In this multicenter, randomized trial comparing early rhythm control with usual care in patients with early atrial fibrillation and cardiovascular conditions, early rhythm control reduced the rate of ...death from cardiovascular causes and cardiovascular complications and did not affect the number of nights in the hospital.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder that causes sudden death and right ventricular heart failure in the young. Clinical data suggest that competitive ...sports may provoke ARVC in susceptible persons. Genetically, loss-of-function mutations in desmosomal proteins (plakophilin, desmoplakin, or plakoglobin) have been associated with ARVC. To test the hypothesis that reduced desmosomal protein expression causes ARVC, we studied the cardiac effects of heterozygous plakoglobin deficiency in mice.
Ten-month-old heterozygous plakoglobin-deficient mice (plakoglobin+/-) had increased right ventricular volume, reduced right ventricular function, and spontaneous ventricular ectopy (all P<0.05). Left ventricular size and function were not altered. Isolated, perfused plakoglobin+/- hearts had spontaneous ventricular tachycardia of right ventricular origin and prolonged right ventricular conduction times compared with wild-type hearts. Endurance training accelerated the development of right ventricular dysfunction and arrhythmias in plakoglobin+/- mice. Histology and electron microscopy did not identify right ventricular abnormalities in affected animals.
Heterozygous plakoglobin deficiency provokes ARVC. Manifestation of the phenotype is accelerated by endurance training. This suggests a functional role for plakoglobin and training in the development of ARVC.
Even on optimal therapy, many patients with heart failure and atrial fibrillation experience cardiovascular complications. Additional treatments are needed to reduce these events, especially in ...patients with heart failure and preserved left ventricular ejection fraction.
This prespecified subanalysis of the randomized EAST-AFNET4 trial (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) assessed the effect of systematic, early rhythm control therapy (ERC; using antiarrhythmic drugs or catheter ablation) compared with usual care (allowing rhythm control therapy to improve symptoms) on the 2 primary outcomes of the trial and on selected secondary outcomes in patients with heart failure, defined as heart failure symptoms New York Heart Association II to III or left ventricular ejection fraction LVEF <50%.
This analysis included 798 patients (300 37.6% female, median age 71.0 64.0, 76.0 years, 785 with known LVEF). The majority of patients (n=442) had heart failure and preserved LVEF (LVEF≥50%; mean LVEF 61±6.3%), the others had heart failure with midrange ejection fraction (n=211; LVEF 40%-49%; mean LVEF 44 ± 2.9%) or heart failure with reduced ejection fraction (n=132; LVEF<40%; mean LVEF 31±5.5%). Over the 5.1-year median follow-up, the composite primary outcome of cardiovascular death, stroke, or hospitalization for worsening of heart failure or for acute coronary syndrome occurred less often in patients randomly assigned to ERC (94/396; 5.7 per 100 patient-years) compared with patients randomly assigned to usual care (130/402; 7.9 per 100 patient-years; hazard ratio, 0.74 0.56-0.97;
=0.03), not altered by heart failure status (interaction
value=0.63). The primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) occurred in 71 of 396 (17.9%) patients with heart failure randomly assigned to ERC and in 87 of 402 (21.6%) patients with heart failure randomly assigned to usual care (hazard ratio, 0.85 0.62-1.17;
=0.33). LVEF improved in both groups (LVEF change at 2 years: ERC 5.3±11.6%, usual care 4.9±11.6%,
=0.43). ERC also improved the composite outcome of death or hospitalization for worsening of heart failure.
Rhythm control therapy conveys clinical benefit when initiated within 1 year of diagnosing atrial fibrillation in patients with signs or symptoms of heart failure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01288352. URL: http://www.controlled-trials.com; Unique identifier: ISRCTN04708680. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2010-021258-20.
In this trial, 14,264 patients with atrial fibrillation were randomly assigned to receive either rivaroxaban or warfarin. In a per-protocol, as-treated analysis, rivaroxaban was noninferior to ...warfarin with respect to the primary end point of stroke or systemic embolism.
Atrial fibrillation is associated with an increase in the risk of ischemic stroke by a factor of four to five
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and accounts for up to 15% of strokes in persons of all ages and 30% in persons over the age of 80 years.
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The use of vitamin K antagonists is highly effective for stroke prevention in patients with nonvalvular atrial fibrillation and is recommended for persons at increased risk.
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However, food and drug interactions necessitate frequent coagulation monitoring and dose adjustments, requirements that make it difficult for many patients to use such drugs in clinical practice.
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Rivaroxaban is . . .
