Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke.

BACKGROUND: Surgical occlusion of the left atrial appendage has been hypothesized to prevent ischemic stroke in patients with atrial fibrillation, but this has not been proved. The procedure can be performed during cardiac surgery undertaken for other reasons. METHODS: We conducted a multicenter, randomized trial involving participants with atrial fibrillation and a CHA2DS2-VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating greater risk of stroke) who were scheduled to undergo cardiac surgery for another indication. The participants were randomly assigned to undergo or not undergo occlusion of the left atrial appendage during surgery; all the participants were expected to receive usual care, including oral anticoagulation, during follow-up. The primary outcome was the occurrence of ischemic stroke (including transient ischemic attack with positive neuroimaging) or systemic embolism. The participants, research personnel, and primary care physicians (other than the surgeons) were unaware of the trial-group assignments. RESULTS: The primary analysis population included 2379 participants in the occlusion group and 2391 in the no-occlusion group, with a mean age of 71 years and a mean CHA2DS2-VASc score of 4.2. The participants were followed for a mean of 3.8 years. A total of 92.1% of the participants received the assigned procedure, and at 3 years, 76.8% of the participants continued to receive oral anticoagulation. Stroke or systemic embolism occurred in 114 participants (4.8%) in the occlusion group and in 168 (7.0%) in the no-occlusion group (hazard ratio, 0.67; 95% confidence interval, 0.53 to 0.85; P = 0.001). The incidence of perioperative bleeding, heart failure, or death did not differ significantly between the trial groups. CONCLUSIONS: Among participants with atrial fibrillation who had undergone cardiac surgery, most of whom continued to receive ongoing antithrombotic therapy, the risk of ischemic stroke or systemic embolism was lower with concomitant left atrial appendage occlusion performed during the surgery than without it. (Funded by the Canadian Institutes of Health Research and others; LAAOS III ClinicalTrials.gov number, NCT01561651.).

COMPARE LAAO: Rationale and design of the randomized controlled trial "COMPARing Effectiveness and safety of Left Atrial Appendage Occlusion to standard of care for atrial fibrillation patients at high stroke risk and ineligible to use oral anticoagulation therapy".

BACKGROUND: Left atrial appendage occlusion (LAAO) provides an alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF). In patients with a long-term or permanent contraindication for OAC randomized controlled trial (RCT) data is lacking. STUDY OBJECTIVES: To assess the efficacy and safety of LAAO in AF patients who are ineligible to use OAC. The co-primary efficacy endpoint is (1) time to first occurrence of stroke (ischemic, hemorrhagic, or undetermined) and (2) time to first occurrence of the composite of stroke, transient ischemic attack (TIA), and systemic embolism (SE). The primary safety endpoint is the 30-day rate of peri-procedural complications. STUDY DESIGN: This is a multicenter, investigator-initiated, open-label, blinded endpoint (PROBE), superiority-driven RCT. Patients with AF, a CHA2DS2-VASc score ≥2 for men and ≥3 for women and a long-term or permanent contraindication for OAC will be randomized in a 2:1 fashion to the device- or control arm. Patients in the device arm will undergo percutaneous LAAO and will receive post-procedural dual antiplatelet therapy (DAPT) per protocol, while those in the control arm will continue their current treatment consisting of no antithrombotic therapy or (D)APT as deemed appropriate by the primary responsible physician. In this endpoint-driven trial design, assuming a 50% lower stroke risk of LAAO compared to conservative treatment, 609 patients will be followed for a minimum of 1 and a maximum of 5 years. Cost-effectiveness and budget impact analyses will be performed to allow decision-making on reimbursement of LAAO for the target population in the Netherlands. SUMMARY: The COMPARE LAAO trial will investigate the clinical superiority in preventing thromboembolic events and cost-effectiveness of LAAO in AF patients with a high thromboembolic risk and a contraindication for OAC use. NCT TRIAL NUMBER: NCT04676880.

Persistent phrenic nerve palsy after atrial fibrillation ablation: Follow-up data from The Netherlands Heart Registration.

