Is there literature to support use of cangrelor in PCI based on angiogram visualization of clot size? Does literature support one intravenous anticoagulant over another based on clot size during PCI?

Comment by InpharmD Researcher

There is no direct evidence to support the selection of cangrelor or any specific intravenous anticoagulant based solely on the angiographic assessment of clot size or burden. Guideline recommendations and major clinical trials, such as CHAMPION PHOENIX, support the use of cangrelor to reduce ischemic events in patients undergoing PCI, but they do not stratify this benefit by the visualized clot size. While one registry demonstrates cangrelor's efficacy in patients with angiographic thrombus, the literature lacks comparative studies that guide the choice of one intravenous anticoagulant over another specifically based on this angiographic feature.

Background

According to the 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes, intravenous cangrelor may be reasonable for patients with ACS undergoing PCI who have not received a P2Y12 inhibitor, as it can help reduce periprocedural ischemic events. The CHAMPION PHOENIX trial demonstrated that cangrelor significantly lowers the 48-hour incidence of the composite endpoint of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis compared with a 300–600 mg clopidogrel loading dose, with consistent benefits observed in both NSTE-ACS and STEMI patients. Importantly, the guideline recommendations for cangrelor are not specifically stratified by angiographic assessment of clot burden. [1]

A 2018 investigation evaluated the impact of cangrelor, a potent intravenous platelet adenosine diphosphate receptor antagonist, on peri-procedural adverse events in patients undergoing percutaneous coronary intervention (PCI). This large-scale analysis from the CHAMPION PHOENIX trial involved 10,854 randomized patients, with angiographic core laboratory analysis completed for 13,418 target lesions. The primary aim was to determine whether the efficacy of cangrelor varied in patients with simple versus complex coronary artery lesions characterized by high-risk features. Patients were categorized based on the number of high-risk features in their target lesions, including long lesions, left main lesions, bifurcation lesions, thrombotic lesions, tortuous lesions (moderate or severe), angulated lesions (moderate or severe), eccentric lesions, calcified lesions (moderate or severe), and multi-lesion treatment. In this investigation, the 48-hour major adverse cardiac event (MACE) rate for clopidogrel-treated patients significantly increased with lesion complexity, rising from 3.3% in patients with no high-risk features to 8.7% in those with three or more features. Cangrelor reduced the 48-hour MACE rate by 21% compared to clopidogrel, with an odds ratio of 0.79 and a P-value of 0.006, demonstrating consistent efficacy regardless of lesion complexity or patient presentation with stable ischemic heart disease or acute coronary syndrome. Multivariable analysis identified the number of high-risk PCI characteristics and treatment with cangrelor versus clopidogrel as independent predictors of the primary 48-hour MACE endpoint. The incidence of major bleeding was unrelated to lesion complexity and was not significantly increased by cangrelor use, underscoring the therapeutic benefit of cangrelor during PCI, especially in patients with complex coronary anatomy. Notably, clot burden was not assessed or considered a high-risk feature in this investigation. [2]

A 2025 study provided an analysis detailing the use of cangrelor as a bailout strategy during percutaneous coronary interventions (PCI). This eight-year observational study, conducted at the MedStar Washington Hospital Center, screened 2,680 patients who received cangrelor during PCI from 2016 to 2023. Of these, 67 patients (2.5%) were administered cangrelor as bailout therapy due to thrombotic complications such as slow flow, no-reflow, stent thrombosis, and acute side branch occlusion. Cangrelor, administered after initial balloon angioplasty or stent deployment, significantly enhanced mean TIMI flow from 1.3 to 2.7, demonstrating improvement in patients who initially presented with TIMI-0 flow. The 2025 investigation into cangrelor's efficacy highlighted several critical outcomes: complete or partial thrombus resolution was observed in patients experiencing stent thrombosis, and procedural efficacy was supported by adjunctive nonpharmacological strategies, including aspiration thrombectomy and additional stenting. This descriptive analysis reported an in-hospital ischemic event rate of 11.9%, a major bleeding incidence of 4.5%, and an average hospital stay of 5.8 days. The compelling findings suggest that cangrelor provides a viable alternative to glycoprotein IIb/IIIa inhibitors for managing thrombotic complications during PCI, paving the way for further investigation into its routine use in all-comer PCI settings. [3]

A 2019 exploratory registry was conducted at a high-volume tertiary care center to evaluate the angiographic and in-hospital clinical outcomes of administering cangrelor immediately before percutaneous coronary intervention (PCI). The research included 223 consecutive patients with angiographic evidence of intracoronary thrombus who underwent PCI. Cangrelor, a rapid-onset intravenous P2Y12 receptor inhibitor, was given at the time of PCI decision-making, followed by a transition to oral antiplatelet therapy post-procedure. The study stratified patients based on their pre-procedure clinical status into either cardiogenic shock or no shock, with further lesion-level analysis according to pre-procedure TIMI-Flow grades. The registry revealed significant improvements in angiographic indices with the use of cangrelor, showing restoration of TIMI-Flow 3 in 96% of cases post-PCI and an absence of angiographic thrombus in 96% of treated lesions. The study demonstrated cangrelor's efficacy in enhancing myocardial perfusion and blush grades, particularly in patients with initial TIMI-Flow 0/1. Major bleeding events occurred in 2.0% of cases, indicating a favorable safety profile. Overall, the research suggests that cangrelor is effective in managing intracoronary thrombus, with a low incidence of major adverse cardiovascular events, supporting its consideration for patients undergoing PCI with visible thrombus. See Table 1 for full study details. [4]

