FOURIER Analysis Touts Evolocumab for Reducing Myocardial Infarction

While the results of the FOURIER trial demonstrated the ability evolocumab (Repatha) to lower the incidence of major adverse cardiovascular events (MACE) in patients with vascular disease, a new analysis of the trial is shedding light on the benefit of evolocumab across multiple myocardial infarction (MI) subtypes.

A prespecified analysis of the multinational phase 3 trial, results indicated LDL-C lowering with evolocumab was effective in reducing risk of MI and evolocumab use showed benefit in plaque rupture, smaller and larger MIs, and both STEMI and non-STEMI.

In an effort to offer further insight, the prespecified analysis of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial was designed to assess the effect of evolocumab in patients who suffered MIs during the study period. While the FOURIER trial examined use of evolocumab in patients with atherosclerotic cardiovascular disease, the analysis examined the effect on different types and sizes of MI among these patients to better understand the events FOURIER prevented.

All MI events occurring in the FOURIER trial were categorized into universal MI subtypes, subtypes related to ECG STEMI or non-STEMI, and by peak cardiac biomarker by the Thrombolysis in Myocardial Infarction clinical events committee.

Due to small numbers in each category, comparison groups were expressed as nonexclusive cumulates bins based on cardiac troponin levels. To evaluate the timing of evolocumab benefit, investigators performed landmark analyses of MU from 0-6 months, 6-12 months, 12-18 months, and greater than 18 months.

Of note, Cox proportional hazards used in the analysis were adjusted for factors including age, sex, BMI, race/ethnicity, region, prior MI at baseline, history of stroke, peripheral artery disease, hypertension, diabetes, congestive heart failure, PCI, coronary artery bypass grafting and treatment group.

The FOURIER study population had a mean age of 62.5 (9.0) years and 75% were men. Results indicated 1107 individuals experienced a total of 1288 MIs during the study period.

Investigators highlight 68% of MIs were atherothrombotic (type 1), 16% were from myocardial oxygen supply-demand mismatch (type 2), 15% were PCI-related (type 4), and less than 2% were type 3 or 5. In regard to ECG type, 78% of MIs were non-STEMI, 18% were STEMI, and 3.5% had a type that could not be determined.

Myocardial infarction size by troponin level elevation was determined for 1150 of the 1288 events that occurred in the study period. Of these 1150 events, 59.8% had troponin levels greater than 10 times the upper limit of normal. Further analysis indicated 23% of these had troponin level elevation 10 to less than 25 times the upper limit of normal, 17% had elevation 25 to less than 100 times the upper limit of normal, and 20% had levels 100 or more times the upper limit of normal.

Results of the analysis indicated evolocumab use significantly reduced risk of first MI by 27% (4.4% vs 6.3%; HR 0.73; 95% CI, 0.65-0.82; P <.001). Further examination of results revealed evolocumab use was associated with a 32% reduced risk for type 1 MIs (2.9% vs 4.5%; HR, 0.68; 95% CI, 0.59-0.79; P <.001), a 35% reduced risk for type 4 MIs (0.8% vs 1.1%; HR, 0.65; 95% CI, 0.48-0.87; P=.004), and no effect on type 2 MIs (0.9% vs 0.8%; HR, 1.09; 95% CI, 0.82- 1.45; P=.56).

Results indicated the apparent benefit of evolocumab was consistent regardless of ECG categorization—use was associated with a 23% (3.5% vs 4.7%; HR, 0.77; 95% CI, 0.68-0.88; P <.001) reduced risk of non-STEMI and a 36% (1.0% vs 1.5%; HR, 0.64; 95% CI, 0.49-0.84; P <.001) reduced risk of STEMI.

Analysis of cardiac troponin levels suggested evolocumab provided benefit regardless of MI size with a 34% reduction in MIs with troponin level greater than or equal to 10 times the upper limit of normal (2.6% vs 3.7%; HR, 0.66; 95% CI, 0.56-0.77; P <.001). Results also indicated evolocumab use was associated with a 20% (1.9% vs 2.4%; HR, 0.80; 95% CI, 0.68-0.94; P=.006), reduction in MI during the first year, with a 35% (2.7% vs 4.2%; HR, 0.65; 95% CI, 0.55-0.77; P <.001) reduction beyond the first year.

This study, “Effect of Evolocumab on Type and Size of Subsequent Myocardial Infarction A Prespecified Analysis of the FOURIER Randomized Clinical Trial,” was published in JAMA Cardiology.