What data are available which evaluate the use of cangrelor in PCI patients with STEMI with cardiogenic shock?

Comment by InpharmD Researcher

The available data suggests that cangrelor is a viable option in the setting of cardiogenic shock to overcome practical challenges in this patient population. It is associated with low incidence of stent thrombosis and a favorable safety profile, with primarily mild to moderate bleeding events. Yet data for specific patient populations, such as use in ST-segment elevation myocardial infarction (STEMI), is lacking, and further high-quality trials are needed to optimize its use in high-risk populations.

Background

A 2021 article discusses the current data for the use of cangrelor as an intravenous (IV) P2Y12 receptor inhibitor. In general, the real-world clinical use of cangrelor is primarily observed in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Lesser data exists for complicated patients, such as those with ST-segment-elevation myocardial infarction (STEMI) presenting with cardiogenic shock. However, one descriptive experience from a single center found cangrelor is associated with lower bleeding events in STEMI patients with cardiogenic shock (see Table 2). In another study by the same author, practice patterns, indications for use, and clinical events in cangrelor recipients were examined by in-hospital records at a large tertiary care institution. Of the 100 patients included, 16% presented with cardiogenic shock, and 49 patients underwent coronary angiography with the intent of PCI for STEMI. One critically ill patient in shock experienced bleeding requiring interruption of oral antiplatelet therapy, but overall, cangrelor was well tolerated. Based on this data, it is evident that physicians are using cangrelor in high-risk patients, such as those complicated by cardiogenic shock, undergoing PCI for STEMI. [1]

The Cangrelor OHCA (Out-of-Hospital Cardiac Arrest) and the DAPT-SHOCK-AMI (Dual Antiplatelet Therapy for Shock Patients With Acute Myocardial Infarction) randomized controlled studies will assess the efficacy of cangrelor compared with ticagrelor in high-risk subgroups, such as patients with cardiogenic shock undergoing PCI. The Cangrelor OHCA trial was completed in November 2021, but results have yet to be published or posted on ClinicalTrials.gov. The DAPT-SHOCK-AMI trial is currently recruiting and is estimated to be completed in May 2024. [1], [2], [3]

A 2024 systematic review and single-arm meta-analysis assessed the safety and efficacy of cangrelor as an antiplatelet therapy in acute myocardial infarction complicated by cardiogenic shock (AMI-CS). A total of 10 studies (N= 678) were analyzed. Cangrelor dosing varied across studies; 57% of patients received the CHAMPION maintenance dose (4 mcg/kg/min), 37% received the BRIDGE trial dose (0.75 mcg/kg/min), and the remaining 6% received lower dosages. In most cases, cangrelor was administered as part of dual antiplatelet therapy (DAPT) alongside aspirin, while a minority of patients received cangrelor as a single agent. Temporary mechanical circulatory support (tMCS), including intra-aortic balloon pumps, venoarterial extracorporeal membrane oxygenation (VA-ECMO), and percutaneous ventricular assist devices, was used in 26% of cases. The results for cangrelor use included calculated pooled rates of major bleeding (17%, 95% CI 11–23%), stent thrombosis (1%, 95% CI 0.3–2.3%), and any thrombotic event (3%, 95% CI 0.4–7%), with an overall pooled hospital survival rate of 66% (95% CI 59–73%). Hemorrhagic complications were more common than thrombotic events, especially in patients receiving tMCS. Studies reporting the highest bleeding rates (49–77%) and thrombotic complications (13–40%) exclusively included patients with extracorporeal support. The findings suggest that while cangrelor offers rapid-onset, organ-independent platelet inhibition in critically ill AMI-CS patients, the optimal dosing strategy remains uncertain. [4]

References:

