Clopidogrel-Mediated P2Y Inhibition According to Renal Function in Patients With Diabetes Mellitus and CAD.

This prospective ex vivo and in vitro pharmacodynamic (PD)/pharmacokinetic investigation was conducted in patients with diabetes mellitus with (n = 31) and without chronic kidney disease (n = 30). PD assessments included platelet reactivity index, maximum platelet aggregation, and P2Y reaction units. Ex vivo pharmacokinetic assessments included plasma levels of clopidogrel and its active metabolite.

P2Y Inhibition in Patients Requiring Oral Anticoagulation After Percutaneous Coronary Intervention: The SWAP-AC-2 Study.

Background: Among patients treated with a novel oral anticoagulant (NOAC) undergoing percutaneous coronary intervention (PCI), combination therapy with clopidogrel (ie, known as dual antithrombotic therapy [DAT]) is the treatment of choice. However, there are concerns for individuals with impaired response to clopidogrel.

Objectives: The authors sought to assess the pharmacodynamic (PD) effects of clopidogrel vs low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score.

Switching From Cangrelor to Prasugrel in Patients Undergoing Percutaneous Coronary Intervention: The Switching Antiplatelet-6 (SWAP-6) Study.

Background: A drug-drug interaction (DDI) may occur when transitioning from intravenous P2Y inhibition with cangrelor to oral P2Y inhibition with prasugrel. However, this has never been tested in patients undergoing percutaneous coronary intervention (PCI).

Objectives: This study sought to rule out a DDI when cangrelor and prasugrel are concomitantly administered in PCI patients.

Switching from Dual Antiplatelet Therapy with Aspirin Plus a P2Y12 Inhibitor to Dual Pathway Inhibition with Aspirin Plus Vascular-Dose Rivaroxaban: The Switching Anti-Platelet and Anti-Coagulant Therapy (SWAP-AC) Study.

Background:  To date, there are no data on switching to dual pathway inhibition (DPI) patients who have completed a guideline-recommended dual antiplatelet therapy (DAPT) regimen.

Objectives:  To assess the feasibility of switching from DAPT to DPI and to compare the pharmacodynamic (PD) profiles of these treatments.

Methods:  This was a prospective, randomized, PD study conducted in 90 patients with chronic coronary syndrome (CCS) on DAPT with aspirin (81 mg/qd) plus a P2Y inhibitor (clopidogrel [75 mg/qd;  = 30], ticagrelor [90 mg/bid;  = 30], or prasugrel [10 mg/qd;  = 30]).

Impact of evolocumab on the pharmacodynamic profiles of clopidogrel in patients with atherosclerotic cardiovascular disease: a randomised, double-blind, placebo-controlled study.

Background: The impact of intense low-density lipoprotein cholesterol (LDL-C) reduction using a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor on profiles of platelet reactivity has yet to be explored.

Aims: Our aim was to investigate the effects of the PCSK9 inhibitor, evolocumab, on platelet reactivity in patients with atherosclerotic cardiovascular disease (ASCVD) on clopidogrel treatment.

Methods: This was a prospective, randomised, double-blind, placebo-controlled pharmacodynamic study in patients with ASCVD on clopidogrel treatment and with LDL-C levels ≥70 mg/dL despite a maximally tolerated statin dose.

Cangrelor in Patients With Coronary Artery Disease Pretreated With Ticagrelor: The Switching Antiplatelet (SWAP)-5 Study.

Background: There are no studies specifically designed to rule out a drug-drug interaction (DDI) when cangrelor is used among patients who have been pretreated with ticagrelor.

Objectives: This study sought to rule out a DDI among cangrelor-treated patients who have been pretreated with ticagrelor.

Methods: In this prospective, randomized, double-blind, placebo-controlled, crossover, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (N = 20) were pretreated with a 180-mg ticagrelor loading dose and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours).

Impact of diabetes mellitus on the pharmacodynamic effects of prasugrel and ticagrelor after switching from clopidogrel in patients with coronary artery disease.

Switching P2Y inhibitors is common in clinical practice. However, data on the pharmacodynamic (PD) effects of switching in clinical settings characterized by high platelet reactivity, such as diabetes mellitus (DM), are limited. This is a post-hoc analysis from a prospective, randomized, open-label study conducted in coronary artery disease patients comparing the PD effects of loading dose (LD) and maintenance dose regimens of prasugrel vs ticagrelor according to DM status.

