In an interview with Pharmacy Times during the 2026 Cardiology Day of Education, Joseph Saseen, PharmD, BCPS, BCACP, associate dean for clinical affairs at the University of Colorado Anschutz Medical Campus Skaggs School of Pharmacy and Pharmaceutical Sciences, discussed evidence-based strategies for lowering low-density lipoprotein cholesterol (LDL-C) beyond statins and overcoming therapeutic inertia in lipid management.
Saseen identified 3 key drivers of therapeutic inertia: previous guideline frameworks that emphasized treatment intensity over numerical goals, limited adoption of combination lipid-lowering therapy compared with other chronic diseases, and inadequate patient awareness that combination therapy is both warranted and guideline-supported.
When sequencing non-statin agents, Saseen emphasized that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, particularly monoclonal antibodies, offer the strongest evidence for both LDL-C reduction and cardiovascular event prevention, with reductions of 50 to 60% compared with roughly 20% from oral agents such as ezetimibe (Zetia; Merck & Co) and bempedoic acid. He recommended PCSK9 inhibitors when patients require more than 25% further LDL-C reduction, while acknowledging that cost and accessibility remain real-world considerations.
On treatment targets, Saseen clarified that while most secondary prevention patients should aim for LDL-C below 55 mg/dL, primary prevention targets vary—and patients with subclinical atherosclerosis may also warrant aggressive therapy regardless of prior cardiovascular events.
Pharmacy Times: Therapeutic inertia is a persistent problem in lipid management. What do you think is the biggest reason pharmacists hesitate to escalate beyond statins, and how do we fix it?
Key Takeaways
- Therapeutic inertia in lipid management stems from a combination of guideline history, unfamiliarity with combination therapy, and patient perception—all addressable through pharmacist-led education and proactive treatment optimization.
- PCSK9 inhibitors provide superior LDL-C lowering (50–60%) compared with oral non-statin agents such as ezetimibe and bempedoic acid (~20%), making them the preferred choice when patients need more than 25% additional reduction to reach their goal.
- LDL-C targets are not one-size-fits-all: while most secondary prevention patients should target below 55 mg/dL, primary prevention patients with subclinical atherosclerosis may also require aggressive LDL-C lowering—a nuance often overlooked in practice.
Joseph Saseen, PharmD, BCPS, BCACP: I think it's probably multifaceted. One reaction that I have is that previous guidelines didn't focus on goals—they focused on intensity-based regimens, which really told us that we didn't need to. I think another consideration is that we haven't fully embraced combination therapy for LDL lowering like we have with other chronic diseases like diabetes or hypertension, so it might just not be natural for pharmacists to think of that. And I think maybe a third factor might be perception of benefits from the patient side—that patients aren't encultured to believe that combination drugs for this disease are warranted when evidence, guidelines, and other proof indicate that we should.
Pharmacy Times: With ezetimibe, PCSK9 inhibitors, and newer agents all on the table, how should pharmacists think about sequencing non-statin therapies when a patient isn't hitting their LDL-C goal?
Saseen: That's a really good question, because we have several non-statins that lower LDL-C. We have the PCSK9 blockers, whether it's monoclonal antibodies or inclisiran (Leqvio; Novartis), which is a small interfering RNA therapy, and then we have the oral options like ezetimibe and bempedoic acid. I think the biggest differentiating point is probably where we have the best evidence, and we actually have the best evidence with the PCSK9 monoclonal antibodies when we're looking at both the ability to lower LDL-C and the reduction in cardiovascular events. There is value to the other oral options like bempedoic acid, but the big difference—a 20% reduction with oral agents versus a 50 to 60% reduction with the PCSK9 blockers—is very pronounced, and our guidelines really tell us that under many circumstances, not all, but many circumstances, it comes down to what's needed to get to the goal.
If you need a large amount of reduction—in my opinion, more than 25%—your best option, if possible, is going with a PCSK9 inhibitor over one of the oral agents, simply because of the higher likelihood of achieving your goal. I realize that considerations related to cost and accessibility are sometimes unable to be ignored, and that may also factor into your decision. But potency related to LDL-C lowering and evidence showing proven benefit, I think, are the purest ways to make your decision, coupled with the reality of what's accessible to your patient.
Pharmacy Times: How do LDL-C targets differ between a patient in primary prevention versus one who's already had a cardiovascular event, and why does that distinction matter so much clinically?
Saseen: In the past, we always followed that the higher-risk patients had the lowest LDL goals, and that primary prevention patients tended to have the same or maybe even higher goals. The truth is, you can have a primary prevention patient who is eligible for a target of less than 100, less than 70, or less than 55 mg/dL. Most of our secondary prevention patients really should be less than 55 mg/dL, so it does create a difference.
But I want to highlight that many primary prevention patients don't need to have an LDL-C goal less than 55 mg/dL—but there are some that do that were never mentioned in the past. And that really comes down to people who are technically categorized as primary prevention but have subclinical atherosclerosis, where we have recommendations to use aggressive therapy to get LDL-C less than 100 mg/dL. In general, we still have this difference between primary prevention—the option of less than 100 or less than 70 mg/dL for most of those patients—but there are some less-than-55 scenarios. And it's essentially the flip for secondary prevention, where most patients are targeting less than 55 mg/dL, with the traditional thought being that less than 70 mg/dL remaining acceptable.