[1] De Luca L, Steg PG, Bhatt DL, Capodanno D, Angiolillo DJ. Cangrelor: Clinical Data, Contemporary Use, and Future Perspectives. J Am Heart Assoc. 2021;10(13):e022125. doi:10.1161/JAHA.121.022125
[2] ClinicalTrials.gov. Cangrelor in Comatose Survivors of OHCS Undergoing Primary PCI (Cangrelor OHCA). Updated December 3, 2021. Accessed February 28, 2023. https://clinicaltrials.gov/ct2/show/results/NCT04005729
[3] ClinicalTrials.gov. Dual Antiplatelet Therapy For Shock Patients With Acute Myocardial Infarction (DAPT-SHOCK-AMI). Updated October 5, 2022. Accessed February 28, 2023. https://clinicaltrials.gov/ct2/show/results/NCT03551964
[4] D'Andria Ursoleo J, Baldetti L, Pieri M, et al. Anti-Platelet Therapy with Cangrelor in Cardiogenic Shock Patients: A Systematic Review and Single-Arm Meta-Analysis. Medicina (Kaunas). 2024;60(12):2092. Published 2024 Dec 21. doi:10.3390/medicina60122092
Literature Review

A search of the published medical literature revealed 6 studies investigating the researchable question:

What data are available which evaluate the use of cangrelor in PCI patients with STEMI with cardiogenic shock?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→


Please see Tables 1-6 for your response.

 

Cangrelor in cardiogenic shock and after cardiopulmonary resuscitation: A global, multicenter, matched pair analysis with oral P2Y12 inhibition from the IABP-SHOCK II trial

Design

Global, multicenter, observational study

N= 136

Objective

To evaluate the clinical course of patients in cardiogenic shock (CS) undergoing percutaneous coronary intervention (PCI) treated with cangrelor or oral P2Y12-receptor inhibitors

Study Groups

Cangrelor-treated patients (n= 88)

Oral P2Y12 inhibitor-treated patients (n= 88)

Inclusion Criteria

Acute coronary syndrome (ACS) complicated by CS, undergoing PCI, and treated with cangrelor

Exclusion Criteria

Age ≥ 90 years, prolonged pre-procedural resuscitation 

Methods

Cangrelor was administered during PCI via bolus of 30 mcg/kg followed by an infusion of 4 mcg/kg/min (or 0.75 mcg/kg/min without a bolus in case of bridging) for at least 2 hours. Patients were given oral P2Y12 receptor inhibitors (clopidogrel, prasugrel, or ticagrelor). Patients were matched to a control cohort from a large randomized Intra-aortic Balloon Pump in Cardiogenic Shock (IABP-SHOCK) II trial that was treated with oral P2Y12 receptor inhibitors. Matching was based on age, sex, cardiac arrest, type of myocardial infarction, culprit lesion localization, glycoprotein IIb/IIIa inhibitor (GPI) use, and oral antiplatelet therapy (clopidogrel vs. prasugrel/ticagrelor either as initial therapy or after switching from cangrelor to oral P2Y12 inhibition). After 1:1 matching, 88 pairs were identified and included in the analysis. 

Duration

November 2015 to August 2017

Outcome Measures

30-day mortality, 12-month mortality, in-hospital moderate and severe bleeding (according to Global Use of Strategies to Open Occluded Coronary Arteries [GUSTO] criteria), definite acute stent thrombosis, thrombolysis in myocardial infarction (TIMI) flow improvement

Baseline Characteristics

  

IABP-SHOCK II matched cohort (n= 88)

Multi-center cangrelor-treated patients (n= 88)

 p-value

Age, years

 70.5  68.5 NS

Female

28.4% 28.4% NS 

NSTE-ACS

 29.5%  29.5% NS 

STEMI

 70.5% 70.5% NS 

Concomitant medications

Glycoprotein IIb/IIIa inhibitor

Aspirin

P2Y12-receptor blocker

Ticagrelor/prasugrel

Clopidogrel

Cangrelor full dose

Cangrelor bridging dose

Unfractionated heparin

Bivalirudin

 

12/88 (13.6%)

81/88 (92.0%)

-

60/88 (56.8%)

38/88 (43.2%)

-

-

74/88 (84.1%)

15/88 (17.0%)

 

12/88 (13.6%)

40/41 (97.6%)

- 

60/88 (56.8%)

38/88 (43.2%)

79/88 (89.9%)

15/88 (17.0%)

84/88 (95.5%)

6/88 (6.8%)

 NS 

PCI

85/88 (96.6%)

77/86 (89.5%)

 NS 

Type of stent 

DES 

BMS

 

44/79 (55.7 %)

36/79 (45.6 %)

 

71/77 (92.2 %)

 

3/77 (3.9 %)

 

< 0.001

< 0.001

BMS, bare metal stent; DES, drug-eluting stent; NS, not significant; NSTE-ACS, non-ST-segment elevation acute coronary syndrome; STEMI, ST-segment elevation myocardial infarction.

