Dramatic LDL Drops Seen in PAD Patients With Team-Based Care

The combination of involving pharmacists and using an algorithm to manage GDMT cut LDL levels by 50% in OPTIMIZE PAD-1.

Dramatic LDL Drops Seen in PAD Patients With Team-Based Care

A team-based approach that weaves together multidisciplinary care and algorithm-based medical therapy can have a big impact on getting LDL-cholesterol levels under control in patients with peripheral artery disease, results from the OPTIMIZE PAD-1 study suggest.

Despite an increased risk for cardiovascular events and major adverse limb events (MALE), as well as compelling data from trials such as VOYAGER PAD and FOURIER showing the importance of optimizing these patients medically, multiple studies have documented the underuse of guideline-directed medical therapy (GDMT) in PAD.

Using a vascular care team strategy, the OPTIMIZE PAD-1 investigators found that at 12 months, patients whose care involved a clinical pharmacist and algorithm-guided intensive lipid management had a nearly 50% decrease in their LDL compared with a mere 5% decrease in the group randomized to usual care plus provider education.

“The algorithm plus pharmacists was what made it work,” senior author Marc P. Bonaca, MD (University of Colorado School of Medicine, Aurora), told TCTMD. “One great thing about all of these drugs and LDL lowering is that it's really safe . . . and we know that the lower you go, the better the patients do.”

Additionally, since the algorithm differed from guideline recommendations by encouraging combination therapy at the initial vascular medicine visit if the clinician felt monotherapy could not achieve the LDL target, “we built into the communication around this that [there was] urgency, like with any sort of bad exposure: the longer you're exposed to high LDL, the worse you are going to do,” he added. “We also know that some patients aren’t going to come back, others will be less receptive on a subsequent visit, . . . things happen, and it all leads to us not getting to where we want to be [with LDL].”

Part of what the trial initiative did was create a chain of helping hands so that repeat lipid checks happened when they were supposed to, titration happened as needed, and patients didn’t fall through cracks.

Bonaca related a story about a patient he enrolled in the trial who had an insurance issue with his prescribed medication when he was at the pharmacy and ended up just leaving without filling a prescription. The pharmacist noticed the problem and sent Bonaca a note in the patient’s electronic health record (EHR), and they were able to switch to a medication on the patient’s formulary and get him back on track.

Like with any sort of bad exposure: the longer you're exposed to high LDL, the worse you are going to do. Marc P. Bonaca

Eric Secemsky, MD (Beth Israel Deaconess Medical Center, Boston, MA), who was not involved in the study, told TCTMD that the results are impressive and show why these kinds of teams lending timely support are important in the management of high-risk PAD patients.

“We clearly can't get this done in the current framework, so we need to flip the model in a way that we still achieve our goals, but not necessarily place all the burden on a busy clinician who just hasn't been able—even knowing what to do—to work this into their patient care pathway,” he said.

The OPTIMIZE PAD-1 investigators further echo this sentiment, noting that underutilization of lipid-lowering therapies among vascular specialists is unlikely to be the result of a knowledge gap since provider education was part of the usual-care arm, yet the change in LDL levels was minimal.

Three Times More Likely to Get to Goal

Led by Connie N. Hess, MD (University of Colorado School of Medicine), OPTIMIZE PAD-1 enrolled 114 patients (mean age 66 years; 36% female; 16% Black), with an LDL of ≥ 70 mg/dL.

All participants underwent cardiovascular risk assessment and had initial treatment recommendations. Those randomized to the vascular care team approach were prescribed lipid-lowering therapies according to the intensive algorithm, all of which were obtained through commercial insurance and payers. This, the researchers said, was a critical aspect of their study design given that cost is an oft-cited factor in not achieving GDMT. Patients in the care-team group also met with a clinical pharmacist who facilitated all access to medications, checking that they were on the person’s formulary and, when needed, helping them obtain manufacturer drug coupons and prior authorizations. Throughout the study, the intervention patients continued to have access to a clinical pharmacist who could suggest alternative medications according to the algorithm and conducted follow-up lipid panels after medication changes and titration. These patients also had access to virtual telehealth visits, phone calls, and visits with a vascular medicine provider at 6 and 12 months.

