Acute Coronary Syndrome: Genotyping Guided Antiplatelet Therapy After Stent Surgery

Dhruv S. Kazi, MD, MSc, MS Assistant Adjunct Professor Division of Cardiology San Francisco General Hospital Department of Medicine, and Department of Epidemiology and Biostatistics University of California San Interview with:
Dhruv S. Kazi, MD, MSc, MS
Assistant Adjunct Professor
Division of Cardiology San Francisco General Hospital
Department of Medicine, and
Department of Epidemiology and Biostatistics
University of California San Francisco What is the background of your study?

Dr. Kazi: When we first asked the research question -what is the role of genotyping among patients receiving a stent for ACS, we quickly realized that there were no RCTs that had directly compared ticagrelor with prasugrel. But in our opinion, that was precisely the reason to build a model and systematically synthesize the available literature. There are nearly half a million PCIs for ACS in the US each year, and each time, the physician and patients have to examine the trade-offs between the various alternatives. What our model does is that it explicates the trade-offs – makes them transparent, and quantifies them.  So patients and physicians can make an informed decision on what is the optimal therapy for them. What are the main findings of the study?

Dr. Kazi: Genotype-guided antiplatelet therapy may improve the cost-effectiveness of prasugrel and ticagrelor after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). This is particularly true for prasugrel, where the benefit of the drug appears to be concentrated among patients who carry one or more loss-of-function alleles, so that risks may outweigh benefits in other sub-groups of patients.   Ticagrelor for all patients independent of genotype may be an economically reasonable alternative in some populations and settings: particularly where the prevalence of loss-of-function alleles is high (e.g. patients with ancestry in Oceania) or where the cost of ticagrelor is relatively low. The availability of point-of-care genotyping makes it feasible to rapidly genotype patients undergoing PCI for ACS, and personalizing the choice of dual antiplatelet regimen based on the patient’s risk for thrombotic and bleeding events. Were any of the findings unexpected?

Dr. Kazi: One of our most exciting findings is that our results counter the general perception that personalized medicine is expensive. Our findings suggest that individualizing therapy based on genotype may be very cost-effective, but may be cost-saving in some settings, because it allows us to target the more expensive therapies at the subgroup of patients most likely to benefit. As the costs of genotyping continue to decline and newer therapies become pricier, a judiciously applied strategy of personalized care may in fact help reduce health care costs. What should clinicians and patients take away from your report?

Dr. Kazi: Although there a reresidual clinical uncertainties about the role of genetic testing in personalizing cardiovascular care, a systematic synthesis of currently available evidence suggests that genotyping may help individualize the care of dual antiplatelet therapy in order to optimize clinical outcomes among patients undergoing PCI for ACS. Our results suggest that it may be time to move away from a one-size-fits-all approach that has traditionally dominated the choice of dual antiplatelet therapy for the past decade. Clinicians should note that our results do not apply to patients undergoing elective PCI – prasugrel and ticagrelor have not been studied in that setting. What recommendations do you have for future research as a result of this study?

Dr. Kazi: We urgently need randomized trials that compare ticagrelor for all patients irrespective of genotype with the selective use of ticagrelor among carriers of loss-of-function alleles and clopidogrel among non-carriers. The genotype-guided strategy has the potential to substantially lower drug costs – because two thirds of patients do not carry the loss-of-function allele and may have acceptable  outcomes on clopidogrel. This cost-effectiveness analysis will need to be updated in the future when we have additional prospective data on the role of genotyping. Until then, the analyses provided in the paper can help clinicians optimize dual antiplatelet therapy among patients receiving PCI for ACS.


  1. UCSF news release, which is available here:
    2.Dhruv S. Kazi, Alan M. Garber, Rashmee U. Shah, R. Adams Dudley, Matthew W. Mell, Ceron Rhee, Solomon Moshkevich, Derek B. Boothroyd, Douglas K. Owens, Mark A. Hlatky; Cost-Effectiveness of Genotype-Guided and Dual Antiplatelet Therapies in Acute Coronary Syndrome. Annals of Internal Medicine. 2014 Feb;160(4):221-232.

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