FOURIER: Evolocumab reduces CV events in patients with recent MI
Patients with recent MI are at very high risk of major adverse cardiovascular events (MACE). A new analysis of the FOURIER trial showed that the risk of MACE for these patients can be reduced significantly with the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, evolocumab (Repatha®, Amgen), given on top of statin therapy. These results, presented at the American Heart Association (AHA) Scientific Sessions 2019, corroborate the 2018 American College of Cardiology (ACC)/AHA recommendations for intensive LDL-cholesterol (LDL-C) lowering after a recent MI.
Evolocumab reduces MACE in ASCVD patients
The FOURIER trial evaluated the efficacy and safety of evolocumab (140 mg Q2W or 420 mg Q4W) vs placebo, added to moderate- or high-intensity statin therapy, in 27,564 patients with stable atherosclerotic cardiovascular disease (ASCVD) and an LDL-cholesterol (LDL-C) level of ≥70 mg/dL (≥1.8 mmol/L) despite the use of statins. Results at 48 weeks showed a 59 percent reduction in LDL-C levels with evolocumab vs placebo (from 92 mg/dL [2.4 mmol/L] at baseline to 30 mg/dL [0.78 mmol/L]; p<0.001). [N Engl J Med 2017;376:1713-1722]
After a median follow-up of 2.2 years, patients in the evolocumab group had a 15 percent relative risk reduction in the primary composite endpoint of five-point MACE (CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) compared with those in the placebo group (9.8 percent vs 11.3 percent; hazard ratio [HR], 0.85; 95 percent confidence interval [CI], 0.79 to 0.92; p<0.001). The relative risk of three-point MACE (CV death, MI, or stroke), which served as a secondary endpoint, was reduced by 20 percent with evolocumab vs placebo (5.9 percent vs 7.4 percent; HR, 0.80; 95 percent CI, 0.73 to 0.88; p<0.001).
FOURIER: Increased MACE risk in patients with recent MI
“Patients with recent MI occurring within the last 12 months are at very high risk of CV events,” said FOURIER investigator, Dr Baris Gencer of the Brigham and Women’s Hospital, Boston, Massachusetts, US. “An analysis of the FOURIER trial was conducted to evaluate the clinical efficacy of evolocumab in patients with recent MI occurring within 12 months [n=5,711] and in those with remote MI occurring more than 12 months [n=16,609] prior to randomization.” [Gencer B, et al, AHA 2019, abstract 13871]
The median time from MI was 4.8 months in patients with recent MI and 59 months in those with remote MI. Patients with recent MI were more likely to be younger (mean age, 60 years vs 63 years; p<0.001) and treated with high-intensity statin (77 percent vs 69 percent; p<0.001), and less likely to have a history of stroke (5 percent vs 8 percent; p<0.001), peripheral artery disease (5 percent vs 9 percent; p<0.001), coronary artery bypass grafting (15 percent vs 24 percent; p<0.001), hypertension (73 percent vs 81 percent; p<0.001), or diabetes (30 percent vs 37 percent; p<0.001).
Compared with patients with remote MI, patients with recent MI had a 45 percent higher relative risk of both five-point MACE (17.2 percent vs 14.4 percent; adjusted HR, 1.45; 95 percent CI, 1.29 to 1.64; p<0.001) and three-point MACE (10.9 percent vs 9.5 percent; adjusted HR, 1.45; 95 percent CI, 1.24 to 1.69; p<0.001) at 3 years. (Figure 1)
Evolocumab reduces MACE in patients with recent MI
“Among patients with recent MI, evolocumab reduced the relative risk of five-point MACE at 3 years by 19 percent vs placebo [13.5 percent vs 17.2 percent; HR, 0.81; 95 percent CI, 0.70 to 0.93; p=0.004],” reported Gencer. “The number needed to treat [NNT] was 27 over 3 years.” (Figure 2)
Patients with recent MI also had a 25 percent reduction in relative risk of three-point MACE at 3 years with evolocumab vs placebo (7.7 percent vs 10.9 percent; HR, 0.75; 95 percent CI, 0.62 to 0.91; p=0.003), with an NNT of 32 over 3 years.
In patients with remote MI, the 3-year rates of five-point MACE did not differ significantly between the two treatment groups (13.3 percent vs 14.4 percent; HR, 0.92; 95 percent CI, 0.84 to 1.01; p=0.075) (NNT for 3 years, 95). However, the relative risk of three-point MACE at 3 years was 15 percent lower with evolocumab vs placebo (8.2 percent vs 9.5 percent; HR, 0.85; 95 percent CI, 0.76 to 0.96; p=0.009) (NNT for 3 years, 79).
“Analysis of the FOURIER trial showed significant reductions in MACE with evolocumab in patients with recent MI. These findings corroborate the 2018 ACC/AHA guidelines, which recommend intensive LDL-C lowering in patients with recent MI and an LDL-C level of ≥70 mg/dL, using a PCSK9 inhibitor added to background high-intensity or maximally tolerated statin therapy,” Gencer concluded. [J Am Coll Cardiol 2019;73:3168-3209]