1. Home
  2. stroke

stroke

Long-Term Anticoagulation Discontinuation After Catheter Ablation for Atrial Fibrillation: The ALONE-AF Randomized Clinical Trial

Author/s: 
Daehoon Kim, MD, Jaemin Shim, MD, Eue-Keun Choi, MD

Importance: Data from randomized clinical trials on a long-term anticoagulation strategy for patients after catheter-based ablation for atrial fibrillation (AF) are lacking.

Objective: To evaluate whether discontinuing oral anticoagulant therapy provides superior clinical outcomes compared with continuing oral anticoagulant therapy in patients without documented atrial arrhythmia recurrence after catheter ablation for AF.

Design, setting, and participants: A randomized clinical trial including 840 adult patients (aged 19-80 years) who were enrolled and randomized from July 28, 2020, to March 9, 2023, at 18 hospitals in South Korea. Enrolled patients had at least 1 non-sex-related stroke risk factor (determined using the CHA2DS2-VASc score [range, 0-9]) and no documented recurrence of atrial arrhythmia for at least 1 year after catheter ablation for AF. The CHA2DS2-VASc score is used as an assessment of stroke risk among patients with AF (calculated using point values for congestive heart failure, hypertension, ≥75 years of age, diabetes, stroke or transient ischemic attack, vascular disease, between 65 and 74 years of age, and sex category). The date of final follow-up was June 4, 2025.

Interventions: The patients were randomly assigned in a 1:1 ratio to discontinue oral anticoagulant therapy (n = 417) or continue oral anticoagulant therapy (with direct oral anticoagulants; n = 423).

Main outcomes and measures: The primary outcome was the first occurrence of a composite of stroke, systemic embolism, and major bleeding at 2 years. Individual components of the primary outcome (such as ischemic stroke and major bleeding) were assessed as secondary outcomes.

Results: Of the 840 adults randomized, the mean age was 64 (SD, 8) years, 24.9% were women, the mean CHA2DS2-VASc score was 2.1 (SD, 1.0), and 67.6% had paroxysmal AF. At 2 years, the primary outcome occurred in 1 patient (0.3%) in the discontinue oral anticoagulant therapy group vs 8 patients (2.2%) in the continue oral anticoagulant therapy group (absolute difference, -1.9 percentage points [95% CI, -3.5 to -0.3]; P = .02). The 2-year cumulative incidence of ischemic stroke was 0.3% in the discontinue oral anticoagulant therapy group vs 0.8% in the continue oral anticoagulant therapy group (absolute difference, -0.5 percentage points [95% CI, -1.6 to 0.6]). Major bleeding occurred in 0 patients in the discontinue oral anticoagulant therapy group vs 5 patients (1.4%) in the continue oral anticoagulant therapy group (absolute difference, -1.4 percentage points [95% CI, -2.6 to -0.2]).

Conclusions and relevance: Among patients without documented atrial arrhythmia recurrence after catheter ablation for AF, discontinuing oral anticoagulant therapy resulted in a lower risk for the composite outcome of stroke, systemic embolism, and major bleeding vs continuing direct oral anticoagulant therapy.

Trial registration: ClinicalTrials.gov Identifier: NCT04432220.

Keywords 
clinical pharmacy and pharmacology Oral Anticoagulation Cardiology atrial fibrillation Rhythm Disorders

Aspirin in Patients with Chronic Coronary Syndrome Receiving Oral Anticoagulation

Author/s: 
Gilles Lemesle, M.D., Ph.D., Romain Didier, M.D., Ph.D., Philippe Gabriel Steg, M.D., Tabassome Simon, M.D., Ph.D., Gilles Montalescot, M.D., Ph.D., Nicolas Danchin, M.D., Christophe Bauters, M.D., Ph.D.

Background: The appropriate antithrombotic regimen for patients with chronic coronary syndrome who are at high atherothrombotic risk and receiving long-term oral anticoagulation remains unknown.

