Risk Of Major Bleeding Complications Research Articles

Objectives and Design of BLEEDS: A Cohort Study to Identify New Risk Factors and Predictors for Major Bleeding during Treatment with Vitamin K Antagonists.

BackgroundRisk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients.ObjectivesTo describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations.MethodsA cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR.ResultsOf 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66–2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations.ConclusionBLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment.

Risk stratification and management of acute pulmonary embolism.

The clinical management of patients with acute pulmonary embolism is rapidly changing over the years. The widening spectrum of clinical management strategies for these patients requires effective tools for risk stratification. Patients at low risk for death could be candidates for home treatment or early discharge. Clinical models with high negative predictive value have been validated that could be used to select patients at low risk for death. In a major study and in several meta-analyses, thrombolysis in hemodynamically stable patients was associated with unacceptably high risk for major bleeding complications or intracranial hemorrhage. Thus, the presence of shock or sustained hypotension continues to be the criterion for the selection of candidates for thrombolytic treatment. Interventional procedures for early revascularization should be reserved to selected patients until further evidence is available. No clinical advantage is expected with the insertion of a vena cava filter in the acute-phase management of patients with acute pulmonary embolism. Direct oral anticoagulants used in fixed doses without laboratory monitoring showed similar efficacy (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.70-1.12) and safety (OR, 0.89; 95% CI, 0.77-1.03) in comparison with conventional anticoagulation in patients with acute pulmonary embolism. Based on these results and on their practicality, direct oral anticoagulants are the agents of choice for the treatment of the majority of patients with acute pulmonary embolism.

Antiplatelet versus anticoagulation treatment for patients with heart failure in sinus rhythm.

Morbidity in patients with chronic heart failure is high, and this predisposes them to thrombotic complications, including stroke and thromboembolism, which in turn contribute to high mortality. Oral anticoagulants (e.g. warfarin) and antiplatelet agents (e.g. aspirin) are the principle oral antithrombotic agents. Many heart failure patients with sinus rhythm take aspirin because coronary artery disease is the leading cause of heart failure. Oral anticoagulants have become a standard in the management of heart failure with atrial fibrillation. However, a question remains regarding the appropriateness of oral anticoagulants in heart failure with sinus rhythm. This update of a review previously published in 2012 aims to address this question. To assess the effects of oral anticoagulant therapy versus antiplatelet agents for all-cause mortality, non-fatal cardiovascular events and risk of major bleeding in adults with heart failure (either with reduced or preserved ejection fraction) who are in sinus rhythm. We updated the searches in September 2015 on CENTRAL (The Cochrane Library), MEDLINE and Embase. We searched reference lists of papers and abstracts from cardiology meetings and contacted study authors for further information. We did not apply any language restrictions. Additionally, we searched two clinical trials registers: ClinicalTrials.gov (www.ClinicalTrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) Search Portal apps.who.int/trialsearch/) (searched in July 2016). We included randomised controlled trials comparing antiplatelet therapy versus oral anticoagulation in adults with chronic heart failure in sinus rhythm. Treatment had to last at least one month. We compared orally administered antiplatelet agents (aspirin, ticlopidine, clopidogrel, prasugrel, ticagrelor, dipyridamole) versus anticoagulant agents (coumarins, warfarin, non-vitamin K oral anticoagulants). Two review authors independently assessed trials for inclusion and assessed the risks and benefits of antithrombotic versus antiplatelet therapy using relative measures of effects, such as risk ratios (RR), accompanied with 95% confidence intervals (CI). The data extracted included data relating to the study design, patient characteristics, study eligibility, quality, and outcomes. We used GRADE criteria to assess the quality of the evidence. This update identified one additional study for inclusion, adding data for 2305 participants. This addition more than doubled the overall number of patients eligible for the review. In total, we included four randomised controlled trials (RCTs) with a total of 4187 eligible participants. All studies compared warfarin with aspirin. One RCT additionally compared warfarin with clopidogrel. All included RCTs studied patients with heart failure with reduced ejection fraction.Analysis of all outcomes for warfarin versus aspirin was based on 3663 patients from four RCTs. All-cause mortality was similar for warfarin and aspirin (RR 1.00, 95% CI 0.89 to 1.13; 4 studies; 3663 participants; moderate quality evidence). Oral anticoagulation was associated with a reduction in non-fatal cardiovascular events, which included non-fatal stroke, myocardial infarction, pulmonary embolism, peripheral arterial embolism (RR 0.79, 95% CI 0.63 to 1.00; 4 studies; 3663 participants; moderate quality evidence). The rate of major bleeding events was twice as high in the warfarin groups (RR 2.00, 95% CI 1.44 to 2.78; 4 studies; 3663 participants; moderate quality evidence). We generally considered the risk of bias of the included studies to be low.Analysis of warfarin versus clopidogrel was based on a single RCT (N = 1064). All-cause mortality was similar for warfarin and clopidogrel (RR 0.93, 95% CI 0.72 to 1.21; 1 study; 1064 participants; low quality evidence). There were similar rates of non-fatal cardiovascular events (RR 0.85, 95% CI 0.50 to 1.45; 1 study; 1064 participants; low quality evidence). The rate of major bleeding events was 2.5 times higher in the warfarin group (RR 2.47, 95% CI 1.24 to 4.91; 1 study; 1064 participants; low quality evidence). Risk of bias for this study can be summarised as low. There is evidence from RCTs to suggest that neither oral anticoagulation with warfarin or platelet inhibition with aspirin is better for mortality in systolic heart failure with sinus rhythm (high quality of the evidence for all-cause mortality and moderate quality of the evidence for non-fatal cardiovascular events and major bleeding events). Treatment with warfarin was associated with a 20% reduction in non-fatal cardiovascular events but a twofold higher risk of major bleeding complications (high quality of the evidence). We saw a similar pattern of results for the warfarin versus clopidogrel comparison (low quality of the evidence). At present, there are no data on the role of oral anticoagulation versus antiplatelet agents in heart failure with preserved ejection fraction with sinus rhythm. Also, there were no data from RCTs on the utility of non-vitamin K antagonist oral anticoagulants compared to antiplatelet agents in heart failure with sinus rhythm.

