ABCD-GENE Score and Clinical Outcomes Following Percutaneous Coronary Intervention: Insights from the TAILOR-PCI Trial

Davide Capodanno, Dominick J Angiolillo, Ryan J Lennon, Shaun G Goodman, Sang-Wook Kim, Fearghas O'Cochlain, Derek Y So, John Sweeney, Charanjit S Rihal, Michael Farkouh, Naveen L Pereira, Davide Capodanno, Dominick J Angiolillo, Ryan J Lennon, Shaun G Goodman, Sang-Wook Kim, Fearghas O'Cochlain, Derek Y So, John Sweeney, Charanjit S Rihal, Michael Farkouh, Naveen L Pereira

Abstract

Background In TAILOR-PCI, genotype-guided selection of P2Y12 inhibitors after percutaneous coronary intervention did not significantly reduce the risk of ischemic events at 12 months. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD-GENE) score identifies patients with high platelet reactivity on clopidogrel at increased risk of ischemic events. The aim of this study was to investigate the value of the ABCD-GENE score for tailoring P2Y12 inhibitor selection after percutaneous coronary intervention. Methods and Results In a post hoc analysis of the TAILOR-PCI, outcomes were analyzed by ABCD-GENE score and allocation to genotype-guided or conventional P2Y12 inhibitor selection. Primary (death, myocardial infarction, or stroke) and secondary (cardiovascular death, myocardial infarction, stroke, stent thrombosis, or severe recurrent ischemia) outcomes were assessed. Among 3883 patients discharged on clopidogrel in the genotype-guided and conventional therapy groups, 15.8% and 84.2% had high (≥10 points) or low (<10) ABCD-GENE scores, respectively. At 12 months, both the primary (5.2% versus 2.6%, P<0.001) and secondary outcomes (7.7% versus 4.6%, P=0.001) were significantly increased in patients with high ABCD-GENE score. Among 4714 patients allocated to genotype-guided or conventional therapy, the former did not significantly reduce the 12-month risk of the primary and secondary outcomes in both the high and low ABCD-GENE score groups (pinteraction=0.48 and 0.27, respectively). Conclusions Among patients with percutaneous coronary intervention on clopidogrel, the ABCD-GENE score was helpful in identifying those at higher risk. The ABCD-GENE score may potentially enhance the precision of tailored selection of P2Y12 inhibitors, which needs to be confirmed in prospective investigations. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01742117.

Keywords: antiplatelet therapy; genetic testing; ischemia; percutaneous coronary intervention.

Figures

Figure 1. Study flowchart.
Figure 1. Study flowchart.
A total of 4714 patients randomized in the TAILOR‐PCI trial had complete data for the calculation of the ABCD‐GENE score. Of them 1014 had a high (≥10) ABCD‐GENE score and 3700 (

Figure 2. Incidence of death, myocardial infarction,…

Figure 2. Incidence of death, myocardial infarction, or stroke in patients discharged on clopidogrel with…

Figure 2. Incidence of death, myocardial infarction, or stroke in patients discharged on clopidogrel with high ABCD‐GENE score ≥10 or
ABCD‐GENE indicates Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping; CVA, cerebrovascular accidents; HR, hazard ratio; and MI, myocardial infarction. The shaded areas represent 95% CIs for the survival curves.

Figure 3. Summary of results.

At 1…

Figure 3. Summary of results.

At 1 year, the risk of death, myocardial infarction, or…

Figure 3. Summary of results.
At 1 year, the risk of death, myocardial infarction, or stroke was significantly predicted by the ABCD‐GENE score (high versus low) but not by the presence of 1 or 2 loss of function alleles. ABCD‐GENE indicates Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping; BMI, body mass index; CKD, chronic kidney disease; HR, hazard ratio, LOF, loss of function; MI, myocardial infarction; and PCI, percutaneous coronary intervention.

