ticagrelor and Gastrointestinal-Hemorrhage

Ticagrelor and prasugrel are third-generation oral P2Y. To compare the risk of gastrointestinal bleeding (GIB) among users of third-generation P2Y. We systematically searched for published randomised controlled trials of ticagrelor or prasugrel versus clopidogrel until September 2018. The primary outcome was the risk of GIB among users of third-generation P2Y. Forty-one studies were included in the analysis of non-CABG major bleeding, of which 12 were included in the analysis of GIB including 58 678 patients. Third-generation P2Y. Third-generation P2Y

Topics: Clopidogrel; Gastrointestinal Hemorrhage; Humans; Odds Ratio; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Ticagrelor

Aspirin and P2Y

Topics: Adenosine; Aspirin; Cardiovascular Diseases; Clopidogrel; Drug Administration Schedule; Drug Dosage Calculations; Drug Interactions; Esomeprazole; Gastrointestinal Hemorrhage; Gene Expression; Humans; Hydrogen-Ion Concentration; Peptic Ulcer; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Ticlopidine

Aspirin, the first antiplatelet agent, has been around since the 19th century, and is one of the most established drugs in history. With the improvement of coronary interventions in the past few decades, there has been more reliance on oral antiplatelet agents to reduce complications of in-stent restenosis/thrombosis. Clopidogrel was initially introduced in 1997, and within the past seven years, two additional oral antiplatelet agents have been approved by the U.S. Food and Drug Administration. With more potent antiplatelet agents comes increased risks of adverse effects. Physicians of all fields should be aware of the common antiplatelet agents used today, and the basic landmark trials that allowed them to be on the market today. The focus of this review article is to evaluate each oral antiplatelet drug, its brief history, relevant trials, indications and management of complications through evidence based guidelines.

Topics: Adenosine; Administration, Oral; Aspirin; Cardiovascular Diseases; Clopidogrel; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Factors; Thrombosis; Ticagrelor; Ticlopidine

Acetylsalicylic acid and P2Y12-receptor antagonists are antiplatelet agents widely used in the treatment and secondary prevention of cardiovascular disease. Since upper gastrointestinal bleeding is common during antiplatelet treatment, many patients are also treated with a proton pump inhibitor. In recent years it has been heavily discussed if proton pump inhibitors may attenuate the cardiovascular protection achieved with oral antiplatelet agents. Pharmacodynamic studies have suggested important drug interactions, but clinical studies have failed to confirm any clinical impact.

Topics: Adenosine; Administration, Oral; Aspirin; Clopidogrel; Cyclooxygenase Inhibitors; Drug Interactions; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Humans; Piperazines; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Factors; Thienopyridines; Thiophenes; Ticagrelor; Ticlopidine

In the European Union Ticagrelor has recently been approved, as another P2Y12-receptor antagonist in addition to clopidogrel and prasugrel, in [corrected] the drug treatment after coronary intervention. [corrected] Dual antithrombotic treatment must be given for 4 weeks after elective implantation [corrected] of bare-metal stents, or for at least 6 months [corrected] with acetylsalicylic acid (ASA) plus clopidogrel after implantation of a drug-eluding stent. After an acute coronary syndrome ASA and clopidogrel (or prasugrel or ticagrelor) must be given for 12 months. In patients requiring urgent oral anticoagulation essential triple-drug treatment should be given over as short a [corrected] space of time if possible. [corrected] Prasugrel and ticagrelor may, to protect against gastroduodenal bleeding, be given without restriction together with a proton-pump inhibitor. Preoperative coagulation management is essential for patients who have been on dual platelet-aggregation inhibitors, but premature withdrawal of this medication should be avoided.

