Erin Michos, MD, MHS, discusses her choices for top studies in lipidology from the American College of Cardiology 2023 Scientific Sessions.
A showcase of the latest advancements in cardiometabolic health, the American College of Cardiology’s (ACC) 2023 Annual Scientific Session Together with the World Congress of Cardiology drew more than 10,000 in-person attendees to New Orleans, LA in addition to nearly 2000 virtual attendees.
Among the multitude of subspecialties highlighted with sessions, posters, and late-breaking presentations at ACC 2023, advances in lipidology took centerstage on more than one occasion throughout the meeting. An example of the precedence these advances took at the meeting, CLEAR Outcomes, the long-awaited cardiovascular outcomes trial of bempedoic acid, was the first study presented in the meeting’s first late-breaking session.
Throughout the meeting, advances in lipidology continued to assume the spotlight in featured clinical research sessions, with major studies including YELLOW III, the Personalized Clinical Decision Support Intervention to Improve Statin Prescribing in Patients with Atherosclerotic Cardiovascular Disease (PCDS Statin) trial, and a phase 2 trial examining an investigational oral PCSK9 inhibitor. During a recent visit to the MJH Life Sciences studio, we sat down with Erin Michos, MD, associate professor of medicine within the Division of Cardiology and director of Women’s Cardiovascular Health at Johns Hopkins School of Medicine.
HCPLive: Can you describe the impact of CLEAR Outcomes for patient populations with statin intolerance?
Michos: We've been waiting for CLEAR Outcomes for a while. This is the cardiovascular outcome trial of bempedoic acid because, in clinical practice, statin intolerance is a major challenge. Maybe it's a nocebo effect, but the statin symptoms are real to the patient, and so many high-risk patients are not achieving their LDL goals. The trial, CLEAR Outcomes, enrolled 14,000 persons who had either stable cardiovascular disease or were at high risk for primary prevention. We saw that all participants who had statin intolerance had their LDL lowered by 21% or 29 milligrams per deciliter on average. This conferred a 13% reduction in 4-point major adverse cardiovascular events (MACE) and a 15% reduction in 3-point MACE.
I'm really excited that this trial included nearly half women, 48% women. Women patients are more likely to have statin intolerance, and historically, they had not been included in cardiovascular clinical trials. Importantly, we saw that the benefit was even larger in the primary prevention group, where the hazard ratio was 0.68. I think this is particularly exciting because in secondary prevention, we have more options for non-statin therapy like PCSK9 monoclonal antibodies and closer in. To have an option for primary prevention that is oral, that is not a statin, and that can achieve LDL goals and reduce major adverse cardiovascular events, is another tool in the toolkit that I'm excited about.
HCPLive: Can you describe the clinical relevancy of the results from the PCDS Statin trial?
Michos: So unfortunately, clinical inertia is a major problem in achieving LDL goals. We saw from the GOULD registry that more than two-thirds of patients with ASCVD remain above an LDL of 70 or higher, and only 17% had their lipid-lowering therapy intensified over 2 years. The PCDS trial within the VA system looked at whether electronic nudges could help urge clinicians to get their patients with ASCVD on high-intensity statins. AI algorithms were used to identify patients at risk, and clinicians were given a tailored message about the patient's ASCVD diagnosis, their current statin therapy, and dose, as well as guideline recommendations about the role of high-intensity statins and algorithms for statin intensity.
Compared to the usual practice groups, the primary care groups that received the clinical nudges had a modest uptick in high-intensity statins. However, more than a third of clinicians opted not to receive the electronic nudges, indicating alert fatigue and suggesting that electronic nudges may not be appealing to many clinicians who have already integrated their workload. We are still trying to figure out the best way to implement the guidelines we already have in place, and AI and electronic nudges may be one tool to move us in that direction.
HCPLive: What was your reaction to the data surrounding MK-0616 presented during ACC.23?
Michos: So, our guidelines and recent statements have emphasized that patients who have ASCVD at very high risk, we not only want to reduce LDL by 50%, but also achieve these more intensive LDL goals of less than 55 milligrams per deciliter. Sometimes it can be hard to get there with statins alone or if patients can't tolerate the statins. Therefore, in our high-risk patients, we have the monoclonal antibody PCSK9 inhibitors or inclisiran, which is a small interfering RNA towards PCSK9.
What's also potentially exciting is an oral PCSK9 inhibitor because we never thought that it would be possible to inhibit PCSK9 with an oral medication and be able to get it in the right place and be absorbed. But there have been a lot of advances in science. This new agent was tested in a phase two B trial, and at the highest doses over an eight-week period, we saw a 60% reduction in LDL, which is really in the same range as we see with LDL reduction with monoclonal antibodies or with an oral medication. There were no safety concerns in the small eight-week trial, but it sets the stage to move to a larger phase three trial. I think it's very exciting to have more tools in the toolkit, more options for our patients to reach these more intensive LDL goals.
HCPLive: How does YELLOW III add to our understanding of the effects of evolocumab?
Michos: So, we know from the outcome trials for PCSK9, such as the FOURIER trial, that PCSK9 inhibitors reduce major adverse cardiovascular events. However, some of these trials are now attempting to discover the exact mechanisms of how they work. YELLOW III looked at high-risk patients who underwent coronary angiography and OCT to examine plaque composition. They found that treatment with evolocumab, which significantly reduces LDL levels, can lead to favorable changes in plaque composition. This suggests that the outcome benefit may be driven by plaque stabilization or regression. These mechanistic studies are really interesting because they help us understand what's happening behind the scenes and why intensive LDL lowering is so important.
Editor’s note: This transcript has been edited for clarity.
Disclosures of note for Erin Michos, MD, MHS, include Esperion, Amgen, Novartis, and others. Click here for a full list.