Overall, the between-group difference in LDL decline at 12 months favored the intervention group by 43.7% (P < 0.0001). The team-care group had a mean baseline of 100.6 mg/dL, which fell to 54.8 mg/dL by week 4 and to 50.1 mg/dL by month 12.

In comparison, the usual-care group had a mean baseline of 106 mg/dL, which fell to 92.9 mg/dL at 6 months and increased to 97.0 mg/dL by month 12.

Overall, the group treated by the vascular care team were more than three times as likely to achieve an LDL level < 70 mg/dL and eight times as likely to achieve an LDL level < 55 mg/dL compared with usual care (P < 0.0001).

While high-intensity statins prescribing increased from 45.6% at baseline to 77.2% at 6 months in the intervention group, the usual-care group saw an increase from 56.1% to just 61.4% during the same period. Additionally, those managed by the vascular care team were much more likely to receive combination lipid-lowering therapy than those managed by usual care (61.4% vs 5.3%; P < 0.0001).

In exploratory analyses, clinical events were infrequent but similar in both treatment groups, with no major safety issues.

Durability and Scalability Questions

In an accompanying editorial, Dave L. Dixon, PharmD (Virginia Commonwealth University School of Pharmacy, Richmond), and colleagues note that there are few trials like OPTIMIZE PAD-1 to provide evidence of the efficacy of this type of management approach.

However, they say the generalizability of the single-center trial is limited by small numbers of patients of color and lack of information on social determinants of health, such as educational status and income.

“The pharmacists also provided support for medication adherence; however, rates of medication adherence were not reported,” Dixon and colleagues add. They suggest that longer-term studies are needed to assess the durability of this type of care model and its impact on prevention of cardiovascular events, as well as its impact on healthcare-related costs.

“Real-world barriers to pharmacist scope of practice expansion, including time, local population needs, and appropriate compensation for services provided, may limit the ability to fully utilize pharmacists as in the OPTIMIZE-PAD-1 trial,” they write.

To TCTMD, Bonaca said the he believes the model is both practical and scalable. The next step of the research will be to take the model out of the healthcare setting and into community pharmacies to push the boundaries and see how clinicians, commercial pharmacists, and the algorithm work together.

Similarly, Secemsky said a model such as this fits into the ongoing expansion of telehealth and shared EHRs, and may enrich the care of patients previously failed by traditional healthcare delivery.

“We’ve seen in diabetes and in hypertension that an allied clinical pharmacist is key,” he said. “Clinical pharmacists know these agents well, they know the interactions, and they can provide really good opportunities to intervene in patient care when it's hard to get in front of the physician or another provider.”

  • Hess and Bonaca report research grant/consulting funding to their institution from Agios, Alexion Pharma Godo Kaisha, Amgen, Anthos Therapeutics, ARCA Biopharma, AstraZeneca Pharma India, AstraZeneca Pharmaceuticals LP, AstraZeneca UK, AstraZeneca Produtos Farmaceuticos, Atentiv, Bayer, Bayer (Proprietary) Limited, Bayer Aktiengesellschaft, Bayer Pharma, Better Therapeutics, Bionest Partners, Bristol Myers Squibb, CellResearch Corporation, Cleerly, Cook Regentec, CSL Behring, Eidos Therapeutics, EPG Communication Holdings, Esperion Therapeutics, Faraday Pharmaceuticals, HeartFlow, Hummingbird Bioscience PTE, Insmed, Ionis Pharmaceuticals, IQVIA, Janssen Pharmaceuticals, Janssen Research and Development, Janssen Scientific Affairs, Lexicon Pharmaceuticals, LSG Corporation, MedImmune Limited, Medpace, Merck, Novartis, Novo Nordisk, Osiris, Pfizer, PPD Development, Prothena Biosciences, Regeneron, Sanifit Therapeutics, Sanofi, Silence Therapeutics, Stealth BioTherapeutics, UCD iC42 Lab, VarmX, and WraSer.
  • Secemsky reports grants to his institution from Abbott/CSI, BD, Boston Scientific, Cook, Medtronic, and Philips; and speaking/consulting fees from Abbott/CSI, BD, Bristol Myers Squibb, Boston Scientific, Cagent, Conavi, Cook, Cordis, Endovascular Engineering, Gore, InfraRedx, Medtronic, Philips, RapidAI, Rampart, Shockwave, Terumo, Thrombolex, VentureMed, and Zoll.