ACC.23 Updates: Part 2

Volume 25, Issue 3

Continuing with last week’s Talking Therapeutics column theme, there are two more exciting trials I’d like to report on from the recent ACC.23 meeting. 

A New Oral PSCK9 Inhibitor?

The currently available PCSK9 inhibitors are available as a subcutaneous injection. While these agents have proven effective for producing profound reductions in low-density lipoprotein (LDL) and reducing the rate of residual major adverse cardiovascular events (MACE) in patients with established atherosclerotic cardiovascular disease (ASCVD), their use is hampered somewhat by the need for frequent parenteral administration. 

Inclisiran, which prevents the formation of the PCSK9 protein, attempts to combat the need for 1 to 2 monthly subcutaneous injections by using a twice-yearly intravenous infusion. While this is significantly more convenient for patients as compared with self-administered subcutaneous injections, the logistics of finding and scheduling outpatient infusions can be limited. 

Bempedoic acid, which we discussed last week, has emerged as an alternative to statins for both lowering LDL and reducing rates of MACE. This agent, however, is not as potent in lowering LDL as the PCSK9 inhibitor class. 

At the ACC.23 meeting, the results of a phase II trial were presented and simultaneously published in Journal of the American College of Cardiology. Results of this study showed a new oral PCSK9 inhibitor produced substantial reductions in LDL over 8 weeks. Among 380 participants treated, all doses of the new agent (dubbed MK-0616) demonstrated statistically significant (P < .001) differences in LDL from baseline to week 8 vs placebo, 41.2% (6 mg), -55.7% (12 mg), -59.1% (18 mg), and -60.9% (30 mg). 

If these findings are confirmed in a larger trial with longer follow up, it could be a break though agent, given the easy of oral administration and the known benefits of this class of medication in reducing rates of MACE. 

No Benefit for Routine Anticoagulation in Patients With COVID-19

Given there was a high number of observed thromboembolic complications associated with COVID-19 infection in the early days of the pandemic, there has always been a strong interest in the medical community in determining the benefit of anticoagulation for these patients. 

The FREEDOM COVID study was presented at the meeting and simultaneously published in Journal of the American College of Cardiology. Results of this study showed that the use of therapeutic anticoagulation did not result in lower rates of the composite outcome of all-cause mortality, requirement for intensive care unit level-of-care, systemic thromboembolism, or ischemic stroke. 

While the trial authors found rates of all-cause mortality and intubation were lower in the therapeutic dose group, these findings could be due to chance. After all, if rates of thromboembolism and stroke were similar, then it does not stand to reason the therapeutic anticoagulation would be responsible for the reduction in all-cause mortality that was observed in the therapeutic dose group.