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Increased risk of adverse events in patients with low-on clopidogrel platelet reactivity after percutaneous coronary intervention: A systematic review and meta-analysis

Alexandra Bálint, Lilla Hanák, Péter Hegyi, Zsolt Szakács, Szimonetta Eitmann, András Garami, Margit Solymár, Katalin Márta, Zoltán Rumbus, András Komócsi
DOI: 10.5603/CJ.a2021.0084
·
Pubmed: 34355778

open access

Ahead of print
Original articles
Published online: 2021-08-02

Abstract

Background: Clinical evidence has been controversial regarding the influence of low platelet reactivity (LPR), ischemic and bleeding outcomes among patients receiving coronary stent implantation. Hence, the present study performed a meta-analysis to systematically evaluate the significance of LPR on adverse cardiovascular events.

Methods: MEDLINE, EMBASE and CENTRAL databases were searched up to November 2020 for relevant studies including patients with acute coronary syndrome undergoing percutaneous coronary intervention. LPR was the exposed arm while the non-LPR group represented the control. The primary outcome of interest was bleeding risk including major and minor bleeding events. Secondary outcomes included all-cause mortality, repeated revascularization, nonfatal myocardial infarction, and stent thrombosis. Study-level outcomes were evaluated in random-effect models.

Results: A total of 20 studies with 19,064 patients were included. Pooled analysis showed that LPR was associated with an increased bleeding risk (relative risk [RR] 2.80, 95% confidence interval [CI] 1.95–4.02, p < 0.01). Patients with LPR had a lower risk of non-fatal myocardial infarction (RR 0.59, 95% CI 0.38–0.91, p < 0.05) and of serious vascular events (RR 0.50, 95% CI 0.30–0.84, p < 0.01).

Conclusions: LPR is associated with an increased bleeding risk of patients who underwent coronary stent implantation. The results suggest possible benefits of this marker in risk stratification, with potential improvement in risk prediction. There are potential advantages using combinations with other factors in prediction models, however, they require further study. PROSPERO registration number: CRD42019136393).

Abstract

Background: Clinical evidence has been controversial regarding the influence of low platelet reactivity (LPR), ischemic and bleeding outcomes among patients receiving coronary stent implantation. Hence, the present study performed a meta-analysis to systematically evaluate the significance of LPR on adverse cardiovascular events.

Methods: MEDLINE, EMBASE and CENTRAL databases were searched up to November 2020 for relevant studies including patients with acute coronary syndrome undergoing percutaneous coronary intervention. LPR was the exposed arm while the non-LPR group represented the control. The primary outcome of interest was bleeding risk including major and minor bleeding events. Secondary outcomes included all-cause mortality, repeated revascularization, nonfatal myocardial infarction, and stent thrombosis. Study-level outcomes were evaluated in random-effect models.

Results: A total of 20 studies with 19,064 patients were included. Pooled analysis showed that LPR was associated with an increased bleeding risk (relative risk [RR] 2.80, 95% confidence interval [CI] 1.95–4.02, p < 0.01). Patients with LPR had a lower risk of non-fatal myocardial infarction (RR 0.59, 95% CI 0.38–0.91, p < 0.05) and of serious vascular events (RR 0.50, 95% CI 0.30–0.84, p < 0.01).

Conclusions: LPR is associated with an increased bleeding risk of patients who underwent coronary stent implantation. The results suggest possible benefits of this marker in risk stratification, with potential improvement in risk prediction. There are potential advantages using combinations with other factors in prediction models, however, they require further study. PROSPERO registration number: CRD42019136393).

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Keywords

low platelet reactivity, acute coronary syndrome, percutaneous coronary intervention, bleeding risk, clopidogrel

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Title

Increased risk of adverse events in patients with low-on clopidogrel platelet reactivity after percutaneous coronary intervention: A systematic review and meta-analysis

Journal

Cardiology Journal

Issue

Ahead of print

Article type

Original Article

Published online

2021-08-02

DOI

10.5603/CJ.a2021.0084

Pubmed

34355778

Keywords

low platelet reactivity
acute coronary syndrome
percutaneous coronary intervention
bleeding risk
clopidogrel

Authors

Alexandra Bálint
Lilla Hanák
Péter Hegyi
Zsolt Szakács
Szimonetta Eitmann
András Garami
Margit Solymár
Katalin Márta
Zoltán Rumbus
András Komócsi

