ACC world congress of cardiology

The TAILOR-PCI Clinical Trial… For Dummies (or at least non medical professionals)

03/26/2020

For those who don’t come from a medical background, reading scientific articles can be intimidating. For example, the American College of Cardiology (ACC) website recently featured a clinical trial using my company’s technology and the article used words I never knew existed. Where’s Bill Nye when you need him?

I thought to myself, ‘We have this incredible trial that accomplished incredible things, but anyone without a scientific background will have trouble understanding what it actually means.’ So, as someone who has no scientific background, I figured I would take a stab at summarizing the key points. Let’s learn together…and please go easy on me.

Where do I begin…

ACC has released a list of the latest practice-changing presentations, which will be featured as virtual sessions between March 28th-30th, 2020 (1). Spartan Bioscience is proud to announce that Spartan’s rapid CYP2C19 system (Spartan RX CYP2C19) was used in the TAILOR-PCI clinical trial, which stands for Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response after Percutaneous Coronary Intervention (2).

CYP2C19 is a liver enzyme that metabolizes 15% of all prescribed drugs; including antiplatelets, antidepressants, and proton pump inhibitors (PPIs) (3). It has been found that approximately 30% of Caucasians and 40% of Asians exhibit CYP2C19 mutations, impairing their ability to metabolize these drugs (4,5).

Generally, people who undergo a cardiac stent procedure are given clopidogrel after (brand name Plavix), an antiplatelet medication that helps to prevent blood clots (5). Numerous studies have shown that patients with a mutation in their CYP2C19 gene are unable to metabolize clopidogrel, resulting in reduced activation and efficacy, and increased risk of major adverse cardiovascular events (for example: death, heart attack, stroke) (,5,6). For cardiac stent patients, most complications from poor clopidogrel response occur in the first 24-48 hours after the procedure (7). This is why a rapid DNA test to screen for CYP2C19 mutations is important. Lab-based DNA tests require a sample to be shipped to a central lab, which means results can take several days to weeks. In contrast, Spartan’s test can provide results in under 1 hour.

What happens if patients are found to carry CYP2C19 mutations? Commonly, alternative antiplatelet therapies will be prescribed, such as ticagrelor (brand name Brilinta) or prasugrel (brand name Effient), since they are not known to be affected by CYP2C19 metabolism (6). In Europe, use of ticagrelor or prasugrel has even become the new standard of care (8). However, in most countries, clopidogrel remains the most commonly prescribed antiplatelet drug (5,6). This is because the known disadvantages of prescribing ticagrelor or prasugrel include an increased risk of bleeding, higher costs, and higher discontinuation rates since patients are more likely to stop taking the medication (8,9).

What Will this Study Accomplish?

The TAILOR-PCI trial investigated whether rapid CYP2C19 genetic testing and personalized antiplatelet therapy could improve health outcomes for heart attack patients receiving cardiac stents (2). This trial included 5,300 patients over the course of 7 years at 41 hospitals in the United States, Canada, Korea, and Mexico (6). TAILOR-PCI is the largest genetics-based clinical trial in cardiology history (10), and positive results could lead to clinical practice guidelines being updated to include routine CYP2C19 testing.

The Results

TAILOR-PCI was a 7-year 5,300-patient clinical trial of precision medicine for cardiac stent patients that was funded by Mayo Clinic and the National Institutes of Health (NIH). TAILOR-PCI is the largest genetics-based clinical trial in cardiology history (9). Spartan’s FDA-cleared rapid CYP2C19 genotyping test was used to personalize antiplatelet therapy with clopidogrel or ticagrelor. The main results were:

• Genotype-guided therapy resulted in 34% fewer adverse events after 12 months such as death, stroke, second heart attack, and stent thrombosis (10).
• Genotype-guided therapy resulted in 80% fewer adverse events in the first 3 months. According to principal investigator Dr. Naveen Pereira: “This finding suggests that the lion’s share of the benefit of genetically guided therapy may occur during this high-risk period.” (10)
Dr. Naveen L. Pereira, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, and co-principal investigator of the study said that these findings also have important clinical implications. “Multiple adverse events represent a higher burden on the patient, so it is encouraging to see a significant reduction in cumulative events with genetically guided therapy,” he said. (10).

What Does This Mean for Spartan?

Spartan’s technology was chosen for this trial because it was the only one that could provide rapid results at the time and location of cardiac stenting. We hope the trial results will lead to CYP2C19 genetic testing becoming the standard of care for cardiac stent patients, and that this trial will increase awareness for the importance of personalized medicine in everyday patient care.

References:
1) https://www.prweb.com/releases/2014/10/prweb12276814.htm
2) Flaten HK, Kim HS, et al. (2016). Am J Emerg Med. 34: 245-249
3) Damani SB and Topol EJ. (2010). J Am Coll Cardiol. 56: 109-111.
4) Tuteja S, Glick H, et al. (2020). Circ Genom Precis Med. 13: e002640
5) Pereira NL, Rihal CS, et al. (2019). Circ Cardiovasc Interv. 12: e007811.
6) Moussa L, Oetgen M, et al. (1999). Circ. 99: 2364-2366.
7) Claassens DMF, Vos GJA, et al. (2019). N Engl J Med. 381: 1621-1631.
8) Dayoub EJ, Seigerman M, et al. (2018). JAMA Intern Med. 178: 943-950.
9) https://grantome.com/grant/NIH/U01-HL128606-03S1
10) https://www.cathlabdigest.com/content/tailor-pci-using-genetic-testing-guide-antiplatelet-therapy-post-pci-misses-goal-cut-rate-cardiovascular-events-half

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