Methods: We conducted a multicenter, double-blind, randomized, placebo-controlled trial in France involving patients with chronic coronary syndrome who had undergone a previous stent implantation (>6 months before enrollment) and were at high atherothrombotic risk and currently receiving long-term oral anticoagulation. The patients were randomly assigned in a 1:1 ratio to receive aspirin (100 mg once daily) or placebo; all the patients continued to receive their current oral anticoagulation therapy. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia. The key safety outcome was major bleeding.

Results: A total of 872 patients underwent randomization; 433 were assigned to the aspirin group, and 439 to the placebo group. The trial was stopped early at the advice of the independent data and safety monitoring board after a median follow-up of 2.2 years because of an excess of deaths from any cause in the aspirin group. A primary efficacy outcome event occurred in 73 patients (16.9%) in the aspirin group and in 53 patients (12.1%) in the placebo group (adjusted hazard ratio, 1.53; 95% confidence interval [CI], 1.07 to 2.18; P = 0.02). Death from any cause occurred in 58 patients (13.4%) in the aspirin group and in 37 (8.4%) in the placebo group (adjusted hazard ratio, 1.72; 95% CI, 1.14 to 2.58; P = 0.01). Major bleeding occurred in 44 patients (10.2%) in the aspirin group and in 15 patients (3.4%) in the placebo group (adjusted hazard ratio, 3.35; 95% CI, 1.87 to 6.00; P<0.001). A total of 467 and 395 serious adverse events were reported in the aspirin group and placebo group, respectively.

Conclusions: Among patients with chronic coronary syndrome at high atherothrombotic risk who were receiving an oral anticoagulant, the addition of aspirin led to a higher risk of cardiovascular death, myocardial infarction, stroke, systemic embolism, coronary revascularization, or acute limb ischemia than placebo, as well as higher risks of death from any cause and major bleeding. (Funded by the French Ministry of Health and Bayer Healthcare; ClinicalTrials.gov number, NCT04217447.).

Keywords 
Chronic Coronary Syndrome Oral Anticoagulation aspirin atherothrombotic risk stent implantation

Patent Foramen Ovale and Stroke A Review

Author/s: 
David M. Kent, Andy Y. Wang

Importance: A patent foramen ovale (PFO), an opening between the right and left atria during normal fetal development that fails to close after birth, is present in approximately 25% of all adults. Paradoxical embolism, a venous thromboembolism that travels to the systemic circulation typically through a PFO, accounts for about 5% of all strokes and 10% of strokes in younger patients.

Observations: Approximately 50% of patients 60 years or younger with an embolic stroke of undetermined source (cryptogenic stroke) have a PFO, compared with 25% of the general population. The Risk of Paradoxical Embolism (RoPE) score incorporates clinical characteristics (age, history of stroke or transient ischemic attack, diabetes, hypertension, smoking, cortical infarct on imaging) to predict the likelihood that embolic stroke of undetermined source was caused by a PFO. Among patients in the lowest RoPE score category (score <3), PFO prevalence was similar to that in the general population (23%), while PFO prevalence was 77% in patients with a RoPE score of 9 or 10. The PFO-Associated Stroke Causal Likelihood (PASCAL) classification system combines the RoPE score and anatomical criteria from echocardiography (large shunt, atrial septal aneurysm) to classify PFO as the “probable,” “possible,” or “unlikely” cause of otherwise cryptogenic stroke. PFO closure reduces recurrent ischemic stroke in patients 60 years or younger with cryptogenic stroke. In a pooled analysis of 6 trials (3740 patients), the annualized incidence of stroke over a median follow-up of 57 months was 0.47% (95% CI, 0.35%-0.65%) with PFO closure vs 1.09% (95% CI, 0.88%-1.36%) with medical therapy (adjusted hazard ratio, 0.41 [95% CI, 0.28-0.60]). However, the benefits and harms of closure were highly heterogeneous across the trial populations. In patients categorized as PASCAL “probable” (ie, younger patients without vascular risk factors and high-risk PFO anatomical features), there was a 90% decreased relative rate of recurrent ischemic stroke after PFO closure at 2 years (hazard ratio, 0.10 [95% CI, 0.03-0.35]; absolute risk reduction, 2.1% [95% CI, 0.9%-3.4%]). PASCAL “unlikely” patients (eg, older patients with vascular risk factors and no high-risk PFO anatomical features) did not have a lower recurrent stroke rate with PFO closure but had higher risk of procedure- and device-related adverse events, such as atrial fibrillation.

