Clinical events preceding switching and discontinuation of oral anticoagulant treatment in patients with atrial fibrillation.

AIMS: Switching between oral anticoagulants and treatment discontinuation are common events related to therapy with non-vitamin K antagonist oral anticoagulants (NOACs). However, knowledge on the reasons leading to these treatment changes is scarce. The aim of this study was to identify clinical events preceding anticoagulant switching and NOAC discontinuation during oral anticoagulant therapy in patients with atrial fibrillation. METHODS AND RESULTS: We performed a nationwide register-based study including Danish atrial fibrillation patients initiating a NOAC between August 2011 and February 2016 (n = 50 623). We explored potential reasons leading to changes in anticoagulant treatment by identifying clinical events preceding switches from vitamin K antagonists (VKA) to NOAC, switches from NOAC to VKA, and discontinuations of NOACs. Among 23 531 anticoagulant users changing treatment, we identified 13 295 switches from VKA to NOAC, 5206 switches from NOAC to VKA, and 8995 discontinuations of NOACs. Approximately half of all treatment changes were preceded by a hospitalization. A relevant specific clinical event or procedure was identified prior to 18.3% of switches from VKA to NOAC, prior to 23.0% of switches from NOAC to VKA, and prior to 26.6% of discontinuations. Switches from VKA to NOAC were most often preceded by thromboembolic events (7.0%), whereas cardioversion was the most common specific event prior to a switch from NOAC to VKA (11.4%). Discontinuations were most often preceded by bleeding events (7.6%). CONCLUSION: For about one in five patients, treatment changes during anticoagulant therapy were preceded by a major clinical event. However, the majority of patients changed treatment for reasons not recorded in health registries.

Use of Antithrombotic Therapy and Long-Term Clinical Outcome Among Patients Surviving Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: The effectiveness and safety of antithrombotic therapy (AT) among patients with a history of intracerebral hemorrhage remain uncertain. We therefore determined the prevalence of indication for AT among patients hospitalized with first-time intracerebral hemorrhage and examined the impact of subsequent AT use on the long-term clinical outcome. METHODS: We performed a population-based cohort study using nationwide Danish medical registries. Patients with risk of thromboembolism surviving the first 30 days after hospitalization because of intracerebral hemorrhage were identified and followed up. We estimated the hazard ratio of all-cause death, thromboembolic events, or major bleeding according to use of AT. RESULTS: We identified 6369 patients between 2005 and 2013. Among these patients, 2978 (47%) had indication for AT, and during the follow-up, (median: 2.3 year) 1281 (43%) died, 497 (17%) had a thromboembolic event, and 536 (18%) had major bleeding. Postdischarge use of oral anticoagulation therapy among patients with indication for oral anticoagulation therapy was associated with a significant lower risk of death (adjusted hazard ratio, 0.59; 95% confidence interval, 0.43-0.82) and thromboembolic events (adjusted hazard ratio 0.58; 95% confidence interval, 0.35-0.97) and no increased risk of major bleeding (adjusted hazard ratio 0.65; 95% confidence interval, 0.41-1.02). In contrast, use of platelet inhibitors among patients with indication for platelet inhibitors was not related to statistically significantly improved clinical outcome. CONCLUSIONS: Approximately 1 of 2 patients surviving intracerebral hemorrhage had a high risk of thromboembolism. Postdischarge use of oral anticoagulation therapy was associated with a lower risk of all-cause mortality and thromboembolic events and no increased risk of major bleeding.

Preadmission oral anticoagulant treatment and clinical outcome among patients hospitalized with acute stroke and atrial fibrillation: a nationwide study.