Results

Endpoint

IABP-SHOCK II matched cohort (n= 88)

Multi-center cangrelor-treated patients (n= 88)

p-value

30-day mortality

 32 (36.4%) 26 (29.5%) 0.34

12-month mortality

 41 (47.1%) 30 (34.1%) 0.079

In-hospital moderate/severe bleeding

 17 (19.3%) 19 (21.6%) 0.71

Definite acute stent thrombosis

 2 (2.3%) 2 (2.3%) 1.00

TIMI flow improvement

At least 1 grade

At least 2 grades

 

69/85 (81.2%)

57/85 (67.1%)

 

78/84 (92.9%)

68/84 (81.0%)

 

0.02

0.04

No differences were reported for other in-hospital complications, including renal replacement therapy, sepsis, and 12-month stroke.

Adverse Events

N/A

Study Author Conclusions

Cangrelor treatment was associated with similar bleeding risk and significantly better TIMI flow improvement compared with oral P2Y12 inhibitors in CS patients undergoing PCI. The use of cangrelor in CS offers a potentially safe and effective antiplatelet option and should be evaluated in randomized trials.

InpharmD Researcher Critique

Due to the non-randomized study design and potential for bias, the results of this study are limited to hypothesis-generating for future investigations. 



References:

Droppa M, Vaduganathan M, Venkateswaran RV, et al. Cangrelor in cardiogenic shock and after cardiopulmonary resuscitation: A global, multicenter, matched pair analysis with oral P2Y12 inhibition from the IABP-SHOCK II trial. Resuscitation. 2019;137:205-212. doi:10.1016/j.resuscitation.2019.02.008

 

Cangrelor Use in Cardiogenic Shock: A Single-Center Real-World Experience

Design

Descriptive, single-center retrospective chart review

N= 38

Objective

 To report patterns of use and periprocedural outcomes in patients in clinical shock who received cangrelor

Study Groups

 Cangrelor-receiving patients (N= 38)

Inclusion Criteria

 Patients presenting with clinical shock, treated with cangrelor

Exclusion Criteria

 N/A

Methods

The presence of clinical shock was defined as requiring vasopressors, inotropes, or mechanical circulatory support immediately before or during cangrelor administration. Dosing of cangrelor varied per the attending physician.

Duration

 November 2015 to April 2017

Outcome Measures

 Stent thrombosis, bleeding event, deaths

Baseline Characteristics

  

Cangrelor-receiving patients (N= 38)

Age (range), years

 65.5 (55.5 to 75.5)

Male

63.2%

Medical history

Diabetes

Hypertension

Prior stroke or transient ischemic attack

Prior myocardial infarction

Prior coronary artery bypass graft (CABG)

 

34.2%

60.5%

7.9%

31.6%

10.5%

Type of shock

Cardiogenic shock

Mixed/distributive shock

 

37 (97.4%)

1 (2.6%)

Shock presentation

Left ventricular ejection fraction

Cardiac arrest

Ventricular tachycardia/fibrillation

Pulseless electrical activity/asystole

 

43%

42.1%

31.6%

10.5%
Received concomitant glycoprotein IIb/IIIa inhibitor

0

Results

Endpoint

Cangrelor-receiving patients (N= 38)

Stent thrombosis at 48 hours

0

Bleeding event

Required ≥ 1 blood transfusion

Access-site related

Gastrointestinal

Genitourinary

Multiple sites

11 (29%)

5

2

2

2

4

Deaths

5

Adverse Events

All bleeding events were classified as mild or moderate

Study Author Conclusions

 The initial data suggest that cangrelor may offer a potent, parenteral strategy in patients in cardiogenic shock and seems to be well-tolerated with low rates of clinically significant ischemic or bleeding events.