Syndrome coronaire aigu : y a-t-il une place pour les anticoagulants oraux directs ?

Venous thromboembolism and atrial fibrillation are two important indications of direct oral anticoagulants. Acute coronary syndrome is another potential indication of prolonged antithrombotic therapy in addition to antiplatelet therapy. Phase2and 3studies were conducted with different molecules at different doses in acute coronary syndrome in addition to dual antiplatelet therapy. Studies have not shown a reduction of ischemic events for dabigatran and apixaban, but an excess of bleeding complications was observed. A reduction of ischemic events and stent thrombosis was observed with low dose of rivaroxaban taken twice a day but with an increased risk of major bleeding complications. This data was used to obtain a European marketing authorization but the positioning of the molecule remains difficult. A new study is currently being conducted to test rivaroxaban in association with a P2Y12inhibitor without aspirin. Direct oral anticoagulants can also be used after percutaneous coronary intervention in patients requiring long-term oral anticoagulants. Dedicated studies are currently being conducted to confirm the optimal doses and the ideal association of antithrombotic drugs.

Transradial versus transfemoral rotablation for heavily calcified coronary lesions in contemporary drug-eluting stent era.

BackgroundAlthough radial access for drug-eluting stent (DES) combined with rotational atherectomy (RA) in patients with calcified coronary lesions may be associated with a lower risk of major bleeding complications and obtain favorable clinical results compared with femoral access, the long-term outcome data of this approach were limited in contemporary DES era.Methods & ResultsThis retrospective study sought to compare in-hospital and long-term outcomes for patients undergoing RA via the transradial (TR) and transfemoral (TF) route in 126 consecutive patients (59 radial, 67 femoral) from 2009 to 2014. TR RA procedures were performed in 44/62 (71%) by the three TR operators, compared with 15/64 (23%) by the four TF operators in the present study. Significantly smaller diameter guide catheters and burrs (1.39 ± 0.16 mm vs. 1.53 ± 0.24 mm, P = 0.001) were used in the TR group. Procedural success rates were similar in both TR and TF groups. There was a significantly less major access site bleeding complications in favor of radial artery access (2% vs. 16%, P = 0.012). The incidence of in-hospital death or myocardial infarction was low in both groups. Although a trend of lower adverse event rate was demonstrated in the TR group compared with the TF one, no statistical significance (21% vs. 27%, P = 0.135) was detected.ConclusionsRadial access, a useful alternative to femoral access for RA and DES, can be safely and successfully performed on up to 71% of the patients with heavily calcified coronary lesions needing RA by experienced TR operators.

