FOURIER Results Explained

Marc Sabatine, MD, presenting " Primary Results of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) Trial" at the American College of Cardiology (ACC) 66th Annual Scientific Session Expo in Washington, DC on March 17th.

American College of Cardiology (ACC) 2017 Scientific Sessions: Evolocumab Added to Statins Cuts Cardiovascular Events in the FOURIER Trial

In addition to significantly lowering levels of LDL-C, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab (Repatha, Amgen) decreased major CV-events risk, according to results from the long-anticipated outcomes trial Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER).

The study, which included more than 27,000 participants with atherosclerotic CVD and already receiving statins, showed that patients who received injections of evolocumab at doses of 140 mg every other week or 420 mg monthly had a significant reduced risk for the composite of MI, stroke, CV death, coronary revascularization, and unstable angina hospitalization compared with those receiving matching placebo.

FOURIER did not include specific analyses of FH patients, though it is anticipated that many FH patients were included. Additionally, analyses on cost-effectiveness and long-term safety need to be conducted. For the FH population, it will be tremendously valuable to gather data in subsets of FH patients, such as those with high lipoprotein(a).

Here are the facts:

	FOURIER was a positive trial. Evolocumab reduced both the primary and secondary composite end points. The absolute risk reduction was 1.5%. Evolocumab resulted in significant (59% reduction) and sustained LDL-C reductions. LDL-C levels went from a mean of 92 mg/dL to a mean of 30 mg/dL. A remarkable 42% of patients on Evolocumab maintained LDL-C below 25 mg/dL.
	FOURIER did not show any major safety issues. The EBBINHAUS trial also showed that diabetes, cataracts, and neurocognitive effects were not reported to be increased in those taking evolocumab.
	FOURIER did not show antibodies against Evolocumab.
	The shortness of follow-up of FOURIER deserves mention. During a 2- year follow up, the FOURIER showed a number needed to treat (NNT) of 74 to prevent a cardiovascular (CV) death, myocardial infarction (MI) or stroke. As we learn more from longer follow-up, it is possible the NNT may improve.
	FOURIER gives our patients and physicians a new, evidence-based tool to combat CVD and reduce CV events.
	FOURIER demonstrated, once again, that "lower is better" regarding LDL-C.
	It is anticipated that new guidelines will take into account the FOURIER results and that decisions about "treat to target" might be influenced.
	FOURIER is in concordance with the previous results of GLAGOV trial and the discontinued SPIRE trial with bococizumab.
	FOURIER results are in consonance with previously estimated impact of genetics on CV events.
	FOURIER (2 years) did not show reduced rates of mortality; TNT (6 years) and IMPROVE-IT trial (7 years) did not demonstrate reduced mortality as well. A longer follow-up is needed to demonstrate such a benefit.
	FOURIER provides high-grade clinical evidence to the decision on whether or not to add PCSK9 inhibitors to baseline medical therapy in secondary prevention.

Finally, the cost of PCSK9 inhibitors and the disproportionate expectation should not overshadow the observed results. Science has advanced and patients and physicians have a new tool to combat CVD.

By Pablo Corral, MD

Internist; Clinical Lipidologist

FASTA University, School of Medicine, Pharmacology Department
Mar del Plata, Argentina

www.theFHFoundation.org

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