Topics: Adenosine; Aftercare; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Coronary Disease; Drug Administration Schedule; Drug Approval; Drug Therapy, Combination; Drug-Eluting Stents; Gastrointestinal Hemorrhage; Humans; Myocardial Revascularization; Piperazines; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Proton Pump Inhibitors; Stents; Thiophenes; Ticagrelor; Ticlopidine

Standard double antiplatelet therapy (aspirin plus clopidogrel) used in patients with coronary artery disease during acute coronary syndromes (ACS) and/or in conjunction with percutaneous coronary interventions (PCI) has some limitations. Relatively large proportion of patients has "laboratory" resistance to clopidogrel - an essential component of standard therapy. Basic weakness of this agent is necessity to be converted into active metabolite by CYP 450 enzymes. Other drugs potentially interfere with this conversion. The puzzle of clinical value of obvious laboratory interaction of clopidogrel with its conjecturally almost obligatory companions proton pump inhibitors is still unresolved. It has been shown recently that loss of function alleles of some CYP450 genes especially CYP2C19*2 are responsible for reduced reaction of platelets to clopidogrel. Detection of this allele is possible. However practical application of such genetic testing is subject of disagreement among experts. Another way for therapy guidance is use of platelet function testing. But at present there is no agreement concerning preferable test. Studies aimed at clarification of practical role of some laboratory test are close to completion. Recognition of resistance by any method calls forth administration of higher doses of clopidogrel or use of novel agents. CURRENT trial has recently demonstrated advantages of clopidogrel double dose in ACS patients subjected to PCI. Novel P2Y12 receptor inhibitors prasugrel and ticagrelor have been shown to be superior to clopidogrel in large randomized trials. Direct P2Y12 antagonist ticagrelor seems to be especially attractive because of effect on total mortality and acceptable rate of bleeding. Among agents under study thrombin receptor blockers appear most promising.

Topics: Acute Coronary Syndrome; Adenosine; Angioplasty, Balloon, Coronary; Aryl Hydrocarbon Hydroxylases; Aspirin; Blood Platelets; Clinical Trials as Topic; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Drug Interactions; Drug Resistance; Gastrointestinal Hemorrhage; Humans; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Polymorphism, Genetic; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic P2Y Receptor Antagonists; Receptor, PAR-1; Thiophenes; Ticagrelor; Ticlopidine; United States; United States Food and Drug Administration

To date, no studies have specifically examined the efficacy of P2Y12 inhibitor monotherapy in patients with acute coronary syndrome (ACS) exhibiting a high risk of gastrointestinal (GI) bleeding following percutaneous coronary intervention (PCI). This was a retrospective cohort study of ACS exhibiting a high GI bleeding risk after PCI admitted to the Affiliated Hospital of the Jiangnan University from August 2016 to December 2019. Of the 308 enrolled patients, 269 were found eligible and were assigned to the ticagrelor monotherapy (TIC) arm (n = 128) and to ticagrelor plus aspirin (TIC + ASP) arm (n = 141) treatment for a 1-year period. The primary study outcome was a composite end point, including bleeding academic research consortium (BARC) type 2, 3, or 5 bleeding and adverse cardiac or cerebrovascular events; 8 (6.3%) in the TIC group and 14 (9.9%) in the combination treatment group reached the primary ischemic end point within 1 year with no significant difference between these groups. BARC type 2, 3, and 5 bleeding events affected significantly more patients in the combination group relative to the TIC group (38 [27.0%] vs. 11 [8.6%], P < 0.001). As the follow-up interval was prolonged, the cumulative BARC type 2, 3, and 5 bleeding incidence in the TIC group remained significantly below than that in the combination treatment group ( P < 0.05). These results indicate that TIC is associated with a lower risk of clinically relevant bleeding events among ACS with a high risk of GI bleeding after PCI relative to combination TIC + ASP treatment, although ischemic outcomes in these 2 groups were similar.

Topics: Acute Coronary Syndrome; Aspirin; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Humans; Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Retrospective Studies; Ticagrelor; Treatment Outcome

Individuals 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 P2Y. In 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.. Twenty 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.. More 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.

