Clinical implementation of clopidogrel pharmacogenetics: the Tailored Antiplatelet Therapy Following PCI (TAILOR-PCI) Trial
Reported from the ACC 2020 (ACC.20) Scientific Sessions
A genotype-guided oral P2Y12 inhibitor strategy compared with conventional clopidogrel therapy with point-of-care genotyping in CYP2C19 LOF patients with ACS and stable CAD undergoing PCI resulted in a no significant reduction in ischemic events at 12-months.
Comment by Jean Marco on this trial
This trial has been conducted with a very original method! The primary end point was not significantly ( P=0.056) reached. Nevertheless it provides us with practical information which could guide practitioners to apply a personalized DAPT strategy by taking into consideration the net benefit for patients and society. This could be amatter for critical self reflection from readers ! And could invite/ stimulate readers to share their own critical thinking, questioning on methodology.
Background
Current clinical guidelines do not recommend testing patients for the CYP2C19 genetic abnormality before prescribing clopidogrel.
Hypothesis
Guiding the choice of post-PCI DAPT according to CYP2C19 loss-of-function (LOF) status will improve outcomes in CYP2C19 LOF carriers versus prescribing clopidogrel for all.
Methodology
- 2 arms, parallel, open-label, international, multicenter randomized superiority clinical trial (NCT01742117).
- Population: ≥ 18 years old patient who underwent PCI (ACS or stable CAD) and needing 12 months of DAPT.
- Primary endpoint: Compositive of CV death, MI, stroke, recurrent ischemia, and stent thrombosis at 1-year after index PCI.
- Secondary endpoint: major and minor bleeding as define by TIMI criteria.
Adapted from Pereira NL et al.1 WT: wild type.
Results
A total of 5,302 patients were randomized, for the primary endpoint analysis 1849 were compared, 903 patients in the genotype-guided therapy, and 946 in the conventional therapy arm. The majority of patients presented with an acute coronary syndrome (84%). The primary outcome, for genotype-guided strategy, compared with standard care strategy (hazard ratio [HR] 0.66, p = 0.056). The outcomes were the same among tested subgroups.
In the secondary outcomes, there were no differences in terms of TIMI major or minor bleeding at 12 months. A prespecified multiple recurrent events analysis showed that for the genotype-guided strategy was associated with a reduction of adverse events when compared with standard care strategy (HR 0.60, p = 0.011).
A post-hoc analysis of the primary endpoint of the 3 months after randomization showed a significative reduction of adverse events in the genotype-guided strategy when compared with standard care strategy (HR 0.21, p = 0.001).
Conclusions
A genotype-guided oral P2Y12 inhibitor strategy compared with conventional clopidogrel therapy with point-of-care genotyping in CYP2C19 LOF patients with ACS and stable CAD undergoing PCI resulted in a no significant reduction in ischemic events at 12-months.
Comments
The Tailor PCI is an international trial funded by the NHLBI, which was designed to answer a very relevant clinical question that has been in studied for more than a decade. The authors compared the standard of care with a genotype-guided therapy with point-of-care genotyping for the CYP2C19. The Spartan RX technology was used (Spartan Bioscience Inc., Ontario, Canada), which is a rapid genotyping platform able to determine the CYP2C19 (*1,*2,*3,*17) allele status within 1 hour.
The primary endpoint was not achieved, although an absolute risk reduction of 1.8% and a relative risk reduction of 44% was observed. The genotype-guided therapy resulted in no significant difference (p=0.056) in reducing ischemic events based on the prespecified analysis plan and the 50% treatment effect that the study was powered to detect.
In general, the results of the trial are robust with an almost achieved primary endpoint and two important secondary endpoints achieved (safety and multiple events). Moreover, the results are in the line of preexisting evidence of the POPular Genetics trial.2 With this background, in my opinion, the results of the TAILOR PCI trial are compelling and may provide an impulse for the implementation of precision medicine (genotype-guided therapy) for DAPT treatment in clinical practice.
Finally, the trial will have an extended follow-up that will enrich the data and evidence in this specific area. We will be expecting them!
Expert comments
Davide Capodanno (@DFCapodanno) shared his take on this trial on Twitter:
1/ My read of TAILOR-PCI in 11 tweets. Interesting design. Investigators started with the hypothesis that genotype-based DAPT based on CYP2C19 status is >35% superior to prescribing clopidogrel for all in CYP2C19 LOF carriers. But they had to change their mind.
— Davide Capodanno (@DFCapodanno) March 28, 2020
References
- Pereira NL, Rihal CS, So DYF, Rosenberg Y, Lennon RJ, Mathew V, Goodman SG, Weinshilboum RM, Wang L, Baudhuin LM, Lerman A, Hasan A, Iturriaga E, Fu YP, Geller N, Bailey K and Farkouh ME. Clopidogrel Pharmacogenetics. Circ Cardiovasc Interv. 2019;12:e007811.
- Claassens DMF, Vos GJA, Bergmeijer TO, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Janssen PWA, Kelder JC, Postma MJ, de Boer A, Boersma C, Deneer VHM and Ten Berg JM. A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI. N Engl J Med. 2019;381:1621-1631.
No comments yet!