BACKGROUND AND PURPOSE: Preadmission oral anticoagulant treatment (OAT) has been linked with less severe stroke and a better outcome in patients with atrial fibrillation. However, the existing studies have methodological limitations and have, with one exception, not included hemorrhagic strokes. We performed a nationwide historic follow-up study using data from population-based healthcare registries to assess the effect of preadmission OAT on stroke outcomes further. METHODS: We identified 11 356 patients with atrial fibrillation admitted to hospital with acute stroke (including ischemic stroke and intracerebral hemorrhage) between 2003 and 2009. Propensity score-matched analyses were used to compare stroke severity (Scandinavian Stroke Scale score) and mortality among 2175 patients with preadmission OAT and 2175 patients without preadmission OAT. RESULTS: A total of 2492 (21.9%) patients received OAT at the time of their stroke. Preadmission OAT was associated with a lower risk of severe stroke (Scandinavian Stroke Scale score at time of admission, <30 point; propensity score-matched odds ratio, 0.74; 95% confidence interval, 0.63-0.86) and lower 30-day mortality rate (propensity score-matched adjusted odds ratio, 0.83; 95% confidence interval, 0.71-0.98). CONCLUSIONS: Only a minority of hospitalized patients with acute stroke with atrial fibrillation received OAT at the time of stroke. Preadmission OAT was associated with less severe stroke and lower 30-day mortality rate in a propensity score-matched analysis.

Inadequate use of prophylaxis against venous thromboembolism in Danish medical departments.

INTRODUCTION: Venous thromboembolism (VTE) constitutes a major risk factor in hospitalized acutely ill medical patients. It has been demonstrated in numerous papers that by using different forms of prophylaxis, a significant reduction of the incidence of VTE can be achieved. In this article we assessed the tendencies in the use of venous thromboprophylaxis (TP) at internal medicine departments in Denmark. The results were compared with results from a similar study conducted in 2005. MATERIAL AND METHODS: All medical departments in Denmark received a two-page questionnaire on TP. The recipients were asked to evaluate the frequency, use of local instructions, form of administration, side-effects and duration of TP at their departments. One reminder was sent out. RESULTS: A total of 188 responses were received (90% response rate), 16 were excluded. Virtually all departments indicated that they used TP (92%). At intensive care units, the TP was used according to local guidelines at 77% of the wards and at the other subspecialties of internal medicine, TP was used in less than 50%. By far the most frequently used prophylaxis method was low molecular weight heparin, which was used by more than 80% of the departments. Side-effects, most often superficial bleeding and haematomas, were reported in 25% of the cases. The following serious side-effects were reported: heparininduced thrombocytopenia (n = 2), stroke (n = 1) and gastrointestinal bleeding (n = 3). No difference was observed between the hospitals of larger cities and those of smaller cities. CONCLUSION: In Denmark, no significant increase in the use of TP at internal medicine departments has been observed since 2005. The guideline's strong recommendation of TP is still not reflected in daily practice. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Treatment Changes among Users of Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation.

Patients with atrial fibrillation discontinuing anticoagulant therapy are left unprotected against ischaemic stroke. Further, switching between oral anticoagulants may be associated with a transiently increased risk of bleeding or thromboembolism. However, there is a paucity of real-life data on pattern of switching and discontinuation of oral anticoagulants. To address this, we conducted a nationwide drug utilization study including all registered Danish atrial fibrillation patients initiating a non-VKA oral anticoagulant (NOAC) between August 2011 and February 2016. We assessed changes in anticoagulant treatment, including switching between oral anticoagulants and discontinuation of NOACs, and explored patient characteristics predicting these changes. We identified 50,632 patients with atrial fibrillation initiating NOAC therapy within the study period. The majority initiated dabigatran (49.9%) and one-third had previously used VKA. Within 1 year, 10.1% switched to VKA, 4.8% switched to another NOAC and 14.4% discontinued treatment. The frequencies of switching to VKA and discontinuation were highest among NOAC users of young age (<55 years) and with low CHA2 DS2 -VASc score (=0). However, the majority of patients (87.3%) stopping NOAC treatment had a CHA2 DS2 -VASc score ≥1. We conclude that switching from VKA to NOAC, and to a lesser extent from NOAC to VKA, is common, as is early treatment discontinuation. The majority of treatment changes are observed in patients at increased risk of stroke. More research is warranted on the risks of bleeding and thromboembolism associated with switching and discontinuation of NOACs as well as the underlying reasons why these treatment changes occur.

[Perioperative heparin bridging is rarely indicated]. / Perioperativ heparin-bridging er sjældent indiceret.

Meta-analyses of cohort studies and a recent randomized, placebo-controlled study have shown that perioperative bridging of warfarin therapy with therapeutic doses of heparin results in a multi-fold increase in major bleeding but no reduction in the incidence of thromboembolism. It is time to reconsider heparin bridging: When is heparin bridging superfluous? When is prophylactic dosage indicated? And when is it safe to use therapeutic dosing?