InpharmD Researcher Critique

 As a descriptive report of a study, there is limited information available. No formal statistical analysis was performed to determine the magnitude of the benefit. Patients who suffered from ST-segment elevation myocardial infarction (STEMI) were not reported.



References:

Vaduganathan M, Qamar A, Badreldin HA, Faxon DP, Bhatt DL. Cangrelor Use in Cardiogenic Shock: A Single-Center Real-World Experience. JACC Cardiovasc Interv. 2017 Aug 28;10(16):1712-1714. doi: 10.1016/j.jcin.2017.07.009. PMID: 28838482.

 

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

All patients (N= 17)

Inclusion Criteria

At least 18 years of age, underwent PCI on admission complicated by cardiogenic shock requiring MCS, received cangrelor in immediate post-PCI period

Exclusion Criteria

Not explicitly stated

Methods

Patients were identified through an internal database in which data were collected using the electronic health record. Types of MCS included venoarterial extracorporeal membrane oxygenation (VA ECMO) and all Impella device platforms. 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 with the VerifyNow Assay, with a range of 50 to 194 platelet reactivity units (PRUs) classified as therapeutic. 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. Dosing selection was determined based on the patient's bleeding risk.

Duration

Received cangrelor while on MCS: June 2017 to September 2019

Outcome Measures

Proportion of patients who experienced bleeding events during cangrelor overlap while receiving MCS

Baseline Characteristics

  

All patients (N= 17)

  

Age, years

 65  

Male

 82%  

Weight

Actual body weight, kg

Ideal body weight, kg

 

89

66

  

History of arterial or venous clot

 5%  

History of bleed

 47%  

Lab values

Hemoglobin, g/dL

Hematocrit, g/dL

Platelets, 103/μL

aPTT, s

 

12

38

245

33

  

Cardiogenic shock

100%

  

Cangrelor bolus

Bolus dose, mcg/kg

6%

30

  

Initial dose, mcg/kg/min (range)

0.75 mcg/kg/min, actual body weight

0.75 mcg/kg/min, nonactual body weight

4 mcg/kg/min

0.5 mcg/kg/min

0.75 (0.5 to 4)

35%

29%

24%

12%

  

Change in cangrelor dosing

Decreased based off low P2Y12

Increased based off high P2Y12

 

12%

6%

  

Values were given as the median or %.

Results

Endpoint

All patients (N= 17)

 

Bleeding while on cangrelor

 10 (59%)  

BARC classification of bleed

Minor bleed

Major bleed

 

3/10 (30%)

7/10 (70%)

  

Cangrelor dose at time of bleed, mcg/kg/min (range)

Dose based on actual body weight

0.75 (0.5 to 4)

8/10 (80%)

  

Concomitant anticoagulation

10/10 (100%)

  

Thrombus while on cangrelor

6 (35%)

  

Cangrelor dose at time of thrombus, mcg/kg/min (range)

0.75 (0.5 to 4)

  

BARC, Bleeding Academic Research Consortium

Adverse Events

See results 

Study Author Conclusions

This case series suggests that cangrelor doses less than 0.75 µg/kg/min may be beneficial. Larger studies should evaluate alternative dosing regimens.

InpharmD Researcher Critique

This study is largely limited by its single-center, retrospective design, and a small cohort of patients. Additionally, the dosing of cangrelor was not standardized but was left to the discretion of the treatment team, potentially limiting the generalizability of the results.



