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Evolocumab reduces CV events in high-risk patients

Evolocumab reduces CV events in high-risk patients

Publication date: Tuesday, 11 April 2017
Contributor(s): Jeremy Bray

A landmark day for PCSK9 inhibition.

The addition of evolocumab, a PCSK9 inhibitor, to statin therapy over several years significantly reduced cardiovascular morbidity and mortality in patients with clinically evident atherosclerotic cardiovascular disease.  

These dramatic results from the randomised, double-blind FOURIER trial were presented at the recent American College of Cardiology meeting in Washington DC, and published in the New England Journal of Medicine.

The multinational trial involved 27,500 patients at 1242 sites in 49 countries including 74 sites in the UK. Patients were aged between 40-85 years and most (81%) had a history of heart attack, 19% had suffered an ischemic stroke and 13% had symptomatic peripheral artery disease. The median baseline LDL cholesterol (LDL-C) was 92 mg/dL. To be included, patients had to have an LDL-C ≥70 mg/dL or a non-HDL cholesterol ≥100 mg/dL and be on optimized statin therapy.

Evolocumab significantly reduced LDL-C by 59% and there was a 15% reduction in the primary endpoint which was a composite of heart attack, stroke, hospitalization for angina, revascularization or cardiovascular death. There was also a 25% reduction in the secondary endpoint of cardiovascular death, heart attack or stroke after the first year. Reductions in the primary and key secondary endpoints were consistent across all the key subgroups.

In June 2016 NICE approved evolocumab for patients at high-risk of cardiovascular events. It is recommended in certain patients who cannot lower their LDL-C below specified thresholds despite optimal treatment with statins, or other cholesterol-lowering therapies1, either because these therapies are not effective enough on their own or the patient cannot tolerate a sufficiently powerful dose. 

Table: key efficacy outcomes from FOURIER.




Hazard ratio
(95%CI, p)


Number of patients (%)


Primary endpoint: CV death MI, stroke, hospitalization for angina, revascularization

1344 (9.8%)

1563 (11.3)

0.85 (0.79-0.92), <0.001

Secondary endpoint:
CV death, MI, stroke

816 (5.9%)

1013 (7.4)

0.80 (0.73-0.88), <0.001


For full details, expert videos and comment on the FOURIER trial results go to the PCSK9 Forum website at



These results are likely to impact clinical guidelines and change practice in patients with unacceptably high LDL-C levels despite maximum tolerated doses of statins. They also highlight the benefit of lowering LDL-C levels to unprecedented low levels.  It remains to be seen how current cost levels of evolocumab affect use in other patient groups.

Sabatine M, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. NEJM 2017, 17 March. DOI: 10.1056/NEJMoa1615664 -

National Institute for Health and Clinical Excellence. Evolocumab for treating primary hypercholesterolaemia and mixed dyslipidaemia. Technology appraisal guidance [TA394]. June 2016 -

Topics covered:
Category: Evidence in Practice
Edition: Volume 2 Number 3 PCCJ Online 2017
Contributor(s): Jeremy Bray

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