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ORLANDO -- Will the second big cardiovascular outcomes trial for a PCSK9 inhibitor, the , shore up the modest benefits seen in the first? Or will clinicians end up figuratively stuck ?
The saga will be center stage in the opening at the American College of Cardiology (ACC) meeting here on Saturday.
Conference chair Jeffrey Kuvin, MD, predicted that the trial will be just as important as the FOURIER cardiovascular outcomes trial for evolocumab (Repatha) that created a "big splash" last year at the same meeting.
"The data are going to be interesting regardless of what we see," he told 51˶ at a preview briefing. "For example, if we see that in ODYSSEY there is an overall mortality benefit, I think that's going to give this class of drugs a lot more interest in terms of what clinicians have to provide to their patients.
"I think if the data are quite similar to FOURIER, in that we see significant reductions in LDL and we see decreased number of events but not necessarily impacting mortality, I think again that's going to reinforce a lipid-lowering pathway that some of our patients will benefit from," he added.
Given the similar large degree of LDL lowering with alirocumab (Praluent) being tested in ODYSSEY and the assumed class effect of these drugs, many are predicting at least as positive results. But while the trial wasn't stopped early for either efficacy or futility, there are a few key differences compared with FOURIER -- lower baseline LDLs, a post-acute coronary syndrome population, and in the primary composite endpoint -- that could send the outcome either way.
"I think there's going to be further discussion about the cost of the medications, the availability of these medications to the patients, in whom should they be prescribed, and I think that this is going to be practice changing almost regardless of what it shows," Kuvin said.
Conference vice chair Andrew Kates, MD, suggested that data reinforcing a cardiovascular prevention benefit of the PCSK9s would boost its position in the armamentarium, considering the cost, and could impact guidelines as well.
"It's always helpful to see a second trial showing benefit of a class of drugs. It really helps reinforce and potentially change the level of recommendation for guidelines," he said in the preview briefing.
The opening "showcase" also features the , notable as the first large randomized trial of the LifeVest wearable defibrillator despite approval more than a decade ago. The trial aims to demonstrate reduced risk of sudden death during the vulnerable first 3 months after a heart attack, before patients are potentially eligible for implantable devices, compared with conventional treatment without the defibrillator.
"That's sure to impact clinical practice," Kates said, calling the findings eagerly awaited.
Other highlights in the late-breaking clinical trial program include:
- ARTEMIS, which tests whether lowering costs for dual antiplatelet therapy boosts real-world adherence to guidelines
- Longer-term MOMENTUM 3 data on the HeartMate 3 versus HeartMate 2 ventricular-assist devices at 2 years, an update from the 6-month data presented last year
- Further interim data from the ANNEXA-4 trial of the factor Xa inhibitor reversal agent andexanet alfa (AndexXa), this time dealing with acute major bleeding risk; a decision from the FDA on approval was due Feb. 3 but has been extended to May 4
- Prevention of cardiotoxicity for breast cancer patients is addressed by the Ceccy trial testing carvedilol (Coreg) against anthracycline-induced damage and a second trial comparing carvedilol and lisinopril in patients receiving trastuzumab (Herceptin)
- A trial of pharmacist-led intensive blood pressure management in black barbershops
- Two trials of perioperative treatment after noncardiac surgery: MANAGE, testing dabigatran (Pradaxa) for myocardial injury after procedures; and long-delayed 1-year data from the POISE trial of beta blocker use during these surgeries
The ACC has stepped up its social media focus at the meeting, with dedicated experts in each cardiology section tweeting with designated hashtags.
While watching the tweets is "not the same as being present," it is a good way to share the science for colleagues who can't attend, ACC president Mary Norine Walsh, MD, said at the preview briefing.
"I actually think that overall, social media has increased the interest in science and the avid discussion after release of data. Peer review used to happen only in letters to the editor a few months after something came out. Peer review now is instant, both for journal article releases and scientific presentations ... there is limitation, but it's not necessarily bad."