References:

Katz A, Lewis TC, Arnouk S, et al. Clinical Use of Cangrelor After Percutaneous Coronary Intervention in Patients Requiring Mechanical Circulatory Support. Ann Pharmacother. 2021;55(10):1215-1222. doi:10.1177/1060028021994621

 

Antithrombotic Therapy with Cangrelor and Bivalirudin in Venoarterial Extracorporeal Membrane Oxygenation Patients Undergoing Percutaneous Coronary Intervention: A Single-Center Experience

Design

Single-center, retrospective, cohort study 

N= 14 

Objective

To describe the preliminary single-center experience with an antithrombotic therapy comprising a single parenteral anticoagulant (bivalirudin) and a single parenteral anti-platelet agent (cangrelor) for patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) during Venoarterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiogenic shock (CS)/cardiac arrest (CA) 

Study Groups

All participants (N= 14)

Inclusion Criteria

Patients receiving PCI and VA-ECMO for ACS-related CA/CS and treated with pre-specified antithrombotic regimen of cangrelor and bivalirudin

Exclusion Criteria

 Not specified 

Methods

Eligible patients received bivalirudin started at a low dose of 0.01–0.07mg/kg/h and subsequently adjusted by increments of ± 0.02-0.04mg/kg/h titrated to achieve an activated thromboplastin time (aPTT) of 50-70 s. Low aPTT targets of 45-55 s were allowed in case of bleeding complications or based on clinical judgment. Cangrelor dose was titrated by ± 0.125 mcg/kg/min dose adjustments and up to a maximum of 0.75 mcg/kg/min maintenance dose. Adjustments were made to progressively reach the 0.75 mcg/kg/min target dose based on clinical stability and absence of bleeding events.

Duration

From November 2019 to December 2021

Outcome Measures

Efficacy: occurrence of thrombotic events 

Safety: major bleeding occurrence

Baseline Characteristics

  

All participants (N= 14)

Age, years

 58

Female

7%

Comorbidities 

Peripheral artery disease 

Coronary artery disease 

Refractory cardiac arrest 

STEMI

Survival after Veno-Arterial ECMO score 

 

21%

29%

64%

93%

-6

Coronary angiography

Single-vessel disease

Three-vessel disease

Left main disease

Stent thrombosis

PCI with stent implantation

 

29%

29%

29%

36%

86%

Stents implanted 

Number (interquartile range [IQR])

Drug-eluting stents

 

2 (1 to 3)

92%

Mechanical circulatory support

Intra-aortic balloon pump

Impella

VA-ECMO

 

93%

79%

100%

Cangrelor doses (IQR)

Initial dose, mcg/kg/min

Max dose, mcg/kg/min

Min dose, mcg/kg/min

Cangrelor discontinuation

Cangrelor duration, days (IQR)

Cangrelor bolus 

 

0.125 (0.119 to 0.142)

0.143 (0.125 to 0.256)

0.125 (0.119 to 0.135)

36%

5 (4 to 10)

21%

Antithrombotic drugs 

GpIIb-IIIa inhibitors bolus

Switch to ticargrelor 

Switch to prasugrel 

Switch to clopidogrel 

 

29%

43%

0

14%

Results

Endpoint

 All participants (N= 14)

Any thrombotic event

Myocardial infarction 

Academic Research Consortium probable or definite stent thrombosis

Deep vein thrombosis/pulmonary embolism 

Ischemic stroke

 

0

0

1 (7%)

0

Any Bleeding Academic Research Consortium (BARC) 3b-5 bleeding

BARC 3a

Bleedings from nasogastric tube treated conservatively

Orotracheal bleeding requiring mechanical hemostasis

Oozing from vascular access

BARC 3b

Orotracheal severe bleeding and right hemopneumothorax

Iatrogenic vascular lesion requiring transfemoral support exchange and diagnostic angiography

BARC 5b

Fatal intracranial hemorrhage

7 (50%)

4 (29%)

2

1

1

2 (14%)

1

1

1 (7%)

1

In-hospital outcomes 

All-cause death

Cardiac death (overall patients; dead patients)

Any stroke

Major surgery

Vascular surgery

Sepsis

Acute liver failure

 

7 (50%)

6/14 (43%); 6/7 (85%)

2 (14%)

1 (7%)

3 (21%)

7 (50%)

10 (71%)

Adverse Events

See results 

Study Author Conclusions

A low-maintenance dose of cangrelor, associated with standard-intensity anticoagulation with bivalirudin, was a feasible antithrombotic strategy in patients undergoing PCI during VA-ECMO support for ACS-related CS/CA. Bleeding events rates outweighed thrombotic events rates in this critically-ill population, although the observed rates were the lowest among currently available studies.

