prasugrel-hydrochloride 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

A large number of patients worldwide receive anticoagulant and antiplatelet agents, collectively known as antithrombotic agents. Several new anticoagulants and antiplatelet agents recently were approved for use. Gastroenterologists may be unfamiliar with the mechanism of action, indications for use, and pharmacokinetics of these newer drugs. In patients undergoing elective and urgent endoscopic procedures, clinicians must be familiar with these medications to optimize outcomes. When the decision is made to continue the newer antithrombotic agents for elective procedures, the clinician must understand the risk that these agents may impart on procedural-induced bleeding. Finally, it is important to understand how to manage these agents in the presence of acute gastrointestinal bleeding. In this article the use of newer antithrombotic agents is reviewed.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation Factors; Cholangiopancreatography, Endoscopic Retrograde; Clopidogrel; Dabigatran; Drug Interactions; Fondaparinux; Gastrointestinal Hemorrhage; Humans; Piperazines; Platelet Aggregation Inhibitors; Polysaccharides; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic P2Y Receptor Antagonists; Thiophenes; 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

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aryl Hydrocarbon Hydroxylases; Aspirin; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Interactions; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Factors; Thienopyridines; Thiophenes; Ticlopidine

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aryl Hydrocarbon Hydroxylases; Aspirin; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Interactions; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Factors; Thienopyridines; Thiophenes; Ticlopidine

Increasing use of antiplatelet therapies is associated with increasing GI complications, such as ulceration and GI bleeding. Identification of high-risk patients and, in such patients, incorporation of strategies to reduce their GI risk would be clinically prudent. After assessment and treatment of H pylori in patients with prior ulcer or GI bleeding histories, further reduction in GI risk in other high-risk patients who require antiplatelet agents is primarily accomplished by prescribing drugs that when coadministered with antiplatelet agents protect against mucosal ulceration, primarily proton pump inhibitors (PPIs). However, observational studies indicate a higher cardiovascular event rate in patients taking PPIs along with clopidogrel and aspirin compared with that of patients undergoing dual antiplatelet therapy without PPIs. Whether concurrent use of a PPI with clopidogrel represents a safety concern or not is currently being evaluated by the US Food and Drug Administration. Until more specific regulatory guidance is available, current recommendations are that patients taking both PPIs and clopidogrel concurrently should probably continue to do so until more data become available.

Topics: Aspirin; Clopidogrel; Gastrointestinal Hemorrhage; Humans; Peptic Ulcer; Peptic Ulcer Hemorrhage; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proton Pump Inhibitors; Risk Factors; Thiophenes; Ticlopidine

The TRITON-TIMI 38 was a head-to-head trial to assess the efficacy and safety of the experimental antiplatelet agent prasugrel vs. standard care with clopidogrel on top of aspirin. Besides some ischemic protection at expense of overwhelming bleeding disadvantage, prasugrel treated patients experienced three times higher rate of colonic neoplasms then after clopidogrel, and this difference was significant. Importantly, known gastrointestinal bleeding preceded the diagnosis of colonic neoplasms only in half of the patients. Three potential mechanisms responsible for such harmful association are reviewed, namely: (i) direct hazard of the experimental drug on cancer occurrence and progression; (ii) indirect modulation of tumor growth; and (iii) enhanced metastatic dissemination due to instability of platelet-tumor cell aggregates, or/and inability to keep the disease locally due by much more potent long-term platelet inhibition should be considered. Significant excess of cancer after prasugrel is alarming, and can be reasonably explained, with critical clinical implications not only for prasugrel further development, but also for existing and future chronic antiplatelet strategies. If the hypothesis that oral aggressive platelet inhibition cause higher cancer risks will turn out to be true, then intensity of platelet inhibition, and especially duration of chronic antiplatelet therapy should be reconsidered. More delicate platelet inhibition, and shorter exposure to oral antiplatelet agents will prevail.