BACKGROUND: Persistent phrenic nerve palsy (PNP) is an established complication of atrial fibrillation (AF) ablation, especially during cryoballoon and thoracoscopic ablation. Data on persistent PNP reversibility is limited because most patients recover <24 h. This study aims to investigate persistent PNP recovery, freedom of PNP-related symptoms after AF ablation and identify baseline variables associated with the occurrence and early PNP recovery in a large nationwide registry study. METHODS: In this study, we used data from the Netherlands Heart Registration, comprising data from 9549 catheter and thoracoscopic AF ablations performed in 2016 and 2017. PNP data was available of 7433 procedures, and additional follow-up data were collected for patients who developed persistent PNP. RESULTS: Overall, the mean age was 62 ± 10 years, and 67.7% were male. Fifty-four (0.7%) patients developed persistent PNP and follow-up was available in 44 (81.5%) patients. PNP incidence was 0.07%, 0.29%, 1.41%, and 1.25%, respectively for patients treated with conventional-RF, phased-RF, cryoballoon, and thoracoscopic ablation respectively. Seventy-one percent of the patients fully recovered, and 86% were free of PNP-related symptoms after a median follow-up of 203 (113-351) and 184 (82-359) days, respectively. Female sex, cryoballoon, and thoracoscopic ablation were associated with a higher risk to develop PNP. Patients with PNP recovering ≤180 days had a larger left atrium volume index than those with late or no recovery. CONCLUSION: After AF ablation, persistent PNP recovers in the majority of patients, and most are free of symptoms. Female patients and patients treated with cryoballoon or thoracoscopic ablation are more prone to develop PNP.

Rate control drugs differ in the prevention of progression of atrial fibrillation.

AIMS: We hypothesize that in patients with paroxysmal atrial fibrillation (AF), verapamil is associated with lower AF progression compared to beta blockers or no rate control. METHODS AND RESULTS: In this pre-specified post hoc analysis of the RACE 4 randomized trial, the effect of rate control medication on AF progression in paroxysmal AF was analysed. Patients using Vaughan-Williams Class I or III antiarrhythmic drugs were excluded. The primary outcome was a composite of first electrical cardioversion (ECV), chemical cardioversion (CCV), or atrial ablation. Event rates are displayed using Kaplan-Meier curves and multivariable Cox regression analyses are used to adjust for baseline differences. Out of 666 patients with paroxysmal AF, 47 used verapamil, 383 used beta blockers, and 236 did not use rate control drugs. The verapamil group was significantly younger than the beta blocker group and contained more men than the no rate control group. Over a mean follow-up of 37 months, the primary outcome occurred in 17% in the verapamil group, 33% in the beta blocker group, and 33% in the no rate control group (P = 0.038). After adjusting for baseline characteristics, patients using verapamil have a significantly lower chance of receiving ECV, CCV, or atrial ablation compared to patients using beta blockers [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.19-0.83] and no rate control (HR 0.64, 95% CI 0.44-0.93). CONCLUSION: In patients with newly diagnosed paroxysmal AF, verapamil was associated with less AF progression, as compared to beta blockers and no rate control.

Impact of anticoagulation strategy after left atrial appendage occlusion in patients requiring direct current cardioversion.

INTRODUCTION: Current guidelines recommend adequate anticoagulation for at least 3 weeks pre- and 4 weeks post-direct current cardioversion (DCCV) to reduce thrombo-embolic risk in patients with atrial fibrillation (AF) lasting greater than 48 h. No specific recommendations exist for DCCV in patients that have undergone left atrial appendage occlusion (LAAO), many of whom are ineligible for anticoagulation. This study aims to observe the efficacy and safety of DCCV post-LAAO in everyday clinical practice. METHODS: This prospective multicenter registry included DCCVs in patients post-LAAO. Imaging strategy or anticoagulation treatment around DCCV were analyzed. Complications during 30-day follow-up were registered. DCCVs performed in accordance with current guidelines for the general AF population were compared to DCCVs performed deviating from these guidelines. RESULTS: In 93 patients (age 65 ± 17 years, CHA2 DS2 -VASC 3.0 ± 1.3) 284 DCCVs were performed between 2010 and 2018, in 271 sinus rhythm was restored. A wide variety of imaging or anticoagulation strategies around DCCV was observed; in 128 episodes strategies deviated from current guidelines. No thrombo-embolic events were observed after any DCCV during 30-day follow-up. In 34 DCCVs trans-esophageal echocardiography (TOE) was performed before DCCV to exclude cardiac thrombi and/or (re-)verify adequate device positioning. In two patients without post-LAAO imaging before DCCV, a device rotation or embolization was observed during scheduled TOE after LAAO. CONCLUSION: DCCV in AF patients after LAAO is highly effective. No thrombo-embolic events were observed in any patient in this observational cohort, regardless of the periprocedural anticoagulation or imaging strategy. Confirmation of adequate device positioning at least once before DCCV seems recommendable.

