Ponencia presentada por el Dr. J. Raúl Moreno Gómez en el directo 'Controversias en tratamiento antitrombótico – Parte II', realizado el 6 de abril de 2021

1. ANTIAGREGANTES ENDOVENOSOS
¿CUÁNDO USARLOS?
Raúl Moreno
Hospital La Paz, Madrid
Controversias en tratamiento antitrombótico - Parte II

2. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
LIMITATIONS DURING PCI
• Peri-procedural thrombotic events.
• More and more complex coronary lesions (increased thrombotic
risk).
• A high proportion of patients are not optimally treated
• Increased proportion of patients with high bleeding risk (risk of
suboptimal ATT).

3. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
PERI-PROCEDURAL THROMBOTIC EVENTS
• 6,591 patients undergoing PCI for ACS in the ACUITY & HORIZONS-AMI trials.
• Intra-procedural thrombotic events in 7.7%.
Wessler JD, et al. Which Intraprocedural Thrombotic Events Impact Clinical Outcomes After Percutaneous Coronary Intervention in Acute Coronary Syndromes?:
A Pooled Analysis of the HORIZONS-AMI and ACUITY Trials. JACC Cardiovasc Interv 2016;9:331-337.

4. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
Adjusted HRs for IPTE and Its Components With 30-Day Outcomes
Wessler JD, et al. Which Intraprocedural Thrombotic Events Impact Clinical Outcomes After Percutaneous Coronary Intervention in Acute Coronary Syndromes?:
A Pooled Analysis of the HORIZONS-AMI and ACUITY Trials. JACC Cardiovasc Interv 2016;9:331-337.

5. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
Bortnick AE, et al. Five-year follow-up of patients treated for coronary artery disease in the face of an increasing burden of co-morbidity and disease complexity (from
the NHLBI Dynamic Registry). Am J Cardiol 2014;113:573-9.
Prevalence in the number of co-morbid conditions*
*Smoking, diabetes, renal insufficiency, peripheral arterial disease,
hypertension, hypercholesterolemia.
Prevalence in the no. of severe CAD characteristics*.
*Calcified stenoses, CTO, LMD ≥ 50%, type C lesions and/or 3-vessel
disease.
GROWING PATIENT AND LESION COMPLEXITY

6. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
LIMITATIONS OF PRE-LOADING
COAST: No benefit of preloading with prasugrel
Montalescot G et al., N Engl J Med 2013
ACCOAST
(Prasugrel in NSTEMI)
Montalescot G, et al. Pretreatment with prasugrel in non-ST-segment
elevation acute coronary síndromes. N Engl J Med 2013;369:999-1010.
Montalescot G, et al. Prehospital ticagrelor in ST-segment elevation
myocardial infarction. N Engl J Med. 2014;371:1016-27
ATLANTIC
(Ticagrelor in STEMI)
Figure S5. Major adverse cardiovascular events (death/MI/stroke/urgent revascularisation/definite
acute stent thrombosis) up to 30 days: Kaplan-Meier curves (mITT analysis set).

7. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
ADVANTAGES OF I.V. ANTIPLATELET DRUGS IN PCI
• More potent anti-platelet effect.
• Quicker effect.
• Not dependent on patient intake.
• Not dependent on gastro-intestinal
function.
• More homogeneous effect.

8. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
WHICH OPTIONS DO WE HAVE IN 2021?
IIB/IIIA
INHIBITORS
P2Y12
ANTAGONIS
TS

9. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
INDICATIONS OF IIB/IIIA INHIBITORS DURING PCI
1Neumann FJ, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019;40:87-165. 2Collet JP, et al. 2020 ESC Guidelines for the
management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2020 Aug 29;ehaa575. 3Ibañez B, et al. 2017
ESC Guidelines for the management of acute myocardial infarction in patients presentingwithST-segmentelevation. Eur Heart J 2018;39:119–177.
Stable CAD1
NSTEMI2
STEMI3

10. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
CANGRELOR: HOW CAN WE IDENTIFY THE BEST PATIENTS?
Steg PG, et al. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data. Lancet 2013;382:1981-92

11. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
INTUBATED PATIENTS IN CARDIOGENIC SHOCK
Osmancik P, et al. A comparison of the VASP index between patients with hemodynamically complicated and uncomplicated acute myocardial infarction. Catheter
Cardiovasc Interv 2010;75:158-66.
Reduced effect of clopidogrel
Comparison of the VASP (vasodilator‐stimulated phosphoprotein) index between patients with
hemodynamically complicated and uncomplicated AMI

12. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
Steg PG, et al. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data. Lancet 2013;382:1981-92
CANGRELOR: HOW CAN WE IDENTIFY THE BEST PATIENTS?
Events: death, MI, ischaemia-driven revascularisation, or stent thrombosis at 48 h

13. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
Steg PG, et al. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data. Lancet 2013;382:1981-92
Events: death, MI, ischaemia-driven revascularisation, or stent thrombosis at 48 h

14. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
CANGRELOR: PATIENTS WITH ACS VS STABLE CAD
Abtan J, et al. Efficacy and Safety of Cangrelor in Preventing Periprocedural Complications in Patients With Stable Angina and Acute Coronary Syndromes Undergoing
Percutaneous Coronary Intervention: The CHAMPION PHOENIX Trial. JACC: Cardiovasc Interv 2016;9:1905-13.

15. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
CANGRELOR: PATIENTS WITH ACS VS STABLE CAD
Genereux G, et al. Impact of intraprocedural stent thrombosis during percutaneous coronary intervention: insights from the CHAMPION PHOENIX Trial (Clinical Trial
Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention). J Am Coll Cardiol 2014;63:619–29

16. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
THE IMPORTANCE OF LESION COMPLEXITY
Stone GW, et al. Impact of lesion complexity on peri-procedural adverse events and the benefit of potent intravenous platelet adenosine diphosphate receptor inhibition
after percutaneous coronary intervention: core laboratory analysis from 10 854 patients from the CHAMPION PHOENIX trial. Eur Heart J 2018;39:4112-4121.
Angiographic complexity and benefit of cangrelor
(13,418 lesions in 10,854 patients from CHAMPION PHOENIX).
CHAMPION PHOENIX Angiographic Analysis
Number of High-Risk Angiographic Risk Factors
Stone GW, Genereux P, Harrington RA, et al…. Bhatt DL. EHJ 2018.
ARR 1.5 ARR 0.6 ARR 0.9 ARR 2.3
• Bifurcation.
• Left main.
• Thrombus.
• Angulated.
• Tortuous.
• Eccentric.
• Calcified.
• Long.
• Multi-lesion.
25% of patients
Number of high-risk PCI
characteristics

17. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
THE IMPORTANCE OF LESION COMPLEXITY
Stone GW, et al. Impact of lesion complexity on peri-procedural adverse events and the benefit of potent intravenous platelet adenosine diphosphate receptor inhibition
after percutaneous coronary intervention: core laboratory analysis from 10 854 patients from the CHAMPION PHOENIX trial. Eur Heart J 2018;39:4112-4121.
ARR 1.6
ARR 3.1
Number of high-risk PCI
characteristics

18. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
THE IMPORTANCE OF LESION COMPLEXITY
Stone GW, et al. Impact of lesion complexity on peri-procedural adverse events and the benefit of potent intravenous platelet adenosine diphosphate receptor inhibition
after percutaneous coronary intervention: core laboratory analysis from 10 854 patients from the CHAMPION PHOENIX trial. Eur Heart J 2018;39:4112-4121.

19. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
“Despite these important considerations, there are several clinical situations where cangrelor could have a major
role. First, because cangrelor is administered intravenously and has rapid onset, it could offer particular
advantages in the STEMI primary PCI setting, especially in patients at high risk, in those experiencing nausea and
vomiting, or in those who are intubated or in cardiogenic shock. There is little opportunity for pretreatment in this
setting and there is invariably a delay to optimum platelet inhibition with even the most effective oral agents. A
randomised trial of cangrelor versus placebo on top of optimum dual oral antiplatelet therapy, including either
ticagrelor or prasugrel, would help solidify its role in this setting. Second, because patients with high-risk non-
STEMI (GRACE score >140) preferentially benefit from early intervention, cangrelor, with its rapid onset and
offset, might offer an advantage in this population. Third, in centres where pretreatment is not routine clinical
practice, cangrelor will probably become a preferred option. Fourth, cangrelor is an attractive option in patients
with high-risk anatomic or clinical features undergoing same-sitting or ad hoc elective PCI for stable coronary
artery disease. There is little opportunity to benefit from preloading in these patients and, somewhat surprisingly,
neither ticagrelor nor prasugrel has been formally studied in this large group of patients”.
Mehta SR, et al. Cangrelor: a new CHAMPION for percutaneous coronary intervention. Lancet 2013;382:1961-2.

20. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
1Rossini R, et al. Antiplatelet Therapy with Cangrelor in Patients Undergoing Surgery after Coronary Stent Implantation: A Real-World Bridging Protocol Experience. TH Open. 2020;4:e437-e445. 2Delvoye
F, et al. Antiplatelet Therapy During Emergent Extracranial Internal Carotid Artery Stenting: Comparison of Three Intravenous Antiplatelet Perioperative Strategies. J Stroke Cerebrovasc Dis.
2021;30:105521. 3Cortez GM, et al. The use of cangrelor in neurovascular interventions: a multicenter experience. Neuroradiology. 2020 Nov 11. 4Cervo A, Ferrari F, Barchetti G, Quilici L, Piano M,
Boccardi E, Pero G. Use of Cangrelor in Cervical and Intracranial Stenting for the Treatment of Acute Ischemic Stroke: A "Real Life" Single-Center Experience. AJNR Am J Neuroradiol. 2020;41:2094-
2099. 5Linfante I, Ravipati K, Starosciak AK, et al. Intravenous cangrelor and oral ticagrelor as an alternative to clopidogrel in acute intervention. J Neurointerv Surg. 2021;13:30-32. 6Fahnhorst SE, et al.
Novel use of cangrelor in pediatrics: A pilot cohort study demonstrating use in ventricular assist devices. Artif Organs. 2021;45:38-45. 7Vargas D, et al. Cangrelor PK/PD analysis in post-operative neonatal
cardiac patients at risk for thrombosis. J Thromb Haemost. 2021;19:202-211.
• Bridging therapy for surgery after coronary stenting1.
• Neurovascular interventions2-5.
• Pediatric patients supported under ventricular assist device6.
• Neonates at high risk of thrombosis7.
INDICATIONS OF CANGRELOR OUTSIDE OF PCI FIELD

21. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
SWITCHING FROM ORAL AGENTS TO CANGRELOR
Expert Consensus Recommendations on Switching
Bridging from oral to intravenous P2Y12 inhibitors
• For both cardiac and noncardiac surgery, if withdrawal of P2Y12 inhibiting therapy is needed, clopidogrel and
ticagrelor should be discontinued for 5 days and prasugrel for 7 days.
Angiolillo DJ, et al. International Expert Consensus on Switching Platelet P2Y 12 Receptor-Inhibiting Therapies. Circulation 2017;136:1955-1975.

22. Antiagregantes endovenosos, ¿cuándo usarlos? J. Raúl Moreno Gómez
CONCLUSIONS
• The use of IIb/IIIa inhibitors should be restricted to bail-out or
procedural complications (intra-procedural thrombotic events).
• Cangrelor prevents peri-procedural thrombotic events both in
patients with ACS and stable CAD.
• Lesion complexity plays a key role for selecting patients candidates
to receive cangrelor.
• Other indications of cangrelor include bridging therapy for surgery
after coronary stenting.