References (43)
  1. Montalescot G, Sechtem U, Achenbach S, et al. Task Force Members, ESC Committee for Practice Guidelines, Document Reviewers. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013; 34(38): 2949–3003.
  2. Wiviott SD, Braunwald E, McCabe CH, et al. TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007; 357(20): 2001–2015.
  3. Wallentin L, Becker RC, Budaj A, et al. PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009; 361(11): 1045–1057.
  4. Buonamici P, Marcucci R, Migliorini A, et al. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol. 2007; 49(24): 2312–2317.
  5. Cuisset T, Cayla G, Frere C, et al. Predictive value of post-treatment platelet reactivity for occurrence of post-discharge bleeding after non-ST elevation acute coronary syndrome. Shifting from antiplatelet resistance to bleeding risk assessment? EuroIntervention. 2009; 5(3): 325–329.
  6. Matetzky S, Shenkman B, Guetta V, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation. 2004; 109(25): 3171–3175.
  7. Sibbing D, Schulz S, Braun S, et al. Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement. J Thromb Haemost. 2010; 8(2): 250–256.
  8. Geisler T, Langer H, Wydymus M, et al. Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation. Eur Heart J. 2006; 27(20): 2420–2425.
  9. Spiliopoulos S, Pastromas G, Katsanos K, et al. Platelet responsiveness to clopidogrel treatment after peripheral endovascular procedures. J Am Coll Cardiol. 2013; 61(24): 2428–2434.
  10. Sibbing D, Aradi D, Jacobshagen C, et al. TROPICAL-ACS Investigators. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet. 2017; 390(10104): 1747–1757.
  11. Claassens DMF, Vos GJA, Bergmeijer TO, et al. A genotype-guided strategy for oral P2Y inhibitors in primary PCI. N Engl J Med. 2019; 381(17): 1621–1631.
  12. Sibbing D, Schulz S, Braun S, et al. Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement. J Thromb Haemost. 2010; 8(2): 250–256.
  13. Cuisset T, Grosdidier C, Loundou AD, et al. Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine: the POBA study (predictor of bleedings with antiplatelet drugs). JACC Cardiovasc Interv. 2013; 6(8): 854–863.
  14. Mangiacapra F, Colaiori I, Ricottini E, et al. Impact of platelet reactivity on 5-year clinical outcomes following percutaneous coronary intervention: a landmark analysis. J Thromb Thrombolysis. 2018; 45(4): 496–503.
  15. Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015; 162(11): 777–784.
  16. Mehran R, Rao S, Bhatt D, et al. Standardized bleeding definitions for cardiovascular clinical trials. Circulation. 2011; 123(23): 2736–2747.
  17. Wolff RF, Moons KGM, Riley RD, et al. PROBAST Group. PROBAST: A Tool to Assess the Risk of Bias and Applicability of Prediction Model Studies. Ann Intern Med. 2019; 170(1): 51–58.
  18. Wells G. A., Shea B., O’Connell D., Peterson J., Welch V., Losos M. et al. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-analyses. 2000. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
  19. 9.5.2 Identifying and measuring heterogeneity. https://handbook-5-1.cochrane.org/chapter_9/9_5_2_identifying_and_measuring_heterogeneity.htm.
  20. Kabbani SS, Watkins MW, Ashikaga T, et al. Usefulness of platelet reactivity before percutaneous coronary intervention in determining cardiac risk one year later. Am J Cardiol. 2003; 91(7): 876–878.
  21. Patti G, Nusca A, Mangiacapra F, et al. Point-of-care measurement of clopidogrel responsiveness predicts clinical outcome in patients undergoing percutaneous coronary intervention results of the ARMYDA-PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome) study. J Am Coll Cardiol. 2008; 52(14): 1128–1133.
  22. Tsukahara K, Kimura K, Morita S, et al. Impact of high-responsiveness to dual antiplatelet therapy on bleeding complications in patients receiving drug-eluting stents. Circ J. 2010; 74(4): 679–685.
  23. Huczek Z, Filipiak KJ, Kochman J, et al. Medium on-treatment platelet reactivity to ADP is favorable in patients with acute coronary syndromes undergoing coronary stenting. Platelets. 2011; 22(7): 521–529.
  24. Patti G, Pasceri V, Vizzi V, et al. Usefulness of platelet response to clopidogrel by point-of-care testing to predict bleeding outcomes in patients undergoing percutaneous coronary intervention (from the Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-Bleeding Study). Am J Cardiol. 2011; 107(7): 995–1000.
  25. Bonello L, Mancini J, Pansieri M, et al. Relationship between post-treatment platelet reactivity and ischemic and bleeding events at 1-year follow-up in patients receiving prasugrel. J Thromb Haemost. 2012; 10(10): 1999–2005.
