Acute arterial events reduced by PCSK9 inhibitor across all vascular territories
Effect of evolocumab on acute arterial events across all vascular territories: results from the FOURIER trial
Introduction and methods
Acute arterial vascular events in the coronary, cerebrovascular, and peripheral beds share related underlying pathophysiological mechanism, but the total burden of acute events is not often reported in patients with high CV risk . In addition, the effect of lipid-lowering therapy on total burden of acute events has not been well studied [2,3].
In the FOURIER trial, the PCSK9 inhibitor evolocumab reduced major adverse CV events compared to placebo in patients with stable atherosclerotic CVD (ASCVD) on statin therapy [4-6]. And there was benefit of evolocumab in reducing coronary, cerebrovascular, and peripheral vascular events.
FOURIER was a randomized, double-blind, placebo-controlled trial that included 27564 patients with prior MI, stroke or peripheral artery disease (PAD). LDL-c had to be ≥70 mg/dL or non-HDL-c ≥100 mg/dL while patients were on statin therapy with or without ezetimibe. Patients were randomized to evolocumab or matching placebo, and followed for a median of 2..2 years (IQR: 1.8-2.5 years).
In this post hoc analysis of the FOURIER trial, the burden of acute arterial events across vascular territories and the effect of lipid lowering by evolocumab on these events was investigated.
Outcomes were acute arterial events defined as a composite of coronary (CHD death, MI or urgent coronary revascularization), cerebrovascular (ischemic stroke, transient ischemic attack or urgent cerebral revascularization), or peripheral vascular (acute limb ischemia, major amputation, or urgent peripheral revascularization) events.
- 2210 patients had an acute arterial event: 1596 an acute coronary event, 451 an acute cerebrovascular event, 79 an acute peripheral vascular event and 84 acute arterial events in two or more beds.
- Patients with polyvascular disease had the highest rate of acute arterial events (18.7%), followed by those with symptomatic PAD (13.2%), prior stroke (10.6%), and prior MI (10.3%).
- Evolocumab reduced risk of a first acute arterial event by 19% compared to placebo (HR 0.81, 95%CI: 0.74-0.88, P<0.001), and with reductions in acute coronary (HR 0.83, 95%CI: 0.75-0.91, P<0.001), acute cerebrovascular (HR 0.77, 95%CI: 0.65-0.92, P=0.004) and acute peripheral vascular (HR 0.58, 95%CI: 0.38-0.88, P=0.01) events.
- Benefits of evolocumab were consistent in major subgroups of patients.
- The magnitude of risk reduction in first acute arterial events with evolocumab increased over time; a 16% reduction (HR 0.84, 95%CI:0.75-0.95, P=0.004) in the first year followed by a 24% reduction (HR 0.76, 95%CI: 0.67-0.85, P<0.001) after 12 months.
- Total acute arterial events were reduced by 24% in the evolocumab group (RR 0.76, 95%CI:0.69-0.85, P<0.001), including a reduction of 19% in first events (HR 0.81, 95%CI: 0.84-0.88, P<0.001) and 35% reduction of subsequent events (RR 0.65, 95%CI:0.58-0.73, P<0.001).
This post hoc analysis of FOURIER showed that treatment with the PCSK9 inhibitor evolocumab in high CV risk patients reduced the risk of acute arterial events in all vascular beds. Acute coronary events were the common events in these high-risk patients, followed by acute cerebrovascular and peripheral vascular events. There was a robust effect of evolocumab over time on reducing both first and recurrent events.