InpharmD Researcher Critique

The study is limited to its single-center experience and limited patients with merely descriptive results available. Additionally, dosing regimens of cangrelor may not readily apply to STEMI patients not receiving VA-ECMO. 



References:

Baldetti L, Nardelli P, Ajello S, et al. Anti-thrombotic Therapy with Cangrelor and Bivalirudin in Venoarterial Extracorporeal Membrane Oxygenation Patients Undergoing Percutaneous Coronary Intervention: A Single-Center Experience [published online ahead of print, 2022 Dec 12]. ASAIO J. 2022;10.1097/MAT.0000000000001871. doi:10.1097/MAT.0000000000001871

 

Impact of Intravenous P2Y12-Receptor Inhibition with Cangrelor in Patients Presenting with Acute Coronary Syndrome and Cardiogenic Shock – a Case Series

Design

Case series 

N= 12

Objective

To report a single-center experience regarding the use of intravenous (IV) P2Y12-receptor inhibitor cangrelor in patients with cardiogenic shock (CS) treated with percutaneous coronary intervention (PCI)

Study Groups

All participants (N= 12)

Inclusion Criteria

Patients with CS treated with PCI and IV cangrelor

Exclusion Criteria

Not specified 

Methods

Eligible patients received peri-interventional administration of cangrelor for up to 2 hours after the procedure. Patients were then loaded with ticagrelor at the time of the procedure, prasugrel 30 minutes before the end of the cangrelor infusion, or clopidogrel at the end of the cangrelor infusion. Most patients received platelet function monitoring via adenosine diphosphate (ADP)-stimulated multiple electrode aggregometry (MEA) before and after PCI, and immediately and 2 hours after stopping the cangrelor infusion. The current report explicitly described three cases, with one patient diagnosed with ST-elevation myocardial infarction (STEMI). 

Duration

 N/A

Outcome Measures

 Platelet function and patient outcomes 

Baseline Characteristics

  

All participants (N= 12)

Age, years

 65.2

Female

16.7% 

Diagnosis 

NSTEMI

STEMI

 

25%

75%

3-vessel disease 

 91.7%

Left ventricular ejection fraction

 30.8%

P2Y12-receptor blocker after cangrelor

Ticagrelor 

Prasugrel 

Clopidogrel 

 

58.3%

33.3%

8.3%

Cardiopulmonary resuscitation 

 75%

Results

Endpoint

 All participants (N= 12)

In-hospital mortality 

 3 (25%)

Patient with STEMI

A 46-year-old man fell from a scaffold during construction work due to a cardiac arrest and received resuscitation and repeated defibrillation. Electrocardiogram confirmed STEMI, and initial computed tomography scan of the brain showed intracerebral contusion-bleeding and asmall subdural hematoma. Coronary angiography revealed severe 3-vessel disease with high-grade stenosis of the proximal left anterior descending (LAD) and right coronary artery (RCA). In the presence of CS, patients received PCI with implantation of 6 drug-eluting stents (DES) in the LAD and RCA. Bivalirudin was utilized as peri-interventional anticoagulation along with aspirin and cangrelor (peri-interventionally bolus of 30 mcg/kg, followed by continuous infusion of 4 mcg/kg/min for 2.5 hours). Head-CT during cangrelor therapy showed no progression of the intracranial hemorrhage, allowing a switch from cangrelor to ticagrelor without further bleeding complications. The patient recovered well without any severe neurological deficit and was transferred to a rehabilitation facility after 26 days. 

Platelet reactivity decreased from 65.9 ± 41.0 U before PCI to 15.8 ± 10.8) U after PCI, 13.4 ± 7.7 U at the end of cangrelor infusion, and 33.8 ± 19.9 U 2 hours after stopping the cangrelor infusion. There was no non-responder with cangrelor (MEA < 46 U).

