Clinical Use of Cangrelor After Percutaneous Coronary Intervention in Patients Requiring Mechanical Circulatory Support

Design

Single-center, retrospective, observational case series

N= 17

Objective

To describe the complications and outcomes of patients who received cangrelor during mechanical circulatory support (MCS) following percutaneous coronary intervention (PCI)

Study Groups

Inclusion Criteria

≥18 years of age, underwent PCI on admission that was complicated by cardiogenic shock requiring MCS, and received cangrelor in the immediate post-PCI period

Exclusion Criteria

N/A

Methods

All patients were started on cangrelor post-PCI and on MCS initiation. Per hospital protocol, unfractionated heparin was used for anticoagulation in patients on MCS, with a goal anti-Xa of 0.15 to 0.5 IU/mL without exceeding an activated partial thromboplastin time (aPTT) of 70 seconds. P2Y12 levels were measured at the discretion of the provider. Per hospital policy, the cangrelor dose was designated as “low” if the initial dose was less than 0.75 mcg/kg/min or if the dose was 0.75 mcg/kg/min using a dosing weight other than actual body weight (ie, ideal or adjusted).

Duration

Time of intervention: June 2017 to September 2019

Outcome Measures

Primary: describe the proportion of patients who experienced thrombotic and bleeding events during cangrelor overlap while receiving MCS

Secondary: stratified bleeding events by location

Baseline Characteristics

All patients (n= 17)

Age, years 

Male 

Actual body weight, kg 

Ideal body weight, kg 

BMI, kg/m² 

Past medical history

      Coronary artery disease

      Hypertension

      Diabetes

      Heart failure

      Atrial fibrillation

      Chronic kidney disease (stage 3-5)

      Malignancy

      Valvular disease

      Vasculitis

16 (94%) 

14 (82%)

10 (58%)

6 (35%)

4 (24%)

4 (24%)

2 (12%)

1 (5%)

1 (5%)

History of arterial or venous clot

      Clot within the past 3 months

1 (5%)

1 (5%)  

History of bleed

      Bleed within the past 3 months

      Major bleed

      Minor bleed

8 (47%) 

9 (64%)

6/9 (67%)

3/9 (33%)

Baseline laboratory values

      Hemoglobin, g/dL 

      Hematocrit, g/dL 

      Platelets, 10³ /micro-L 

      aPTT, s 

      INR 

12 (9.9 to 13.8) 

38 (31 to 44)

245 (187 to 272)

33 (27.3 to 50.2)

1 (1 to 1.2)

                                               Cangrelor dosing scheme

Results

Endpoint

≥0.75 mcg/kg/min: Dosing weight, Actual body weight (ABW)

Bleeding, n = 10

      Major bleeding prior to cangrelor (n= 2)

6/10 (60%)

2 (100%)

2/10 (20%)

0 (0)

2/10 (20%)

0 (0)

Bleeding Academic Research Consortium (BARC) classification*

      Type 2

      Type 3a

      Type 3b

      Type 5

0 (0)

1/10 (10%) 

3/10 (30%)

2/10 (20%)

0 (0)

1/10 (10%)

1/10 (10%)

0 (0) 

1/10 (10%)

0 (0)

1/10 (10%) 

0 (0)

Device at time of bleed

      Impella CP

      VA ECMO**/Impella

      VA ECMO

3/6 (50%)

1/6 (16%)

2/6 (33%) 

1/2 (50%)

1/2 (50%) 

0 (0)

0 (0)

1/2 (50%)

1/2 (50%)

Coagulation values observed while on heparin

      aPTT, s 

          Supratherapeutic aPTT, s 

      Anti-Xa, IU/mL 

          Supratherapeutic anti-Xa, IU/mL 

53 (35 to 76) 

85 (71 to 197.8)

0.5 (0.2 to 0.7)

0.89 (0.56 to 1.47)

51.7 (48 to 56)

142 (89 to 195)

0.17 (0.13 to 0.2)

1.37 

40 (33 to 47)

138 (75 to 200)

0.14 (0.07 to 0.21)

0.51 

Dose adjustments made after bleeding event

      Decreased cangrelor dose to 0.5 µg/kg/min

      Duration maintained at adjusted dose, hours

1/10 (10%)

24

---

1/10 (10%)

29

Description of thrombotic events based on dosing scheme

      Thrombosis (n= 6)

          In-stent thrombosis

          Cannula associated thrombus

          Cardioembolic stroke

          Arterial clot

          LV thrombus

3/6 (50%)

0 (0)

1/6 (16%)

1/6 (16%)

1/6 (16%)

0 (0)

1/6 (16%)

0 (0)

1/6 (16%) 

0 (0)

0 (0)

0 (0)

