thienopyridine and Hemorrhage

The study aimed to compare the efficacy and safety outcome associated with a short and a prolonged duration of thienopyridine therapy in patients with chronic kidney disease (CKD) after coronary stenting. We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 1 January 2019 for studies comparing short and prolonged thienopyridine therapy in patients with CKD. Ischemic and bleeding events were considered as the clinical endpoints in this analysis. Odds Ratios (OR) with 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. Seven studies comprising a total of 17,628 CKD patients were included in the evaluation. Prolonged duration of thienopyridine use, when compared to short-term thienopyridine, was associated with reduced risk of all-cause mortality (odds ratio 0.75, 95% confidence interval: 0.70-0.81,

Topics: Aged; Coronary Artery Disease; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Pyridines; Renal Insufficiency, Chronic; Risk Assessment; Stents; Stroke; Time Factors

Antithrombotics are one of the most commonly prescribed classes of medication around the world. The thienopyridines are an integral part of antithrombotic therapy and are prescribed for various indications including acute coronary syndrome, peripheral vascular disease and cerebrovascular disease. These drugs have distinct metabolic pathways, which lead to the formation of active metabolites that produce both observed clinical differences as well as pharmacokinetic and pharmacodynamic differences in response.. The authors describe the pharmacokinetic and pharmacodynamic behavior of three of the currently available thienopyridines, namely ticlopidine, clopidogrel and prasugrel. The authors also describe and discuss the drug interaction and pharmacogenomic factors which may impact safety and drug efficacy.. P2Y(12)-ADP receptor antagonism has proven to be effective at preventing thrombosis. Differences in the activation of these drugs, cytochrome metabolism, concomitant drug use and pharmacogenomics have an impact on thienopyridine use. Clopidogrel remains the thienopyridine drug with the most approved indications for use. Prasugrel has proven to be efficacious but is associated with a higher bleeding risk in comparison to clopidogrel and therefore has to be used in appropriate clinical indications.

Topics: Acute Coronary Syndrome; Aryl Hydrocarbon Hydroxylases; Clopidogrel; Cytochrome P-450 CYP2C19; Drug Interactions; Fibrinolytic Agents; Hemorrhage; Humans; Inactivation, Metabolic; Pharmacogenetics; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Pyridines; Thiophenes; Ticlopidine

Early studies of glycoprotein IIb/IIIa inhibitors (GPIs) demonstrated benefit during percutaneous coronary intervention for acute coronary syndromes (ACS). Since their introduction, the magnitude of benefit of GPIs has become unclear.. We hypothesized that adding a GPI to unfractionated heparin in ACS patients treated with stents and thienopyridines is beneficial.. We searched the MEDLINE, Cochrane, and clinicaltrials.gov databases for randomized clinical trials that studied the use of GPIs during ACS. We required that patients be randomly assigned to unfractionated heparin plus a GPI versus unfractionated heparin plus placebo (or control). Additional inclusion criteria included the use of coronary stents and periprocedural thienopyridines. Outcomes were assessed at 30 days. Random effects DerSimonian-Laird summary risk ratios (RR) and 95% confidence intervals (CIs) were constructed.. Sixteen studies with 7611 patients were included. Myocardial infarction was 3.1% with GPI versus 4.4% with control (RR = 0.74; 95% CI, 0.59-0.94, P = 0.014); revascularization, 1.7% versus 2.7% (RR = 0.64; 95% CI, 0.46-0.89, P = 0.008); major bleeding, 2.5% versus 2.1% (RR = 1.21; 95% CI, 0.89-1.63, P = 0.22); minor bleeding, 5.5% versus 4.1% (RR = 1.37; 95% CI, 1.06-1.78, P = 0.016); and mortality, 2.2% versus 2.9% (RR = 0.79; 95% CI, 0.59-1.06, P = 0.12), respectively.. Among ACS patients treated with stents and thienopyridines, GPIs were associated with reduced myocardial infarction and revascularization. Minor, but not major bleeding was increased with GPIs. Mortality was similar between the groups. © 2011 Wiley Periodicals, Inc. Supporting information may be found in the online version of this article This work was supported by an unrestricted grant from the Florida Heart Research Institute, which had no role in the study design, data collection, analysis, or interpretation, manuscript writing, or decision to proceed with publication. Anthony A Bavry has received research support from Novartis Pharmaceuticals and serves as a contractor for American College of Cardiology Cardiosource. The other authors have no funding, financial relationships, or conflicts of interest to disclose.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Drug Therapy, Combination; Hemorrhage; Heparin; Humans; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Randomized Controlled Trials as Topic; Stents

Inhibition of platelet aggregation (IPA) has been a drug development target in acute coronary syndrome (ACS) for almost 2 decades. The relationship between IPA and cardiovascular (CV) events has not been quantified. Cardiovascular (non fatal myocardial infarction, death) and major bleeding events were extracted from phase 2 or 3 randomized, double-blind trials that evaluated oral and intravenous glycoprotein 2b/3a (GP2b/3a) antagonists and thienopyridines. IPA was extracted from different sources that studied a similar regimen in a similar population. Events were correlated to IPA using a linear relative-risk mixed-effects model. Covariates included type of drug, mean age, gender percentage, and ADP. Clinical trial simulations were conducted to evaluate the relationship between IPA and the likelihood of observing a CV event in a 6-month end point trial. Data from 81918 subjects in 20 studies were extracted from the literature. To achieve a 20% relative reduction in CV events would require a further 77% (56%-100%) absolute increase in IPA for IV GP2b/3a antagonists or a further 27%(20%-41%) absolute increase for thienopyridines. CV risk reduction was less in studies with older subjects and greater in studies with greater percentages of male subjects. Assuming a 3% major bleeding rate in the control group, these drugs had a 1% increase in absolute risk as absolute platelet inhibition increases by 60% (range, 40%-80%). This relationship in intrinsic bleeding may be different in different population subtypes. Assuming a 12% event rate, a 6-month active-controlled thienopyridine trial with 3000 subjects could detect a relationship between CV events and IPA with 80% likelihood. Target IPA increases in ACS are an absolute increase of 80% for IV GP2b/3a antagonists and 30% for thienopyridines. Quantitative models using literature data on IPA and CV events can be used to select dose regimens in early stages of drug development.

Topics: Acute Coronary Syndrome; Age Factors; Biomarkers; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Hemorrhage; Humans; Models, Biological; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Randomized Controlled Trials as Topic; Risk Assessment; Sex Factors

Acute coronary syndrome (ACS) is associated with a persistent prothrombotic state, placing patients at high risk of subsequent ischemic events. Guidelines recommend the use of dual antiplatelet therapy with aspirin + a thienopyridine (clopidogrel) for at least a year after ACS in most patients, except those who undergo coronary artery bypass grafting. Clinical studies demonstrate that this strategy significantly reduces the risk of ischemic events at the expense of a small increase in the risk of bleeding. Physicians must balance the risk of bleeding against the benefit of ischemia prevention, bearing in mind that ischemic events are generally more common than major bleeding and often associated with more catastrophic consequences or ongoing morbidity. The relationship between bleeding and mortality is complicated by the fact that many risk factors for bleeding are also those for mortality and that bleeding may lead to discontinuation of antiplatelet therapy, thereby increasing the risk for an ischemic event. Data suggest that physicians tend to overestimate the risk of bleeding and underestimate the risk of ischemia. Careful patient selection and thorough patient education are the keys to managing antiplatelet therapy after ACS, especially as newer more potent antiplatelet agents, such as prasugrel, become available.

Topics: Acute Coronary Syndrome; Aspirin; Clinical Trials as Topic; Clopidogrel; Coronary Artery Bypass; Hemorrhage; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Pyridines; Risk Factors; Thiophenes; Thrombosis; Ticlopidine

In a series of articles the authors consider clinical pharmacology and experience of clinical application of blockers of platelet P2Y12 receptors, most well known representatives of which ticlopidine and clopidogrel according to chemical structure belong to thienopyridine derivatives. In the fifth communication we consider data of two randomized studies in which efficacy and safety of clopidogrel in combination with acetylsalicylic acid (ASA) has been assessed in comparison with ASA in stable patients with atherothrombotic cardiovascular disease. It has been shown in both studies that in stable patients with atherothrombotic cardiovascular disease long-term therapy with combination of clopidogrel and ASA was no more effective than monotherapy with ASA or clopidogrel but was associated with high risk of hemorrhagic complications. Thus contrary to acute coronary syndromes and percutaneous interventions with stenting combinations of clopidogrel and ASA is not indicated to patients with stable course cardiovascular diseases.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Arteriosclerosis; Aspirin; Cardiovascular Diseases; Clopidogrel; Coronary Circulation; Death, Sudden, Cardiac; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors; Streptokinase; Stroke; Thrombosis; Ticlopidine; Time Factors

Platelets are critical modulators of atherothrombotic events. In the acute setting, platelets are activated and aggregate on the surface of atherosclerotic plaque that has ruptured, fissured, or developed erosions. The overlying thrombus leads to sudden development of arterial luminal obstruction, inducing ischemia and cellular necrosis. Inhibiting platelet reactivity is an important therapeutic goal in patients at risk for acute cardiovascular events. The thienopyridines are potent inhibitors of platelet aggregation and block the binding of adenosine 5'-diphosphate to purinergic receptors on the surface of the platelet membrane. The thienopyridine class includes ticlopidine, clopidogrel, and prasugrel. Clopidogrel is the most intensively studied. In recent years it has become apparent that approximately 20% to 25% of patients who would be expected to benefit from clopidogrel therapy are resistant to this drug, largely due to a polymorphism in the gene for cytochrome P450 2C19. The efficacy of clopidogrel can also be reduced if patients are receiving concomitant therapy with a proton pump inhibitor such as omeprazole. Prasugrel is a third-generation thienopyridine with faster time to onset and greater consistency in inhibiting platelet activity, and it has shown superiority to clopidogrel for reducing cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary interventions.