References:

[1] Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
[2] Stone GW, Généreux P, Harrington RA, 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(46):4112-4121. doi:10.1093/eurheartj/ehy562
[3] Chaturvedi A, Hill AP, Creechan P, et al. Bailout Use of Cangrelor During Percutaneous Coronary Intervention and Associated Outcomes. Am J Cardiol. 2025;256:89-92. doi:10.1016/j.amjcard.2025.07.022
[4] Hideo-Kajita A, Rogers T, Buchanan K, et al. Effects of Cangrelor as Adjunct Therapy to Percutaneous Coronary Intervention. Am J Cardiol. 2019;123(8):1228-1238. doi:10.1016/j.amjcard.2019.01.031

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Is there literature to support use of cangrelor in PCI based on angiogram visualization of clot size? Does literature support one intravenous anticoagulant over another based on clot size during PCI?

Level of evidence

X - No data  Read more→



Please see Table 1 for your response.


Effects of Cangrelor as Adjunct Therapy to Percutaneous Coronary Intervention
Design

Exploratory registry study

N= 223

Objective To assess the pre- and postprocedure angiographic and in-hospital clinical outcomes in all-comers patients with and without cardiogenic shock receiving cangrelor before PCI
Study Groups

TIMI-Flow 0/1 (n= 106)

TIMI-Flow 2/3 (n= 97)

Cardiogenic shock (n= 20)

Inclusion Criteria Patients >18 years old, all-comer patients (i.e., stable angina pectoris, unstable angina pectoris, STEMI, and NSTEMI) referred to cardiac catheterization and underwent PCI and received intraprocedure cangrelor
Exclusion Criteria Not specified
Methods Patients received cangrelor as an IV bolus of 30 mg/kg and subsequent continuous pump infusion of 4 mg/kg/min during the procedure. Angiographic assessments of TIMI-Flow, TIMI-Thrombus, MBG, and TMPG were performed before and post-PCI. Clinical events were recorded during the procedure and at discharge
Duration September 2016 to December 2017
Outcome Measures

Primary: Pre- and post-PCI assessment of changes in coronary blood flow, intraluminal thrombus, and myocardium microcirculation

Secondary: In-hospital outcomes including MACE, definite ST, and major bleeding

Baseline Characteristics   TIMI-Flow 0/1 (n= 106) TIMI-Flow 2/3 (n= 97) Cardiogenic Shock (n= 20)
Age, years 60.5 ± 12.2 66.4 ± 11.1 63.05 ± 11.4
Men 75 (70.7%) 48 (49.5%) 13 (65.0%)
Diabetes mellitus 39 (37.5%) 37 (38.9%) 8 (40.0%)
Systemic arterial hypertension 80 (76.2%) 83 (86.5%) 13 (65.0%)
Hyperlipidemia 67 (64.4%) 75 (78.1%) 10 (50.0%)
Smoker 57 (53.8%) 54 (55.7%) 9 (45.0%)
Heart failure 25 (24.0%) 20 (21.5%) 3 (15.0%)
Left ventricle ejection fraction % 0.42 ± 0.13 0.49 ± 0.13 0.38 ± 0.14

Lesion classification

          Type A

          Type B1

          Type B2

          Type C

 

0 (0.0%)

0 (0.0%)

3 (2.8%)

106 (97.2%)

 

11 (9.6%)

22 (19.1%)

27 (23.5%)

55 (47.8%)

 

1 (5.0%)

1 (5.0%)

0 (0.0%)

18 (90.0%)

American College of Cardiology/American Heart Association (ACC/AHA) lesion Classification.
Results   TIMI-Flow 0/1 (n= 106) TIMI-Flow 2/3 (n= 97) Cardiogenic Shock (n= 20)
TIMI-Flow 3 restored 96% 96% 96%
Angiographic absence of thrombus 96% 96% 96%
MACE-free 94.3% 100% 75.0%
Major bleeding 1.9% 2.1% 10.0%
Adverse Events Major bleeding rate was 2.0%. No definite or probable stent thrombosis cases. Hematoma in 3.5% of cases, gastrointestinal bleeding in 1.0%
Study Author Conclusions Cangrelor is effective in restoring TIMI-Flow 3, reducing thrombus burden, and improving myocardial perfusion when administered before PCI in patients with visible intracoronary thrombus. It is associated with low MACE and bleeding rates.
Critique The study provides valuable insights into the use of cangrelor as adjunct therapy in PCI, showing significant improvements in angiographic outcomes. However, the single-center design and lack of a control group limit the generalizability of the findings. The heterogeneity of patient groups may obscure specific benefits for certain subgroups.
References:

Hideo-Kajita A, Rogers T, Buchanan K, et al. Effects of Cangrelor as Adjunct Therapy to Percutaneous Coronary Intervention. Am J Cardiol. 2019;123(8):1228-1238. doi:10.1016/j.amjcard.2019.01.031