Complications in pulmonary vein isolation in the Netherlands Heart Registration differ with sex and ablation technique.

AIMS: Pulmonary vein isolation (PVI) has become a cornerstone of the invasive treatment of atrial fibrillation. Severe complications are reported in 1-3% of patients. This study aims to compare complications and follow-up outcome of PVI in patients with atrial fibrillation. METHODS AND RESULTS: The data were extracted from the Netherlands Heart Registration. Procedural and follow-up outcomes in patients treated with conventional radiofrequency (C-RF), multielectrode phased RF (Ph-RF), or cryoballoon (CB) ablation from 2012 to 2017 were compared. Subgroup analysis was performed to identify variables associated with complications and repeat ablations. In total, 13 823 patients (69% male) were included. The reported complication incidence was 3.6%. Patients treated with C-RF developed more cardiac tamponades (C-RF 0.8% vs. Ph-RF 0.3% vs. CB 0.3%, P ≤ 0.001) and vascular complications (C-RF 1.7% vs. Ph-RF 1.2% vs. CB 1.3%, P ≤ 0.001). Ph-RF was associated with fewer bleeding complications (C-RF: 1.0% vs. Ph-RF: 0.4% vs. CB: 0.7%, P = 0.020). Phrenic nerve palsy mainly occurred in patients treated with CB (C-RF: 0.1% vs. Ph-RF: 0.2% vs. CB: 1.5%, P ≤ 0.001). In total, 18.4% of patients were referred for repeat ablation within 1 year. Female sex, age, and CHA2DS2-VASc were independent risk factors for cardiac tamponade and bleeding complications, with an adjusted OR for female patients of 2.97 (95% CI 1.98-4.45) and 2.02 (95% CI 1.03-4.00) respectively. CONCLUSION: The reported complication rate during PVI was low. Patients treated with C-RF ablation were more likely to develop cardiac tamponades and vascular complications. Female sex was associated with more cardiac tamponade and bleeding complications.

Nurse-led vs. usual-care for atrial fibrillation.

BACKGROUND: Nurse-led integrated care is expected to improve outcome of patients with atrial fibrillation compared with usual-care provided by a medical specialist. METHODS AND RESULTS: We randomized 1375 patients with atrial fibrillation (64 ± 10 years, 44% women, 57% had CHA2DS2-VASc ≥ 2) to receive nurse-led care or usual-care. Nurse-led care was provided by specialized nurses using a decision-support tool, in consultation with the cardiologist. The primary endpoint was a composite of cardiovascular death and cardiovascular hospital admissions. Of 671 nurse-led care patients, 543 (81%) received anticoagulation in full accordance with the guidelines against 559 of 683 (82%) usual-care patients. The cumulative adherence to guidelines-based recommendations was 61% under nurse-led care and 26% under usual-care. Over 37 months of follow-up, the primary endpoint occurred in 164 of 671 patients (9.7% per year) under nurse-led care and in 192 of 683 patients (11.6% per year) under usual-care [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.69 to 1.04, P = 0.12]. There were 124 vs. 161 hospitalizations for arrhythmia events (7.0% and 9.4% per year), and 14 vs. 22 for heart failure (0.7% and 1.1% per year), respectively. Results were not consistent in a pre-specified subgroup analysis by centre experience, with a HR of 0.52 (95% CI 0.37-to 0.71) in four experienced centres and of 1.24 (95% CI 0.94-1.63) in four less experienced centres (P for interaction <0.001). CONCLUSION: Our trial failed to show that nurse-led care was superior to usual-care. The data suggest that nurse-led care by an experienced team could be clinically beneficial (ClinicalTrials.gov NCT01740037). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT01740037).