[Monitoring options and reversal agents for oral anticoagulants].

The approval of the oral direct thrombin inhibitor dabigatranetexilat and the oral factor Xa inhibitors rivaroxaban and apixaban as thromboprophylaxis challenges the position of the vitamin K antagonists (VKA). Predictable pharmacodynamics gives the new oral anticoagulants an advantageous profile. Unlike VKAs there is no specific reversal agent available for the new oral anticoagulants. Experience with haemostatic products for the emergency management of critical bleeding caused by these agents is limited.

[Pulmonary embolus after adder bite].

The clinical course after adder bites (Vipera berus) is unpredictable. Antivenom can reduce morbidity markedly. Preventive use of low-molecular-weight heparin is not routinely recommended. We present a case report, where indication for antivenom was not found, and the patient developed pulmonary embolus. Thrombotic complications are known, but to our knowledge pulmonary embolus has not previously been described in the literature.

Preadmission oral anticoagulant therapy and clinical outcome in patients hospitalised with acute stroke and atrial fibrillation.

INTRODUCTION: Information about the effect of preadmission oral anticoagulant therapy (OAT) on stroke outcome in patients with atrial fibrillation (AF) is scarce. A systematic review was done of the existing data on the association between preadmission OAT and stroke outcome in patients with AF. METHOD: We performed a systematic search in the PubMed Database, the Embase Database and the Cochrane Database of Systematic Reviews identifying 13 studies that met the inclusion criteria. RESULTS: The studies included a total of 18,523 patients with AF and admission with stroke. Of these, 1,169 had a haemorrhagic stroke. The proportion of patients in preadmission OAT varied from 5 to 37%, and the proportion who did not receive any antithrombotic therapy (AT) varied from 22 to 75%. The risk of having a severe stroke for patients with an international normalised ratio (INR) < 2 ranged from 26 to 43% compared with a 15-36% range for patients with an INR ≥ 2. The risk of death or disability among patients not receiving any AT ranged from 22 to 56% compared with 15-59% for those on platelet inhibitors, 16-48% for those on OAT with an INR < 2 and 6-37% among patients with an INR ≥ 2. These patterns were confirmed after adjustment for confounding factors. CONCLUSION: Only a minority of AF patients with stroke received OAT at the time of hospitalisation. Overall, preadmission OAT was associated with less severe strokes and a lower risk of death or disability. Further efforts seem warranted to ensure OAT for all eligible AF patients.

[Anticoagulant therapy in stroke patients]. / Antikoagulansbehandling og apopleksi.

Stroke is a common disease, which is associated with high morbidity and high mortality. Up to 25% of cerebral ischaemic infarcts are caused by cardio-embolic events, most commonly associated with atrial fibrillation. It has previously been shown that antithrombotic therapy is insufficiently used in patients at increased risk of stroke. This article reviews evidence and practical management of anticoagulant therapy in stroke patients and provides an update on risk stratification for thromboembolism and bleeding complications in patients with atrial fibrillation.

[Lethal recurrent pulmonary embolism]. / Dødeligt forløbende recidiverende lungeemboli trods antikoagulansbehandling.

An otherwise healthy 68 year-old man experienced three episodes of life-threatening pulmonary embolism (PE) over a short period. The last episode had lethal outcome. After the first episode the patient was resuscitated and received embolectomy and after the second he received thrombolytic treatment. The last episode was not recognised until the autopsy. The second and the third episode occurred during anticoagulant therapy. Even in non-malignant patients recurrent PE may occur during anticoagulant therapy and implementing a prophylactic permanent filter in vena cava inferior in these patients in case of recurrent major PE could be considered.

New oral anticoagulants: a review of the literature with particular emphasis on patients with impaired renal function.