Figure 4. Incidence of death, myocardial infarction,…

Figure 4. Incidence of death, myocardial infarction, or stroke in patients who received genotype‐guided or…

Figure 4. Incidence of death, myocardial infarction, or stroke in patients who received genotype‐guided or conventional therapy by ABCD‐GENE score groups.
At 1 year, the risk of death, myocardial infarction, or stroke was not significantly reduced in the genotype‐guided therapy arm compared with the conventional therapy in both the high and low ABCD‐GENE score g subgroups. ABCG‐GENE denotes Age, Body Mass Index, Chronic Kidenye Disease, Diabetes, and Genotyping; CVA, cerebrovascular accidents; HR, hazard ratio; and MI, myocardial infarction.
Figure 2. Incidence of death, myocardial infarction,…
Figure 2. Incidence of death, myocardial infarction, or stroke in patients discharged on clopidogrel with high ABCD‐GENE score ≥10 or
ABCD‐GENE indicates Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping; CVA, cerebrovascular accidents; HR, hazard ratio; and MI, myocardial infarction. The shaded areas represent 95% CIs for the survival curves.
Figure 3. Summary of results.
Figure 3. Summary of results.
At 1 year, the risk of death, myocardial infarction, or stroke was significantly predicted by the ABCD‐GENE score (high versus low) but not by the presence of 1 or 2 loss of function alleles. ABCD‐GENE indicates Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping; BMI, body mass index; CKD, chronic kidney disease; HR, hazard ratio, LOF, loss of function; MI, myocardial infarction; and PCI, percutaneous coronary intervention.
Figure 4. Incidence of death, myocardial infarction,…
Figure 4. Incidence of death, myocardial infarction, or stroke in patients who received genotype‐guided or conventional therapy by ABCD‐GENE score groups.
At 1 year, the risk of death, myocardial infarction, or stroke was not significantly reduced in the genotype‐guided therapy arm compared with the conventional therapy in both the high and low ABCD‐GENE score g subgroups. ABCG‐GENE denotes Age, Body Mass Index, Chronic Kidenye Disease, Diabetes, and Genotyping; CVA, cerebrovascular accidents; HR, hazard ratio; and MI, myocardial infarction.