Topics: Hemorrhage; Humans; Prognosis; Pyridines; Risk Factors; Secondary Prevention; Thrombosis

Cilostazol has been associated with reduction in restenosis in patients undergoing coronary and peripheral arterial angioplasty. Our objective was to evaluate the impact of cilostazol on restenosis in patients undergoing contemporary PCI with bare metal (BMS) or drug eluting stents (DES) and treated with aspirin and thienopyridine.. Ten randomised trials (n=2,809 patients) comparing triple antiplatelet therapy (aspirin, thienopyridine and cilostazol) with standard dual antiplatelet therapy were included. Summary risk ratios for restenosis, late loss, target lesion revascularisation (TLR) and target vessel revascularisation (TVR) were calculated using fixed-effects models. Cilostazol was associated with a significant reduction in late loss in BMS (mean difference 0.24 mm, 95% CI 0.15-0.33, p<0.001) and DES groups (mean difference 0.12 mm, 95% CI 0.07-0.18, p<0.001). Cilostazol therapy was associated with a significant reduction in angiographic restenosis (Odds ratio [OR] 0.52, 95% CI 0.41- 0.66, p<0.001) with consistent benefits in patients treated with BMS (OR 0.49, 95% CI 0.35-0.70, p<0.001) or DES (OR 0.54, 95% CI 0.38-0.76, p=0.001). Addition of cilostazol to dual antiplatelet therapy was associated with a significant reduction in TLR (OR 0.38, 95% CI 0.25-0.58, p<0.001), with no difference in subacute stent thrombosis (OR 1.91, 95% CI 0.33-11.08, p=0.47), or major bleeding (OR 0.87, 95% CI 0.44-1.74, P=0.69) but with an increased risk of skin rash (OR 3.67, 95% CI 1.86-7.24, p<0.001).. Cilostazol in addition to dual antiplatelet therapy is associated with a reduction in angiographic restenosis in patients undergoing stent based PCI. This inexpensive drug may be particularly beneficial in patients who are at high risk of restenosis and it should undergo further evaluation in large, definitive randomised controlled trials.

Topics: Aged; Angioplasty, Balloon, Coronary; Aspirin; Cilostazol; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug Therapy, Combination; Drug-Eluting Stents; Exanthema; Female; Hemorrhage; Humans; Male; Metals; Middle Aged; Odds Ratio; Platelet Aggregation Inhibitors; Prosthesis Design; Publication Bias; Pyridines; Randomized Controlled Trials as Topic; Risk Assessment; Stents; Tetrazoles; Thrombosis; Treatment Outcome

In a series of articles the authors consider clinical pharmacology and experience of clinical application of blockers of platelet P2Y12 receptors, most well known representatives of which ticlopidine and clopidogrel according to chemical structure belong to thienopyridine derivatives. In the third communication we consider data of randomized studies in which efficacy and safety of clopidogrel monotherapy has been assessed in comparison with acetylsalicylic acid (ASA), ticlopidine, warfarin, as well as ASA in combination with extended release form of dipyridamole in various cardio-vascular diseases. Results of these studies indicate that efficacy of monotherapy with clopidogrel is comparable with that of ASA, ticlopidine, warfarin, and ASA in combination with extended release form of dipyridamole. Clopidogrel significantly more rarely causes ulcerogenic and other hemorrhagic complications than ticlopidine, but is substantially more expensive. Therefore prescribing of clopidogrel as monotherapy is justified only in those cases when ASA and ticlopidine are contraindicated or induce pronounced side effects.

Topics: Aspirin; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Pyridines; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Ticlopidine; Ulcer

The importance of the dissolution and prevention of thrombosis in treating patients with ST-segment elevation myocardial infarction (STEMI) has motivated the development of novel therapies targeting platelet aggregation and thrombus formation. In contemporary practice, the current challenge is the integration of these therapies into reperfusion strategies that may include fibrinolytic therapy or percutaneous coronary revascularization (PCI). Evidence from clinical trials shows that addition of glycoprotein IIb/IIIa inhibition to PCI for treatment of STEMI has substantially lowered the incidence of recurrent ischemic events and improved early survival. In contrast, current trials evaluating a strategy termed facilitated PCI, or planned early PCI after pharmacologic reperfusion therapy, have presently demonstrated an increased risk of bleeding events and mortality. Additional trials have extended the role of antithrombotic agents to STEMI that previously were reserved for patients undergoing elective revascularization or among those treated with non-ST-segment elevation acute coronary syndromes. For example, the recent studies have demonstrated the benefit of clopidogrel treatment among STEMI patients treated with fibrinolysis in reducing the incidence of infarct artery reocclusion and improving early survival. Other anticoagulants under investigation in the management of STEMI include enoxaparin, bivalirudin, and fondaparinux. This review summarizes the current status of pharmacologic and invasive strategies for the treatment of STEMI and describes recent and ongoing directions for clinical investigation.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Blood Platelets; Cardiovascular Diseases; Clinical Trials as Topic; Combined Modality Therapy; Drug Therapy, Combination; Fibrinolysis; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Research Design; Treatment Outcome

Patients with a recent acute coronary syndrome (ACS) receiving oral antiplatelets and anticoagulants are at risk for bleeding and subsequent adverse non-bleeding-related events.. In this post hoc analysis, we evaluated 7,392 high-risk patients (median follow-up 241 days) with a recent ACS randomized to apixaban or placebo in APPRAISE-2. Clinical events during a 30-day period after Thrombolysis in Myocardial Infarction (TIMI) major/minor bleeding were analyzed using unadjusted and adjusted Cox proportional-hazards models.. In total, 153 (2.1%) patients experienced TIMI major/minor bleeding during follow-up. Bleeding risk for patients on triple therapy (apixaban, thienopyridine, and aspirin) was increased compared with those on dual therapy (apixaban plus aspirin: hazard ratio [HR] 2.02, 95% CI 1.08-3.79; thienopyridine plus aspirin: HR 1.99, 95% CI 1.41-2.83). Those receiving apixaban/aspirin had similar bleeding risk compared with those receiving thienopyridine/aspirin (HR 1.01, 95% CI 0.53-1.95). Patients who experienced TIMI major/minor bleeding had an increased risk of 30-day all-cause mortality (HR 24.7, 95% CI 15.34-39.66) and ischemic events (HR 6.7, 95% CI 3.14-14.14).. In a contemporary cohort of high-risk patients after ACS, bleeding was associated with a significantly increased risk of subsequent ischemic events and mortality regardless of antithrombotic or anticoagulant strategy. Patients receiving apixaban plus aspirin had a similar bleeding risk compared with those receiving thienopyridine plus aspirin. Interventions to improve outcomes in patients after ACS should include strategies to optimize the reduction in ischemic events while minimizing the risk of bleeding.

Topics: Aged; Aspirin; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Outcome and Process Assessment, Health Care; Platelet Aggregation Inhibitors; Proportional Hazards Models; Pyrazoles; Pyridines; Pyridones; Risk Assessment; Risk Factors; Thrombolytic Therapy

Vorapaxar is effective in the prevention of secondary atherothrombotic events, although the efficacy/safety balance appears less favorable in the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS). We hypothesized that patients with NSTE ACS already receiving thienopyridine prior to the ACS event may show differential efficacy/safety effects with vorapaxar vs. placebo added to their standard care.. We studied 12,944 patients from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial with respect to thienopyridine use before admission for the index NSTE ACS event. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, rehospitalization for ischemia, and urgent revascularization. The key secondary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Safety endpoints were bleeding complications.. TRACER was largely conducted in thienopyridine-naïve patients with unknown tolerance to multiple antiplatelet treatments. Patients receiving thienopyridine before the index event may have had an attenuated increase in bleeding when adding vorapaxar, whereas concomitantly adding vorapaxar and thienopyridine in naïve patients may have uncovered a latent susceptibility to bleeding.