Adverse Events

 See results 

Study Author Conclusions

Patients with CS are often intubated and ventilated, making oral medication administration difficult, especially in the emergency setting. Another problem is impaired absorption of oral antiplatelet drugs. Due to low cardiac output, impaired blood flow to gastrointestinal mucosa may cause slow absorption. Slow metabolism of drugs requiring transformation into active metabolites is another potential challenge. These problems can be further exacerbated by therapeutic hypothermia, which is often used after cardiac arrest. Delayed onset of platelet inhibition due to the above issues is associated with thrombotic complications after PCI and adverse patient outcomes. 

Due to its favorable PK/PD profile, cangrelor overcomes problems with reduced absorption and effects of oral P2Y12-receptor inhibitors and should be considered for peri-procedural treatment of patients with CS. 

InpharmD Researcher Critique

While presented data reflect the promising role of cangrelor in the setting of acute coronary syndrome with cardiogenic shock, included patients are not exclusive to STEMI. Further prospective trials are needed to confirm the findings from the case series. 



References:

Droppa M, Borst O, Rath D, et al. Impact of Intravenous P2Y12-Receptor Inhibition with Cangrelor in Patients Presenting with Acute Coronary Syndrome and Cardiogenic Shock - a Case Series. Cell Physiol Biochem. 2017;42(4):1336-1341. doi:10.1159/000478962

The Use of Cangrelor in Cardiogenic Shock: Insights from the CAMEO Registry
Design

Multicenter observational registry study

N= 2352
Objective To examine the infusion duration of cangrelor in patients with cardiogenic shock (CS), the patterns of transition from cangrelor to an oral P2Y12 inhibitor, and the ischemic and bleeding outcomes of patients with CS treated with cangrelor
Study Groups

Cangrelor-treated patients with CS (n= 249)
Inclusion Criteria

Patients ≥18 years of age; underwent coronary angiography for STEMI or NSTEMI; received any P2Y12 inhibitor during the first 48 hours after hospitalization for MI
Exclusion Criteria

Patients with transition times less than -3 hours were excluded from the time to transition subanalysis
Methods

Data were collected from 10 U.S. centers capable of PCI and coronary artery bypass grafting. Patients were treated with cangrelor and transitioned to oral P2Y12 inhibitors. Infusion durations and transition times were analyzed, and bleeding and MACE events were recorded.
Duration

The CAMEO registry began enrolling patients in October 2019 and is ongoing
Outcome Measures

Infusion duration of cangrelor, transition patterns to oral P2Y12 inhibitors, ischemic and bleeding outcomes
Baseline Characteristics Characteristic Cardiogenic Shock (n= 249) All Cangrelor-Treated Patients (n= 2352)
Age, median (25th,75th) 66.0 (57.0, 76.0) 64.0 (55.0, 73.0)
Female 31.7% 29.5%
Diabetes 35.3% 34.0%
Prior HF 20.5% 10.0%
Chronic lung disease 12.9% 8.3%
MCS used 59.5% 12.0%
Results Outcome Percentage
Bleeding 24.1%
MACE 41.8%

Infusion duration - Short [0.1 to 3.9 hrs]

Bleeding

MACE

 

15.1%

37.3%

  

Infusion duration - Long [4.0 to 475.4 hrs]

Bleeding

MACE

 

33.3%

46.3%

  
Adverse Events

Among cangrelor-treated patients with CS, 24.1% had a bleeding event and 41.8% had a MACE event. Longer cangrelor infusion duration was associated with increased risk of bleeding
Study Author Conclusions

The median duration of cangrelor infusion was longer for patients presenting with CS. Use of MCS was associated with longer cangrelor infusion durations in patients with CS. Further work is needed to understand the pharmacodynamics of antiplatelet agents in patients with CS.
Critique

The study provides valuable insights into the use of cangrelor in patients with CS, highlighting the association between longer infusion durations and increased bleeding risk. However, the observational nature and lack of adjudication of clinical events may limit the ability to draw causal conclusions. Additionally, the study's reliance on site-reported data for CS diagnosis could introduce variability in patient classification.

 

References:

Rymer J, Pichan C, Page C, et al. The Use of Cangrelor in Cardiogenic Shock: Insights from the CAMEO Registry. J Card Fail. 2024;30(10):1233-1240. doi:10.1016/j.cardfail.2024.08.003