New analysis has revealed that lowering low-density lipoprotein cholesterol (LDL-C) levels with evolocumab reduced the risk of cardiovascular events in a sub-group of patients with a history of stroke from the evolocumab cardiovascular outcomes study (FOURIER).
Nineteen per cent of patients in the study had a prior history of non-hemorrhagic stroke (n=5,337). In this analysis, stroke patients treated with evolocumab experienced a 56 per cent mean reduction in LDL-C levels, compared to placebo (median LDL-C level of 29 mg/dL for patients on evolocumab versus median LDL-C of 89 mg/dL for placebo; p<0.001).
The hazard ratio of evolocumab compared to placebo for the composite primary endpoint, which included hospitalisation for unstable angina, coronary revascularisation, heart attack, stroke or cardiovascular death, was 0.85 (95 percent CI, 0.72-1.00; p=0.047).
The hazard ratio of evolocumab compared to placebo for the secondary composite endpoint of heart attack, stroke or cardiovascular death was 0.89 (95 percent CI, 0.74-1.08).
The hazard ratios of evolocumab compared to placebo for coronary revascularisation, heart attack, stroke and cardiovascular death were 0.68 (95 percent CI, 0.52-0.90), 0.74 (95 percent CI, 0.55-1.00), 0.90 (95 percent CI, 0.68-1.19) and 1.11 (95 percent CI, 0.80-1.56), respectively.
In the sub-group of patients with a history of stroke, there were no notable differences in the overall rate of adverse events, serious adverse events or adverse events leading to study drug discontinuation. Rates of adjudicated new onset diabetes (2.1 percent evolocumab 2.0 percent placebo), cataract (1.0 percent evolocumab; 0.8 percent placebo), and neurocognitive adverse events (1.0 percent evolocumab; 1.0 percent placebo) were similar between the two arms.
The primary analysis consisted of 27,564 patients with established cardiovascular disease. The study was statistically powered around the hard major adverse cardiovascular event (MACE) composite endpoint of first heart attack, stroke or cardiovascular death (key secondary composite endpoint), finding that adding evolocumab to optimised statin therapy resulted in a 20 per cent (p<0.001) reduction in these events.
There was also a 15 per cent reduction (p<0.001) in the risk of the extended MACE composite (primary) endpoint, which included hospitalisation for unstable angina, coronary revascularisation, heart attack, 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 low-density lipoprotein cholesterol (LDL-C).
The results from the study were presented last week during a Late-Breaking Clinical Trials Session at the American College of Cardiology 66th Annual Scientific Session and simultaneously published in the New England Journal of Medicine.
Additionally, the new analysis from the evolocumab cardiovascular outcomes study showed a relationship between lower achieved low-density lipoprotein cholesterol (LDL-C) levels and lower cardiovascular event rates in patients with established atherosclerotic cardiovascular disease.
“With this analysis, we’ve further demonstrated the safety and efficacy of achieving an LDL-C well below current targets,” stated Robert P. Giugliano, M.D., S.M., Brigham and Women’s Hospital and Harvard Medical School, Boston and lead author on the analysis.
He claimed that their findings support the use of intensive lipid-lowering therapies, such as the combination of evolocumab and statin therapy, in high-risk patients to help reduce the risk of another cardiovascular event.
These further results were presented at the European Society of Cardiology (ESC) Congress and simultaneously published in The Lancet.