References

    1. Capodanno D, Alfonso F, Levine GN, Valgimigli M, Angiolillo DJ. ACC/AHA versus ESC guidelines on dual antiplatelet therapy. J Am Coll Cardiol. 2018;72:2915–2931. doi: 10.1016/j.jacc.2018.09.057
    1. Angiolillo DJ, Fernandez‐Ortiz A, Bernardo E, Alfonso F, Macaya C, Bass TA, Costa MA. Variability in individual responsiveness to clopidogrel. J Am Coll Cardiol. 2007;49:1505–1516. 10.1016/j.jacc.2006.11.044
    1. Marín F, González‐Conejero R, Capranzano P, Bass TA, Roldán V, Angiolillo DJ. Pharmacogenetics in cardiovascular antithrombotic therapy. J Am Coll Cardiol. 2009;54:1041–1057. 10.1016/j.jacc.2009.04.084
    1. Galli M, Franchi F, Rollini F, Cavallari LH, Capodanno D, Crea F, Angiolillo DJ. Genetic testing in patients undergoing percutaneous coronary intervention: rationale, evidence and practical recommendations. Expert Rev Clin Pharmacol. 2021;14(8):1–16. 10.1080/17512433.2021.1927709
    1. Shuldiner AR, O’Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, Damcott CM, Pakyz R, Tantry US, Gibson Q, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009;302:849–857. 10.1001/jama.2009.1232
    1. Price MJ, Murray SS, Angiolillo DJ, Lillie E, Smith EN, Tisch RL, Schork NJ, Teirstein PS, Topol EJ. Influence of genetic polymorphisms on the effect of high‐ and standard‐dose clopidogrel after percutaneous coronary intervention: the GIFT (Genotype Information and Functional Testing) study. J Am Coll Cardiol. 2012;59:1928–1937. 10.1016/j.jacc.2011.11.068
    1. Mega JL, Simon T, Collet J‐P, Anderson JL, Antman EM, Bliden K, Cannon CP, Danchin N, Giusti B, Gurbel P, et al. Reduced‐function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta‐analysis. JAMA. 2010;304:1821–1830. 10.1001/jama.2010.1543
    1. Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, et al. Randomized double‐blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease. Circulation. 2009;120:2577–2585. 10.1161/CIRCULATIONAHA.109.912550
    1. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045–1057. 10.1056/NEJMoa0904327
    1. Franchi F, Angiolillo DJ. Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol. 2015;12:30–47. 10.1038/nrcardio.2014.156
    1. Sibbing D, Aradi D, Alexopoulos D, ten Berg J, Bhatt DL, Bonello L, Collet J‐P, Cuisset T, Franchi F, Gross L, et al. Updated expert consensus statement on platelet function and genetic testing for guiding P2Y12 receptor inhibitor treatment in percutaneous coronary intervention. JACC Cardiovasc Interv. 2019;12:1521–1537. doi: 10.1016/j.jcin.2019.03.034
    1. Pereira NL, Rihal C, Lennon R, Marcus G, Shrivastava S, Bell MR, So D, Geller N, Goodman SG, Hasan A, et al. Effect of CYP2C19 genotype on ischemic outcomes during oral P2Y12 inhibitor therapy: a meta‐analysis. JACC Cardiovasc Interv. 2021;14:739–750. doi: 10.1016/j.jcin.2021.01.024
    1. 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, et al. A genotype‐guided strategy for Oral P2Y 12 inhibitors in primary PCI. N Engl J Med. 2019;381:1621–1631. doi: 10.1056/NEJMoa1907096
    1. Galli M, Benenati S, Capodanno D, Franchi F, Rollini F, D’Amario D, Porto I, Angiolillo DJ. Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta‐analysis. Lancet. 2021;397:1470–1483. 10.1016/S0140-6736(21)00533-X
    1. Pereira NL, Farkouh ME, So D, Lennon R, Geller N, Mathew V, Bell M, Bae J‐H, Jeong MH, Chavez I, et al. Effect of genotype‐guided oral P2Y12 inhibitor selection vs conventional clopidogrel therapy on ischemic outcomes after percutaneous coronary intervention. JAMA. 2020;324:761. 10.1001/jama.2020.12443
    1. Hochholzer W, Trenk D, Fromm MF, Valina CM, Stratz C, Bestehorn H‐P, Büttner HJ, Neumann F‐J. Impact of cytochrome P450 2C19 loss‐of‐function polymorphism and of major demographic characteristics on residual platelet function after loading and maintenance treatment with clopidogrel in patients undergoing elective coronary stent placement. J Am Coll Cardiol. 2010;55:2427–2434. 10.1016/j.jacc.2010.02.031
    1. Angiolillo DJ, Capodanno D, Danchin N, Simon T, Bergmeijer TO, ten Berg JM, Sibbing D, Price MJ. Derivation, validation, and prognostic utility of a prediction rule for nonresponse to clopidogrel. JACC Cardiovasc Interv. 2020;13:606–617. doi: 10.1016/j.jcin.2020.01.226
    1. Pereira NL, Rihal CS, So DYF, Rosenberg Y, Lennon RJ, Mathew V, Goodman SG, Weinshilboum RM, Wang L, Baudhuin LM, et al. Clopidogrel pharmacogenetics. Circ Cardiovasc Interv. 2019;12(4). doi: 10.1161/CIRCINTERVENTIONS.119.007811
    1. Saito Y, Nishi T, Wakabayashi S, Ohno Y, Kitahara H, Ariyoshi N, Kobayashi Y. Validation of the ABCD‐GENE score to identify high platelet reactivity in east Asian patients undergoing percutaneous coronary intervention. Int J Cardiol. 2021;327:15–18. 10.1016/j.ijcard.2020.11.022
    1. Capodanno D, Morice M‐C, Angiolillo DJ, Bhatt DL, Byrne RA, Colleran R, Cuisset T, Cutlip D, Eerdmans P, Eikelboom J, et al. Trial design principles for patients at high bleeding risk undergoing PCI. J Am Coll Cardiol. 2020;76:1468–1483. doi: 10.1016/j.jacc.2020.06.085
    1. Franchi F, Rollini F, Rivas J, Rivas A, Agarwal M, Briceno M, Wali M, Nawaz A, Silva G, Shaikh Z, et al. Prasugrel versus ticagrelor in patients with CYP2C19 loss‐of‐function genotypes. JACC Basic to Transl Sci. 2020;5:419–428. 10.1016/j.jacbts.2020.02.009
    1. Moliterno DJ, Smyth SS, Abdel‐Latif A. CYP2C19 genotyping to guide antiplatelet therapy after percutaneous coronary interventions: one size rarely fits all. JAMA. 2020;324:747–749. doi: 10.1001/jama.2020.13094

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する