Conclusions and Relevance: Patent foramen ovale is present in approximately 25% of all adults and is a common cause of stroke in young and middle-aged patients. The PASCAL classification system can help guide patient selection for PFO closure. Percutaneous PFO closure substantially reduces the risk of stroke recurrence in well-selected patients younger than 60 years after cryptogenic stroke.

Keywords 
Congenital Defects pediatrics female

Early Invasive or Conservative Strategies for Older Patients With Acute Coronary Syndromes: A Meta-Analysis

Author/s: 
Rohin K Reddy, David Koeckerling, Christian Eichhorn, Yasser Jamil, Maddalena Ardissino, Volker Braun, Haitham Abu Sharar, Norbert Frey, James P Howard, Yousif Ahmad

Importance: The optimal management strategy for older patients who present with acute coronary syndrome (ACS) remains unclear due to a paucity of randomized evidence. New large and longer-term randomized data are available.

Objective: To test the association of an early invasive strategy vs a conservative strategy with clinical outcomes for patients 70 years or older who present with ACS.

Data sources: A literature search strategy was designed in collaboration with a medical librarian. MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched ,with no language restrictions from inception through October 2024. Bibliographies of previous reviews and conference abstracts from major cardiovascular scientific meetings were handsearched.

Study selection: Studies were deemed eligible following review by 2 independent, masked investigators if they randomly allocated patients 70 years or older who presented with ACS to early invasive or conservative management and reported clinical end points. Observational analyses were excluded. No trials were excluded based on sample size or follow-up duration.

Data extraction and synthesis: Data were extracted independently and in triplicate. Clinical end points were pooled in meta-analyses that applied fixed-effects and random-effects modeling to calculate summary estimates for relative risks (RRs) and hazard ratios, along with their corresponding 95% CIs.

Main outcomes and measures: The prespecified primary end point was all-cause death. Secondary end points included recurrent myocardial infarction (MI), repeated coronary revascularization, major bleeding, cardiovascular death, death or MI, stroke, heart failure hospitalization, major adverse cardiac events, major adverse cardiovascular or cerebrovascular events, and length of hospital stay.

Results: The sample size-weighted mean age of participants across included trials was 82.6 years, and 46% were female. In the pooled analysis, there was no significant difference in all-cause death between the invasive and conservative strategies (RR, 1.05; 95% CI, 0.98-1.11; P = .15; I2 = 0%). An early invasive strategy was associated with a reduced risk of recurrent MI of 22% (RR, 0.78; 95% CI, 0.67-0.91; P = .001; I2 = 0%) and repeated coronary revascularization during follow-up of 57% (RR, 0.43; 95% CI, 0.30-0.60; P < .001; I2 = 33.3%). However, an invasive strategy was associated with an increased risk of major bleeding (RR, 1.60; 95% CI, 1.01-2.53; P = .05; I2 = 16.7). No differences were observed in secondary end points. Results in the non-ST-elevation ACS population were consistent with the overall findings.

Conclusions and relevance: The results of this systematic review and meta-analysis suggest that, in older patients with ACS, an early invasive strategy was not associated with reduced all-cause death compared with conservative management. An early invasive strategy was associated with reduced recurrent MI and repeated coronary revascularization during follow-up but increased risk of major bleeding. Competing risks associated with an early invasive strategy should be weighed in shared therapeutic decision-making for older patients with ACS.

