Mary McGowan, MD, FNLA: We have a second analysis, and the second analysis was to assess the consequences of the failure to achieve the LDL [low-density lipoprotein] guideline thresholds in patients at elevated risk, again using the same Family Heart database. But we are using it in a slightly different way. It’s the same 324 million individuals from 2012 to 2021. But in this data set, it’s a retrospective analysis looking at annual cardiovascular event rates. This is 56,000 individuals who met the following criteria: had to have 48 months or more of sufficient diagnostic, procedure, prescription, and lab data; [and] had to have more than 3 cholesterol levels—and this was something that eliminated a lot of people. It’s amazing how few people get regular cholesterol checking, even if they’re not at below threshold. Then we looked at those above or below thresholds for 70% of the time during the study period, including the baseline. We used the same guideline thresholds for high-risk primary and secondary prevention.

The patient histories were divided into contiguous episodes characterized by lipid-lowering therapies, whether it’s monotherapy, combination therapy, or, far too often, no therapy, prescriptions filled, and LDL levels, and we’ll look at the figure with that. We used an 18-month baseline period, and this was used to determine the covariates for the propensity score matching that we did. Individuals with a cardiac event during the baseline period were excluded. Following the baseline period, individuals were observed for 30 months or longer to determine that first cardiovascular event [and] the annual incidence rates. We also looked at second events too.

In total, there were 39,000 individuals who met the criteria for above threshold for greater than 70% of the time, and 17,000 who met the [criteria for] below threshold for 70% of the time. Then we one-to-one propensity score matched, giving us 14,755 individuals in each group. These patients were followed for a long period of time, 2091 days. What we found was not surprising but disturbing. Real-world data from the Family Heart database demonstrates that US residents in the above-threshold group had an annual incidence rate of first cardiovascular event [that was] 44% higher—this is a little over 4 years—than those below threshold. The event rates [were] 2.2% vs 1.5%, [respectively]. Total cardiovascular event—some people went on to a second event—in the above-threshold group was also 49% higher than those in the below-threshold group. This is a rather busy slide, but I’ll just say if you look at the individuals who are in the above-threshold group that’s represented by the top group of real-world evidence, you can see a lot of white, yellow—which is not on any drug—and pink and red—meaning on 1 or more medicines but still not at threshold. Below, where individuals were over 70% of the time below threshold, there's lots of green indicating below threshold on a single agent, or dark-green [indicating] below threshold on multiple agents. Our conclusion for this second analysis is that real-world evaluation of high-risk individuals achieving guideline recommended thresholds [showed] substantial reduction in the occurrence of a cardiovascular event. If you get to that below threshold [goal], you’re going to do better. So, a greater emphasis, as we’re all talking about today, on achieving LDL control will improve cardiovascular health at the population level.

Transcript Edited for Clarity