Anemia predicts thromboembolic events, bleeding complications and mortality in patients with atrial fibrillation: insights from the RE‐LY trial

Anemia may predispose to thromboembolic events or bleeding in anticoagulated patients with atrial fibrillation (AF). To investigate whether anemia is associated with thromboembolic events and bleeding in patients with AF. We retrospectively analyzed the RE-LY trial database, which randomized 18113 patients with AF and a risk of stroke to receive dabigatran or warfarin for a median follow-up of 2years. Cox regression analysis was used to determine whether anemia predicted cardiovascular events and bleeding complications in these patients. Anemia was present in 12% of the population at baseline, and the presence of anemia was associated with a higher risk of thromboembolic cardiovascular events, including the composite endpoint of all-cause mortality or myocardial infarction (adjusted hazard ratio [HR]1.50, 95% confidence interval [CI]1.32-1.71) and the primary RE-LY outcome of stroke or systemic embolism (adjusted HR1.41, 95%CI1.12-1.78). Anemia was also associated with a higher risk of major bleeding complications (adjusted HR2.14, 95%CI1.87-2.46) and discontinuation of anticoagulants (adjusted HR1.40, 95%CI1.28-1.79). The association between anemia and outcome was similar irrespective of cardiovascular comorbidities, randomized treatment allocation, or prior use of warfarin. The incidence of events was lower in patients with transient anemia than in patients in whom anemia was sustained (adjusted HR0.66, 95%CI0.49-0.91). Anemia is associated with an increased risk of thromboembolic events, bleeding complications and mortality in anticoagulated patients with AF. These findings suggest that patients with anemia should be monitored closely during all types of anticoagulant treatment.

The HAS-BLED Score Identifies Patients with Acute Venous Thromboembolism at High Risk of Major Bleeding Complications during the First Six Months of Anticoagulant Treatment.

ObjectiveThe HAS-BLED score enables a risk estimate of major bleeds in patients with atrial fibrillation on vitamin K-antagonists (VKA) treatment, but has not been validated for patients with venous thromboembolism (VTE). We analyzed whether the HAS-BLED score accurately identifies patients at high risk of major bleeds during VKA treatment for acute VTE.MethodsMedical records of 537 patients with acute VTE (primary diagnosis pulmonary embolism in 223, deep vein thrombosis in 314) starting VKA treatment between 2006-2007 were searched for items on the HAS-BLED score and the occurrence of major bleeds during the first 180 days of follow-up. The hazard ratio (HR) for the occurrence of major bleeds comparing non-high with high-risk patients as defined by a HAS-BLED score ≥ 3 points was calculated using Cox-regression analysis.ResultsMajor bleeds occurred in 11/537 patients (2.0%, 5.2/100 person years, 95% CI 2.8-9.2). Cumulative incidences of major bleeds were 1.3% (95% CI 0.1-2.5) in the non-high (HAS-BLED < 3) and 9.6% (95%CI 2.2-17.0) in the high-risk group (HAS-BLED ≥ 3), (p <0.0001 by Log-Rank test), with a HR of 8.7 (95% CI 2.7-28.4). Of the items in the HAS-BLED score, abnormal renal function (HR 10.8, 95% CI 1.9-61.7) and a history of bleeding events (HR 10.4, 95% CI 2.5-42.5) were independent predictors of major bleeds during follow-up.ConclusionAcute VTE patients with a HAS-BLED score ≥ 3 points are at increased risk of major bleeding. These results warrant for correction of the potentially reversible risk factors for major bleeding and careful International Normalized Ratio monitoring in acute VTE patients with a high HAS-BLED score.