Topics: Acute Coronary Syndrome; Aged; Female; Hemorrhage; Humans; Lactones; Male; Middle Aged; Platelet Aggregation Inhibitors; Pyridines; Secondary Prevention; Treatment Outcome

In the dual antiplatelet therapy (DAPT) study, continued thienopyridine beyond 12 months after drug-eluting stent placement was associated with increased mortality compared with placebo. We sought to evaluate factors related to mortality in randomized patients receiving either drug-eluting or bare metal stents in the DAPT study.. Patients were enrolled after coronary stenting, given thienopyridine and aspirin for 12 months, randomly assigned to continued thienopyridine or placebo for an additional 18 months (while taking aspirin), and subsequently treated with aspirin alone for another 3 months. A blinded independent adjudication committee evaluated deaths. Among 11 648 randomized patients, rates of all-cause mortality rates were 1.9 vs. 1.5% (continued thienopyridine vs. placebo, P = 0.07), cardiovascular mortality, 1.0 vs. 1.0% (P = 0.97), and non-cardiovascular mortality, 0.9 vs. 0.5% (P = 0.01) over the randomized period (Months 12-30). Rates of fatal bleeding were 0.2 vs. 0.1% (P = 0.81), and deaths related to any prior bleeding were 0.3 vs. 0.2% (P = 0.36), Months 12-33). Cancer incidence did not differ (2.0 vs. 1.6%, P = 0.12). Cancer-related deaths occurred in 0.6 vs. 0.3% (P = 0.02) and were rarely related to bleeding (0.1 vs. 0, P = 0.25). After excluding those occurring in patients with cancer diagnosed before enrolment, rates were 0.4 vs. 0.3% (P = 0.16).. Bleeding accounted for a minority of deaths among patients treated with continued thienopyridine. Cancer-related death in association with thienopyridine therapy was mainly not related to bleeding and may be a chance finding. Caution is warranted when considering extended thienopyridine in patients with advanced cancer.. clinicaltrials.gov Identifier: NCT00977938.

Topics: Aspirin; Cause of Death; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Neoplasms; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pyridines; Treatment Outcome

The purpose of this study was to characterize outcomes for everolimus-eluting stent (EES)-treated subjects according to treatment with continued thienopyridine plus aspirin versus aspirin alone 12 to 30 months after stenting.. In the DAPT (Dual Antiplatelet Therapy) study, continued thienopyridine plus aspirin beyond 1 year after coronary stenting reduced ischemic events. Given low rates of stent thrombosis and myocardial infarction (MI) for current drug-eluting stents, we examined outcomes among EES-treated subjects in the DAPT study.. The DAPT study enrolled 25,682 subjects (11,308 EES-treated) after coronary stenting. Following 12 months of treatment with thienopyridine and aspirin, eligible subjects continued treatment with aspirin and 9,961 (4,703 with EES) were randomized to 18 months of continued thienopyridine or placebo. Stent type was not randomized, and the EES subset analysis was post hoc.. Among EES-treated patients, continued thienopyridine reduced stent thrombosis (0.3% vs. 0.7%, hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.15 to 0.97; p = 0.04) and MI (2.1% vs. 3.2%, HR: 0.63, 95% CI: 0.44 to 0.91; p = 0.01) versus placebo but did not reduce a composite of death, MI, and stroke (4.3% vs. 4.5%, HR: 0.89, 95% CI: 0.67 to 1.18; p = 0.42), and increased moderate/severe bleeding (2.5% vs. 1.3%, HR: 1.79, 95% CI: 1.15 to 2.80; p = 0.01), and death (2.2% vs. 1.1%, HR: 1.80, 95% CI: 1.11 to 2.92; p = 0.02). Death due to cancer and not related to bleeding was increased (0.64% vs. 0.17%; p = 0.01).. In EES-treated subjects, significant reductions in stent thrombosis and MI and an increase in bleeding were observed with continued thienopyridine beyond 1 year compared with aspirin alone. (The Dual Antiplatelet Therapy Study [DAPT Study]); NCT00977938).

Topics: Aged; Aspirin; Cardiovascular Agents; Coronary Artery Disease; Coronary Thrombosis; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Everolimus; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prosthesis Design; Pyridines; Risk Factors; Time Factors; Treatment Outcome

Dual antiplatelet therapy after percutaneous coronary intervention (PCI) reduces ischemia but increases bleeding.. To develop a clinical decision tool to identify patients expected to derive benefit vs harm from continuing thienopyridine beyond 1 year after PCI.. Among 11,648 randomized DAPT Study patients from 11 countries (August 2009-May 2014), a prediction rule was derived stratifying patients into groups to distinguish ischemic and bleeding risk 12 to 30 months after PCI. Validation was internal via bootstrap resampling and external among 8136 patients from 36 countries randomized in the PROTECT trial (June 2007-July 2014).. Twelve months of open-label thienopyridine plus aspirin, then randomized to 18 months of continued thienopyridine plus aspirin vs placebo plus aspirin.. Ischemia (myocardial infarction or stent thrombosis) and bleeding (moderate or severe) 12 to 30 months after PCI.. Among DAPT Study patients (derivation cohort; mean age, 61.3 years; women, 25.1%), ischemia occurred in 348 patients (3.0%) and bleeding in 215 (1.8%). Derivation cohort models predicting ischemia and bleeding had c statistics of 0.70 and 0.68, respectively. The prediction rule assigned 1 point each for myocardial infarction at presentation, prior myocardial infarction or PCI, diabetes, stent diameter less than 3 mm, smoking, and paclitaxel-eluting stent; 2 points each for history of congestive heart failure/low ejection fraction and vein graft intervention; -1 point for age 65 to younger than 75 years; and -2 points for age 75 years or older. Among the high score group (score ≥2, n = 5917), continued thienopyridine vs placebo was associated with reduced ischemic events (2.7% vs 5.7%; risk difference [RD], -3.0% [95% CI, -4.1% to -2.0%], P < .001) compared with the low score group (score <2, n = 5731; 1.7% vs 2.3%; RD, -0.7% [95% CI, -1.4% to 0.09%], P = .07; interaction P < .001). Conversely, continued thienopyridine was associated with smaller increases in bleeding among the high score group (1.8% vs 1.4%; RD, 0.4% [95% CI, -0.3% to 1.0%], P = .26) compared with the low score group (3.0% vs 1.4%; RD, 1.5% [95% CI, 0.8% to 2.3%], P < .001; interaction P = .02). Among PROTECT patients (validation cohort; mean age, 62 years; women, 23.7%), ischemia occurred in 79 patients (1.0%) and bleeding in 37 (0.5%), with a c statistic of 0.64 for ischemia and 0.64 for bleeding. In this cohort, the high-score patients (n = 2848) had increased ischemic events compared with the low-score patients and no significant difference in bleeding.. Among patients not sustaining major bleeding or ischemic events 1 year after PCI, a prediction rule assessing late ischemic and bleeding risks to inform dual antiplatelet therapy duration showed modest accuracy in derivation and validation cohorts. This rule requires further prospective evaluation to assess potential effects on patient care, as well as validation in other cohorts.. clinicaltrials.gov Identifier: NCT00977938.

Topics: Age Factors; Aged; Antineoplastic Agents, Phytogenic; Aspirin; Diabetes Mellitus; Drug-Eluting Stents; Female; Hemorrhage; Humans; Ischemia; Linear Models; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pyridines; Risk Assessment; Risk Factors; Smoking; Thrombosis; Time Factors

The DAPT (Dual Antiplatelet Therapy) study enrolled patients after coronary stenting. Patients randomized to continued thienopyridine and aspirin after 12 months had lower ischemic risk but higher bleeding risk than those treated with placebo and aspirin.. This study sought to determine whether a decision tool (DAPT score) aids prescription of dual antiplatelet therapy duration in patients with or without prior myocardial infarction (MI) treated with coronary stents.. Patients were categorized according to any history of MI before the index procedure or no history of MI. Risk differences during the randomized treatment period (12 to 30 months) for ischemic (MI and/or stent thrombosis) and bleeding (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries moderate/severe) events were compared according to DAPT score.. Rates of MI were 3.8% versus 2.4% (p = 0.01) for patients with any MI versus no MI. Continued thienopyridine reduced late MI compared with placebo regardless of MI history (hazard ratio [HR] for any MI: 0.46; p < 0.001; HR for no MI: 0.60; p = 0.003) and increased bleeding (HR: 1.86, p = 0.01 any MI; HR: 1.58, p = 0.01 no MI). DAPT scores ≥2 were associated with reductions in MI/stent thrombosis with continued thienopyridine compared with placebo (2.7% vs. 6.0%, p < 0.001 any MI; 2.6% vs. 5.2%, p = 0.002 no MI), with comparable bleeding rates. Among patients with DAPT scores <2 in both groups, continued thienopyridine was associated with significantly increased bleeding but similar rates of ischemia.. Patients with previous MI have greater risk of late ischemic events than those with no MI history. The DAPT score improves prediction of patient benefit and harm from continued dual antiplatelet therapy beyond assessment of MI history alone. (The Dual Antiplatelet Therapy Study; NCT00977938).