Topics: Animals; Aspirin; Clopidogrel; Colonic Neoplasms; Gastrointestinal Hemorrhage; Humans; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Thiophenes; Ticlopidine

Triple antithrombotic therapy, including dual antiplatelet therapy and oral anticoagulant (OAC), is recommended for a short-term period after percutaneous coronary intervention (PCI) in patients requiring anticoagulation therapy. The purpose of this study was to compare in-hospital clinical outcomes between low-dose prasugrel (3.75 mg/day) and clopidogrel, as part of triple antithrombotic therapy, using a large database in Japan.. Patients with ischemic heart disease who underwent PCI between January 2015 and December 2019, and were prescribed triple therapy with aspirin, a P2Y12 inhibitor (clopidogrel or low-dose prasugrel), and OAC (direct oral anticoagulant: DOAC or vitamin K antagonist: VKA), were selected from the Diagnosis Procedure Combination database. The primary outcome was in-hospital mortality. The secondary outcomes were myocardial infarction, ischemic stroke, bleeding stroke, gastrointestinal bleeding, and blood transfusion.. Overall, 5,777 patients were eligible in this analysis. The patients were divided into 4 subgroups according to the type of P2Y12 inhibitor and OAC: clopidogrel/DOAC (n = 1,628), clopidogrel/VKA (n = 1,334), prasugrel/DOAC (n = 1,607), and prasugrel/VKA (n = 1,208). There was no significant difference in the incidence of death and gastrointestinal bleeding among the 4 subgroups. The prasugrel/DOAC group had significantly lower incidence of MI (OR 0.566, 95% CI 0.348-0.921). The incidence of ischemic stroke was significantly lower in the prasugrel/DOAC group (OR 0.701, 95% CI 0.502-0.979), and significantly higher in the clopidogrel/VKA group (OR 1.680, 95% CI 1.273-2.216). Need for blood transfusion was less frequent in the prasugrel/DOAC group (OR 0.729, 95% CI 0.598-0.890), and more frequent in both the clopidogrel/VKA group (OR 1.424, 95% CI 1.187-1.708) and the prasugrel/VKA group (OR 1.633, 95% CI 1.367-1.950).. Combination of low-dose prasugrel and DOAC was associated with lower incidence of MI, ischemic stroke, and blood transfusion. Low-dose prasugrel may be feasible as part of triple therapy in patients undergoing PCI.

Topics: Anticoagulants; Clopidogrel; Drug Therapy, Combination; Fibrinolytic Agents; Gastrointestinal Hemorrhage; Humans; Ischemic Stroke; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; 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

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

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Clinical Trials, Phase III as Topic; Clopidogrel; Drug-Related Side Effects and Adverse Reactions; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proton Pump Inhibitors; Purinergic P2Y Receptor Antagonists

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

Proton pump inhibitors (PPIs) reduce gastrointestinal bleeding events but may alter clopidogrel metabolism. We sought to understand the comparative effectiveness and safety of prasugrel versus clopidogrel in the context of proton pump inhibitor (PPI) use.. Using data on 11 955 acute myocardial infarction (MI) patients treated with percutaneous coronary intervention at 233 hospitals and enrolled in the TRANSLATE-ACS study, we compared whether discharge PPI use altered the association of 1-year adjusted risks of major adverse cardiovascular events (MACE; death, MI, stroke, or unplanned revascularization) and Global Use of Strategies To Open Occluded Arteries (GUSTO) moderate/severe bleeding between prasugrel- and clopidogrel-treated patients. Overall, 17% of prasugrel-treated and 19% of clopidogrel-treated patients received a PPI at hospital discharge. At 1 year, patients discharged on a PPI versus no PPI had higher risks of MACE (adjusted hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.21-1.58) and GUSTO moderate/severe bleeding (adjusted HR 1.55, 95% CI 1.15-2.09). Risk of MACE was similar between prasugrel and clopidogrel regardless of PPI use (adjusted HR 0.88, 95% CI 0.62-1.26 with PPI, adjusted HR 1.07, 95% CI 0.90-1.28 without PPI, interaction P=0.31). Comparative bleeding risk associated with prasugrel versus clopidogrel use differed based on PPI use but did not reach statistical significance (adjusted HR 0.73, 95% CI 0.36-1.48 with PPI, adjusted HR 1.34, 95% CI 0.79-2.27 without PPI, interaction P=0.17).. PPIs did not significantly affect the MACE and bleeding risk associated with prasugrel use, relative to clopidogrel.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01088503.