Keywords 
stroke older patients heart heart failure

What Is Atrial Fibrillation?

Author/s: 
Rebecca Voelker

Atrial fibrillation is an abnormal heart rhythm that can cause stroke, heart failure, heart attack, chronic kidney disease, dementia, and death.

Atrial fibrillation is classified as paroxysmal (intermittent episodes lasting 7 days or less), persistent (lasting more than 7 days), long-standing persistent (lasting more than 1 year), or permanent.1

In the US, atrial fibrillation affects about 10.55 million people and is more common among men than women. Other risk factors include older age, smoking, high blood pressure, diabetes, heart disease, high alcohol consumption, sleep apnea, an overactive thyroid gland, and possibly genetic factors.

Keywords 
atrial fibrillation Cardiology Patient Information jama Patient Information Rhythm Disorders

Invasive Versus Conservative Treatment Strategy in Older Patients With Non-ST Segment Elevation Acute Coronary Syndromes: A Meta-Analysis of Randomized Controlled Trials

Author/s: 
Mushood Ahmed, Areeba Ahsan, Aimen Shafiq, Tallal Mushtaq Hashmi

Background
Non-ST segment elevation acute coronary syndromes (NSTE-ACS) are a common cause of hospital admission in older patients. Our study aims to synthesize the available evidence from randomized controlled trials (RCTs) to compare clinical outcomes with invasive versus conservative medical management in this population.

Methods
A literature search of online databases including PubMed/MEDLINE, Embase, and the Cochrane Library was conducted from inception to September 1, 2024. The search aimed to identify RCTs that reported clinical outcomes with invasive versus conservative strategies in older patients (≥ 70 years) with NSTE-ACS. The risk ratios (RRs) were used as summary estimates.

Results
Seven RCTs with 2998 patients were included; 1490 patients in the invasive group and 1508 patients in the conservatively managed group. The pooled analysis demonstrated no statistically significant difference between the two strategies for the risk of all-cause death (RR: 1.03, 95% CI: 0.92–1.15), cardiovascular death (RR: 1.04, 95% CI: 0.82–1.33), stroke (RR: 0.78, 95% CI: 0.53–1.15), and major bleeding (RR: 1.23, 95% CI: 0.90–1.69). However, the invasive strategy was associated with a significantly reduced risk of myocardial infarction (RR: 0.74, 95% CI: 0.57–0.96) and unplanned revascularization (RR: 0.29, 95% CI: 0.21–0.40) compared to the conservative strategy.

Conclusion
In older patients with NSTE-ACS, an invasive strategy reduces the risk of repeat myocardial infarction and unplanned revascularization without a significant increase in stroke or major bleeding. There was no associated reduction in all-cause or cardiovascular mortality with the invasive strategy compared to conservative management.

Keywords 
NSTEMI Conservative treatment invasive treatment revascularization unstable angina pectoris

Management of Atrial Fibrillation

Author/s: 
Francis J Alenghat, Jason T Alexander, Gaurav A Upadhyay

Atrial fibrillation has a lifetime prevalence of 15% to 40% and predisposes patients to stroke and cardiac dysfunction. This JAMA Clinical Guidelines Synopsis focuses on recommendations for long-term management of AF, including new paradigms for rhythm control and stroke risk reduction.

Keywords 
atrial fibrillation coronary artery disease heart disease Cardiology Rhythm Disorders heart failure

Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial

Author/s: 
Mackenzie, I. S., Rogers, A., Poulter, N. R., Williams, B., Brown, M. J., Webb, D. J., Ford, I., Rorie, D. A., Guthrie, G., Grieve, J. W. K., Pigazzani, F., Rothwell, P. M., Young, R., McConnachie, A., Struthers, A. D., Lang, C. C., MacDonald, T. M.