Topics: Aspirin; Decision Support Techniques; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pyridines; Risk Assessment; Secondary Prevention; Stents; Thrombosis

Despite antirestenotic efficacy of coronary drug-eluting stents (DES) compared with bare metal stents (BMS), the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Although dual antiplatelet therapy (DAPT) beyond 1 year provides ischemic event protection after DES, ischemic event risk is perceived to be less after BMS, and the appropriate duration of DAPT after BMS is unknown.. To compare (1) rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE; composite of death, myocardial infarction, or stroke) after 30 vs 12 months of thienopyridine in patients treated with BMS taking aspirin and (2) treatment duration effect within the combined cohorts of randomized patients treated with DES or BMS as prespecified secondary analyses.. International, multicenter, randomized, double-blinded, placebo-controlled trial comparing extended (30-months) thienopyridine vs placebo in patients taking aspirin who completed 12 months of DAPT without bleeding or ischemic events after receiving stents. The study was initiated in August 2009 with the last follow-up visit in May 2014.. Continued thienopyridine or placebo at months 12 through 30 after stent placement, in 11,648 randomized patients treated with aspirin, of whom 1687 received BMS and 9961 DES.. Stent thrombosis, MACCE, and moderate or severe bleeding.. Among 1687 patients treated with BMS who were randomized to continued thienopyridine vs placebo, rates of stent thrombosis were 0.5% vs 1.11% (n = 4 vs 9; hazard ratio [HR], 0.49; 95% CI, 0.15-1.64; P = .24), rates of MACCE were 4.04% vs 4.69% (n = 33 vs 38; HR, 0.92; 95% CI, 0.57-1.47; P = .72), and rates of moderate/severe bleeding were 2.03% vs 0.90% (n = 16 vs 7; P = .07), respectively. Among all 11,648 randomized patients (both BMS and DES), stent thrombosis rates were 0.41% vs 1.32% (n = 23 vs 74; HR, 0.31; 95% CI, 0.19-0.50; P < .001), rates of MACCE were 4.29% vs 5.74% (n = 244 vs 323; HR, 0.73; 95% CI, 0.62-0.87; P < .001), and rates of moderate/severe bleeding were 2.45% vs 1.47% (n = 135 vs 80; P < .001).. Among patients undergoing coronary stent placement with BMS and who tolerated 12 months of thienopyridine, continuing thienopyridine for an additional 18 months compared with placebo did not result in statistically significant differences in rates of stent thrombosis, MACCE, or moderate or severe bleeding. However, the BMS subset may have been underpowered to identify such differences, and further trials are suggested.. clinicaltrials.gov Identifier: NCT00977938.

Topics: Aged; Aspirin; Cardiovascular Diseases; Coronary Restenosis; Double-Blind Method; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Intention to Treat Analysis; Male; Middle Aged; Platelet Aggregation Inhibitors; Pyridines; Risk; Stents

The optimal duration of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) is not known. Factors influencing DAPT duration are not well described.. We hypothesized that continued DAPT 12 months beyond ACS would be associated with patient factors such as stent type and that it may be associated with lower rates of ischemic events.. The TIMI 38 Coronary Stent Registry (CSR) followed patients who completed the TRITON-TIMI 38 trial, received a stent, and were alive and event free. Continuation of DAPT was determined by the treating physician.. The CSR enrolled 2110 patients (1679>12 months from index ACS) and followed for a median of 2.1 additional years. DAPT was continued in 554 (26%) and was more likely to be continued in patients with drug-eluting stents (DES; 54%) and in North America. The rate of cardiovascular death, MI, or stroke was 2.35% per year, and 13 patients (0.6%) experienced Academic Research Consortium definite or probable ST. Recurrent ischemic events were similar between patients who continued thienopyridine therapy and those who stopped at registry entry (P = 0.74 for cardiovascular death/MI/stroke; P = 0.72 for definite or probable ST). After propensity score adjustment, there was no significant difference in cardiovascular death/MI/stroke (P = 0.55) or bleeding (P = 0.51) with prolonged DAPT.. Patients stabilized for a year after ACS and stenting have low rates of ST relative to overall cardiovascular events. The decision to continue DAPT maybe associated with stent type (DES vs bare-metal stent) and region.

Topics: Acute Coronary Syndrome; Aged; Combined Modality Therapy; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prospective Studies; Pyridines; Registries; Stents; Stroke; Survival Analysis; Treatment Outcome

Optimum duration of dual antiplatelet treatment (DAPT) after coronary stenting remains uncertain, with an unknown efficacy to safety ratio of extended treatment leading to discrepancies between international guidelines and clinical practice. We assessed whether DAPT continuation beyond 1 year after coronary stenting is beneficial.. This analysis was a planned extension of the previously published ARCTIC-Monitoring trial, in which we randomly allocated 2440 patients to a strategy of platelet function testing with antiplatelet treatment adjustment or a conventional strategy after coronary stenting with drug-eluting stent (DES). We recruited patients (aged 18 years or older) scheduled for planned DES implantation at 38 centres in France. After 1 year of follow-up, patients without contraindication to interruption of DAPT were eligible for a second randomisation to this second phase of the study (ARCTIC-Interruption). Using a computer-generated randomisation sequence (1:1; stratified by centre), we allocated patients to a strategy of interruption of DAPT where the thienopyridine was interrupted and single aspirin antiplatelet treatment was maintained (interruption group) or a strategy of DAPT continuation for 6-18 months (continuation group). The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularisation, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00827411.. Between Jan 4, 2011, and March 3, 2012, 1259 eligible patients were randomly allocated to treatment in ARCTIC-Interruption: 624 to the interruption group and 635 to the continuation group. After a median follow-up of 17 months (IQR 15-18), the primary endpoint occurred in 27 (4%) patients in the interruption group and 24 (4%) patients in the continuation group (hazard ratio [HR] 1·17 [95% CI 0·68-2·03]; p=0·58). STEEPLE major bleeding events occurred more often in the continuation group (seven [1%] patients) compared with the interruption group (one [<0·5%] patient; HR 0·15 [0·02-1·20]; p=0·073). Major or minor bleedings were also more common in the continuation group compared with the interruption group (12 [2%] patients vs three [1%] patients; HR 0·26 [0·07-0·91]; p=0·04).. Our finding suggests no apparent benefit but instead harm with extension of DAPT beyond 1 year after stenting with DES when no event has occurred within the first year after stenting. No conclusion can be drawn for high-risk patients who could not be randomised. The consistency between findings from all trials of such interruption suggests the need for a reappraisal of guidelines for DAPT after coronary stenting towards shorter duration of treatment.. Allies in Cardiovascular Trials Initiatives and Organized Networks (ACTION Study Group), Fondation de France, Sanofi-Aventis, Cordis, Medtronic, Boston Scientific, Fondation SGAM.

Topics: Adolescent; Adult; Aged; Aspirin; Coronary Artery Disease; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Pyridines; Treatment Outcome; Young Adult

We assessed the impact of smoking on outcomes in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention using alternative antithrombotic regimens and stent types. In the HORIZONS-AMI trial 3,602 patients were randomly assigned to unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) or bivalirudin alone and paclitaxel-eluting stents or bare-metal stents. Compared to nonsmokers, smokers had significantly lower rates of mortality and major bleeding at 30 days and at 1 year; however, the differences were no longer significant after covariate adjustment. Smoking was associated with increased rates of definite/probable stent thrombosis (ST) at 1 year (adjusted RR 1.99, 95% confidence interval 1.28 to 3.10) mainly because of a higher rate of late ST after paclitaxel-eluting stent implantation (1.9% vs 0.4%, p = 0.0006). In smokers bivalirudin monotherapy compared to UFH plus a GPI was associated with lower mortality at 30 days (0.5% vs 2.2%, p = 0.002) and at 1 year (1.8% vs 4.0%, p = 0.008). No decrease in mortality was seen with bivalirudin in nonsmokers. Major bleeding was significantly decreased with bivalirudin regardless of smoking status (smokers 3.7% vs 8.9%, p <0.0001; nonsmokers 6.5% vs 9.6%, p = 0.01). In conclusion, in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention, smoking is an independent predictor of definite/probable ST at 1 year. Bivalirudin monotherapy compared to UFH plus a GPI decreased major bleeding regardless of smoking status but may have different effects on individual components of ischemic events.

