In this post, I link to and excerpt from Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab – ODYSSEY OUTCOMES, Nov 04, 2020 from American College of Cardiology Latest in Cardiology.
All that follows is from the above resource.
Contribution To Literature:
The ODYSSEY OUTCOMES trial showed that use of alirocumab, taken every other week, significantly reduces ischemic events, including all-cause mortality and MI, compared with placebo among patients with an ACS event within the preceding 1-12 months.
The goal of the trial was to compare the safety and efficacy of alirocumab compared with placebo among patients with recent acute coronary syndrome (ACS) already on intensive or maximum-tolerated statin therapy.
The results of this landmark trial indicate that the use of alirocumab, taken every other week, significantly reduces ischemic events, including all-cause mortality and MI, among patients with an ACS event within the preceding 1-12 months. First and total nonfatal events were lower with alirocumab. Nearly 90% of these patients were on a high dose of a potent statin (atorvastatin or rosuvastatin). Of note, the target LDL-C in this trial was 25-50 mg/dl, and the dose was adjusted to keep the LDL-C above 15 mg/dl. LDL-C reductions of >50% were observed early, and appeared more or less sustained during follow-up. This is one of the first trials to show a therapeutic benefit with reduction in Lp(a) that is independent of LDL-C. This was particularly meaningful for patients with high baseline Lp(a) levels. This may represent a novel therapeutic target among ACS patients.
A few points to consider: This trial differs from the other PCSK9 inhibitor outcomes trial (FOURIER – evolocumab) in the patient population enrolled – post-ACS vs. stable established atherosclerotic disease. Differences in mortality noted in this trial were not noted in FOURIER, possibly due to the higher risk patient population enrolled in ODYSSEY OUTCOMES; reductions in LDL-C seemed qualitatively similar. Secondly, this trial further reinforces the “lower is better” hypothesis with LDL-C, and will likely once again reopen the debate about treating patients based on lipid levels rather than intensity of statin therapy alone. Interestingly, the CTT meta-analysis suggests an approximate 22% reduction in CHD events with every 1 mmol/L (38 mg/dl) reduction in LDL-C; the benefits noted in this trial seem somewhat attenuated compared with this maxim. Next, there was a slight attenuation of reduction in LDL-C over long-term follow-up in this trial. This trend upward in the LDL is thought to be due to the study design of reducing treatment dose in the face of very low LDL levels and not due to a significant presence of neutralizing antibodies. The SPIRE trial program with bococizumab had to be abandoned due to this issue of neutralizing antibodies.
Finally, PCSK9 inhibitors are very expensive medications; the cost-effectiveness analysis is important, and suggests that the cost-benefit ratio is more favorable among patients with LDL-C ≥100 mg/dl.