Access and non-access site bleeding after percutaneous coronary intervention and risk of subsequent mortality and major adverse cardiovascular events: systematic review and meta-analysis.

The prognostic impact of site-specific major bleeding complications after percutaneous coronary intervention (PCI) has yielded conflicting data. The aim of this study is to provide an overview of site-specific major bleeding events in contemporary PCI and study their impact on mortality and major adverse cardiovascular event outcomes. We conducted a meta-analysis of PCI studies that evaluated site-specific periprocedural bleeding complications and their impact on major adverse cardiovascular events and mortality outcomes. A systematic search of MEDLINE and Embase was conducted to identify relevant studies and random effects meta-analysis was used to estimate the risk of adverse outcomes with site-specific bleeding complications. Twenty-five relevant studies including 2,400,645 patients that underwent PCI were identified. Both non-access site (risk ratio [RR], 4.06; 95% confidence interval [CI], 3.21-5.14) and access site (RR, 1.71; 95% CI, 1.37-2.13) related bleeding complications were independently associated with an increased risk of periprocedural mortality. The prognostic impact of non-access site-related bleeding events on mortality related to the source of anatomic bleeding, for example, gastrointestinal RR, 2.78; 95% CI, 1.25 to 6.18; retroperitoneal RR, 5.87; 95% CI, 1.63 to 21.12; and intracranial RR, 22.71; 95% CI, 12.53 to 41.15. The prognostic impact of bleeding complications after PCI varies according to anatomic source and severity. Non-access site-related bleeding complications have a similar prevalence to those from the access site but are associated with a significantly worse prognosis partly related to the severity of the bleed. Clinicians should minimize the risk of major bleeding complications during PCI through judicious use of bleeding avoidance strategies irrespective of the access site used.

Antithrombotic treatments for patients with atrial fibrillation and a requirement for a coronary artery stent

&lt;p&gt;&lt;span&gt;Background: &lt;/span&gt;Patients with atrial fibrillation and a coronary artery stent require anticoagulation to provide prophylaxis&lt;/p&gt;&lt;p&gt;against stroke and dual antiplatelet therapy to provide prophylaxis against stent thrombosis (triple therapy).&lt;/p&gt;&lt;p&gt;This combination increases the risk of major bleeding complications compared to either treatment alone. It is&lt;/p&gt;&lt;p&gt;suggested that an alternative to triple therapy is high dose dual antiplatelet therapy (aspirin 325mg/day and&lt;/p&gt;&lt;p&gt;clopidogrel 75 mg/day), which would have similar efficacy to triple therapy in relation to prophylaxis against&lt;/p&gt;&lt;p&gt;both stroke and stent thrombosis with a lower risk of bleeding complications.&lt;/p&gt;&lt;p&gt;&lt;span&gt;Summary: &lt;/span&gt;1. Patients with atrial fibrillation and a coronary artery stent require triple therapy, which is associated with&lt;/p&gt;&lt;p&gt;increased bleeding risk.&lt;/p&gt;&lt;p&gt;2. In everyday practice 50% of patients do not receive this, because of the excess bleeding risk.&lt;/p&gt;&lt;p&gt;3. It is suggested that for patients at increased bleeding risk and for whom it is felt that triple therapy is not&lt;/p&gt;&lt;p&gt;suitable, Aspirin (325mg daily) and clopidogrel (75mg daily) should be considered.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;

Efficacy and safety of direct oral anticoagulants in patients undergoing cardioversion for atrial fibrillation: A systematic review and meta-analysis of the literature