Platelet P2Y12 inhibiting therapy in adjunct to vascular dose of rivaroxaban or aspirin: a pharmacodynamic study of dual pathway inhibition vs. dual antiplatelet therapy.

Aims: Dual pathway inhibition (DPI) by adding a vascular dose of rivaroxaban to a single antiplatelet agent has emerged as a promising antithrombotic strategy. However, in most studies the antiplatelet agent of choice used in adjunct to a vascular dose of rivaroxaban was aspirin, and data on a P2Y12 inhibitor and how this DPI regimen compares with standard dual antiplatelet therapy (DAPT) are limited.

Methods And Results: This investigation was a substudy analysis conducted in selected cohorts of patients with stable atherosclerotic disease enrolled from a larger prospective, open-label, parallel-group pharmacodynamic (PD) study.

Pharmacodynamic Profiles of Dual-Pathway Inhibition with or without Clopidogrel versus Dual Antiplatelet Therapy in Patients with Atherosclerotic Disease.

Aim:  Inhibition of thrombin-mediated signaling processes using a vascular dose of rivaroxaban in adjunct to antiplatelet therapy, known as dual-pathway inhibition (DPI), reduces atherothrombotic events in patients with stable atherosclerotic disease. However, there are limited data on the pharmacodynamic (PD) effects of this strategy and how it compares to standard dual antiplatelet therapy (DAPT).

Methods And Results:  This investigation was conducted in selected cohorts of patients ( = 40) with stable atherosclerotic disease-enrolled within a larger prospective, open-label, parallel-group PD study-who were treated with either aspirin plus clopidogrel (DAPT), aspirin plus rivaroxaban 2.

Impact of chronic kidney disease on the pharmacodynamic and pharmacokinetic effects of ticagrelor in patients with diabetes mellitus and coronary artery disease.

Aims: Patients with diabetes mellitus (DM) and chronic kidney disease (CKD) are at increased risk of atherothrombotic events. Ticagrelor reduces ischaemic events compared to clopidogrel, with the greatest risk reduction in patients with both DM and CKD. How CKD status affects the pharmacodynamic (PD) and pharmacokinetic (PK) profiles of different ticagrelor maintenance dose regimens in patients with DM is unknown.

Prasugrel Versus Ticagrelor in Patients With CYP2C19 Loss-of-Function Genotypes: Results of a Randomized Pharmacodynamic Study in a Feasibility Investigation of Rapid Genetic Testing.

The feasibility of rapid genetic testing in patients undergoing percutaneous coronary intervention (PCI) and the comparison of the pharmacodynamic effects of prasugrel versus ticagrelor among carriers of cytochrome P450 2C19 loss-of-function alleles treated with PCI has been poorly explored. Rapid genetic testing using the Spartan assay was shown to be feasible and provides results in a timely fashion in a real-world setting of patients undergoing coronary angiography (n = 781). Among patients (n = 223, 28.

Pharmacodynamic Effects of Vorapaxar in Prior Myocardial Infarction Patients Treated With Potent Oral P2Y Receptor Inhibitors With and Without Aspirin: Results of the VORA-PRATIC Study.

Background Vorapaxar as an adjunct to dual antiplatelet therapy (DAPT) reduces thrombotic events in patients with prior myocardial infarction at the expense of increased bleeding. Withdrawal of aspirin has emerged as a bleeding reduction strategy. The pharmacodynamic effects of vorapaxar with potent P2Y inhibitors as well as the impact of dropping aspirin is unexplored and represented the aim of the VORA-PRATIC (Vorapaxar Therapy in Patients With Prior Myocardial Infarction Treated With Newer Generation P2Y Receptor Inhibitors Prasugrel and Ticagrelor) study.

Pharmacodynamic Effects of Vorapaxar in Patients With and Without Diabetes Mellitus: Results of the OPTIMUS-5 Study.

Vorapaxar reduces thrombotic cardiovascular events at the expense of increased bleeding. However, the differential pharmacodynamic (PD) effects of vorapaxar according to diabetes mellitus (DM) status are unknown. Moreover, although withdrawal of aspirin has emerged as a bleeding reduction strategy, the PD effects of stopping aspirin in patients treated with vorapaxar also are unknown.

