 65.5 mg/dL to 21.0 mg/dL.
Evolocumab has consistently reduced the risk of the composite primary endpoint, which included hospitalization for unstable angina, coronary revascularization, myocardial infarction, stroke or cardiovascular death, regardless of whether baseline LDL-C was below or above 70 mg/dL ( 20% in patients with baseline less than 70 mg/dL; 14% in patients with baseline greater than or equal to 70 mg/dL, P-interaction=0.65 ).
The results were also consistent for the more robust, secondary composite endpoint of myocardial infarction, stroke or cardiovascular death where patients with a baseline LDL-C less than 70 mg/dL experienced a 30% reduction in cardiovascular events and patients with a baseline LDL-C greater than or equal to 70 mg/dL experienced a 19% reduction in cardiovascular events ( P-interaction=0.44 ).
In patients on maximum-intensity statins ( n=7,533 ), Evolocumab has reduced the median baseline LDL-C from 93 mg/dL to 32 mg/dL.
Additionally, Evolocumab has consistently reduced the risk of major cardiovascular events in patients on maximum-intensity and less intense statin therapy in both the composite primary endpoint ( 14% in patients on maximum-intensity statin therapy; 15% in patients on less intense statin therapy, P-interaction=0.88 ) and the composite secondary endpoint ( 22% in patients on maximum-intensity statin therapy; 19% in patients on less intense statin therapy, P-interaction=0.71 ).
In the two analyses, there were no differences in the rates of adverse events leading to discontinuation between treatment groups in patients who had a baseline LDL-C below 70 mg/dL ( 4.4% Evolocumab; 4.6% placebo ) or in patients on maximum-intensity statin therapy ( 3.9% Evolocumab; 3.7% placebo ).
Results from the primary analysis of the 27,564-patient Evolocumab cardiovascular outcomes study were also presented at the meeting.
The study was statistically powered around the hard major adverse cardiovascular event ( MACE ) composite endpoint of first myocardial infarction, stroke or cardiovascular death ( key secondary composite endpoint ) and found that adding Evolocumab to optimized statin therapy resulted in a statistically significant 20% ( p less than 0.001 ) reduction in these events.
The study also found a statistically significant 15% reduction ( p less than 0.001 ) in the risk of the extended MACE composite ( primary ) endpoint, which included hospitalization for unstable angina, coronary revascularization, myocardial infarction, stroke or cardiovascular death.
No new safety concerns were identified in this large clinical trial with roughly 60,000 patient-years of follow-up; this included the assessment of patients who achieved very low levels of LDL-C.
Evolocumab is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 ( PCSK9 ). Evolocumab binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein receptor ( LDLR ), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Evolocumab increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels. ( Xagena )
Source: Amgen, 2017