Topics: Aged; Clopidogrel; Gastrointestinal Hemorrhage; Humans; Kidney Failure, Chronic; Middle Aged; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Renal Dialysis; Retrospective Studies; Ticagrelor

Ticagrelor may be superior to aspirin after minor ischemic stroke or TIA, particularly in patients with symptomatic atherosclerotic disease. However, there may be an increased risk of intracerebral hemorrhage in patients with moderate to severe ischemic stroke, and ticagrelor has not been studied in this patient population. Therefore, we sought to evaluate the safety of ticagrelor after moderate or severe ischemic stroke.. Retrospective chart review of all patients admitted with acute ischemic stroke and NIHSS 6 or greater who were discharged on ticagrelor between January 2016 and December 2019. Patients who underwent angioplasty, stenting or carotid revascularization during the hospitalization were excluded.. Of 183 patients discharged on ticagrelor, 61 patients were included. Median age was 61 (IQR 52-68); 33 (54%) patients were men. Median NIHSS was 11 (IQR 8-15). Fourteen (23%) patients received IV alteplase and 35 (57%) patients received mechanical thrombectomy. Stroke mechanism was large artery atherosclerosis in 53 (87%) of patients, of which 40 (71%) were deemed intracranial atherosclerosis. Final infarct volume was greater than 10 mL in 32 (52%) patients. Follow-up information was available for 53 (87%) patients; median length of follow-up was 3 (IQR 2-6) months. Six (10%) patients experienced recurrent ischemic stroke. No patients experienced symptomatic intracerebral hemorrhage after initiation of ticagrelor. One (2%) patient experienced major bleeding.. This study provides preliminary evidence supporting the potential safety of ticagrelor following moderate or severe acute ischemic stroke. These findings support the need for future prospective studies.

Topics: Aged; Cerebral Hemorrhage; Epistaxis; Female; Gastrointestinal Hemorrhage; Hematuria; Humans; Ischemic Stroke; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Retrospective Studies; Risk Factors; Severity of Illness Index; Ticagrelor; Treatment Outcome

Observational studies comparing ticagrelor and prasugrel in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) have yielded contradictory results, but these studies often did not consider differential censoring (eg, for treatment switching or insurance disenrollment) or confounding by time-dependent factors.. Our objective was to conduct a comparative effectiveness and safety analysis of ticagrelor and prasugrel in patients who underwent PCI after being hospitalized for an ACS.. This study used the Optum's de-identified Clinformatics. Included in the analysis were 2559 patients initiated on ticagrelor and 4456 patients initiated on prasugrel following PCI. Patients initiated on ticagrelor were 10% more likely to have eligibility disenrollment (Ticagrelor: 57%, Prasugrel: 47%, p < 0.01) and 7 percentage-points more likely to switch medication (Ticagrelor: 35%, Prasugrel: 28%, p < 0.01). After adjusting for multiple factors, including time-varying exposure and censoring imbalance, ticagrelor was associated with a higher risk of all-cause death, MI, or stroke when compared to prasugrel (Hazard ratio (HR): 1.33; 95% CI: 1.04-1.68). Similarly, ticagrelor was associated with a higher risk in bleeding events when compared with prasugrel (HR: 1.61; 95% CI: 1.19-2.17).. When compared with ticagrelor, prasugrel use following PCI for ACS was associated with a lower risk of death, MI, or stroke, as well as a reduced risk of major bleeding.

