Conference Coverage
Evolocumab strikes gold in FOURIER trial
WASHINGTON - A PCSK9 inhibitor reduced hard cardiovascular endpoints on top of statin therapy.
Bruce Jancin/Frontline Medical News
Dr. Marc S. Sabatine
The use of evolocumab in patients with at least one of the three high-risk features was associated with a 22% relative risk reduction and an absolute 2.5% risk reduction, compared with placebo. The event curves diverged at about 6 months, and the gap between them steadily widened during follow-up. Extrapolating from this pattern, it’s likely that evolocumab would achieve an absolute 5% risk reduction in MACE, compared with placebo over 5 years, with an NNT of 20, according to Dr. Sabatine, professor of medicine at Harvard Medical School and chairman of the Thrombolysis in Myocardial Infarction (TIMI) Study Group.
Lingering questions
Dr. Braun was particularly impressed that the absolute risk reduction in MACE was even larger in patients with baseline PAD but no history of stroke or MI than in PAD patients with such a history. She added that, while she recognizes the value of selecting objectively assessable hard clinical MACE as the primary endpoint in FOURIER, her own patients care even more about other outcomes.
“What my patients with PAD care most about is whether profound LDL lowering translates to less claudication, improved quality of life, and greater physical activity tolerance. These were prespecified secondary outcomes in FOURIER, and I look forward to future reports addressing those issues,” she said.
Another unanswered question involves the mechanism by which intensive LDL cholesterol lowering results in fewer MACE and MALE events in high-risk subgroups. The possibilities include the plaque regression that was documented in the GLAGOV trial, an anti-inflammatory plaque-stabilizing effect being exerted through PCSK9 inhibition, or perhaps the PCSK9 inhibitors’ ability to moderately lower lipoprotein(a) cholesterol levels.
Simultaneous with Dr. Bonaca’s presentation at the AHA, the FOURIER PAD analysis was published online in Circulation (2017 Nov 13; doi: 10.1161/CIRCULATIONAHA.117.032235).
The FOURIER trial was sponsored by Amgen. Dr. Bonaca and Dr. Sabatine reported receiving research grants from and serving as consultants to Amgen and other companies.