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Drug Therapy, Combination; Drug Utilization; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Paclitaxel; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Recombinant Proteins; Smoking; Stents

Rivaroxaban is an oral direct factor Xa inhibitor that has been effective in prevention of venous thromboembolism in patients undergoing elective orthopaedic surgery. However, its use after acute coronary syndromes has not been investigated. In this setting, we assessed the safety and efficacy of rivaroxaban and aimed to select the most favourable dose and dosing regimen.. In this double-blind, dose-escalation, phase II study, undertaken at 297 sites in 27 countries, 3491 patients stabilised after an acute coronary syndrome were stratified on the basis of investigator decision to use aspirin only (stratum 1, n=761) or aspirin plus a thienopyridine (stratum 2, n=2730). Participants were randomised within each strata and dose tier with a block randomisation method at 1:1:1 to receive either placebo or rivaroxaban (at doses 5-20 mg) given once daily or the same total daily dose given twice daily. The primary safety endpoint was clinically significant bleeding (TIMI major, TIMI minor, or requiring medical attention); the primary efficacy endpoint was death, myocardial infarction, stroke, or severe recurrent ischaemia requiring revascularisation during 6 months. Safety analyses included all participants who received at least one dose of study drug; efficacy analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00402597.. Three patients in stratum 1 and 26 in stratum 2 never received the study drug. The risk of clinically significant bleeding with rivaroxaban versus placebo increased in a dose-dependent manner (hazard ratios [HRs] 2.21 [95% CI 1.25-3.91] for 5 mg, 3.35 [2.31-4.87] for 10 mg, 3.60 [2.32-5.58] for 15 mg, and 5.06 [3.45-7.42] for 20 mg doses; p<0.0001). Rates of the primary efficacy endpoint were 5.6% (126/2331) for rivaroxaban versus 7.0% (79/1160) for placebo (HR 0.79 [0.60-1.05], p=0.10). Rivaroxaban reduced the main secondary efficacy endpoint of death, myocardial infarction, or stroke compared with placebo (87/2331 [3.9%] vs 62/1160 [5.5%]; HR 0.69, [95% CI 0.50-0.96], p=0.0270). The most common adverse event in both groups was chest pain (248/2309 [10.7%] vs 118/1153 [10.2%]).. The use of an oral factor Xa inhibitor in patients stabilised after an acute coronary syndrome increases bleeding in a dose-dependent manner and might reduce major ischaemic outcomes. On the basis of these observations, a phase III study of low-dose rivaroxaban as adjunctive therapy in these patients is underway.. Johnson & Johnson Pharmaceutical Research & Development and Bayer Healthcare AG.

Topics: Acute Coronary Syndrome; Administration, Oral; Aspirin; Chest Pain; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Myocardial Infarction; Proportional Hazards Models; Pyridines; Recurrence; Risk Reduction Behavior; Rivaroxaban; Safety; Statistics, Nonparametric; Stroke; Thiophenes; Treatment Outcome

Cilostazol has been associated with reduction in restenosis in patients undergoing coronary and peripheral arterial angioplasty. Our objective was to evaluate the impact of cilostazol on restenosis in patients undergoing contemporary PCI with bare metal (BMS) or drug eluting stents (DES) and treated with aspirin and thienopyridine.. Ten randomised trials (n=2,809 patients) comparing triple antiplatelet therapy (aspirin, thienopyridine and cilostazol) with standard dual antiplatelet therapy were included. Summary risk ratios for restenosis, late loss, target lesion revascularisation (TLR) and target vessel revascularisation (TVR) were calculated using fixed-effects models. Cilostazol was associated with a significant reduction in late loss in BMS (mean difference 0.24 mm, 95% CI 0.15-0.33, p<0.001) and DES groups (mean difference 0.12 mm, 95% CI 0.07-0.18, p<0.001). Cilostazol therapy was associated with a significant reduction in angiographic restenosis (Odds ratio [OR] 0.52, 95% CI 0.41- 0.66, p<0.001) with consistent benefits in patients treated with BMS (OR 0.49, 95% CI 0.35-0.70, p<0.001) or DES (OR 0.54, 95% CI 0.38-0.76, p=0.001). Addition of cilostazol to dual antiplatelet therapy was associated with a significant reduction in TLR (OR 0.38, 95% CI 0.25-0.58, p<0.001), with no difference in subacute stent thrombosis (OR 1.91, 95% CI 0.33-11.08, p=0.47), or major bleeding (OR 0.87, 95% CI 0.44-1.74, P=0.69) but with an increased risk of skin rash (OR 3.67, 95% CI 1.86-7.24, p<0.001).. Cilostazol in addition to dual antiplatelet therapy is associated with a reduction in angiographic restenosis in patients undergoing stent based PCI. This inexpensive drug may be particularly beneficial in patients who are at high risk of restenosis and it should undergo further evaluation in large, definitive randomised controlled trials.

Topics: Aged; Angioplasty, Balloon, Coronary; Aspirin; Cilostazol; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug Therapy, Combination; Drug-Eluting Stents; Exanthema; Female; Hemorrhage; Humans; Male; Metals; Middle Aged; Odds Ratio; Platelet Aggregation Inhibitors; Prosthesis Design; Publication Bias; Pyridines; Randomized Controlled Trials as Topic; Risk Assessment; Stents; Tetrazoles; Thrombosis; Treatment Outcome

This analysis sought to investigate the complementary effect of thienopyridine pretreatment and platelet glycoprotein (GP) IIb/IIIa integrin blockade in coronary stent intervention.. Definitive evidence supporting combined antiplatelet therapy consisting of thienopyridine pretreatment and GP IIb/IIIa receptor blockade in patients undergoing percutaneous coronary intervention (PCI) with stent implantation is limited.. We retrospectively analyzed clinical outcomes by thienopyridine use in the 2,040 patients randomized to eptifibatide or placebo who underwent PCI in the ESPRIT trial.. A total of 901 patients received a loading dose of thienopyridine before PCI (group 1), 123 received thienopyridine pretreatment without a loading dose (group 2), and 1,016 were not treated with thienopyridine before PCI (group 3). The composite incidence of death or myocardial infarction at 30 days was significantly lower in group 1 than in groups 2 and 3 combined (OR, 0.71 [95%CI, 0.52-0.99]; P = 0.0417). A similar trend was seen for the composite of death, myocardial infarction, or urgent target vessel revascularization (unadjusted OR, 0.77 [0.57-1.05]; P = 0.1025). After adjusting for baseline characteristics, these differences were no longer significant. No interactions were identified with eptifibatide assignment for any of the group comparisons.. Pretreatment with a loading dose of thienopyridine lowers the rate of ischemic complications regardless of treatment with a GP IIb/IIIa inhibitor. Conversely, the efficacy of eptifibatide is maintained whether or not a loading dose of a thienopyridine is administered. Optimal outcomes are achieved in patients receiving thienopyridine pretreatment along with platelet GP IIb/IIIa inhibitor therapy.

Topics: Aged; Angioplasty, Balloon, Coronary; Clopidogrel; Drug Administration Schedule; Drug Therapy, Combination; Eptifibatide; Female; Hemorrhage; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Peptides; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Retrospective Studies; Risk Assessment; Stents; Ticlopidine; Time Factors; Treatment Outcome

Despite the current standard antiplatelet regimen of aspirin and clopidogrel (with or without glycoprotein IIb/IIIa inhibitors) in percutaneous coronary intervention patients, periprocedural and postprocedural ischemic events continue to occur. Prasugrel (CS-747, LY640315), a novel potent thienopyridine P2Y(12) receptor antagonist, has the potential to achieve higher levels of inhibition of ADP-induced platelet aggregation than currently approved doses of clopidogrel.. Joint Utilization of Medications to Block Platelets Optimally-Thrombolysis In Myocardial Infarction 26 (JUMBO-TIMI 26) was a phase 2, randomized, dose-ranging, double-blind safety trial of prasugrel versus clopidogrel in 904 patients undergoing elective or urgent percutaneous coronary intervention. Patients were randomized to either standard dosing with clopidogrel or 1 of 3 prasugrel regimens. Subjects were monitored for 30 days for bleeding and clinical events. The primary end point of the trial was clinically significant (TIMI major plus minor) non-CABG-related bleeding events in prasugrel- versus clopidogrel-treated patients. Hemorrhagic complications were infrequent, with no significant difference between patients treated with prasugrel or clopidogrel in the rate of significant bleeding (1.7% versus 1.2%; hazard ratio, 1.42; 95% CI, 0.40, 5.08). In prasugrel-treated patients, there were numerically lower incidences of the primary efficacy composite end point (30-day major adverse cardiac events) and of the secondary end points myocardial infarction, recurrent ischemia, and clinical target vessel thrombosis.. In this phase 2 study, which was designed to assess safety when administered at the time of percutaneous coronary intervention, prasugrel and clopidogrel both resulted in low rates of bleeding. The results of this trial serve as a foundation for the large phase 3 clinical trial designed to assess both efficacy and safety.