Oral anticoagulant therapy (OAT) is widely used to prevent and treat thromboembolic events. Traditionally, warfarin has been the drug of choice and, indeed, this drug is effective and provides a more than 60% reduction in stroke risk in patients with atrial fibrillation. However, OAT entails an increased bleeding risk, and management of this is challenging. Among other things, new oral anticoagulant drugs offer fixed dosing, more predictable pharmacokinetics and fewer interactions with drugs and food. Moreover, these drugs seem to provide an improved benefit-risk ratio with respect to thromboembolic events and bleeding complications in a broad patient population. The new drugs differ from traditional OAT with respect to their mechanism of action and pharmacokinetics, especially with respect to elimination through the kidneys. These drugs may potentially cause bleeding complications in patients with reduced drug excretion due to impaired renal function. Dabigatran etexilate and rivaroxaban carry the highest risk due to a high degree of renal excretion, whereas the risk for apixaban, edoxaban and betrixaban seems lower. Pharmacokinetic studies and data from clinical studies have provided information on how to guide dosing in patients with renal impairment. However, the risk of drug accumulation and bleeding may be amplified by several drug-drug interactions. This article provides a review of the literature on the pharmacology of new anticoagulant drugs with particular focus on the impact of impaired renal function.

Cardiac arrest caused by multiple recurrent pulmonary embolism.

Pulmonary embolism is a common condition with a high mortality. We describe a previously healthy 68-year-old male who suffered three pulmonary embolisms during a short period of time, including two embolisms while on anticoagulant treatment. This paper illustrates three important points. (1) The importance of optimal anticoagulant treatment in the prevention of pulmonary embolism reoccurrence. (2) The benefit of immediate accessibility to echocardiography in the handling of haemodynamically unstable patients with an unknown underlying cause. (3) Thrombolytic treatment should always be considered and may be life-saving in patients with cardiac arrest suspected to be caused by pulmonary embolism.

[Unfractionated heparin and low molecular weight heparin for acute coronary syndromes--assessment of a Cochrane review]. / Ufraktioneret og lavmolekylaert heparin ved akutte koronare syndromer--en gennemgang af et Cochrane-review.

In aspirin-treated patients with acute coronary syndromes without ST-segment elevation unfractionated heparin (UFH) or low molecular weight heparin (LMWH) treatment < 7 days significantly reduce the risk of acute myocardial infarction (AMI), and LMWH furthermore reduces revascularisation. There is a non-significant effect on mortality compared with placebo and an insignificantly increased risk of haemorrhagic complications. No net clinical benefit of LMWH was found compared to UHF, but LMWH has pharmacokinetic advantages. The optimal duration of heparin treatment remains controversial.

[Unfractionated heparin and low molecular weight heparin for acute coronary syndromes--assessment of a Cochrane review]. / Ufraktioneret og lavmolekylaert heparin ved akutte koronare syndromer--en gennemgang af et Cochrane-review.

In aspirin-treated patients with acute coronary syndromes without ST-segment elevation unfractionated heparin (UFH) or low molecular weight heparin (LMWH) treatment < 7 days significantly reduce the risk of acute myocardial infarction (AMI), and LMWH furthermore reduces revascularisation. There is a non-significant effect on mortality compared with placebo and an insignificantly increased risk of haemorrhagic complications. No net clinical benefit of LMWH was found compared to UHF, but LMWH has pharmacokinetic advantages. The optimal duration of heparin treatment remains controversial.

[Superficial thrombophlebitis. Etiology, diagnosis and treatment]. / Superficiel tromboflebitis. Aetiologi, diagnose og behandling.

Superficial thrombophlebitis is a common disease. Recently, a relatively high incidence of concomitant venous thromboembolism has been found. Graduated compressing stockings and low-molecular heparin subcutaneously in weight-based therapeutic doses for 10-30 days are considered the best treatment. Non-steroidal-anti-inflammatory drugs or local treatment with heparinoid may reduce the pain. A new Cochrane analysis concludes that the existing studies do not demonstrate strong recommendations for any treatment. Ongoing trials will add to our knowledge about optimal treatment of ST.

[Deep venous thrombosis--epidemiology, diagnosis and treatment]. / Dyb venøs trombose--epidemiologi, diagnose og behandling.

The pathogenesis of deep vein thrombosis (DVT) involves vascular changes or injury, stasis and alterations in the blood composition. The risk increases with age; however, important risk factors are cancer, surgery, immobilisation and hormone therapy. DVT most often appears in the crural veins. The diagnosis is based on ultrasound, d-dimer and clinical examination. Correct treatment requires gradient compression hosiery, low-molecular heparins and anticoagulant therapy. Duration of treatment depends on the individual risk of recurrence.