Combining left atrial appendage closure and catheter ablation for atrial fibrillation: 2-year outcomes from a multinational registry.

AIMS: Clinical practice guidelines do not recommend discontinuation of long-term oral anticoagulation in patients with a high stroke risk after catheter ablation for atrial fibrillation (AF). Left atrial appendage closure (LAAC) with Watchman has emerged as an alternative to long-term anticoagulation for patients accepting of the procedural risks. We report on the long-term outcomes of combining catheter ablation procedures for AF and LAAC from multicentre registries. METHODS AND RESULTS: Data were pooled from two prospective, real-world Watchman LAAC registries running in parallel in Europe/Middle-East/Russia (EWOLUTION) and Asia/Australia (WASP) between 2013 and 2015. Of the 1140 patients, 142 subjects at 11 centres underwent a concomitant AF ablation and LAAC procedure. The mean CHA2DS2-VASc score was 3.4 ± 1.4 and HAS-BLED score 1.5 ± 0.9. Successful LAAC was achieved in 99.3% of patients. The 30-day device and/or procedure-related serious adverse event rate was 2.1%. After a mean follow-up time of 726 ± 91 days, 92% of patients remained off oral anticoagulation. The rates of the composite endpoint of ischaemic stroke/transient ischaemic attack/systemic thromboembolism were 1.09 per 100 patient-years (100-PY); and for non-procedural major bleeding were 1.09 per 100-PY. These represent relative reductions of 84% and 70% vs. expected rates per risk scores. CONCLUSION: The long-term outcomes from these international, multicentre registries show efficacy for all-cause stroke prevention and a significant reduction in late bleeding events in a population of high stroke risk post-ablation patients who have been withdrawn from oral anticoagulation.

Combined atrial fibrillation ablation and left atrial appendage closure: long-term follow-up from a large multicentre registry.

Aims: Long-term freedom from atrial fibrillation (AF) after catheter ablation (CA) and consequently the potential for stroke reduction remain unpredictable. Percutaneous left atrial appendage closure (LAAC) is an effective mechanical alternative to oral anticoagulation (OAC) for stroke prevention in AF patients. This study aims to evaluate long-term clinical results of combined CA and LAAC in one single procedure. Methods and results: Patients with non-valvular AF who underwent combined CA and LAAC procedure were included in the retrospective compilation of independent prospective general LAAC registries at the individual centres. Transoesophageal echocardiography (TOE) was used to evaluate device position and LAA sealing. Between 2009 and 2015, 349 patients with AF (58% male, age 63.1 ± 8.2 years; score for stroke prediction in AF patients (CHA2DS2-VASc) 3.0; score for major bleeding in patients on anticoagulation (HAS-BLED) 3.0; 56% paroxysmal AF) were included. Indications for LAAC included previous stroke (38%), history of bleeding (22%), and physician/patient preference (29%). Periprocedural complications up to 30 days included pericardial effusion (1.5%) and one minor stroke (0.3%) but no death. After 6 weeks, TOE showed successful sealing of the LAA in 98.9%. After 35 months of follow-up, 51% of patients had AF recurrence. A total of nine ischaemic strokes were recorded, resulting in an annualized stroke rate of 0.9% compared to an expected stroke rate of 3.2% without anticoagulation and combined treatment. Conclusion: This large pooled multicentre analysis of five prospective registries shows that combining CA and LAAC is feasible, safe, and successful. Long-term follow-up shows greatly reduced stroke and bleeding rates despite recurrence of AF in more than half of the patients.

Combining Watchman left atrial appendage closure and catheter ablation for atrial fibrillation: multicentre registry results of feasibility and safety during implant and 30 days follow-up.