Topics: Adolescent; Adult; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Diseases; Clopidogrel; Dose-Response Relationship, Drug; Double-Blind Method; Female; Hemorrhage; Humans; Incidence; Male; Membrane Proteins; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Pyridines; Receptors, Purinergic P2Y12; Thiophenes; Ticlopidine

Biological age is a strong determinant of prognosis in patients with acute myocardial infarction (AMI). We sought to examine the impact of age after primary percutaneous coronary intervention in AMI and to determine whether routine coronary stent implantation and/or platelet glycoprotein IIb/IIIa inhibitors improve clinical outcomes in elderly patients after primary angioplasty.. In the CADILLAC trial, 2082 patients with AMI were randomized to balloon angioplasty, angioplasty plus abciximab, stenting alone, or stenting plus abciximab. No patient was excluded on the basis of advanced age; patients ranging from 21 to 95 years of age were enrolled. One-year mortality increased for each decile of age, exponentially after 65 years of age (1.6% for patients <55 years, 2.1% for 55 to 65 years, 7.1% for 65 to 75 years, 11.1% for patients >75 years; P<0.0001). Elderly patients also had increased rates of stroke and major bleeding compared with their younger counterparts. Among elderly patients (> or =65 years), 1-year rates of ischemic target revascularization (7.0% versus 17.6%; P<0.0001) and subacute or late thrombosis (0% versus 2.2%; P=0.005) were reduced with stenting compared with balloon angioplasty. Routine abciximab administration, although safe, was not of definite benefit in elderly patients. Rates of mortality, reinfarction, disabling stroke, and major bleeding in the elderly were independent of reperfusion modality.. Despite contemporary mechanical reperfusion strategies, mortality, major bleeding, and stroke rates remain high in elderly patients undergoing primary percutaneous coronary intervention, outcomes that are not affected by stents or glycoprotein IIb/IIIa inhibitors. By reducing restenosis, however, stent implantation improves clinical outcomes in elderly patients with AMI.

Topics: Abciximab; Adrenergic beta-Antagonists; Adult; Age Factors; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Aspirin; Cohort Studies; Combined Modality Therapy; Coronary Angiography; Coronary Restenosis; Female; Hemorrhage; Humans; Immunoglobulin Fab Fragments; Life Tables; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Pyridines; Stents; Stroke; Treatment Outcome

According to the Italian National Report on drug use, thienopyridines (ticlopidine, clopidogrel and prasugrel) and ticagrelor represent the most prescribed antiplatelet agents, beside aspirin. The aim of this study was to analyse the safety profile of these drugs using data from spontaneous reporting of suspected adverse reactions (ADRs).. Suspected ADRs for ticlopidine, clopidogrel, prasugrel and ticagrelor, reported on the Italian National Pharmacovigilance Network between January 2009 and December 2016, were included in the analysis. All suspected ADRs were classified by frequency, seriousness, outcome, age and system organ class.. Clopidogrel showed the highest absolute number of suspected ADRs, followed by ticlopidine. However, these data need to be contextualized in view of the differences in marketing authorization dates, prescription rates and a characterization of the relative seriousness of ADRs per each drug. After the correction for prescription rate, ticagrelor showed the highest reporting trend and ticlopidine the lowest. Most ADRs occurred in the elderly, in particular for ticlopidine. Bleeding represents one of the most reported events (ticlopidine 40%, clopidogrel 26%, prasugrel 42%, ticagrelor 30%) and aspirin was the most frequently associated suspected drug. The majority of ADRs had complete recovery and were non-serious, except for ticlopidine (serious ADRs 53%). Prasugrel showed the highest percentage of 'life-threatening' events and 'death'.. Based on the analysis conducted on spontaneous ADRs reporting system in Italy, the safety profile of antiplatelet drugs seems favourable. However, the overall risk-benefit ratio of these drugs needs to be reassessed taking into account the appropriateness of use in particular populations at risk, such as the elderly. Based on this information, we believe that more attention from clinicians and/or an implementation of regulatory measures could be useful for clinical practice.

Topics: Adenosine; Adult; Aged; Aged, 80 and over; Aspirin; Female; Hemorrhage; Humans; Italy; Male; Middle Aged; Pharmacovigilance; Platelet Aggregation Inhibitors; Pyridines; Ticagrelor

Early cardiovascular and bleeding events after coronary stenting are associated with high risk of morbidity and mortality.. To assess the prognosis of cardiovascular and bleeding events occurring beyond 1 year after coronary stenting.. This secondary analysis is derived from data from the Dual Antiplatelet Therapy (DAPT) Study, a multicenter trial involving 220 US and international clinical sites from 11 countries. The study dates were August 2009 to May 2014. Individuals who underwent coronary stenting and completed 12 months of thienopyridine plus aspirin therapy without ischemic or bleeding events remained on an aspirin regimen and were randomized to continued thienopyridine therapy vs placebo for 18 additional months. Individuals were then followed up for 3 additional months while receiving aspirin therapy alone. The analysis began in August 2015.. Ischemic events (myocardial infarction not related to stent thrombosis, stent thrombosis, and ischemic stroke) and bleeding events (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries [GUSTO] classification moderate or severe bleeding).. Ischemic events (myocardial infarction not related to stent thrombosis, stent thrombosis, and ischemic stroke) and bleeding events (GUSTO classification moderate or severe bleeding). Death at 21 months after randomization (33 months after coronary stenting).. In total, 25 682 individuals older than 18 years with an indication for coronary stenting were enrolled, and 11 648 (mean age, 61.3 years; 25.1% female) were randomized. After randomization, 478 individuals (4.1%) had 502 ischemic events (306 with myocardial infarction, 113 with stent thrombosis, and 83 with ischemic stroke), and 232 individuals (2.0%) had 235 bleeding events (155 with moderate and 80 with severe bleeding). Among individuals with ischemic events, 52 (10.9%) died. The annualized mortality rate after an ischemic event was 27.2 (95% CI, 20.3-35.7) per 100 person-years. The cumulative incidence of death after an ischemic event among the total randomized study population was 0.5% (0.3% with myocardial infarction, 0.1% with stent thrombosis, and 0.1% with ischemic stroke). Among individuals with bleeding events, 41 (17.7%) died. The annualized mortality rate after a bleeding event was 21.5 (95% CI, 15.4-29.1) per 100 person-years. The cumulative incidence of death after a bleeding event among the total randomized study population was 0.3% (0.1% with moderate and 0.2% with severe bleeding).. In patients treated with dual antiplatelet therapy for at least 1 year after coronary stenting, ischemic events were more frequent than bleeding events, and both events were associated with high risk of mortality.. clinicaltrials.gov Identifier: NCT00977938.

Topics: Aged; Aspirin; Brain Ischemia; Coronary Artery Disease; Coronary Thrombosis; Drug Therapy, Combination; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Mortality; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Pyridines; Stents; Stroke

Patients with diabetes mellitus (DM) experience higher rates of in-stent restenosis and greater benefit from drug-eluting stents implant at the time of percutaneous coronary intervention (PCI), necessitating prolonged dual anti-platelet therapy (DAPT). While DAPT reduces risk of ischemic events post-PCI, it also increases risk of bleeding. Whether bleeding rates differ among patients with and without DM, receiving long-term DAPT is unknown.. Among patients who underwent PCI and were maintained on DAPT for 1 year in a multicenter US registry, we assessed patient-reported bleeding over one year following PCI in patients with and without DM. Multivariable, hierarchical Poisson regression was used to evaluate the association of DM with bleeding during follow-up.. Among 2334 PCI patients from 10 US hospitals (mean age 64, 54% ACS), 32.6% had DM. In unadjusted analyses, patients with DM had fewer bleeding events over the year following PCI (DM vs no DM: BARC = 1: 78.0% vs 87.7%, P < .001; BARC ≥2: 4.3% vs 5.3%, P = .33). Following adjustment, patients with (vs without DM) had a lower risk of BARC ≥1 bleeding during follow-up (relative risk [RR] 0.89, 95% CI 0.83-0.96). This decreased bleeding risk persisted after removing bruising from the endpoint definition.. In a real-world PCI registry, patients with DM experienced lower risk of bleeding risk on DAPT. As patients with DM also derive greater ischemic benefit from drug-eluting stents, which requires prolonged DAPT, our findings suggest that the balance between benefit and risk of this therapeutic approach may be even more favorable in patients with DM than previously considered.