BackgroundDOACs are increasingly used in patients with NVAF. Information on efficacy and safety of these compounds in patients undergoing electrical or pharmacological cardioversion is limited. Thus, we performed a systematic review and a meta-analysis of the literature to address this issue. MethodsRandomized controlled trials comparing the efficacy and safety of DOACs and VKAs in patients with NVAF were systematically searched in Medline, Web of Science, Scopus, Cochrane, and EMBASE databases (up to September 2014). Pooled relative risk (RR) and the corresponding 95% confidence interval (CI) were calculated for each outcome. ResultsFour randomized controlled trials (3635 patients), for a total of 4517 cardioversions (2869 with DOACs and 1648 with VKAs), were included in the analysis. DOACs and VKAs appeared equally effective in the prevention of stroke/systemic embolism (0.41% vs 0.61%; RR: 0.73, 95% CI: 0.31, 1.72; P=0.48) and of post-cardiovascular death (0.52% vs 0.81%; RR: 0.73, 95% CI: 0.27, 2.03; P=0.55), with a similar risk of major bleeding complications (0.81% vs 0.60%; RR: 1.23, 95% CI: 0.55, 2.71). Heterogeneity among studies was generally absent. Furthermore, the Weighted Mean Incidence (WMI) of complications appeared very low in patients randomized to DOACs (WMI: 0.6% and 0.9% for stroke/systemic embolism and major bleeding, respectively). ConclusionOur results suggest that DOACs are at least as effective and safe as VKAs in patients with NVAF undergoing to an electrical or pharmacological cardioversion. Thus, DOACs may be considered a valid and practical alternative to VKAs.

Bleeding complications of targeted oral anticoagulants: what is the risk?

The vitamin K antagonists (VKAs) are a widely used class of agent to prevent thromboembolism. In recent years, numerous alternatives to VKAs have been developed, the target-specific oral anticoagulants (TSOACs), which are available in clinical practice. Currently available agents target thrombin and factor Xa. The most significant side effect of these agents, as with VKAs, is the development of bleeding complications. In this review, the risks of major bleeding complications with the TSOACs will be discussed. Data from meta-analyses, randomized controlled trials, and observational studies will be used to highlight bleeding complications associated with TSOACs and warfarin. We highlight the most common causes of major bleeding, GI and intracranial hemorrhage.

Low-dose Thrombolysis for Thromboembolic Lower Extremity Arterial Occlusions is Effective Without Major Hemorrhagic Complications

To evaluate the efficacy and bleeding complications associated with a low-dose thrombolysis protocol for thromboembolic lower extremity arterial occlusions. A retrospective cohort study. A retrospective analysis was performed using data from all consecutive patients who underwent catheter-directed, intra-arterial thrombolysis for thromboembolic lower extremity arterial occlusions between January 2004 and May 2013. All patients were treated on a standard surgical ward. Endpoints were incidence of bleeding complications, duration of thrombolysis, angiographic patency rate, 30-day mortality rate, and amputation-free rate at 6 months. Of the 171 cases analyzed, 129 cases underwent low-dose thrombolysis and 42 underwent high-dose thrombolysis. No major bleeding complications occurred in the low-dose group versus 5% in the high-dose group (p = .01). The median duration of thrombolysis was 67 hours (4–304 hours) in the low-dose and 49 hours (2–171 hours) in the high-dose group (p = .027). Angiographic patency was restored in 67% of the cases in the low-dose group versus 79% of the high-dose group (p = .17). The 30-day mortality rates were 1% in the low-dose versus 5% in the high-dose group (p = .09). However, this higher mortality rate was not related to bleeding complications. Major amputation-free rates at 6 months were 81% in the low-dose group and 88% in the high-dose group (p = .22). Based on this data series, low-dose thrombolysis for thromboembolic lower extremity arterial occlusions is as effective as high-dose thrombolysis; however, the risk of major bleeding complications is substantially lower when using low-dose thrombolysis.

Ability of Nafamostat Mesilate to Prolong Filter Patency during Continuous Renal Replacement Therapy in Patients at High Risk of Bleeding: A Randomized Controlled Study