Topics: Acute Coronary Syndrome; Gastrointestinal Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Stroke; Ticagrelor; Treatment Outcome

Bleeding risk stratification is an unresolved issue in older adults. Anemia may reflect subclinical blood losses that can be exacerbated after percutaneous coronary intervention . We sought to prospectively determine the contribution of anemia to the risk of bleeding in 448 consecutive patients aged 75 or more years, treated by percutaneous coronary interventions without concomitant indication for oral anticoagulation. We evaluated the effect of WHO-defined anemia on the incidence of 1-year nonaccess site-related major bleeding. The prevalence of anemia was 39%, and 13.1% of anemic and 5.2% of nonanemic patients suffered a bleeding event (hazard ratio 2.75, 95% confidence interval 1.37 to 5.54, p = 0.004). Neither PRECISE-DAPT nor CRUSADE scores were superior to hemoglobin for the prediction of bleeding. In conclusion, anemia is a powerful predictor of bleeding with potential utility for simplifying tailoring therapies.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anemia; Angina, Unstable; Anticoagulants; Antithrombins; Aspirin; Cause of Death; Clopidogrel; Comorbidity; Coronary Artery Disease; Drug-Eluting Stents; Female; Gastrointestinal Hemorrhage; Hemorrhage; Heparin; Hirudins; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Postoperative Hemorrhage; Prasugrel Hydrochloride; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Risk Assessment; Stents; Ticagrelor; Urologic Diseases

Gastrointestinal bleeding (GIB) frequently occurs following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) with the prescription of P2Y. To compare GIB rates associated with clopidogrel, prasugrel and ticagrelor using national medical and pharmacy claims data from privately insured and Medicare Advantage enrollees .. Propensity score and inverse probability treatment weighting were used to balance baseline characteristics among treatment groups. The 1-year GIB risk was calculated using weighted Cox proportional hazard models and expressed as hazard ratios (HR) with 95% confidence intervals (CI) and number needed to harm (NNH).. We identified 37 019 patients with ACS (non-ST elevation ACS [NSTE-ACS] and ST-elevation myocardial infarction [STEMI]) within 14 days of a PCI (mean age 63 years and 70% male). Clopidogrel prescription was most common (69%) with prasugrel (16%) and ticagrelor (14%) prescribed less frequently. When compared with clopidogrel, ticagrelor was associated with a 34% risk reduction (HR 0.66; 95% CI: 0.54-0.81) in GIB overall and with NSTE-ACS, and a 37% GIB risk reduction (HR 0.63; 95% CI: 0.42-0.93) in STEMI patients. When compared with clopidogrel, prasugrel was associated with a 21% risk reduction (HR 0.79; 95% CI: 0.64-0.97) overall, a 36% GIB risk reduction (HR 0.64; 95% CI: 0.49-0.85) in STEMI patients but no reduction of GIB risk in NSTE-ACS patients.. In the first year following PCI, ticagrelor or prasugrel are associated with fewer GIB events than clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Cohort Studies; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Retrospective Studies; Thromboembolism; Ticagrelor; Treatment Outcome; United States

Topics: Acute Coronary Syndrome; Clopidogrel; Gastrointestinal Hemorrhage; Humans; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Ticagrelor

Topics: Acute Coronary Syndrome; Clopidogrel; Gastrointestinal Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor

The initial EROSION study (Effective Anti-Thrombotic Therapy Without Stenting: Intravascular Optical Coherence Tomography-Based Management in Plaque Erosion) demonstrated that patients with acute coronary syndrome caused by plaque erosion might be stabilized with aspirin and ticagrelor without stenting for ≤1 month. However, a long-term evaluation of outcomes is lacking. The aim of this study was to assess whether the initial benefit of noninterventional therapy for patients with acute coronary syndrome caused by plaque erosion is maintained for ≤1 year.. Among 53 patients who completed clinical follow-up, 49 underwent repeat optical coherence tomography imaging at 1 year. Median residual thrombus volume decreased significantly from 1 month to 1 year (0.3 mm. One-year follow-up optical coherence tomography demonstrated a further decrease in thrombus volume between 1-month and 1-year follow-up. A majority (92.5%) of patients with acute coronary syndrome caused by plaque erosion managed with aspirin and ticagrelor without stenting remained free of major adverse cardiovascular event for ≤1 year.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02041650.