Topics: Aged; Aspirin; Comorbidity; Coronary Artery Disease; Diabetes Mellitus; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Long Term Adverse Effects; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Pyridines; Registries; Risk Assessment

The optimal antithrombotic regimen in patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation for complex coronary artery disease is unclear. We compared the net clinical outcomes of triple antithrombotic therapy (TAT; aspirin, thienopyridine, and warfarin) and dual antiplatelet therapy (DAPT; aspirin and thienopyridine) in AF patients who had undergone DES implantation.. A total of 367 patients were enrolled and analyzed retrospectively; 131 patients (35.7%) received TAT and 236 patients (64.3%) received DAPT. DAPT and warfarin were maintained for a minimum of 12 and 24 months, respectively. The primary endpoint was the 2-year net clinical outcomes, a composite of major bleeding and major adverse cardiac and cerebral events (MACCE). Propensity score-matching analysis was carried out in 99 patient pairs.. The 2-year net clinical outcomes of the TAT group were worse than those of the DAPT group (34.3 vs. 21.1%, P=0.006), which was mainly due to the higher incidence of major bleeding (16.7 vs. 4.6%, P<0.001), without any significant increase in MACCE (22.1 vs. 17.7%, P=0.313). In the multivariate analysis, TAT was an independent predictor of worse net clinical outcomes (odds ratio 1.63, 95% confidence interval 1.06-2.50) and major bleeding (odds ratio 3.54, 95% confidence interval 1.65-7.58). After propensity score matching, the TAT group still had worse net clinical outcomes and a higher incidence of major bleeding compared with the DAPT group.. In AF patients undergoing DES implantation, prolonged administration of TAT may be harmful due to the substantial increase in the risk for major bleeding without any reduction in MACCE.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Cerebrovascular Disorders; Chi-Square Distribution; Coronary Artery Disease; Drug Therapy, Combination; Female; Fibrinolytic Agents; Hemorrhage; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Propensity Score; Proportional Hazards Models; Pyridines; Republic of Korea; Retrospective Studies; Risk Factors; Stents; Time Factors; Treatment Outcome; Warfarin

Coronary artery disease remains a leading cause of morbidity and mortality worldwide. Each year, millions of patients undergo stent placement to treat coronary artery disease. As stents are prone to thrombosis, which can potentially be devastating, patients are treated with dual antiplatelet therapy with aspirin plus a thienopyridine for at least 6-12 months after stent placement. New evidence suggests that long-term dual antiplatelet therapy beyond 1 year prevents ischemic events but also leads to increased risk of bleeding. To determine the optimal strategy for dual antiplatelet therapy after stent placement, the benefits and risks must be carefully considered and individualized for each patient.

Topics: Aspirin; Coronary Artery Disease; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Pyridines; Risk; Stents; Thrombosis

Optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation has not been yet fully elucidated.. We assessed the influence of prolonged thienopyridine therapy on clinical outcomes with landmark analysis at 4 and 13 months after DES implantation. Among 6802 patients with at least 1 DES implantation in the CREDO-Kyoto Registry Cohort-2, 6309 patients (on thienopyridine, 5438 patients; off thienopyridine, 871 patients) and 5901 patients (on thienopyridine, 4098 patients; off thienopyridine, 1803 patients) were eligible for the 4- and 13-month landmark analyses, respectively. The majority of patients had stable coronary artery disease (73%) and received sirolimus-eluting stents (93%), and approximately 90% of thienopyridine was ticlopidine. Patients taking thienopyridine had more complex comorbidities and more complex lesion and procedural characteristics as compared with patients not taking thienopyridine. After adjusting for confounders, thienopyridine use was not associated with decreased risk for death/myocardial infarction/stroke (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.89-1.43, P=0.32 in the 4-month landmark analysis; HR, 1.14; 95% CI, 0.90-1.45, P=0.29 in the 13-month landmark analysis, respectively), whereas the risk for GUSTO moderate/severe bleeding tended to be higher in patients taking thienopyridine (HR, 1.51; 95% CI, 1.00-2.23, P=0.049 in the 4-month landmark analysis; HR, 1.44; 95% CI, 0.99-2.09, P=0.057 in the 13-month landmark analysis, respectively).. Prolonged thienopyridine therapy beyond 4 and 13 months appeared not to be associated with reduction in ischemic events but to be associated with a trend toward increased bleeding. Optimal duration of DAPT after DES implantation might be shorter than the currently recommended 1-year interval.

Topics: Aged; Angioplasty, Balloon, Coronary; Aspirin; Chi-Square Distribution; Clopidogrel; Cohort Studies; Coronary Artery Disease; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Japan; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prosthesis Design; Pyridines; Registries; Stroke; Ticlopidine; Time Factors; Treatment Outcome

Few studies have examined whether high-responsiveness to antiplatelet therapy is associated with an increased risk of bleeding in patients receiving dual antiplatelet therapy.. Elective drug-eluting stent implantation was performed in 184 patients treated with aspirin and a thienopyridine (200 mg/day of ticlopidine or 75 mg/day of clopidogrel). The subjects were divided into 3 groups according to post-treatment platelet reactivity before stenting as measured by the response to adenosine diphosphate: the 1(st) quartile group was defined as high-responders, the 4(th) as low-responders, and the other 2 quartiles as middle-responders. Major bleeding occurred more frequently in high-responders than in middle- or low-responders during an average of 16 months' follow-up (15 vs 4, 2%, P=0.02). High-responsiveness was the independent predictor of major bleeding (odds ratio 4.26, P=0.03). Adverse cardiac events were less frequent in high- and middle-responders than in low-responders (24, 16 vs 37%, P=0.02). Middle-responders had better net clinical outcomes, defined as the sum of major bleeding and adverse cardiac events, than did high- or low-responders (21 vs 39, 39%, P=0.02).. In the present study high-responsiveness to antiplatelet therapy was associated with an increased risk of bleeding with no reduction in adverse cardiac events. Measuring platelet reactivity may be useful for risk stratification according to bleeding complications, as well as adverse cardiac events, in patients treated with drug-eluting stents.

Topics: Aged; Angioplasty, Balloon, Laser-Assisted; Aspirin; Clopidogrel; Coronary Artery Disease; Drug Therapy, Combination; Drug-Eluting Stents; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Myocardial Ischemia; Platelet Aggregation Inhibitors; Pyridines; Retrospective Studies; Risk Factors; Ticlopidine; Treatment Outcome

Although combination therapy for various cardiac conditions with dual antiplatelet therapy (aspirin and thienopyridine derivatives) and warfarin sodium has become increasingly popular, the safety and effectiveness of this aggressive treatment regimen remain unknown.. We retrospectively enrolled and analyzed 575 consecutive patients who had been implanted with drug-eluting coronary stents. The primary and secondary endpoints were major bleeding complications and major adverse cardiovascular events (MACE), respectively. At the time of discharge, 525 patients (91.3%) were prescribed with dual antiplatelet therapy, and 50 (8.7%) of them received dual antiplatelet plus anticoagulant therapy (triple therapy). The patients treated with triple therapy had a greater prevalence of comorbid conditions, including left ventricular systolic dysfunction and multi-vessel coronary disease compared to those on the dual antiplatelet regimen. During a median follow-up of 459 days, 14 (2.7%) patients receiving dual, and 9 (18.0%) receiving triple therapy reached the primary endpoint (p<0.001). These results show that warfarin use was associated with an increased risk of subsequent major bleeding. On the other hand, the incidence of MACE did not differ between the two groups (p=0.108 by the log-rank test). Multivariate analysis showed that renal impairment was an independent predictor of the risk of subsequent major bleeding in the triple therapy group.. Triple therapy increased the hemorrhagic complications in patients after percutaneous coronary intervention with drug-eluting stents, especially in patients with impaired renal function. Great caution should be taken with patients who necessitate the addition of anticoagulation therapy with warfarin to dual antiplatelet therapy.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Cardiovascular Diseases; Coronary Disease; Drug-Eluting Stents; Female; Hemorrhage; Humans; Kidney Diseases; Male; Platelet Aggregation Inhibitors; Prognosis; Pyridines; Retrospective Studies; Ventricular Dysfunction; Warfarin

To investigate how thienopyridine treatment, with or without associated fibrinolysis, affects the rates of major bleeding and inhospital death in patients with ST-elevation myocardial infarction (STEMI).. The rates of major bleeding and in-hospital death were studied in 14,259 consecutive patients with STEMI. During hospitalization, 5340 (38%) received thienopyridines, 3007 (21%) received fibrinolytic drugs, and 2044 (14%) received both.. Major bleeding occurred more frequently in patients who received thienopyridines with or without fibrinolytics, in 4.6% and 4.1%, respectively, compared with 2.3% in those who received fibrinolytics alone and 2.8% in those who received neither (P< .001). Multivariate analysis, which included adjustments for risk factors for bleeding, percutaneous coronary intervention and cardiac catheterization, showed that thienopyridine treatment was an independent risk factor for bleeding (odds ratio=1.68; 95% confidence interval, 1.23-2.31). In-hospital mortality was lower in patients who received a thienopyridine, and such treatment was an independent predictor of lower mortality (odds ratio=0.50; 95% confidence interval, 0.39-0.60).. Thienopyridine treatment was associated with an increased risk of major bleeding but also with a better in-hospital prognosis. These findings in unselected patients with STEMI, who are representative of those seen in daily clinical practice, complement, but do not replace, the data obtained in randomized clinical trails of selected patients.

