The pattern of atrial fibrillation (AF) occurrence-paroxysmal, persistent, or permanent-is associated with progressive stages of atrial dysfunction and structural changes and may therefore be ...associated with progressively higher stroke risk. However, previous studies have not consistently shown AF pattern to predict stroke but have been hampered by methodological shortcomings of low power, variable event ascertainment, and variable anticoagulant use.
We analysed the rates of stroke and systemic embolism in 6563 aspirin-treated patients with AF from the ACTIVE-A/AVERROES databases. There was thorough searching for events and adjudication. Multivariable analyses were performed with the adjustment for known risk factors for stroke. Mean age of patients with paroxysmal, persistent, and permanent AF was 69.0 ± 9.9, 68.6 ± 10.2, and 71.9 ± 9.8 years (P < 0.001). The CHA2DS2-VASc score was similar in patients with paroxysmal and persistent AF (3.1 ± 1.4), but was higher in patients with permanent AF (3.6 ± 1.5, P < 0.001). Yearly ischaemic stroke rates were 2.1, 3.0, and 4.2% for paroxysmal, persistent, and permanent AF, respectively, with adjusted hazard ratio of 1.83 (P < 0.001) for permanent vs. paroxysmal and 1.44 (P = 0.02) for persistent vs. paroxysmal. Multivariable analysis identified age ≥ 75 year, sex, history of stroke or TIA, and AF pattern as independent predictors of stroke, with AF pattern being the second strongest predictor after prior stroke or TIA.
In a large population of non-anticoagulated AF patients, pattern of AF was a strong independent predictor of stroke risk and may be helpful to assess the risk/benefit for anticoagulant therapy, especially in lower risk patients.
In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in ...patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban.
Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event death, ischaemic stroke, or myocardial infarction (MI) was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI.
Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the importance of preventing bleeding in anti-coagulated patients. ClinicalTrials.gov Identifier: NCT00412984.
Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk.
We performed a 3 × 2 partial ...factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation.
There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval CI, 0.67–1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28–0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27–0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609–2528).
In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.
Abstract
Aims
The Routine vs. Aggressive risk factor driven upstream rhythm Control for prevention of Early persistent atrial fibrillation (AF) in heart failure (HF) (RACE 3) trial demonstrated that ...targeted therapy of underlying conditions improved sinus rhythm maintenance at 1 year. We now explored the effects of targeted therapy on the additional co-primary endpoints; sinus rhythm maintenance and cardiovascular outcome at 5 years.
Methods and results
Patients with early persistent AF and mild-to-moderate stable HF were randomized to targeted or conventional therapy. Both groups received rhythm control therapy according to guidelines. The targeted group additionally received four therapies: angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers (ARBs), statins, mineralocorticoid receptor antagonists (MRAs), and cardiac rehabilitation. The presence of sinus rhythm and cardiovascular morbidity and mortality at 5-year follow-up were assessed. Two hundred and sixteen patients consented for long-term follow-up, 107 were randomized to targeted and 109 to conventional therapy. At 5 years, MRAs 76 (74%) vs. 10 (9%) patients, P < 0.001 and statins 81 (79%) vs. 59 (55%), P < 0.001 were used more in the targeted than conventional group. Angiotensin-converting enzyme inhibitors/ARBs and physical activity were not different between groups. Sinus rhythm was present in 49 (46%) targeted vs. 43 (39%) conventional group patients at 5 years (odds ratio 1.297, lower limit of 95% confidence interval 0.756, P = 0.346). Cardiovascular mortality and morbidity occurred in 20 (19%) in the targeted and 15 (14%) conventional group patients, P = 0.353.
Conclusion
In patients with early persistent AF and HF superiority of targeted therapy in sinus rhythm maintenance could not be preserved at 5-year follow-up. Cardiovascular outcome was not different between groups.
Trial registration number
Clinicaltrials.gov NCT00877643.
Summary
Background
Anemia may predispose to thromboembolic events or bleeding in anticoagulated patients with atrial fibrillation (AF).
Objectives
To investigate whether anemia is associated with ...thromboembolic events and bleeding in patients with AF.
Patients and methods
We retrospectively analyzed the RE‐LY trial database, which randomized 18 113 patients with AF and a risk of stroke to receive dabigatran or warfarin for a median follow‐up of 2 years. Cox regression analysis was used to determine whether anemia predicted cardiovascular events and bleeding complications in these patients.
Results
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 HR 1.41, 95% CI 1.12–1.78). Anemia was also associated with a higher risk of major bleeding complications (adjusted HR 2.14, 95% CI 1.87–2.46) and discontinuation of anticoagulants (adjusted HR 1.40, 95% CI 1.28–1.79). 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 HR 0.66, 95% CI 0.49–0.91).
Conclusions
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.
Previously, we demonstrated that inferolateral mitral annular disjunction (MAD) is more prevalent in patients with idiopathic ventricular fibrillation (IVF) than in healthy controls. In the present ...study, we advanced the insights into the prevalence and ventricular arrhythmogenicity by inferolateral MAD in an even larger IVF cohort.
This retrospective multi-centre study included 185 IVF patients median age 39 (27, 52) years, 40% female. Cardiac magnetic resonance images were analyzed for mitral valve and annular abnormalities and late gadolinium enhancement. Clinical characteristics were compared between patients with and without MAD. MAD in any of the 4 locations was present in 112 (61%) IVF patients and inferolateral MAD was identified in 24 (13%) IVF patients. Mitral valve prolapse (MVP) was found in 13 (7%) IVF patients. MVP was more prevalent in patients with inferolateral MAD compared with patients without inferolateral MAD (42 vs. 2%, P < 0.001). Pro-arrhythmic characteristics in terms of a high burden of premature ventricular complexes (PVCs) and non-sustained ventricular tachycardia (VT) were more prevalent in patients with inferolateral MAD compared to patients without inferolateral MAD (67 vs. 23%, P < 0.001 and 63 vs. 41%, P = 0.046, respectively). Appropriate implantable cardioverter defibrillator therapy during follow-up was comparable for IVF patients with or without inferolateral MAD (13 vs. 18%, P = 0.579).
