Heart intertwined with DNA strands

Decoding Ticagrelor: Can Your Genes Affect How Well It Works?

Lena Voss in Health & Wellness November 2025 • 4 min read.

"A New Study Reveals How a Common Genetic Variation Could Influence Platelet Reactivity in Heart Patients"

When it comes to managing heart health after an acute coronary syndrome (ACS), dual antiplatelet therapy is a cornerstone of treatment. Among the antiplatelet medications available, ticagrelor has emerged as a more potent and predictable option compared to clopidogrel. Ticagrelor works by inhibiting the ADP receptor, a key player in platelet activation, and also taps into adenosine-mediated pathways, which have been linked to improved outcomes.

However, not everyone responds to ticagrelor in the same way. Some individuals still exhibit suboptimal platelet inhibition, raising concerns about their risk of future cardiovascular events. While genetics is known to play a significant role in how well clopidogrel works, less is known about its influence on ticagrelor response.

A groundbreaking study has shed light on how a specific genetic variation in the adenosine A2a receptor (ADORA2a) can impact platelet reactivity in patients undergoing chronic treatment with ticagrelor. This discovery could pave the way for more personalized approaches to antiplatelet therapy, optimizing treatment strategies, and improving patient outcomes.

The Genetic Link: ADORA2a Polymorphism and Ticagrelor Response

The study, published in Pharmacological Research, explored the impact of the rs5751876 C>T polymorphism of the adenosine A2a receptor (ADORA2a) on platelet reactivity in patients receiving ticagrelor. Researchers from the Novara Atherosclerosis Study Group (NAS) in Italy conducted this in-depth analysis. They aimed to determine if this common genetic variation could explain why some patients experience a less-than-optimal response to ticagrelor.

The study enrolled 244 patients who were being treated with both aspirin and ticagrelor following a recent ACS event or elective coronary revascularization. To assess how well the medication was working, platelet reactivity was measured using multiple-electrode aggregometry (MEA) between 30 and 90 days post-discharge. High residual platelet reactivity (HRPR) for ticagrelor was defined as an ADP-test result greater than 417 AUmin.

Genetic analysis revealed that 174 patients (71.3%) carried the T allele of the rs5751876 polymorphism, with 51 (20.9%) being homozygous for the T allele (T/T).
C-allele carriers (those with the C/C or C/T genotype) had similar baseline characteristics to T/T homozygotes, except for lower HDL-cholesterol levels.
Interestingly, a lower rate of HRPR on ticagrelor was observed in T/T homozygotes (p = 0.03), suggesting a protective effect.
Multivariate analysis confirmed that carrying the C allele was independently associated with a higher rate of HRPR on ticagrelor (adjusted OR[95%CI] = 4.63[1.02-21.01], p = 0.048).

In essence, the study demonstrated that individuals with the C allele of the rs5751876 polymorphism were more likely to exhibit high residual platelet reactivity while on ticagrelor treatment.

Personalized Antiplatelet Therapy: A Glimpse into the Future

The findings from this study offer valuable insights into the complex interplay between genetics and drug response. By identifying a specific genetic variation that influences ticagrelor effectiveness, it opens the door to more personalized approaches to antiplatelet therapy. Ultimately, tailoring treatment strategies based on an individual's genetic makeup could lead to better outcomes for patients with heart disease.

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This article is based on research published under:

DOI-LINK: 10.1016/j.phrs.2017.12.035, Alternate LINK

Title: Impact Of Adenosine A2A Receptor Polymorphism Rs5751876 On Platelet Reactivity In Ticagrelor Treated Patients

Subject: Pharmacology

Journal: Pharmacological Research

Publisher: Elsevier BV

Authors: Matteo Nardin, Monica Verdoia, Patrizia Pergolini, Roberta Rolla, Lucia Barbieri, Paolo Marino, Giorgio Bellomo, Elvin Kedhi, Harry Suryapranata, Alessandro Carriero, Giuseppe De Luca

Published: 2018-03-01

Everything You Need To Know

What is ticagrelor, and how does it function to prevent blood clots after a heart event?

Ticagrelor is an antiplatelet medication commonly used after heart events to prevent blood clots. It primarily works by inhibiting the ADP receptor on platelets, reducing their activation. Additionally, it interacts with adenosine-mediated pathways, which may contribute to improved cardiovascular outcomes. This dual mechanism makes it a potent option for dual antiplatelet therapy, especially when compared to other medications like clopidogrel.

Which specific genetic variation was examined in the study, and what was the research trying to understand about its influence on ticagrelor's effectiveness?

The study focused on the rs5751876 C>T polymorphism of the adenosine A2a receptor (ADORA2a). Researchers aimed to determine if this genetic variation could explain why some patients exhibit a less-than-optimal response to ticagrelor. This is crucial because individuals respond differently to ticagrelor, and understanding the genetic factors can help tailor treatment for better outcomes.

What were the main findings of the study regarding the relationship between the ADORA2a gene polymorphism and ticagrelor response?

The study revealed that individuals carrying the C allele of the rs5751876 polymorphism of ADORA2a were more likely to exhibit high residual platelet reactivity (HRPR) while on ticagrelor treatment. Specifically, a lower rate of HRPR on ticagrelor was observed in T/T homozygotes, suggesting a protective effect. Multivariate analysis confirmed that carrying the C allele was independently associated with a higher rate of HRPR on ticagrelor.

What is 'high residual platelet reactivity' (HRPR), and why is it a concern in patients taking ticagrelor?

High residual platelet reactivity (HRPR) is when platelets remain overly reactive despite antiplatelet therapy. In the context of ticagrelor treatment, HRPR increases the risk of future cardiovascular events because platelets are still prone to forming clots. The study defined HRPR for ticagrelor as an ADP-test result greater than 417 AU*min, measured using multiple-electrode aggregometry (MEA).

What are the potential implications of this study's findings for personalized antiplatelet therapy with ticagrelor, and how might it change treatment strategies in the future?

The study conducted by the Novara Atherosclerosis Study Group (NAS) suggests that genetic testing for the rs5751876 polymorphism of ADORA2a could help personalize antiplatelet therapy with ticagrelor. Identifying individuals with the C allele, who are more likely to exhibit high residual platelet reactivity, could lead to adjusted treatment strategies. However, further research is needed to determine the best course of action for these patients, potentially involving higher doses of ticagrelor or alternative antiplatelet agents. The long-term goal is to optimize treatment strategies and improve outcomes for patients with heart disease, moving towards personalized medicine approaches.