Topics: Acute Disease; Aged; Aged, 80 and over; Coronary Disease; Electrocardiography; Endpoint Determination; Female; Fibrinolytic Agents; Hemorrhage; Hospital Mortality; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Pyridines; Registries

Topics: Adenosine; Clinical Trials as Topic; Clopidogrel; Coronary Thrombosis; Cost-Benefit Analysis; Hemorrhage; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Prognosis; Purinergic P2 Receptor Antagonists; Pyridines; Risk Assessment; Survival Rate; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Topics: Anticoagulants; Aspirin; Atrial Fibrillation; Dose-Response Relationship, Drug; Heart Valve Prosthesis; Hemorrhage; Humans; Mitral Valve; Platelet Aggregation Inhibitors; Pyridines; Risk Factors; Thromboembolism

Bleeding among patients with acute myocardial infarction (AMI) is associated with worse long-term outcomes. Although the mechanism underlying this association is unclear, a potential explanation is that withholding antiplatelet therapies long beyond resolution of the bleeding event may contribute to recurrent events.. We examined medication use at discharge, 1, 6, and 12 months after AMI among 2498 patients in the Prospective Registry Evaluating Myocardial Infarction: Events and Recovery (PREMIER) registry. Bleeding was defined as non-coronary artery bypass graft-related Thrombolysis of Myocardial Infarction major/minor bleeding or transfusion among patients with baseline hematocrit > or =28%. Logistic regression was used to evaluate the association between bleeding during the index AMI hospitalization and medication use. In-hospital bleeding occurred in 301 patients (12%) with AMI. Patients with in-hospital bleeding were less likely to be discharged on aspirin or thienopyridine (adjusted odds ratio=0.45; 95% CI, 0.31 to 0.64; and odds ratio=0.62; 95% CI, 0.42 to 0.91, respectively). At 1 month after discharge, although patients with in-hospital bleeding remained significantly less likely to receive aspirin (odds ratio=0.68; 95% CI, 0.50 to 0.92), use of thienopyridines in the 2 groups started to become similar. By 1 year, antiplatelet therapy use was similar among patients with and without bleeding. Postdischarge cardiology follow-up was associated with greater antiplatelet therapy use than either primary care or no clinical follow-up.. Patients whose index AMI is complicated by bleeding are less likely to be treated with antiplatelet therapies during the first 6 months after discharge. Early reassessment of antiplatelet eligibility may represent an opportunity to reduce the long-term risk of adverse outcomes associated with bleeding.

Topics: Acute Disease; Adult; Aged; Aspirin; Female; Follow-Up Studies; Hematocrit; Hemorrhage; Hospitals; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Pyridines; Registries; Regression Analysis

Prolonged periods of dual antiplatelet therapy (DAT), i.e., aspirin plus a thienopyridine, are currently recommended to prevent late drug-eluting stent (DES) thrombosis. The aim of our study was to determine the risk and predictors of bleeding and compliance associated with such prolongation of DAT. In this observational study we examined 2,355 consecutive patients undergoing successful DES implantation at 4 hospitals in Italy from June 2002 to December 2004. Bleeding events occurring on DAT and warfarin or in the first 30 days after stent implantation were excluded. Median duration of DAT was 209 days (interquartile range 178 to 444) and only 158 patients (6.7%) prematurely discontinued DAT. The overall bleeding rate was 1.9% (45), with major bleeding in 19 (0.8%) and minor bleeding in 26 (1.1%). Independent predictors of bleeding were DAT (hazard ratio 19.8, 95% confidence interval [CI] 3.69 to 106.34, p <0.001) and age >65 years (hazard ratio 2.15, 95% CI 1.16 to 4.00, p = 0.02). In patients on DAT, the incidence rate (30 days to 18 months) of any bleeding event was 2.57 per 100 person-years (95% CI 1.85 to 3.48) and major bleeding was 1.10 per 100 person-years (95% CI 0.65 to 1.74). In conclusion, DAT after DES implantation is well tolerated and associated with a very low risk of major bleeding.

Topics: Aged; Angioplasty, Balloon, Coronary; Aspirin; Confidence Intervals; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Immunosuppressive Agents; Incidence; Italy; Male; Middle Aged; Myocardial Infarction; Patient Compliance; Platelet Aggregation Inhibitors; Prospective Studies; Pyridines; Risk Factors; Sirolimus; Time Factors

Thienopyridine use, in particular clopidogrel in acute coronary syndromes, has been associated with an improvement in outcome. However, little information is available regarding their bleeding risk when used in combination with other antithrombotic agents and revascularisation.. In a large, multinational, prospective registry, the Global Registry of Acute Coronary Events, the major bleeding rate (using GRACE criteria) of 27,358 patients with unstable angina or non-ST-elevation myocardial infarction was recorded during index admission. The interaction of thienopyridines on major bleeding with other antithrombotic agents and with revascularisation was analysed.. The 11,478 patients who received thienopyridines during hospitalisation experienced a significant increase in major bleeding (2.8% with thienopyridines, 2.2% without thienopyridines; p=0.002). No significant interaction with glycoprotein IIb/IIIa inhibitors and thienopyridines was seen with regard to bleeding. Thienopyridines with unfractionated heparin did not alter bleeding risk, but thienopyridines with low molecular weight heparin was associated with a significant excess of bleeding (2.1% with thienopyridines, 1.3% without thienopyridines; p=0.004). There was no significant difference in major bleeding with thienopyridines in patients who did or did not undergo revascularisation.. Major bleeding was increased in patients receiving thienopyridines. No increase in bleeding risk was seen in patients having revascularisation.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Bypass; Electrocardiography; Female; Hemorrhage; Hospital Mortality; Humans; International Cooperation; Male; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Revascularization; Probability; Prognosis; Prospective Studies; Pyridines; Registries; Risk Assessment; Severity of Illness Index; Survival Analysis; Thromboembolism

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Contraindications; Cyclooxygenase Inhibitors; Drug Combinations; Drug Monitoring; Drug Prescriptions; Drug Resistance; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Pyridines; Surgical Procedures, Operative; Thrombolytic Therapy; Venous Thrombosis

To assess bleeding complications among patients undergoing percutaneous coronary intervention (PCI) and receiving triple therapy of warfarin, aspirin, and a thienopyridine.. Triple therapy of warfarin, aspirin, and a thienopyridine is strongly discouraged, given the potential risk of bleeding complications.. Post-PCI patients receiving triple therapy thereafter underwent assessment for bleeding complications. Continuous variables are presented as median (25th-75th percentiles). The study group included 180 patients (80% males; age 65 (52, 75.5)). PCI was on an urgent/emergent basis in 86.6%. The main indications for warfarin use were left ventricular mural thrombus and atrial fibrillation (46.9 and 36.9% respectively). Glycoprotein IIb/IIIa receptor antagonists were used in 47.7%. Post-PCI triple therapy duration was 30 days (30, 30). During the post-triple therapy, 104 patients (57.8%) continued treatment with warfarin and aspirin for 376 days (150, 775). During the triple therapy period, 20 patients developed bleeding complications, (mean INR 2.1 +/- 0.7 at 7 (6, 8.5) days post-PCI): 2 major groin hematoma (initial phase of warfarin treatment during overlap with heparin) and 18 minor. During post-triple therapy, primarily under warfarin and aspirin, 19 patients developed bleeding complications: 1 major and 18 minor.. Short-term triple therapy after PCI was not associated with prohibitively high bleeding complication rates, and thus should be favorably considered in patients with a clear indication for warfarin use.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Blood Coagulation Tests; Coronary Angiography; Coronary Disease; Drug Administration Schedule; Drug Therapy, Combination; Echocardiography, Doppler; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Prognosis; Pyridines; Research Design; Retrospective Studies; Survival Analysis; Warfarin