A high prevalence of inferolateral MAD and MVP is a consistent finding in this large IVF cohort. The presence of inferolateral MAD is associated with a higher PVC burden and non-sustained VTs. Further research is needed to explain this potential interplay.
Anxiety has been associated with adverse clinical outcomes in patients who have received an implantable cardioverter defibrillator (ICD). However, results are inconclusive likely due to different ...measures being used to assess anxiety. Hence, the current study aims to examine the prevalence and the association between anxiety, ventricular tachyarrhythmia's (VTa's) and all-cause mortality, respectively.
Patients who received an ICD for the first time were recruited from 6 Dutch referral hospitals as part of the WEBCARE trial. Patients filled in validated questionnaires (GAD-7, STAI-S, HADS-A, ANX4, ICDC, FSAS) to assess their baseline anxiety symptomatology. Logistic regression analysis and Cox Regression analysis were performed to examine the association between anxiety with 1) VTa's and 2) mortality, respectively.
A total of 214 Patients were included in the analysis with mean age 58.9 and 82.7% being male. The prevalence rates of anxiety varied depending on which questionnaire was used 12.4% (GAD-7), 17.5% (HADS-A), and 28.1% (STAI-S). (Cox) Regression analysis revealed that none of the anxiety measures was associated with VTa's or all-cause mortality in the current sample. Stratifying the sample by gender, the analysis showed that GAD-7, STAI-S, and ANX4 scores were associated with increased risk of VTa's but only in male patients.
Prevalence rates of anxiety varied depending on the measurement tool used. No significant association between anxiety and VTa's and all-cause mortality was observed in the total sample. GAD-7, STAI-S, and ANX4 were associated with increased risk for VTa's but only in male patients.
•Anxiety is highly prevalent in ICD patients.•Anxiety is associated with ventricular arrhythmias in male ICD patients.•Anxiety not associated with all-cause mortality in ICD patients•Individual differences might explain inconsistent findings in previous studies.
Summary Background In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and ...previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. Methods Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18 201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0–3·0). The median duration of follow-up was 1·8 years (IQR 1·4–2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov , number NTC00412984. Findings Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio HR 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI −0·08 to 1·63) in patients with and 0·22 (−0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09–2·04) in patients with and 0·93 (0·54–1·32) in those without previous stroke or TIA. Interpretation The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. Funding Bristol-Myers Squibb and Pfizer.
Risk stratification within the ICD population warrants the examining of the role of protective- and risk factors. Current study examines the association between Type D personality, pessimism, and ...optimism and risk of ventricular tachyarrhythmias (VTa's) and mortality in patients with a first-time ICD 6 years post implantation.
A total of 221 first-implant ICD patients completed questionnaires on optimism and pessimism (Life Orientation Test) and Type D personality (Type D scale DS14) 10 to 14 days after implantation. VTa's and all-cause mortality 6 years post implant comprised the study endpoints.
Ninety (40.7%) patients had experienced VTa's and 37 (16.7%) patients died, 12 (5.4%) due to a cardiac cause. Adjusted logistic regression analysis showed that pessimism was significantly associated with increased risk of VTa's (OR = 1.09; 95% CI = 1.00–1.19; p = .05). Type D personality (OR = 1.05; 95% CI = 0.47–2.32; p = .91) and optimism (OR = 1.00; 95% CI = 0.90–1.12; p = .98) were not associated with VTa's. None of the personality types were associated with mortality.
Pessimism was associated with VTa's but not with mortality. No significant association with either of the endpoints was observed for Type D personality and optimism. Future research should focus on the coexistent psychosocial factors that possibly lead to adverse cardiac prognosis in this patient population.
Abstract Background Long-term aspirin prevents vascular events but is only modestly effective. Rivaroxaban alone or in combination with aspirin might be more effective than aspirin alone for vascular ...prevention in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). Both rivaroxaban and aspirin increase upper gastrointestinal (GI) bleeding and this might be prevented by proton pump inhibitor (PPI) therapy. Methods COMPASS is a double-blind superiority trial comparing rivaroxaban 2.5mg twice-daily in combination with aspirin 100mg once-daily or rivaroxaban 5mg twice-daily versus aspirin 100mg once-daily for prevention of myocardial infarction, stroke, or cardiovascular death in patients with stable CAD or PAD. Patients not taking a PPI were also randomized, using a partial factorial design, to pantoprazole 40mg once-daily or placebo. The trial was designed to have at least 90% power to detect a 20% reduction in each of the rivaroxaban-treatment arms compared with aspirin and to detect a 50% reduction in upper GI complications with pantoprazole compared with placebo. Results Between February 2013 and May 2016, we recruited 27,395 participants from 602 centers in 33 countries; 17,603 participants were included in the pantoprazole versus placebo comparison. At baseline, mean age was 68.2years, 22.0% were female, 90.6% had CAD, and 27.3% had PAD. Conclusion COMPASS will provide information on the efficacy and safety of rivaroxaban, alone or in combination with aspirin, in the long-term management of patients with stable CAD or PAD, and on the efficacy and safety of pantoprazole in preventing upper GI complications in patients receiving antithrombotic therapy.
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