Continuous renal replacement therapy (CRRT) is considered as an effective modality for renal replacement therapy in hemodynamically unstable patients within intensive care units (ICUs). However, the role of heparin anticoagulation, which is used to maintain circuit patency, is equivocal due to the risk of bleeding and morbidity. Among various alternative anticoagulants, nafamostat mesilate has been shown to be an effective anticoagulant in patients prone to bleeding. Hence, we conducted a prospective, randomized controlled study investigating the effect of nafamostat mesilate on mortality, CRRT filter life span and adverse events in patients with bleeding tendency. Seventy-three Patients were randomized into either the futhan or no-anticoagulation group. Thirty-six subjects in the futhan group received nafamostat mesilate, while thirty seven subjects in the no-anticoagulation group received no anticoagulants. Baseline characteristics and appropriate laboratory tests were taken from each group. The mortality between the two groups was not significantly different. Nevertheless, between the futhan group and the no-anticoagulation group, the overall number of filters used during CRRT (2.71±2.12 vs. 4.50±3.25; p = 0.042) and the number of filters changed due to clots per 24 hours (1.15±0.81 vs. 1.74±1.62; p = 0.040) were significantly different. When filter life span was subdivided into below and over 12 hours, the number of filters functioning over 12 hours was significantly higher in the futhan group than in the no-anticoagulation group (p = 0.037, odds ratio 1.84). There were no significant differences in transfusion, mortality, or survival between the two groups, and no adverse events related to nafamostat mesilate were noted. Hence, nafamostat mesilate may be used as an effective and safe anticoagulant, without increasing the risk of major bleeding complications, in patients prone to bleeding.Trial RegistrationClinicaltrials.gov NCT01761994

Low-dose Thrombolysis for Thromboembolic Lower Extremity Arterial Occlusions is Effective Without Major Hemorrhagic Complications

To evaluate the efficacy and bleeding complications associated with a low-dose thrombolysis protocol for thromboembolic lower extremity arterial occlusions. A retrospective cohort study. A retrospective analysis was performed using data from all consecutive patients who underwent catheter-directed, intra-arterial thrombolysis for thromboembolic lower extremity arterial occlusions between January 2004 and May 2013. All patients were treated on a standard surgical ward. Endpoints were incidence of bleeding complications, duration of thrombolysis, angiographic patency rate, 30-day mortality rate, and amputation-free rate at 6 months. Of the 171 cases analyzed, 129 cases underwent low-dose thrombolysis and 42 underwent high-dose thrombolysis. No major bleeding complications occurred in the low-dose group versus 5% in the high-dose group (p = .01). The median duration of thrombolysis was 67 hours (4-304 hours) in the low-dose and 49 hours (2-171 hours) in the high-dose group (p = .027). Angiographic patency was restored in 67% of the cases in the low-dose group versus 79% of the high-dose group (p = .17). The 30-day mortality rates were 1% in the low-dose versus 5% in the high-dose group (p = .09). However, this higher mortality rate was not related to bleeding complications. Major amputation-free rates at 6 months were 81% in the low-dose group and 88% in the high-dose group (p = .22). Based on this data series, low-dose thrombolysis for thromboembolic lower extremity arterial occlusions is as effective as high-dose thrombolysis; however, the risk of major bleeding complications is substantially lower when using low-dose thrombolysis.

Long-term treatment of venous thromboembolism.

Long term treatment of venous thromboembolism is essential to complete therapy of the index episode and to reduce recurrences. Vitamin K antagonists are the mainstay for the long term treatment of venous thromboembolism for the majority of the patients as they allow oral administration. Low-molecular weight heparins are recommended for the long term treatment of cancer patients. The duration of long term anticoagulation depends on the features of the index venous thromboembolism and on the presence of associated risk factors. Patients at high risk for recurrence - mainly those who suffered unprovoked venous thromboembolism and those with cancer - should be evaluated for extended anticoagulation. The risk for major bleeding complications and the inconvenience for monitoring, dose adjustment and drug-food interactions are the main constraints for indefinite anticoagulant treatment. New anticoagulants with more favourable efficacy- safety profile and reduced need for monitoring could improve the feasibility of extended anticoagulation.

The quality of antiplatelet and anticoagulant medication administration among ST-segment elevation myocardial infarction patients transferred for primary percutaneous coronary intervention

