Precision Medicine Informs Cost-Effective Heart Disease Treatments

Using precision medicine approaches to tailor heart disease therapies could lead to more cost-effective treatments and improved patient outcomes, according to a study led by researchers at the University of Alabama at Birmingham (UAB).

Patients who experience a heart attack have sharply reduced blood flow in coronary arteries, as well as a high risk of heart failure or death. Coronary angioplasty, a procedure to open narrowed or blocked arteries in the heart, and percutaneous coronary intervention (PCI) can restore blood flow to minimize heart damage. These procedures reduce the risk of subsequent major adverse cardiovascular events (MACE), which include heart attacks, strokes, or death.  

After these procedures, providers have to make a treatment decision. After PCI, all patients receive two antiplatelet agents for up to one year. The most commonly used antiplatelet combination after PCI is aspirin and clopidogrel. Clopidogrel is converted to its active form by an enzyme called CYP2C19, but patients respond to this treatment differently depending on their genetic makeup.

Over 30 percent of people have loss-of-function variants in the CYP2C19 gene that decreases the effectiveness of clopidogrel. These patients may not get the full benefit of clopidogrel, which would increase their risk of MACE. The FDA recommends that providers consider different treatments for these individuals, such as prasugrel or ticagrelor, to replace clopidogrel.

In 2018, UAB and researchers at nine universities across the US showed that patients with loss-of-function variants who were treated with clopidogrel had elevated risks. The study revealed that there was a twofold risk of MACE in PCI patients, and a threefold risk for MACE among patients with acute coronary syndrome who received PCI, as compared to patients prescribed prasugrel or ticagrelor instead of clopidogrel.

While prasugrel and ticagrelor are not influenced by loss-of-function variants and can substitute for clopidogrel, these drugs are much more costly and can bring a higher risk of bleeding.

Using this real-world data, the research team set out to conduct an economic analysis of the best treatments for heart disease patients. The study compared three main strategies: treating all patients with clopidogrel, treating all patients with ticagrelor, and genotyping all patients and using ticagrelor in those with loss-of-function variants.

The group considered differences in event rates for heart attacks and stent thrombosis in patients receiving clopidogrel versus ticagrelor versus genotype-guided therapy, during the one-year period following PCI. They also considered medical costs from events like admissions, procedures, medications, clinical visits, and genetic testing. The study used an economic measure known as the quality-adjusted life year (QALY).

“First, we looked at which strategy provided the highest QALY,” Limdi said. “The QALY is the gold standard for measuring benefit of an intervention — in our case, genotype-guided treatment compared to treatment without genotyping. Universal ticagrelor and genotype-guided antiplatelet therapy had higher QALYs than universal clopidogrel — so those are the best for the patient.” 

Researchers then analyzed whether those interventions that have higher QALYs were also reasonable from a cost perspective, which includes a payer’s or patient’s willingness to pay.

“In our case, the payor would recognize that ticagrelor is more expensive than clopidogrel — $360 per month vs. $10 per month — and there is a $100 cost for each genetic test,” Limdi said. “So, from the payor perspective, the more effective strategy (one with a higher QALY) — if more expensive (higher cost) — would have to lower the risks of bad outcomes like heart attacks and strokes for the gains in QALY that are at, or below, the willingness-to-pay threshold.”

A measure called incremental cost-effectiveness ratios (ICERs) assesses the incremental cost of the benefit, or improvement in QALY. In the US, a treatment is considered cost-effective if its associated ICER is at or below the willingness-to-pay threshold of $100,000 per QALY.

“In our assessment, the two strategies with the highest QALY had very different ICERs,” Limdi said. “The genotype-guided strategy was cost-effective at $42,365 per QALY. Universal ticagrelor was not; it had an ICER of $227,044 per QALY.”

The study results demonstrate the effectiveness of genotyping and precision medicine strategies for tailoring treatments and improving patient outcomes.

“We showed that tailoring antiplatelet selection based on genotype is a cost-effective strategy,” said Nita Limdi, PharmD, PhD. “Support is now growing to change the clinical guidelines, which currently do not recommend genotyping in all cases. Evidence like this is needed to advance the field of precision medicine.”