Aims: Long-term results from catheter ablation therapy for atrial fibrillation (AF) remain uncertain and clinical practice guidelines recommend continuation of long-term oral anticoagulation in patients with a high stroke risk. Left atrial appendage closure (LAAC) with Watchman has emerged as an alternative to long-term anticoagulation for patients accepting of the procedural risks. We report on the initial results of combining catheter ablation procedures for AF and LAAC in a multicentre registry. Methods and results: Data were pooled from two prospective, real-world Watchman LAAC registries running in parallel in Europe/Middle-East/Russia (EWOLUTION) and Asia/Australia (WASP) between 2013 and 2015. Of the 1140 patients, 139 subjects at 10 centres underwent a concomitant AF ablation and LAAC procedure. The mean CHA2DS2-VASc score was 3.4 ± 1.4 and HAS-BLED score 1.5 ± 0.9. Successful Watchman implantation was achieved in 100% of patients. The overall 30-day serious adverse event (SAE) rate was 8.7%, with the device and/or procedure-related SAE rate of 1.4%. One pericardial effusion required percutaneous drainage, but there were no strokes, device embolization, or deaths at 30 days. The 30-day bleeding SAE rate was 2.9% with 55% of patients prescribed NOAC and 38% taking warfarin post-procedure. Conclusion: The outcomes from these international, multicentre registries support the feasibility and safety of performing combined procedures of ablation and Watchman LAAC for patients with non-valvular AF and high stroke risk. Further data are needed on long-term outcomes for the hybrid technique on all-cause stroke and mortality.

Previous Exercise Levels and Outcome in Patients with New Atrial Fibrillation: 'Past Achievements Do Not Predict the Future'.

INTRODUCTION: Long-term endurance exercise is suspect to elevate the risk of atrial fibrillation (AF),but little is known about cardiovascular outcome and disease progression in this subgroup of AF patients. We investigated whether previous exercise level determines cardiovascular outcome. METHODS: In this post hoc analysis of the RACE 4 randomized trial, we analyzed all patients with a completed questionnaire on sports participation. Three subgroups were made based on lifetime sports hours up to randomization and previous compliance to the international physical activity guidelines. High lifetime hours of high dynamic activity patients were defined as more than 150 min/week of high intense physical exercise. The primary endpoint was a composite of cardiovascular death and hospital admissions. RESULTS: A total of 879 patients were analyzed, divided in 203 high lifetime hours of high dynamic activity -, 192 high lifetime hours of activity- and 484 low lifetime hours of activity patients. Over a mean follow up of 36 months (±14), the primary endpoint occurred in 61 out of 203 (30%) high lifetime hours of high dynamic activity -, 53 out of 192 (27%) high lifetime hours of activity- and 135 out of 484 low lifetime hours of activity patients (28%) (p = 0.74). During follow up 42 high lifetime hours of high dynamic activity- (35%), 43 high lifetime hours of activity- (32%) and 104 low lifetime hours of activity patients (34%) with paroxysmal AF received electrical or chemical cardioversion or atrial ablation (p = 0.90). CONCLUSIONS: In patients included in the RACE 4, there appears to be no relation between previous activity levels and cardiovascular outcome and the need for electrical or chemical cardioversion or atrial ablation. Cardiovascular outcome was driven by AF related arrhythmic events.

Costs of minor bleeds in atrial fibrillation patients using a non-vitamin K antagonist oral anticoagulant.

BACKGROUND: A very common side effect of non-vitamin K antagonist oral anticoagulant (NOAC) is (minor) bleeding. Data about impact and costs of minor bleeds in NOAC therapy is still limited or not present in current literature. In this patient orientated study, we aim to provide an estimate of the costs of minor bleeds in patients with atrial fibrillation (AF) treated with a NOAC. METHODS: A retrospective observational cohort study was conducted. Patients with AF and on NOAC therapy were included. Data was obtained by questionnaires and information from electronic patient records. Reference prices were used to calculate the costs per patient. Furthermore, cost of minor bleeds per patient is compared with literature-based costs of minor and major bleeding. RESULTS: 139 patients were included. A total of 94 minor bleed were reported by 71 patients. The sum of minor bleeding costs from societal perspective were €9,851.49, or on average €70,87 (95% CI €54,37- €85,68) per patient with AF. The biggest cost drivers were rectal and vaginal bleeds, epistaxis was most commonly reported. CONCLUSION: Total costs of minor bleeds from a societal perspective, in AF patients using NOACs, are non-trivial and exceed the costs presented in existing literature.

