A welcome addition for managing lipid disorders
PARIS – The first-ever randomized trial of in-hospital initiation of a PCSK9 inhibitor on top of guideline-recommended high-intensity statin therapy in the very-high-risk acute phase of an acute coronary syndrome (ACS) safely resulted in dramatically lower LDL cholesterol levels than with early prescribing of a high-intensity statin alone, Konstantinos C. Koskinas, MD, reported at the annual congress of the European Society of Cardiology.
Dr. Konstantinos C. Koskinas
compared with 11% of patients randomized to high-intensity atorvastatin at 40 mg/day plus placebo injections. Moreover, 96% of patients on atorvastatin 40 mg/day plus evolocumab at 420 mg per subcutaneous injection were below the former target of an LDL cholesterol less than 70 mg/dL, as were 38% of those on the high-intensity statin alone, according to Dr. Koskinas, a cardiologist at the University of Bern (Switzerland).
The seven-center Swiss EVOPACS trial, featuring 308 ACS patients, could be considered a proof-of-concept study, as it lacked the size and duration to be powered to assess clinical outcomes.
“The clinical impact of very early LDL lowering with evolocumab initiated in the acute setting of ACS warrants further investigation in a dedicated cardiovascular outcomes trial,” Dr. Koskinas asserted. “We see this as the natural next step. Discussions are underway about a long-term trial with clinical endpoints, but no decisions have been made.”
The rationale for the EVOPACS trial is based upon current standard practice in ACS management, which includes initiation of a high-intensity statin during the acute phase of ACS, a particularly high-risk period for recurrent events. This practice has a Class IA recommendation in the guidelines based on published evidence that it results in a significantly reduced rate of the composite of death, MI, or rehospitalization for ACS within 30 days, compared with a less aggressive approach to LDL cholesterol lowering.
Yet even though the PCSK9 inhibitors are the 800-lb gorillas of LDL cholesterol lowering, they’ve never been tested in the setting of acute-phase ACS. For example, in the landmark ODYSSEY OUTCOMES trial, alirocumab was initiated on average 2.6 months after ACS, while in FOURIER the lag time between ACS and the start of evolocumab was 3.4 years, the cardiologist noted.
In contrast, all of the 37% of EVOPACS participants with an ST-segment elevation MI were enrolled in the study and on treatment within 24 hours after symptom onset. So were more than one-third of those with non–ST-elevation ACS, with the remainder getting onboard 24-72 hours after symptom onset.
The safety and tolerability of dual LDL cholesterol–lowering therapy were excellent in the brief EVOPACS study. There were no significant between-group differences in adverse events or serious adverse events, nor in prespecified events of special interest, including muscle pain, neurocognitive changes, or elevated liver enzyme levels.
The LDL cholesterol lowering achieved with dual therapy in EVOPACS was jaw dropping: Over the course of 8 weeks, the mean LDL cholesterol went from 132 to 31 mg/dL. In patients on early high-intensity atorvastatin alone, LDL cholesterol went from 139 to 80 mg/dL.
The full details of the EVOPACS trial have been published (J Am Coll Cardiol. 2019 Aug 16. doi: 10.1016/j.jacc.2019.08.010.
The trial was funded by Amgen. Dr. Koskinas reported receiving honoraria from Amgen and Sanofi.