American Heart Association Scientific Sessions

Praluent Cost-Effectiveness Gleaned From Large Outcome Trial

Researchers shared estimates of the long-term cost-effectiveness of the PCSK9 inhibitor Praluent (alirocumab) in patients after an acute coronary syndrome (ACS) who had elevated low-density lipoprotein (LDL) cholesterol levels, despite use of high-intensity statins. The findings were presented at the Scientific Sessions 2018 in Chicago, Illinois.

“Phase 3 trials have shown that PCSK9 inhibitors reduce ischemic cardiovascular events in patients with atherosclerotic cardiovascular disease, with a well-tolerated safety profile,” researchers wrote. “However, the substantial cost of these drugs makes it imperative to estimate their cost-effectiveness in clinical practice.”

For the study, researchers used patient-level data from ODYSSEY Outcomes, a 18,924-patient, international, randomized, clinical trial. The trial demonstrated reduced major adverse cardiovascular events with Praluent compared with placebo in patients 1 to 12 months post-ACS with elevated LDL cholesterol levels despite intensive statin therapy.

In addition to patient-level data, ODYSSEY Outcomes offered longer-term outcome data for analysis compared with previous cost-effectiveness analyses of PCSK9 inhibitors, researchers explained. The mean follow-up period for this cost-effectiveness analysis was 2.8 years.

At the conference, researchers presented findings on the cost-effectiveness of Praluent compared with placebo based on estimated lifetime cost increases and quality-adjusted life year gains. —Jolynn Tumolo

Nearly 1 in 5 With High Cholesterol in Community Sample Show Genetic Cause 

In a community-based cohort of adults with primary high cholesterol, or hypercholesterolemia, the overall presence of an identifiable genetic cause was 17%, according to a study presented at the Scientific Sessions 2018 in Chicago, Illinois.

“Prior reports of the genetic etiology of hypercholesterolemia are affected by referral bias, inclusion of individuals with secondary hypercholesterolemia, and variability in identifying pathogenic variants,” researchers from the Mayo Clinic explained in the study abstract. “We sought to assess the prevalence of monogenic and polygenic etiologies in a community-based cohort of adults with primary hypercholesterolemia ([low-density lipoprotein cholesterol] LDL-C ≥155 mg/dL after excluding secondary causes).”

Researchers considered familial hypercholesterolemia present when Dutch Lipid Clinic Network (DLCN) scores were 6 or higher. DLCN scores between 3 and 5 indicated possible familial hypercholesterolemia. Participants underwent sequencing of familial hypercholesterolemia genes (LDLR, APOB, PCSK9) and genotyping of 12 single-nucleotide polymorphisms with known LDL-C association.

A pathogenic variant in LDLR, APOB, or PCSK9 was present in 1.3% of adults in the study, researchers reported. Polygenic etiology was present in 15.4%. Meanwhile, 0.2% had both a monogenic and polygenic etiology.

The overall prevalence of definite familial hypercholesterolemia in the study population was 0.9%; probable familial hypercholesterolemia, 6.1%; and possible familial hypercholesterolemia, 30%.

Among adults with definite familial hypercholesterolemia, a monogenic etiology was present in 2.4% and a polygenic etiology in 19.1%, according to the abstract. Among adults with probable familial hypercholesterolemia, a monogenic etiology was present in 9.5% and a polygenic etiology in 21%. And among those with possible familial hypercholesterolemia, a monogenic etiology was present in 26.7% and a polygenic etiology in 13.3%.

Just over half of participants with a monogenic etiology and 9.7% of participants with a polygenic etiology met criteria for familiar hypercholesterolemia. —Jolynn Tumolo

Decision Aid Guides Patients Through Familial Hypercholesterolemia Treatment Choices 

Researchers from the Mayo Clinic have developed an online decision aid prototype to support treatment-related discussion between providers and patients with familial hypercholesterolemia. They described the work-in-progress at the Scientific Sessions 2018 in Chicago, Illinois.

“Patients with familial hypercholesterolemia may not reach target low-density lipoprotein (LDL) cholesterol levels despite maximally tolerated statin (± ezetimibe) therapy,” researchers explained in the session abstract. “The American Heart Association scientific statement on familial hypercholesterolemia highlighted the need for developing decision aids to facilitate shared decision making regarding additional therapy, including PCSK9 inhibitors.”

To develop a decision aid that is user-centered, researchers analyzed videos of encounters between patients with familial hypercholesterolemia and healthcare providers to see how decisions concerning lipid-lowering therapy were made. Of the nine recorded encounters, three involved a genetic counselor and six involved a specialist in familiar hypercholesterolemia. 

The resulting prototype aims to explain a patient’s risk of adverse cardiovascular events and therapies that may help. The patient’s 5- and 10-year atherosclerotic cardiovascular disease risk are included in the decision aid, which presents them using phrases such as, “Out of 100 persons like you...”

Therapeutic options covered in the decision aid include watchful waiting, bile acid sequestrants, and PCSK9 inhibitors. The degree of risk reduction, costs, and side effects expected with each option are also addressed.

Researchers said they are currently refining the tool, which will eventually be placed in the electronic health record. —Jolynn Tumolo

To Prevent Cardio Vascular Death in At-Risk Patients With Diabetes: Zetia Appears Cost-Effective Choice 

Adding Zetia (ezetimibe) instead of Repatha (evolocumab) to statins to prevent cardiovascular death in patients with type 2 diabetes and established cardiovascular disease appears to be a major cost-savings strategy, researchers shared with attendees at the Scientific Sessions 2018 in Chicago, Illinois.

“[Repatha], a PCSK9 inhibitor, and ezetimibe were both proven to significantly reduce the incidence of major adverse cardiovascular events in type 2 diabetes patients with established cardiovascular disease and low-density lipoprotein (LDL) cholesterol >70 mg/dL treated with statins,” investigators explained. 

“However, the addition of either [Repatha] or [Zetia] to current statin treatment regimens may be a significant burden on healthcare systems.”

For the cost-effectiveness analysis, researchers tapped efficacy data from the FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) and IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) trials and analyzed it alongside 2017 drug cost data.

FOURIER data showed [Repatha] prevented 91 major adverse cardiovascular events over 12,135-patient years, according to the abstract. IMPROVE-IT showed ezetimibe prevented 118 major adverse cardiovascular events over 14,754-patient years.

With an annual cost of $14,513 for evolocumab and $389 for generic Zetia, the cost to prevent one major adverse cardiovascular event would be $1.9 million for Repatha compared with $48,576 for Zetia, researchers reported.

While cost-savings with Zetia appear to be significant, researchers clarified that study results should be interpreted alongside drug-specific and individual patient factors. —Jolynn Tumolo