Topics: Acute Coronary Syndrome; Adenosine; Adult; Aspirin; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Disease-Free Survival; Drug Therapy, Combination; Female; Fibrinolytic Agents; Follow-Up Studies; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Myocardial Revascularization; Plaque, Atherosclerotic; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prospective Studies; Risk Factors; Thrombectomy; Ticagrelor; Time Factors; Tomography, Optical Coherence; Treatment Outcome

A 68 year-old man, initially managed with primary percutaneous coronary intervention (PCI) to the right coronary artery (RCA) for an inferior ST elevation myocardial infarction (STEMI) with residual disease requiring coronary artery bypass graft surgery (CABG), re-presented with chest pain. There were no acute ischaemic changes on ECG and his pain settled with nitrates. A day later, he developed left sided abdominal pain and hypovolaemic shock after straining in the toilet. A subsequent computed tomography (CT) scan of his abdomen revealed an omental bleed. He proceeded to emergency laparotomy, recovered well, and was discharged on aspirin and clopidogrel. Apart from dual antiplatelet therapy with aspirin and ticagrelor, and presumed raised intra-abdominal pressure, there were no other identified risk factors for increased bleeding.

Topics: Adenosine; Aged; Aspirin; Clopidogrel; Gastrointestinal Hemorrhage; Humans; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Ticagrelor is a reversible inhibitor of platelet-aggregation, and is used instead of clopidogrel in the treatment of acute coronary syndrome (ACS). Ticagrelor has documented better outcomes as shown in the PLATO-study, when compared to clopidogrel. However, more major non-CABG bleedings are observed with ticagrelor. Treatment of ACS with platelet-inhibitors is the standard, but there is no antidote for ticagrelor or clopidogrel, making haemostasis problematic in the case of a major bleeding. The following case describes a 76-year-old woman, who after admission for chronic obstructive pulmonary disease and ACS, was treated with ticagrelor and developed a major gastrointestinal bleeding.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Coronary Artery Bypass; Female; Gastrointestinal Hemorrhage; Humans; Pulmonary Disease, Chronic Obstructive; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Treatment Outcome

Current guidelines offer a choice of P2Y12 receptor antagonist among clopidogrel, prasugrel or ticagrelor on top of aspirin (ASA) for dual antiplatelet therapy (DAPT) in patients after acute coronary syndromes (ACS). However, the comparative risks of gastrointestinal (GI) adverse events during DAPT are not clear. Two large ACS trials (TRITON and PLATO) provide a valuable opportunity to directly match the risks of GI complications among current antiplatelet regimens. We compared the rates of GI adverse events after prasugrel and ticagrelor versus clopidogrel based on the Food and Drug Administration (FDA) clinical safety reviews. When compared with ticagrelor, clopidogrel is safer with regard to GI-related risks including fewer overall GI/anal bleeding events and spontaneous GI hemorrhagic episodes, less nausea, vomiting, dyspepsia and diarrhea, and a lower rate of presence of Helicobacter pylori. Among GI symptoms, only constipation was more common after clopidogrel than following ticagrelor. There were extrahepatic risks observed with ticagrelor but not with prasugrel when compared to clopidogrel. Prasugrel unquestionably caused more bleeding from the GI tract and GI malignancies than clopidogrel. However, the entire spectrum of GI effects of prasugrel is much less well known and mostly based on sponsor analysis rather than FDA-verified numbers. Among 3 DAPT options on top of ASA, clopidogrel seems to represent the safest alternative, although comprehensive data on direct prasugrel-associated GI effects are lacking or inconclusive.

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Chemical and Drug Induced Liver Injury; Clinical Trials, Phase III as Topic; Clopidogrel; Double-Blind Method; Female; Gastrointestinal Hemorrhage; Gastrointestinal Neoplasms; Humans; Kaplan-Meier Estimate; Male; Multicenter Studies as Topic; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Factors; Thiophenes; Ticagrelor; Ticlopidine