Summary Background In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate ...whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). Methods In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2·0–3·0). Patients and investigators were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov , number NCT00403767. Findings 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2·79% rivaroxaban vs 2·96% warfarin; hazard ratio HR 0·94, 95% CI 0·77–1·16) and those without (1·44% vs 1·88%; 0·77, 0·58–1·01; interaction p=0·23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13·31% rivaroxaban vs 13·87% warfarin; HR 0·96, 95% CI 0·87–1·07) and those without (16·69% vs 15·19%; 1·10, 0·99–1·21; interaction p=0·08). Interpretation There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA. These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF. Funding Johnson and Johnson Pharmaceutical Research and Development and Bayer HealthCare.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Non-vitamin K oral anticoagulants have become the standard therapy for preventing stroke and ischemic thromboembolism in most patients with atrial fibrillation (AF). The effectiveness and safety of ...non-vitamin K oral anticoagulants in patients on hemodialysis is not well known.
From June 2017 through May 2022, AXADIA-AFNET 8 (Compare Apixaban and Vitamin K Antagonists in Patients With Atrial Fibrillation and End-Stage Kidney Disease), an investigator-initiated PROBE (prospective randomized open blinded end point) outcome assessment trial, randomized patients with AF on chronic hemodialysis to either apixaban (2.5 mg BID) or the vitamin K antagonist (VKA) phenprocoumon (international normalized ratio, 2.0 to 3.0). The composite primary safety outcome was defined by a first event of major bleeding, clinically relevant nonmajor bleeding, or all-cause death. The primary efficacy outcome was a composite of ischemic stroke, all-cause death, myocardial infarction, and deep vein thrombosis or pulmonary embolism. Our hypothesis was that apixaban is noninferior to VKA.
Thirty-nine sites randomized 97 patients (30% women; mean age 75 years; mean CHA
DS
-VASc congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, female sex score, 4.5; baseline characteristics balanced between groups): 48 to apixaban and 49 to VKA. The median follow-up time was 429 days (range, 37 to 1370) versus 506 days (range, 101 to 1379), respectively. Adherence to apixaban was >80% in 44 of 48 patients; the median time in therapeutic range on VKA was 50.7%. Composite primary safety outcome events occurred in 22 patients (45.8%) on apixaban and in 25 patients (51.0%) on VKA (hazard ratio, 0.93 95% CI, 0.53-1.65;
=0.157). Composite primary efficacy outcome events occurred in 10 patients (20.8%) on apixaban and in 15 patients (30.6%) on VKA (
=0.51; log rank). There were no significant differences regarding individual outcomes (all-cause mortality, 18.8% versus 24.5%; major bleeding, 10.4% versus 12.2%; and myocardial infarction, 4.2% versus 6.1%, respectively).
In this randomized trial comparing apixaban and VKA in patients with AF on hemodialysis with long follow-up, no differences were observed in safety or efficacy outcomes. Even on oral anticoagulation, patients with AF on hemodialysis remain at high risk of cardiovascular events. Larger randomized trials are needed to determine the optimal anticoagulation regimen for patients with AF on hemodialysis.
URL: https://www.
gov; Unique identifier: NCT02933697.
Abstract
Aims
Clinical practice guidelines restrict rhythm control therapy to patients with symptomatic atrial fibrillation (AF). The EAST-AFNET 4 trial demonstrated that early, systematic rhythm ...control improves clinical outcomes compared to symptom-directed rhythm control.
Methods and results
This prespecified EAST-AFNET 4 analysis compared the effect of early rhythm control therapy in asymptomatic patients (EHRA score I) to symptomatic patients. Primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome, analyzed in a time-to-event analysis. At baseline, 801/2633 (30.4%) patients were asymptomatic mean age 71.3 years, 37.5% women, mean CHA2DS2-VASc score 3.4, 169/801 (21.1%) heart failure. Asymptomatic patients randomized to early rhythm control (395/801) received similar rhythm control therapies compared to symptomatic patients e.g. AF ablation at 24 months: 75/395 (19.0%) in asymptomatic; 176/910 (19.3%) symptomatic patients, P = 0.672. Anticoagulation and treatment of concomitant cardiovascular conditions was not different between symptomatic and asymptomatic patients. The primary outcome occurred in 79/395 asymptomatic patients randomized to early rhythm control and in 97/406 patients randomized to usual care (hazard ratio 0.76, 95% confidence interval 0.6; 1.03), almost identical to symptomatic patients. At 24 months follow-up, change in symptom status was not different between randomized groups (P = 0.19).
Conclusion
The clinical benefit of early, systematic rhythm control was not different between asymptomatic and symptomatic patients in EAST-AFNET 4. These results call for a shared decision discussing the benefits of rhythm control therapy in all patients with recently diagnosed AF and concomitant cardiovascular conditions (EAST-AFNET 4; ISRCTN04708680; NCT01288352; EudraCT2010-021258-20).
Graphical Abstract
Graphical Abstract
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