Topics: Acute Coronary Syndrome; Aftercare; Aged; Cardiovascular Diseases; Clopidogrel; Comparative Effectiveness Research; Female; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proportional Hazards Models; Proton Pump Inhibitors; Purinergic P2Y Receptor Antagonists; Recurrence; Stroke; Ticlopidine; Treatment Outcome

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Arteriovenous Malformations; Aspirin; Drug Therapy, Combination; Fatal Outcome; Gastrointestinal Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Stents; Thiophenes; Thrombosis; Warfarin

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

Patients taking antiplatelet agents for the prevention of cardiovascular diseases who develop gastrointestinal bleeding represent a serious challenge in clinical practice. The initial step in reducing gastrointestinal risk of antiplatelet therapy is to assess whether the patient has a continued need for antiplatelet therapy. The next step is to eliminate the risk factors that may place the patient at increased gastrointestinal risk. In the management of bleeding ulcer patients with high-risk stigmata of recent hemorrhage, resuming antiplatelet agents at 3-5 days after the last dosing is a reasonable strategy. However, patients with low-risk stigmata can keep taking antiplatelet agents immediately following endoscopy. In the management of aspirin-related uncomplicated peptic ulcers in patients requiring antiplatelet therapies, continuing aspirin plus a powerful proton pump inhibitor is the choice of treatment. Patients who require antiplatelet agents for the prevention of cardiovascular diseases should be tested and treated for Helicobacter pylori infection before starting antiplatelet therapy. Additionally, those with high risks for upper gastrointestinal bleeding should receive co-therapy with a gastroprotective drug, preferably a proton pump inhibitor at standard dose. H2-receptor antagonist can significantly reduce upper gastrointestinal bleeding risk in patients taking low-dose aspirin but it is ineffective in the prevention of upper gastrointestinal bleeding in clopidogrel users. Although several retrospective studies reported that patients prescribed clopidogrel who also took proton pump inhibitors had significant increases in cardiovascular events, the current evidence from a prospective randomized trial does not justify a conclusion that proton pump inhibitors are associated with cardiovascular events among clopidogrel users.

Topics: Aspirin; Cardiovascular Diseases; Clopidogrel; Drug Interactions; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Peptic Ulcer; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proton Pump Inhibitors; Thiophenes; Ticlopidine

Antiplatelet agents are critical to prevent thrombotic events in patients with acute coronary syndromes, particularly those who undergo percutaneous coronary intervention. Prasugrel is a potent P2Y(12)-adenosine diphosphate receptor antagonist that is superior to clopidogrel in such patients. Previous studies have observed that nuisance and internal bleedings were relatively frequent in patients under clopidogrel therapy and were associated with noncompliance. Furthermore, premature drug discontinuation is associated with thrombotic recurrences. The aim of the present study was to investigate the rate of nuisance or internal bleedings in patients receiving prasugrel and its relation with compliance. This prospective multicenter study included 396 patients. Bleeding events were recorded and classified as alarming, nuisance, or internal according. Compliance with prasugrel therapy was assessed. Almost half of the patients (48.5%) were included for ST-segment elevation acute coronary syndromes. During the 1-month follow-up period, 54 patients (13.6%) had bleeding events. Most bleeding events were classified as internal or nuisance (96%). Internal and nuisance bleedings were associated with high rates of prasugrel discontinuation (16.6% and 14.7%, respectively). Nuisance and internal bleedings were significantly associated with prasugrel discontinuation in multivariate analysis (odds ratio 3.1, 95% confidence interval 1.01 to 9.2, p = 0.04). The rate of major adverse cardiovascular events was 2.3%. No relation was observed between minor bleeds, compliance, and major adverse cardiovascular events. In conclusion, in the present study, minor bleedings were common during the first month after percutaneous coronary intervention and were significantly associated with prasugrel withdrawal.

Topics: Acute Coronary Syndrome; Female; Gastrointestinal Hemorrhage; Humans; Male; Medication Adherence; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Thiophenes

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Clopidogrel; Drug Interactions; Gastrointestinal Hemorrhage; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Proton Pump Inhibitors; Pyridines; Randomized Controlled Trials as Topic; Thiophenes; Ticlopidine