Dataset Information

Risk of Bleeding Among Cangrelor-Treated Patients Administered Upstream P2Y₁₂ Inhibitor Therapy: The CAMEO Registry.

ABSTRACT:

Background

Little is known about the bleeding risk associated with cangrelor use in patients with myocardial infarction (MI) who are exposed to an oral P2Y₁₂ inhibitor before coronary angiography.

Methods

Cangrelor in Acute MI: Effectiveness and Outcomes (CAMEO) is an observational registry studying platelet inhibition for patients with MI. Upstream oral P2Y₁₂ inhibition was defined as receipt of an oral P2Y₁₂ inhibitor within 24 hours before hospitalization or in-hospital before angiography. Among cangrelor-treated patients, we compared bleeding after cangrelor use through 7 days postdischarge between patients with and without upstream oral P2Y₁₂ inhibitor exposure.

Results

Among 1802 cangrelor-treated patients with MI, 385 (21.4%) received upstream oral P2Y₁₂ inhibitor treatment. Of these, 101 patients (33.8%) started cangrelor within 1 hour, 103 (34.4%) between 1 and 3 hours, and 95 (31.8%), >3 hours after in-hospital oral P2Y₁₂ inhibitor administration; the remaining received an oral P2Y₁₂ inhibitor before hospitalization. There was no statistically significant difference in rates of bleeding among cangrelor-treated patients with and without upstream oral P2Y₁₂ inhibitor exposure (6.5% vs 8.8%; adjusted odds ratio [OR], 0.62; 95% CI, 0.38-1.01). Bleeding was observed in 5.0%, 10.7%, and 3.2% of patients treated with cangrelor <1, 1 to 3, and >3 hours after the last oral PY₁₂ inhibitor dose, respectively; bleeding rates were not statistically different between groups (1-3 hours vs <1 hour: adjusted OR, 2.70; 95% CI, 0.87-8.32; >3 hours vs <1 hour: adjusted OR, 0.65; 95% CI, 0.15-2.85).

Conclusions

Bleeding risk was not observed to be significantly higher after cangrelor treatment in patients with and without upstream oral P2Y12 inhibitor exposure.

SUBMITTER: Rymer J

PROVIDER: S-EPMC11308101 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Risk of Bleeding Among Cangrelor-Treated Patients Administered Upstream P2Y<sub>12</sub> Inhibitor Therapy: The CAMEO Registry.

Rymer Jennifer J Alhanti Brooke B Kemp Steven S Bhatt Deepak L DL Kochar Ajar A Angiolillo Dominick J DJ Diaz Miguel M Garratt Kirk N KN Wimmer Neil J NJ Waksman Ron R Kirtane Ajay J AJ Ang Lawrence L Bach Richard R Barker Colin C Jenkins Ronald R Basir Mir B MB Sullivan Alex A El-Sabae Hijrah H Brothers Leo L Ohman E Magnus EM Jones W Schuyler WS Washam Jeffrey B JB Wang Tracy Y TY

Journal of the Society for Cardiovascular Angiography & Interventions 20231127 2

<h4>Background</h4>Little is known about the bleeding risk associated with cangrelor use in patients with myocardial infarction (MI) who are exposed to an oral P2Y<sub>12</sub> inhibitor before coronary angiography.<h4>Methods</h4>Cangrelor in Acute MI: Effectiveness and Outcomes (CAMEO) is an observational registry studying platelet inhibition for patients with MI. Upstream oral P2Y<sub>12</sub> inhibition was defined as receipt of an oral P2Y<sub>12</sub> inhibitor within 24 hours before hospi ...[more]

PMID: 39132213

Similar Datasets

Project description:Background In clinical trials, cangrelor has been shown to reduce percutaneous coronary intervention-related ischemic complications without increasing major bleeding. This study was performed to examine cangrelor use and transition to oral P2Y12 inhibitors in routine clinical practice. Methods and Results The CAMEO (Cangrelor in Acute Myocardial Infarction: Effectiveness and Outcomes) registry is a multicenter, retrospective observational study of platelet inhibition strategies for patients with myocardial infarction undergoing percutaneous coronary intervention. In phase 1, data were collected on consecutive patients with myocardial infarction (n=482) treated with any P2Y12 inhibitor to understand cangrelor use by hospital. In phase 2, data were collected in a 2:1 (cangrelor-: non-cangrelor-treated) ratio of patients with myocardial infarction (n=873). In phase 1, cangrelor use varied across hospitals (overall, 50.4% [range, 6.0%-100%]). Of patients receiving cangrelor in both phases (n=819), 3.3% received either the bolus or infusion only. Cangrelor was infused for a median of 121 (76-196) minutes; and 38.3% received an infusion for <2 hours. Most patients transitioned from cangrelor to ticagrelor (ticagrelor, 85.3%; clopidogrel, 9.5%; prasugrel, 5.2%). Many patients (16.4%) had a >1-hour gap between cangrelor cessation and oral P2Y12 inhibitor initiation; this was highest among those transitioned to clopidogrel (56.6% versus 34.5% prasugrel versus 10.8% ticagrelor; P<0.001). Only 27.3% were dosed with cangrelor and transitioned to an oral P2Y12 inhibitor in a fashion consistent with the pivotal trials and US Food and Drug Administration label. Conclusions This multicenter registry demonstrated interhospital variability in how cangrelor was administered and transitioned to an oral P2Y12 inhibitor. These findings highlight opportunities for optimization of cangrelor dosing, infusion duration, and transition of care from the catheterization laboratory to the ward setting.

