Adjunct Lipid Therapies Offer Options for Lowering LDL

Pharmacists and clinicians face many challenges when providing care for patients with atherosclerotic cardiovascular disease (ASCVD) or at high risk for cardiovascular events. In a Pharmacy Times Clinical Forum moderated by Kelsey E. Norman, PharmD, BCCP, BCACP, BCPS, ambulatory clinical pharmacy specialist at Boston Medical Center in Massachusetts, pharmacists discussed unmet needs in cholesterol management, the use of low-density lipoprotein (LDL)–lowering therapies and nonstatin agents, overcoming insurance barriers, and the role of pharmacists in optimizing treatment outcomes for patients with ASCVD.

In 2019, more than 24 million people in the US had ASCVD, which is approximately 10% of the population of individuals older than 21 years. Of those individuals with a history of ASCVD, 31.2% are at very high risk of recurring adverse events and many do not meet current guideline recommendations for LDL goals, according to the American College of Cardiology (ACC) and the American Heart Association (AHA).

Image credit: Sebastian Kaulitzki | stock.adobe.com

Specifically, patients at high risk for cardiovascular events should be on a high-intensity statin regimen to lower their cholesterol by approximately 50%, according to 2018 ACC and AHA guidelines. For patients on a maximally tolerated statin or high-intensity statin at the maximum dose with an LDL level above 70 mg/dL, ezetimibe (Zetia; Merck) is recommended in addition to statin treatment. PCSK9 inhibitors are recommended to be administered after ezetimibe for patients with an LDL level above 90. Despite guidelines strongly recommending use of high-intensity statin therapy to lower LDL level, there are still significant gaps in access to this treatment for women, younger patients, and patients with specific comorbidities.

“Women tended to be less adherent as [did] minority groups. Younger and older patients were less likely [to be adherent] compared with adults [aged] 65 to 74 years. And compared with patients with high-intensity statin with a medication possession ratio greater than 90%, patients with low statin adherence had an elevated risk of a recurrent or first adverse cardiovascular outcome,” Norman said.

Based on the 2018 ACC and AHA guidelines on cholesterol, ezetimibe is recommended as an additional therapy in patients at high risk who are not reaching LDL goals prior to prescribing PCSK9 inhibitors. Statistics provided by Norman show that ezetimibe post statin can increase the magnitude of LDL reduction by approximately 13% to 20%. However, she points out that patients may not reach LDL goals on ezetimibe due to insurance coverage changes, noting that “after ezetimibe, adding a PCSK9 inhibitor would be reasonable.”

The addition of PCSK9 inhibitors to maximally tolerated statin therapy has significant capabilities in further reducing LDL levels by 43% to 64%, which is beneficial for patients not achieving targeted LDL with statin therapy alone or in conjunction with ezetimibe. Despite success with use of high-intensity statin therapies with PCSK9, pharmacists and patients face obstacles receiving and adhering to the treatment.

Ana Safri, PharmD, MBA, PGY-2 clinical specialist in ambulatory care at Boston Medical Center, commented on the insurance complications faced when treating a patient who lacks tolerance for a specific treatment, such as PCSK9 inhibitors. “I think one other insurance obstacle that I’ve run into recently is putting a patient on a PCSK9 inhibitor and then, if they don’t tolerate it, insurance not approving inclisiran [Leqvio; Alnylam Pharmaceuticals] until they’ve tried the other PCSK9 inhibitor,” Safri said. “So sometimes it works, but at least the last 2 times I’ve tried it, they want them to try the other one. And then one of the patients is very hesitant to try the other PCSK9 inhibitor.”

Insurance barriers can be substantial obstacles for patients, placing pharmacists in a crucial role of communicating with providers and insurance companies to secure treatment coverage. In some cases, insurance requires routine follow-up laboratory tests prior to authorizing the treatment. However, Kelly Nguyen, PharmD, BCPS, BCCP, cardiology clinical pharmacy specialist at Tufts Medical Center in Boston, notes improvements in insurance coverage of PCSK9 inhibitors.

“But as far as PCSK9 inhibitors and other adjunct therapies, insurances are covering them a lot more than they were,” Nguyen said. “So it’s been a little easier from that standpoint to get our patients on these medications.”

Sarah Beargie, PharmD, BCCP, cardiology pharmacist at Massachusetts General Hospital in Boston, added that providers today are great at prescribing high-intensity statins for those who need it. “But it’s all these other agents that we’re talking about; that’s where pharmacist intervention is great,” Beargie said.

Pharmacists play a crucial role at every treatment touchpoint, from securing a patient’s prescription and offering counseling on proper administration of treatment to providing continued treatment maintenance, all to improve overall health outcomes. Additionally, pharmacists often struggle with patient adherence to prescribed treatments, citing patient comfort as a key factor that may prevent them from reaching their LDL goals.

According to Norman, patients prescribed a single-pill regimen had 87% greater odds of being highly adherent to treatment compared with those prescribed a 2-pill regimen. Patients with high adherence to treatment had a 55% decrease in risk of cardiovascular events. The speakers noted complications with adherence to both oral and injectable treatments, citing that more complex treatment regimens can compromise patient adherence and thereby lead to poorer health outcomes. Some patients may be resistant to injection therapies, opting for oral treatments that may not help them reach their LDL goals.

“So that’s made it a little more challenging. But I ask whether they’re open to rediscussing injections in 3 months,” Norman said. “Going through options and trying to inform patients as much as possible [are important].”

Integration of lipid-lowering therapies is crucial for achieving LDL level targets in patients with ASCVD or at high risk for cardiovascular events, especially for those who don’t meet their LDL goals, according to the panelists. Pharmacists and clinicians encounter significant challenges in managing cholesterol, including navigating insurance complexities and promoting patient adherence to treatment.

However, through consistent support, education, and intervention, there is a growing opportunity for pharmacists to play a more crucial role in patient outcomes. By leveraging their expertise and dedication, pharmacists can bridge gaps in care, ensuring that individuals with ASCVD receive appropriate and effective treatment.