2/6 (33%)

0 (0)

1/6 (16%)

0 (0)

0 (0)

1/6 (16%)

P2Y12 level, PRU 

Device at the time of thrombosis

      Impella

      VA ECMO/Impella

      VA ECMO

1/3 (33%)

1/3 (33%)

1/3 (33%)

1/1 (100%)

0 (0)

0 (0)

0 (0)

1/2 (50%)

1/2 (50%)

*Type 3b or higher is defined as major bleeding event

**VA ECMO: venoarterial (VA) extracorporeal membrane oxygenation (ECMO)

Adverse Events

Common Adverse Events: bleeding

Serious Adverse Events: major bleeding occurred in 7/10 patients at the peripheral cannulation site (40%) and gastrointestinal tract (30%)

Percentage that Discontinued due to Adverse Events: N/A

Study Author Conclusions

This retrospective, observational case series highlights the challenges associated with balancing the risks of bleeding and thrombosis for patients receiving MCS. Given the high bleeding risk on MCS, in conjunction with other risk factors, including postoperative coagulopathy, cangrelor doses <0.75 mcg/kg/min may be beneficial when combined with intravenous heparin and aspirin. These lower doses of cangrelor should be balanced with the risk of in-stent thrombosis, and P2Y12 levels may be monitored to ensure adequate platelet inhibition. Future research should explore a comparison of different doses of cangrelor in patients receiving MCS. More data are needed to standardize an optimal P2Y12 PRU range in order to correlate its use to predicting short-term outcomes in an acute setting.

InpharmD Researcher Critique

This study is limited by its single-center, retrospective design, and small sample size, as well as the lack of standardized dosing of cangrelor and a protocol for monitoring P2Y12 levels.

Effect of Platelet Inhibition by Cangrelor Among Obese Patients Undergoing Coronary Stenting: Insights From CHAMPION

Design

3 prospective, randomized, double-blind, double-dummy CHAMPION trials

N= 24,893 patients

Objective

To assess whether there is a differential treatment response with respect to major adverse cardiovascular events (MACE) or bleeding among obese versus nonobese patients who were treated with cangrelor versus placebo at the time of PCI

Study Groups

Body mass index (BMI)≥30 (n= 8,979)

BMI<30 (n= 15,914) 

Inclusion Criteria

≥18 years of age, requiring percutaneous intervention for stable or acute coronary disease

Exclusion Criteria

Recent P2Y₁₂ inhibitor use, fibrinolytic, and glycoprotein IIb/IIIa inhibitor therapy

Methods

Patients from the 3 CHAMPION trials (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) who were randomized to cangrelor versus clopidogrel during the percutaneous coronary intervention were stratified by BMI. Patients were divided into 2 groups according to their BMI; obese patients (BMI≥30), and nonobese patients (BMI<30). Participants were randomly assigned to receive a cangrelor infusion (30 mcg/kg bolus, followed by a 4 mcg/kg per minute infusion for at least 2 hours, or the duration of PCI, whichever was longer) or clopidogrel. 

Duration

48 hours

Outcome Measures

Primary: cumulative incidence of a composite of death, myocardial infarction, ischemia-driven revascularization, and stent thrombosis at 48 hours

Secondary: incidence of the same composite endpoint at 30 days as well as the individual components

Baseline Characteristics

BMI>30 (n=8979)

BMI<30 (n=15 914)

Age, years

Female

White race

Weight, kg

Diagnosis at presentation

Stable angina

Abbreviations: BMI, body mass index; NSTE-ACS, non–ST-segment–elevation acute coronary syndrome; STEMI, ST-segment–elevation

Results

Endpoint

BMI≥30 (N=9151)

BMI<30 (N=16 211)

Event rate ratio (95% CI)

p-value

Death/MI/IDR/ST

Death

MI

Adverse Events

Not disclosed

Study Author Conclusions

There was a consistent benefit of cangrelor versus clopidogrel in obese and nonobese patients undergoing PCI, with respect to short-term efficacy. Also, there was no significant increase in periprocedural bleeding among obese patients undergoing PCI. Periprocedural cangrelor is a safe and effective antiplatelet option in obese patients.

InpharmD Researcher Critique

There is a consistent benefit when choosing cangrelor over clopidogrel at the time of percutaneous coronary intervention, without any excess bleeding complications, among obese patients (body mass index ≥30). However, patients with lower body mass index had a higher risk of bleeding regardless of antiplatelet strategy compared with patients with higher body mass index.

The study has limitations, including unplanned BMI analysis with exploratory p-values and no adjustments for multiple comparisons. The trials spanned an extended period, potentially limiting generalizability due to advancements in practice and technology. Randomized treatment allocation and a large sample size minimize confounding.