Timely and appropriate use of antiplatelet and anticoagulant therapies has been shown to improve outcomes among ST-segment elevation myocardial infarction (STEMI) patients but has not been well described in patients transferred for primary percutaneous coronary intervention (PCI). We examined 16,801 (26%) transfer and 47,329 direct-arrival STEMI patients treated with primary PCI at 441 Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines hospitals. Medication use was compared between transfer and direct-arrival patients to determine if these therapies were delayed or dosed in excess. Although transfer patients were more likely to receive antiplatelet and anticoagulant therapies before catheterization, they had longer delays to initiation of heparin (35 vs. 25 minutes), clopidogrel (119 vs. 84 minutes), and glycoprotein IIb/IIIa inhibitor (107 vs. 60 minutes, P < .0001 for both). Administration of low-molecular-weight heparin and glycoprotein IIb/IIIa inhibitor at the STEMI-referring hospital was associated with longer delays to reperfusion compared with deferred administration at the STEMI-receiving hospital, whereas early use of unfractionated heparin was not. Among treated patients, those transferred were more likely to receive excess heparin dosing (adjusted odds ratio [OR] 1.28 [95% CI 1.04-1.58] for unfractionated heparin, adjusted OR 1.54 [95% CI 1.09-2.18] for low-molecular-weight heparin) and are associated with higher risks of major bleeding complications (adjusted OR 1.10, 95% CI 1.03-1.17). ST-segment elevation myocardial infarction patients transferred for primary PCI in community practice are at risk for delayed and excessively dosed antithrombotic therapy, highlighting the need for continued quality improvement to maximize the appropriate use of these important adjunctive therapies.

Acute dysphagia after myocardial infarction: an unusual complication of anticoagulation therapy

Antiplatelet medications such as aspirin, clopidogrel or prasugrel are commonly used in patients with myocardial infarction (MI) and stent implantation. Additionally, thrombolytic therapy is recommended for patients in whom a coronary intervention cannot be performed in a timely manner. Both classes of drugs put patients at risk for major bleeding complications. However, also unusual bleeding complications can lead to serious complications. A 55-year-old male contacted the emergency medical service with acute onset of chest pain beginning 1.5 h before. The ECG showed typical ST-segment elevations (Fig. 1). An inferior MI was diagnosed, and a pre-hospital thrombolytic therapy with 10,000 units of tenecteplase was administered. On admission to our hospital, the chest pain was still present but reduced. The ECG showed persistent ST-segment elevations and a rescue percutaneous coronary intervention was performed. An additional 6,000 IE of heparin were given for the intervention. An acute occlusion of the right coronary artery was successfully reopened and a drug-eluting stent (tacrolimus-eluting-stent, TAXUS®, Boston Scientific) was placed (Fig. 2). In the clinical course, cardiac ultrasound showed a moderate impairment of left ventricular function (LVEF 40%). The patient was treated with aspirin 100 mg/d and prasugrel 10 mg/d. Two days later, the patient developed a progressively sore throat and reported new-onset dysphagia. Within the next few hours, a progressive swelling of the left cervical region occurred. Emergency computed tomography of the neck showed a massive left sided tumour, consistent with a large bleeding into a thyroidal cyst. The diameters of the haematoma were 13 × 7 × 6 cm, with displacement and compression of trachea to 6 mm (Fig. 3). To secure the airways, the patient was endotracheally intubated without problems. An immediate left hemithyreoidectomy with decompression of the haematoma was performed. The patient recovered quickly after the operation. Histological findings showed no evidence of malignancy. Spontaneous haemorrhage into a thyroid cyst is a rare condition. When causing airway obstruction, this life-threatening situation requires immediate airway protection before complete obstruction occurs. In the literature, some cases of retropharyngeal or thyreoideal haematoma have been reported as complications of medical manoeuvres such as intubation or thyroid puncture, or as a complication of chronic anticoagulation therapy with warfarin or marcumar. To the best of our knowledge, this is the first description of a spontaneous haemorrhage into a thyroid cyst under aspirin and prasugrel. Prasugrel is known to lead to more pronounced platelet inhibition than clopidogrel, resulting in a four to five times longer bleeding time and a faster onset of action. Clearly, the faster and more effective platelet inhibition obtained by prasugrel may lead to an increased risk of major and even atypical bleeding events after previous fibrinolytic therapy.

