Updates From ACC’s 2024 Scientific Sessions With John Fanikos

by John Fanikos, RPh, MBA

Each year, our team looks forward to the “Late Breaking Clinical Trials”, presented at the American College of Cardiology Scientific Sessions. These sessions provide a glimpse into the future with new drugs, give updates on existing drugs, and re-evaluate existing practices. This year, we were inspired by all of the findings that were presented, and are especially excited by the trials with new medications.

New medication trial highlights included:

• The KARDIA-2 trial introduced a long-acting RNAi therapy, zilebesiran. Among 700 adults with uncontrolled hypertension, a single zilebesiran 600mg subcutaneous injection, when added to existing anti-hypertensive agents, significantly reduced systolic blood pressure at three months compared with placebo. These reductions were sustained after six months of treatment. We may now have a medication that is given twice a year for control of high blood pressure.
• The oligonucleotide* plozasiran was evaluated in the SHASTA-2 trial for patients with severe hypertriglyceridaemia. In 229 patients plozasiran lowered triglyceride levels by an average of 74% after 24 weeks versus 17% for placebo, with more than 90% of patients reaching their triglyceride goal. Promising early results.
• Olezarsen is an oligonucleotide* that was evaluated in the BRIDGE-TIMI 73a for patients with familial chylomicronemia syndrome (FCS). FCS is a rare form of severe hypertriglyceridaemia for which no treatments have been approved. Olezarsen 50mg subcutaneously once monthly reduced triglyceride (TG) levels by 49% and by 53% with an 80mg dose. Effective doses have been established, more trials can move forward to evaluate patient outcomes with long term treatment.
• The AEGIS-II trial explored the use of a new cholesterol efflux enhancer, intended to raise HDL. The intravenous administration every 4 weeks after acute MI did not reduce another myocardial infarction, stroke, or death through 90 days of follow-up. However, among the almost 18,000 patients, there were some that did find benefit.

Exciting news for existing medications included:

• The VICTORION-INITIATE study focused on starting the medication inclisiran (Leqvio©) quickly in patients with existing atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL who are already receiving a statin (Lipitor©, Crestor©, Zocor©, Pravachol©). Early Inclisiran therapy reduced LDL-C by 60% allowing patients to reach their target goal as compared with 7% of patients receiving routine care. Strong results, demonstrating the need to start therapy early rather than watch and wait.
• STEP-HFpEF DM trial showed that patients with obesity-related heart failure with type 2 diabetes see significant improvement in symptoms and physical limitations after a year of therapy on once-weekly semaglutide (Wegovy©), despite losing less weight than patients who don’t have diabetes. This suggests that weight loss is not the only factor in improving heart failure. Semaglutide has other benefits that are disease-modifying, possibly by improving vascular tone, skeletal muscle, or reducing inflammation.
• The EMPACT-MI trial employed the early use of empagliflozin (Jardiance©) shortly after an acute MI but it did not reduce the risk of subsequent heart failure (HF) hospitalization or death combined. But when the authors looked closer at individual events, the rates of first heart failure hospitalization and the total number of heart failure hospitalizations were reduced in the patients treated with empagliflozin. The SGLT2 inhibitors (Jardiance©, Farxiga©, Invokana©, Impefa©) have shown benefits in reducing heart failure, chronic kidney disease, and diabetes. You need to find the silver lining in this study.

Finally, it’s always critical to evaluate existing trials, including:

• The management of MI has changed over the last 20 years, moving from using just medications to a modern era of intervention with balloons and stents placed in the blocked vessels. The REDUCE MI trial studied the use of beta blockers in patients with acute MI who underwent intervention. Patients were treated with a beta-blocker (metoprolol, bisoprolol) or no treatment. Over the following 3.5 years there was no difference in all-cause mortality or MI in those treated with a beta-blocker and in those who did not receive a beta-blocker. There are more trials on-going studies (DANBLOCK, BETAMI, REBOOT, ABYSS) of beta-blockers for post-MI patients that will help clarify their role. Stay tuned.
• Almost 10 years ago the TACT trial used metal chelation therapy in patients after suffering from MI and reported a reduction in subsequent cardiovascular events. Now the TACT2 trial tested edetate disodium (EDTA) in 1,000 post-MI diabetic patients. While the therapy showed a reduction in heavy metals, like lead, EDTA had no effect on the occurrence of death, MI, stroke, coronary revascularization, or hospitalization for unstable angina. Times have changed, it’s probably back to the drawing board.

In summary, both new medications that are coming, as well as existing therapies, are impacting factors that heighten thrombosis risk. We can’t wait to see what comes next!

* Oligonucleotides are emerging treatment options in cardiovascular disease. They use the existing metabolic machinery to translate messenger RNA into proteins that interrupt the disease process