Project description:BackgroundIndividuals aged ≥75 years are the fastest-growing population starting dialysis for end-stage kidney disease (ESKD) due to living longer with coronary artery disease. ESKD alone can increase bleeding risk, but P2Y12 inhibitor (P2Y12-I) antiplatelet medications prescribed for cardiovascular treatment can exacerbate this risk in patients with ESKD. The age-specific rates of bleeding complications in dialysis patients with ESKD on P2Y12-I remain unclear, as does how age modifies the bleeding risk from P2Y12-I use in these patients.MethodsIn a retrospective cohort study, we collected data on 40,972 patients receiving maintenance hemo- or peritoneal dialysis who were newly prescribed P2Y12-I therapy between 2011 and 2015 from the USRDS registry. We analyzed the effect of age on the time to first bleed and the interactions between age and P2Y12-I type on modifying the effects of a bleed.ResultsTwenty percent of the cohort were aged ≥75 years. There were 3096 (8%) gastrointestinal (GI) and 1298 (3%) intracranial (IC) bleeding events during a median follow-up of 1 year. Annual incidence rates for IC bleeds were 2% in those aged <55 years and 3% in those aged ≥75 years. Rates for GI bleeds were 4% in those aged <55 years and 9% in those aged ≥75 years. On clopidogrel, prasugrel, and ticagrelor, for every decade increase in age of the cohort members, the risk of IC bleed increased by 9%, 55%, and 59%, and the risk of GI bleed increased by 21%, 28%, and 39%, respectively. At age ≥75 years, prasugrel was associated with a greater risk of IC bleed than clopidogrel. At age ≥60 years, ticagrelor was associated with a greater risk of GI bleed than clopidogrel.ConclusionsMore potent P2Y12-Is (prasugrel and ticagrelor) were associated with a disproportionately higher risk of IC bleed with increasing age compared with that of clopidogrel-prasugrel was much worse than clopidogrel at age ≥75 years. All three drugs were associated with only modest increase in the risk of GI bleed with every decade increase in age-ticagrelor was much worse than clopidogrel at ≥60 years of age. These results highlight the need for head-to-head clinical trials for the use of P2Y12-Is in patients with ESKD to determine age cutoffs where the risk of bleeding outweighs the benefits of thrombosis prevention.

Project description:Selatogrel is a potent and reversible P2Y12 receptor antagonist developed for subcutaneous self-administration by patients with suspected acute myocardial infarction. After single-dose emergency treatment with selatogrel, patients are switched to long-term treatment with oral P2Y12 receptor antagonists. Selatogrel shows rapid onset and offset of inhibition of platelet aggregation (IPA) to overcome the critical initial time after acute myocardial infarction. Long-term benefit is provided by oral P2Y12 receptor antagonists such as clopidogrel, prasugrel, and ticagrelor. A population pharmacokinetic (PK)/pharmacodynamic (PD) model based on data from 545 subjects in 4 phase I and 2 phase II studies well described the effect of selatogrel on IPA alone and in combination with clopidogrel, prasugrel, and ticagrelor. The PK of selatogrel were described by a three-compartment model. The PD model included a receptor-pool compartment to which all drugs can bind concurrently, reversibly or irreversibly, depending on their mode of action. Furthermore, ticagrelor and its active metabolite can bind to the selatogrel-receptor complex allosterically, releasing selatogrel from the binding site. The model provided a framework for predicting the effect on IPA of selatogrel followed by reversibly and irreversibly binding oral P2Y12 receptor antagonists for sustained effects. Determining the timepoint for switching from emergency to maintenance treatment is critical to achieve sufficient IPA at all times. Simulations based on the interaction model showed that loading doses of clopidogrel and prasugrel administered 15 h and 4.5 h after selatogrel, respectively, provide sustained IPA with clinically negligible drug interaction. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Selatogrel is a potent reversible P2Y12 receptor antagonist developed for subcutaneous self-administration by patients in case of suspected acute myocardial infarction. Transition to oral P2Y12 receptor antagonists without drug interaction and sufficient inhibition of platelet aggregation must be assured at all times. WHAT QUESTION DID THIS STUDY ADDRESS? The pharmacokinetic/pharmacodynamic model semimechanistically describes the effect of selatogrel on platelet inhibition alone and in combination with the oral P2Y12 receptor antagonists clopidogrel, prasugrel, and ticagrelor. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Model-based simulations showed that loading doses of clopidogrel and prasugrel can be administered from 15 h and 4.5 h after selatogrel, respectively. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? These results support guiding the clinical transition from selatogrel emergency treatment to oral maintenance therapy in a safe and efficacious way.

Dataset Information

Risk of Bleeding Among Cangrelor-Treated Patients Administered Upstream P2Y₁₂ Inhibitor Therapy: The CAMEO Registry.

Background

Methods

Results

Conclusions

Publications

Risk of Bleeding Among Cangrelor-Treated Patients Administered Upstream P2Y<sub>12</sub> Inhibitor Therapy: The CAMEO Registry.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Risk of Bleeding Among Cangrelor-Treated Patients Administered Upstream P2Y12 Inhibitor Therapy: The CAMEO Registry.

Background

Methods

Results

Conclusions

Publications

Risk of Bleeding Among Cangrelor-Treated Patients Administered Upstream P2Y<sub>12</sub> Inhibitor Therapy: The CAMEO Registry.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Risk of Bleeding Among Cangrelor-Treated Patients Administered Upstream P2Y₁₂ Inhibitor Therapy: The CAMEO Registry.