Triple Antithrombotic Therapy Is the Independent Predictor for the Occurrence of Major Bleeding Complications

Triple antithrombotic therapy increases the risk of bleeding events in patients undergoing percutaneous coronary intervention. However, it remains unclear whether good control of percent time in therapeutic range is associated with reduced occurrence of bleeding complications in patients undergoing triple antithrombotic therapy. This study included 2648 patients (70 ± 11 years; 2037 men) who underwent percutaneous coronary intervention with stent in the Ibaraki Cardiovascular Assessment Study registry and received dual antiplatelet therapy with or without warfarin. Clinical end points were defined as the occurrence of major bleeding complications (MBC), major adverse cardiac and cerebrovascular event, and all-cause death. Among these 2648 patients, 182 (7%) patients received warfarin. After a median follow-up period of 25 months (interquartile range, 15-35 months), MBC had occurred in 48 (2%) patients, major adverse cardiac and cerebrovascular event in 484 (18%) patients, and all-cause death in 206 (8%) patients. Multivariable Cox regression analysis revealed that triple antithrombotic therapy was the independent predictor for the occurrence of MBC (hazard ratio, 7.25; 95% confidence interval, 3.05-17.21; P<0.001). The time in therapeutic range value did not differ between the patients with and without MBC occurrence (83% [interquartile range, 50%-90%] versus 75% [interquartile range, 58%-87%]; P=0.7). However, the mean international normalized ratio of prothrombin time at the time of MBC occurrence was 3.3 ± 2.1. Triple antithrombotic therapy did not have a predictive value for the occurrence of all-cause death (P=0.1) and stroke (P=0.2). Triple antithrombotic therapy predisposes patients to an increased risk of MBC regardless of the time in therapeutic range.

Antithrombotic Therapy for Patients with Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Review

Patients with atrial fibrillation who have risk factors for thromboembolism benefit from chronic oral anticoagulation therapy, and antiplatelet therapy alone is of relatively little benefit for prevention of ischemic stroke and systemic embolism. Patients undergoing percutaneous coronary intervention with drug-eluting stents require dual antiplatelet therapy with aspirin and a thienopyridine for 3 to 12 months or more prevention of stent thrombosis and recurrent ischemic events. When patients with atrial fibrillation undergo percutaneous coronary intervention, the need to combine dual antiplatelet therapy and warfarin raises the risk of major bleeding complications considerably. Recent trials have explored the option of omitting aspirin with promising results. The introduction of novel oral anticoagulants that specifically inhibit factor IIa (dabigatran) or factor Xa (rivaroxaban, apixaban, and edoxaban) and antiplatelet agents that inhibit the P(2)Y(12) receptor (prasugrel and ticagrelor) makes management of these patients even more challenging, but future trials addressing myriad alternative regimens may identify better tolerated strategies.

Clopidogrel Added to Aspirin Adds No Benefit but Bleeding Risk in Patients With Recent Lacunar Stroke

Patients with transient ischemic attack or ischemic stroke have a high risk of recurrent stroke. Antiplatelet therapy has shown efficacy in secondary stroke prevention and is recommended by guidelines.1–3 In patients without cardiac source of embolism aspirin, clopidogrel or the combination of aspirin and dipyridamole is recommended. In cardiology, the combination of aspirin and clopidogrel was superior to aspirin monotherapy in the prevention of vascular events after acute coronary syndrome4 but carried a higher bleeding risk. In patients with atrial fibrillation the combination of aspirin plus clopidogrel was superior to aspirin alone in preventing strokes,5 but was again associated with a significant higher risk of major bleeds. In early secondary stroke prevention after transient ischemic attack or minor stroke combination, antiplatelet therapy seems to be superior to monotherapy, but larger randomized trials are needed.6,7 Combination antiplatelet therapy carries a consistent higher risk of major bleeding complications than monotherapy. Therefore, the possible benefit of a reduction in vascular events has to be balanced against the bleeding risk, especially in stroke patients. In the Management of Atherothrombosis with Clopidogrel in High-risk patients (MATCH) trial, aspirin plus clopidogrel was investigated against aspirin monotherapy in high-risk patients with recent transient ischemic attack or ischemic stroke.8 Similar to the Secondary Prevention of Small Subcortical Strokes (SPS3) trial, patients with a cardiac source of embolism and significant carotid stenosis requiring surgery were excluded. About 50% of patients were categorized to have small vessel disease with suspected lacunar strokes, but in contrast to the SPS3 trial, …