Minor bleeding in patients with atrial fibrillation using a non-vitamin-K antagonist oral anticoagulant.

AIMS: We sought to investigate the magnitude of minor bleeding and identify risk factors for minor bleeds during non-vitamin-K antagonist oral anticoagulant (NOAC) therapy. METHODS: This was an observational cohort study of patients with atrial fibrillation (AF) referred to a regional NOAC outpatient clinic between February 2013 and October 2017. The study population consisted of 875 consecutive patients with AF who visited the NOAC outpatient unit to initiate treatment with apixaban (N = 303), dabigatran (N = 267) or rivaroxaban (N = 305) for long-term ischemic stroke prophylaxis. Minor bleed was defined as every overt bleeding that does not fulfil the criteria of major or non-major clinically relevant bleeding according to the International Society on Thrombosis and Haemostasis. RESULTS: Overall rate of minor bleeds was 19.2 per 100 patient years of follow-up. Bleeding rates for apixaban, dabigatran and rivaroxaban were 26, 8.3 and 23 per 100 patient-years of follow-up. Next to the type of NOAC, the main risk indicators for minor bleedings during NOAC therapy were a HAS-BLED score of 3 or higher and novel anticoagulant use (no history of vitamin K antagonist use). LIMITATION: This was a retrospective observational study evaluating NOAC treatment in a non-randomized setting. CONCLUSION: Our data showed that minor bleeds are common in novel NOAC users, especially when using apixaban and rivaroxaban. In the latter two NOACs, hematoma (bruises) and nose bleeds were more frequently observed and accounted for the difference with dabigatran. Besides type of NOAC, a higher HAS-BLED score and novel anticoagulant drug use were associated with an increased risk of minor bleeding.

Reasons for discontinuation of novel oral anticoagulant therapy in patients with atrial fibrillation.

Aims: We sought to investigate the reasons for, and rates of, novel oral anticoagulant (DOAC) therapy discontinuation.Methods: This was an observational cohort study of patients with atrial fibrillation (AF) referred to a regional DOAC outpatient clinic between February 2013 and October 2017. The study population consisted of 875 consecutive patients with AF who visited the DOAC outpatient unit to initiate treatment with apixaban (N = 303), dabigatran (N = 267) or rivaroxaban (N = 305) for long-term ischemic stroke prophylaxis. All the patients came from the Leeuwarden Medical Center cardiology outpatient clinic, which offers a well structured and nurse-run DOAC unit in cooperation with the hospital's thrombosis service. This clinic operates according to the Dutch nationwide guidelines on integration of anticoagulation services.Results: Overall rate of discontinuation was 11.9 per 100 patient-years of follow-up. Discontinuation rates for apixaban, dabigatran and rivaroxaban were 8.1, 16.6 and 11.5 per 100 patient-years of follow-up.Apixaban had the lowest rate of discontinuation during the 36 month follow-up period. Dabigatran and rivaroxaban had high discontinuation rates during the 3-6 month period following DOAC therapy initiation. The main reasons for discontinuation of DOAC therapy were adverse side effects, patient-initiated discontinuation and any bleed.Limitation: This was a retrospective and non-randomized study, and our results should be interpreted in light of these observations.Conclusion: DOAC discontinuation rates varied significantly and appeared related to drug-specific side effects, patient-initiated discontinuation and bleeding. We observed longer-term administration of apixaban, suggesting that this drug is better tolerated than dabigatran or rivaroxaban.

[The antithrombotic jungle: an overview of the recent literature]. / Oerwoud van antitrombotica: een overzicht van recente literatuur.

Physicians encounter patients who use antithrombotics in virtually every area of medical specialisation. As antithrombotic use is often chronic, it is important for medication monitoring that physicians have sufficient knowledge of the latest developments, even if they do not prescribe antithrombotics themselves. The risk of thrombosis must be weighed against the risk of bleeding in every patient who is eligible to be treated with antithrombotics. In this article we describe the main indications for treatment with antithrombotics based on articles published within the past five years.

