Evolocumab Improves Features Of Plaque Stability In patients of ACS: HUYGENS trial

USA: Repatha (evolocumab) in addition to optimized statin therapy, in comparison with optimized statin therapy alone, significantly improved features of plaque stability in patients with coronary artery disease (CAD), show results from HUYGENS Phase 3 study. 

The results were presented during an oral presentation at ESC Congress 2021, organized by the European Society of Cardiology, Aug. 27-30.

Heart attacks are often the result of vulnerable plaque ruptures. Key features of vulnerable plaques are a large lipid core with a thin fibrous cap that serves as a wall or barrier around the plaque to keep it intact. The HUYGENS study assessed whether Repatha, in addition to optimized statin therapy, could increase the thickness of the fibrous caps, to ultimately improve a feature of plaque stability.

The HUYGENS study met its primary endpoint, with Repatha in addition to optimized statin therapy increasing fibrous cap thickness by 42.7 um in comparison with an increase of 21.5 um (75% increase versus 39%) on optimized statin therapy alone (p=0.01), as measured by optical coherence tomography (OCT). Thus, the addition of Repatha improved this feature twice as well as statins alone. Repatha also improved all of the study's secondary endpoints, including decreasing the maximum lipid arc by -57.5° versus -31.4° (p=0.01), as measured by OCT.

"The majority of acute coronary syndrome events are caused by plaque rupture, and those who have had a heart attack are especially vulnerable to additional episodes of plaque rupture, demonstrating the importance of maintaining the thickness of the fibrous cap to help stabilize plaques," said Stephen J. Nicholls, M.D., Ph.D., professor of Cardiology and director, Monash University Victorian Heart Institute, Melbourne, Australia and first author of the HUYGENS study. "These encouraging results reaffirm the potential of Repatha and highlight the benefits of Repatha in ACS patients who initiated treatment early."

Results from the randomized, double-blind 52-week study in ACS patients on optimized statin therapy demonstrate that Repatha treatment, initiated within a week after the ACS event, reduced LDL-C from 140 to 28 mg/dL (-80%) versus reductions from 142 to 87 mg/dL (-39%) with statin optimization alone. No new safety risks were identified. The most common treatment-emergent adverse events (>3%) were angina pectoris, myalgia, hypertension, diarrhea, fatigue and cough.

"Amgen continues to build a body of evidence to support the clinical profile of Repatha and demonstrate its benefit in patients at elevated risk of suffering another heart attack or stroke," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "This study builds on the findings from the GLAGOV study and provides evidence that low LDL-C levels can change characteristics of coronary plaque, which may explain the biology of cardiovascular event reduction we saw in the FOURIER study."

While HUYGENS did not evaluate cardiovascular outcomes, the results build on the growing body of evidence already supporting the clinical profile of Repatha. The HUYGENS study results add relevant insights to the science of plaque biology and contribute to our understanding of the important benefits of initiating Repatha after a heart attack. Fifty clinical trials, conducted with over 47,000 patients randomized to Repatha or placebo, have demonstrated the clinical benefits of Repatha, which include reduction in myocardial infarction and stroke, rapid (within four weeks) and dramatic LDL-C lowering over the long term (median 2.2 years), and consistent safety over a five-year treatment period generally consistent with the FOURIER study.

About the Data

Previous studies include GLAGOV which showed Repatha, when added to optimal statin therapy, reduced plaque burden by decreasing plaque atheroma volume in patients with CAD.8 This was the first study to demonstrate that lowering LDL-C levels through PCSK9 inhibition reduces atherosclerotic plaque burden.

HUYGENS demonstrated that Repatha in addition to optimized statin therapy, in comparison with optimized statin therapy alone, significantly improved a key feature of plaque stability in patients with CAD by increasing the fibrous cap thickness. HUYGENS may offer mechanistic insight for the CV event reduction seen in the FOURIER outcomes study.