  26. Cuisset T, Gaborit B, Dubois N, et al. Platelet reactivity in diabetic patients undergoing coronary stenting for acute coronary syndrome treated with clopidogrel loading dose followed by prasugrel maintenance therapy. Int J Cardiol. 2013; 168(1): 523–528.
  27. Mangiacapra F, Patti G, Barbato E, et al. A therapeutic window for platelet reactivity for patients undergoing elective percutaneous coronary intervention: results of the ARMYDA-PROVE (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity for Outcome Validation Effort) study. JACC Cardiovasc Interv. 2012; 5(3): 281–289.
  28. Mangiacapra F, Cavallari I, Barbato E, et al. Impact of chronic kidney disease on platelet reactivity and outcomes of patients receiving clopidogrel and undergoing percutaneous coronary intervention. Am J Cardiol. 2014; 113(7): 1124–1129.
  29. Alfredsson J, Lindahl TL, Gustafsson KM, et al. Large early variation of residual platelet reactivity in Acute Coronary Syndrome patients treated with clopidogrel: results from Assessing Platelet Activity in Coronary Heart Disease (APACHE). Thromb Res. 2015; 136(2): 335–340.
  30. Li S, Liu H, Liu J. Predictive performance of adding platelet reactivity on top of CRUSADE score for 1-year bleeding risk in patients with acute coronary syndrome. J Thromb Thrombolysis. 2016; 42(3): 360–368.
  31. Jin L, Yu H, Dong T, et al. The prognostic value of ADP-induced platelet aggregation for bleeding complications in low: intermediate risk patients with acute coronary syndrome taking clopidogrel after percutaneous coronary intervention. Heart Lung Circ. 2017; 26(1): 49–57.
  32. Deharo P, Quilici J, Camoin-Jau L, et al. Benefit of switching dual antiplatelet therapy after acute coronary syndrome according to on-treatment platelet reactivity: the TOPIC-VASP pre-specified analysis of the topic randomized study. JACC Cardiovasc Interv. 2017; 10(24): 2560–2570.
  33. Su Nam L, Moon D, Sung MK, et al. Impact of platelet reactivity on long-term prognosis in Korean patients receiving percutaneous coronary intervention. Platelets. 2019; 30(8): 1030–1035.
  34. Aradi D, Gross L, Trenk D, et al. Platelet reactivity and clinical outcomes in acute coronary syndrome patients treated with prasugrel and clopidogrel: a pre-specified exploratory analysis from the TROPICAL-ACS trial. Eur Heart J. 2019; 40(24): 1942–1951.
  35. Mshelbwala FS, Hugenberg DW, Kreutz RP. Intensified P2Y12 inhibition for high-on treatment platelet reactivity. J Thromb Thrombolysis. 2020; 50(3): 619–627.
  36. Nakamura M, Kadota K, Takahashi A, et al. PENDULUM Registry Investigators*. Relationship Between Platelet Reactivity and Ischemic and Bleeding Events After Percutaneous Coronary Intervention in East Asian Patients: 1-Year Results of the PENDULUM Registry. J Am Heart Assoc. 2020; 9(10): e015439.
  37. Cornel JH, Ohman EM, Neely B, et al. Relationship of platelet reactivity with bleeding outcomes during long-term treatment with dual antiplatelet therapy for medically managed patients with non-ST-segment elevation acute coronary syndromes. J Am Heart Assoc. 2016; 5(11).
  38. Aradi D, Kirtane A, Bonello L, et al. Bleeding and stent thrombosis on P2Y12-inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J. 2015; 36(27): 1762–1771.
  39. Piqueras-Flores J, Jurado-Román A, López-Lluva MT, et al. Efficacy and safety of loading doses with P2Y12-receptor antagonists in patients without dual antiplatelet therapy undergoing elective coronary intervention. J Cardiovasc Pharmacol. 2019; 73(1): 56–59.
  40. Tekkeşin Aİ, Kaya A, Çakıllı Y, et al. The first six-month clinical outcomes and risk factors associated with high on-treatment platelet reactivity of clopidogrel in patients undergoing coronary interventions. Anatol J Cardiol. 2016; 16(12): 967–973.
  41. Wakabayashi S, Ariyoshi N, Kitahara H, et al. Efficacy of 2.5-mg prasugrel in elderly or low-body-weight patients. Circ J. 2018; 82(9): 2326–2331.
  42. Droppa M, Tschernow D, Müller KAL, et al. Evaluation of clinical risk factors to predict high on-treatment platelet reactivity and outcome in patients with stable coronary artery disease (PREDICT-STABLE). PLoS One. 2015; 10(3): e0121620.
  43. Komócsi A, Aradi D, Kehl D, et al. Meta-analysis of randomized trials on access site selection for percutaneous coronary intervention in ST-segment elevation myocardial infarction. Arch Med Sci. 2014; 10(2): 203–212.

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