Effects of Edoxaban on the Cellular and Protein Phase of Coagulation in Patients with Coronary Artery Disease on Dual Antiplatelet Therapy with Aspirin and Clopidogrel: Results of the EDOX-APT Study.

In patients requiring dual antiplatelet therapy (DAPT) who also have an indication to be treated with oral anticoagulant (OAC) drugs, aspirin withdrawal reduces the risk of bleeding. There is limited data on the pharmacodynamic effects associated with adding a nonvitamin K antagonist OAC on a background of aspirin and a P2Y inhibitor as well as dropping aspirin. Seventy-five patients on DAPT (aspirin plus clopidogrel) were randomized to DAPT plus high-dose edoxaban (60 mg once daily, Group A), DAPT plus low-dose edoxaban (30 mg once daily, Group B), or DAPT only (Group C) for 10 ± 2 days (Phase I).

Effects of Methylnaltrexone on Ticagrelor-Induced Antiplatelet Effects in Coronary Artery Disease Patients Treated With Morphine.

Objectives: The aim of this study was to assess if intravenous methylnaltrexone can counteract the effects of morphine on the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ticagrelor.

Background: Morphine delays the onset of action of oral P2Y receptor inhibitors, including ticagrelor, by inhibiting gastric emptying and leading to delayed drug absorption. Methylnaltrexone is a peripheral opioid receptor antagonist that has the potential to prevent opioid-induced peripherally mediated side effects (e.

Platelet Inhibition With Cangrelor and Crushed Ticagrelor in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Background: The platelet inhibitory effects induced by oral P2Y receptor antagonists are delayed in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (P-PCI). In turn, this leads to a gap in platelet inhibition, exposing patients to an increased risk of early thrombotic complications and underscoring the need to define strategies associated with more effective platelet inhibition in the peri-primary percutaneous coronary intervention period. Cangrelor is an intravenous P2Y inhibitor with prompt and potent antiplatelet effects.

Pharmacodynamic Effects of Switching From Ticagrelor to Clopidogrel in Patients With Coronary Artery Disease: Results of the SWAP-4 Study.

Background: Switching between different classes of P2Y inhibitors, including de-escalation from ticagrelor to clopidogrel, commonly occurs in clinical practice. However, the pharmacodynamic profiles of this strategy have been poorly explored.

Methods: This was a prospective, randomized, open-label study conducted in patients on maintenance dosing (MD) of aspirin (81 mg/d) and clopidogrel (75 mg/d).

Should endovascular approach be the first line of treatment for retroperitoneal bleeding with hemodynamic shock following percutaneous intervention? A case series.

Objectives: To report a series of consecutive patients that developed retroperitoneal hemorrhage (RPH) and persistent hypotension treated with endovascular approach.

Background: RPH is a rare complication of percutaneous cardiovascular interventions associated with high morbidity and mortality. The standard approach to treat this complication has been a conservative management for stable patients, and urgent vascular surgery for those with persistent hypovolemic shock.

Pharmacodynamic Comparison of Prasugrel Versus Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study.

Background: Patients with diabetes mellitus (DM) are at increased risk of atherothrombotic events, underscoring the importance of effective platelet inhibiting therapies. Prasugrel and ticagrelor reduce thrombotic complications to a greater extent than clopidogrel. Subgroup analyses of pivotal clinical trials testing prasugrel and ticagrelor versus clopidogrel showed DM patients to have benefits that were consistent with the overall trial populations, although the magnitude of the ischemic risk reduction appeared to be enhanced with prasugrel.

Impact of timing from blood sampling to pharmacodynamic assessment on measures of platelet reactivity in patients treated with P2Y receptor inhibitors.

Several platelet function tests (PFT) are available to assess the pharmacodynamic (PD) effects of P2Y inhibitors. However, there are technical variances between PFT, and P2Y inhibitors differ in pharmacological properties. Manufactures of PFT recommend a time-frame within which assessments needs to be executed.

Pharmacodynamic Effects of Switching From Prasugrel to Ticagrelor: Results of the Prospective, Randomized SWAP-3 Study.

Objectives: This study sought to assess the pharmacodynamic (PD) effects of switching to ticagrelor patients who were treated with prasugrel after undergoing percutaneous coronary intervention in the setting of an acute coronary syndrome.

Background: In clinical practice, there is a frequent need to switch between P2Y12 receptor inhibitors. However, concerns on drug interactions have emerged when switching therapies.