New data from the 27,564-patient cardiovascular outcomes study, FOURIER, established for the first time that maximally reducing low-density lipoprotein cholesterol (LDL-C) levels with evolocumab (Repatha), beyond what is possible with the current best therapy alone, leads to a further reduction in major cardiovascular events, including heart attacks, strokes and coronary revascularisations. 

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) and found that adding evolocumab to optimised statin therapy resulted in a statistically significant 20% (p<0.001) reduction in these events. The robust benefit in this objective measure started as early as six months and continued to accrue through the median 2.2 years of the study. In fact, the magnitude of the risk reduction in the hard MACE composite endpoint grew over time, from 16% in the first year to 25% beyond the first year.

The study also found a statistically significant 15% 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.

Patients on evolocumab experienced a reduction in the risk of heart attack (27%, nominal p<0.001), stroke (21%, nominal p=0.01) and coronary revascularisation (22% nominal p<0.001). Consistent with recent trials of more intensive LDL lowering, there was no observed effect on cardiovascular mortality. Similarly, there was no observed effect on hospitalisation for unstable angina. In an exploratory analysis, the relative risk reduction for fatal and non-fatal heart attack or stroke was 19% in the first year (p=0.003) and 33% beyond the first year (p<0.00001).

Marc S Sabatine, chairman of the TIMI Study Group, the Lewis Dexter, Distinguished Chair in Cardiovascular Medicine at Brigham and Women’s Hospital, and Professor of Medicine, Harvard Medical School, Boston, said: “We now show for the first time in a dedicated outcomes study that decreasing LDL cholesterol with PCSK9 inhibition results in clinically meaningful cardiovascular benefit. These benefits were achieved with lowering LDL cholesterol down to a median of 30mg/dL, which is well below current targets, and the magnitude of risk reduction increased the longer patients were on therapy. These results support the need for long-term, vigorous LDL cholesterol reduction in our patients with cardiovascular disease.”