[Frameworks for responsible anticoagulation care: a contribution to a collective view]. / Kaders voor verantwoorde antistollingszorg.

Until recently, vitamin K antagonists (VKAs) were the only form of anticoagulation for the prevention of thromboembolic complications in patients with atrial fibrillation or venous thromboembolisms. Various caregivers are involved in anticoagulation care. Criticism of the support by the thrombosis department focused mainly on the lack of guarantees regarding the interinstitutional anticoagulation chain of care. Initiatives have now been deployed to improve this support, as described in the national integrated anticoagulation care standard (LSKA, Landelijke Standaard Ketenzorg Antistolling) and the national primary care anticoagulation agreement (LESA, Landelijke Eerstelijns Samenwerkingsafspraken). However, rapidly increasing use of direct oral anticoagulants (DOACs) has dramatically altered anticoagulation care. Patients and caregivers are more often confronted with uncertainty about treatment coordination. This article aims to sketch frameworks for responsible anticoagulation care. We examine different topics, such as coordination, organisation of follow-up, availability for answering questions and switching from VKA to DOAC.

Statins associated with reduced mortality in patients admitted for congestive heart failure.

BACKGROUND: Statins may be of potential benefit in patients with congestive heart failure (CHF) due to modulation of neurohormones and their antioxidant, antiinflammatory, and antifibrotic properties. To test this hypothesis, we performed a case-control study by using a prospective registry of patients admitted to our hospital for CHF. METHODS AND RESULTS: The Maastricht Registry of Congestive Heart Failure consists of a cohort of all patients who were admitted to the University Hospital Maastricht because of CHF for the first time between 1998 and 2000. Elective admissions were not included in the database. Drug treatment was left at the discretion of the attending physician. From a total of 840 patients admitted, we selected patients with an uncomplicated survival for at least 1 month after hospital discharge. For each survivor a nonsurvivor was matched for age, sex, left ventricular ejection fraction, and renal function. Drugs were considered in use only if they were administered for at least 90% of follow-up time. Five hundred twenty-four patients were included with a mean follow-up after discharge of 31 +/- 18 months. Twenty percent used statins. In Cox multivariate regression analysis, the use of statins remained significantly associated with decreased mortality independent of the cause of CHF. However, there appeared no additional benefit of statins in patients using beta-blockers. Mortality rates were constant over time after discharge. Statins were as effective in ischemic as in nonischemic heart failure and in patients with depressed as well as preserved LVEF. CONCLUSION: Statins appear associated with improved survival in CHF independent of its etiology. No additional benefit was seen in patients treated with beta-blockers.

Rationale and design of the Left Atrial Appendage Occlusion Study (LAAOS) III.

BACKGROUND: Occlusion of the left atrial appendage (LAA) is a promising approach to stroke prevention in atrial fibrillation (AF). However, evidence of its efficacy and safety to date is lacking. We herein describe the rationale and design of a definitive LAA occlusion trial in cardiac surgical patients with AF. METHODS: We plan to randomize 4,700 patients with AF in whom on-pump cardiac surgical procedure is planned to undergo LAA occlusion or no LAA occlusion. The primary outcome is the first occurrence of stroke or systemic arterial embolism over a mean follow-up of four years. Other outcomes include total mortality, operative safety outcomes (chest tube output in the first post-operative 24 hours, rate of post-operative re-exploration for bleeding in the first 48 hours post-surgery and 30-day mortality), re-hospitalization for heart failure, major bleed, and myocardial infarction. RESULTS: Left Atrial Appendage Occlusion Study (LAAOS) III is funded in a vanguard phase by the Canadian Institutes for Health Research (CIHR), the Canadian Network and Centre for Trials Internationally, and the McMaster University Surgical Associates. As of September 9, 2013, 162 patients have been recruited into the study. CONCLUSIONS: LAAOS III will be the largest trial to explore the efficacy of LAA occlusion for stroke prevention. Its results will lead to a better understanding of stroke in AF and the safety and efficacy of surgical LAA occlusion.