Background: Studies have suggested that evening dosing with antihypertensive therapy might have better outcomes than morning dosing. The Treatment in Morning versus Evening (TIME) study aimed to investigate whether evening dosing of usual antihypertensive medication improves major cardiovascular outcomes compared with morning dosing in patients with hypertension.

Methods: The TIME study is a prospective, pragmatic, decentralised, parallel-group study in the UK, that recruited adults (aged ≥18 years) with hypertension and taking at least one antihypertensive medication. Eligible participants were randomly assigned (1:1), without restriction, stratification, or minimisation, to take all of their usual antihypertensive medications in either the morning (0600-1000 h) or in the evening (2000-0000 h). Participants were followed up for the composite primary endpoint of vascular death or hospitalisation for non-fatal myocardial infarction or non-fatal stroke. Endpoints were identified by participant report or record linkage to National Health Service datasets and were adjudicated by a committee masked to treatment allocation. The primary endpoint was assessed as the time to first occurrence of an event in the intention-to-treat population (ie, all participants randomly assigned to a treatment group). Safety was assessed in all participants who submitted at least one follow-up questionnaire. The study is registered with EudraCT (2011-001968-21) and ISRCTN (18157641), and is now complete.

Findings: Between Dec 17, 2011, and June 5, 2018, 24 610 individuals were screened and 21 104 were randomly assigned to evening (n=10 503) or morning (n=10 601) dosing groups. Mean age at study entry was 65·1 years (SD 9·3); 12 136 (57·5%) participants were men; 8968 (42·5%) were women; 19 101 (90·5%) were White; 98 (0·5%) were Black, African, Caribbean, or Black British (ethnicity was not reported by 1637 [7·8%] participants); and 2725 (13·0%) had a previous cardiovascular disease. By the end of study follow-up (March 31, 2021), median follow-up was 5·2 years (IQR 4·9-5·7), and 529 (5·0%) of 10 503 participants assigned to evening treatment and 318 (3·0%) of 10 601 assigned to morning treatment had withdrawn from all follow-up. A primary endpoint event occurred in 362 (3·4%) participants assigned to evening treatment (0·69 events [95% CI 0·62-0·76] per 100 patient-years) and 390 (3·7%) assigned to morning treatment (0·72 events [95% CI 0·65-0·79] per 100 patient-years; unadjusted hazard ratio 0·95 [95% CI 0·83-1·10]; p=0·53). No safety concerns were identified.

Interpretation: Evening dosing of usual antihypertensive medication was not different from morning dosing in terms of major cardiovascular outcomes. Patients can be advised that they can take their regular antihypertensive medications at a convenient time that minimises any undesirable effects.

Funding: British Heart Foundation.

Keywords 
Intention to Treat Analysis Antihypertensive Agents Cardiovascular Diseases Surveys and Questionnaires United Kingdom

Use of Recommended Health Care Measures to Prevent Selected Complications of Sickle Cell Anemia in Children and Adolescents — Selected U.S. States, 2019

Author/s: 
Schieve, L. A., Simmons, G. M., Payne, A. B., Abe, K., Hsu, L. L., Hulihan, M., Pope, S., Rhie, S., Dupervil, B., Hooper, W. C.

Introduction: Sickle cell disease (SCD), a group of inherited blood cell disorders that primarily affects Black or African American persons, is associated with severe complications and a >20-year reduction in life expectancy. In 2014, an expert panel convened by the National Heart, Lung, and Blood Institute issued recommendations to prevent or reduce complications in children and adolescents with the most severe SCD subtypes, known as sickle cell anemia (SCA); recommendations included 1) annual screening of children and adolescents aged 2–16 years with transcranial Doppler (TCD) ultrasound to identify those at risk for stroke and 2) offering hydroxyurea therapy to children and adolescents aged ≥9 months to reduce the risk for several life-threatening complications.

Methods: Data from the IBM MarketScan Multi-State Medicaid Database were analyzed. TCD screening and hydroxyurea use were examined for 3,352 children and adolescents with SCA aged 2–16 years and continuously enrolled in Medicaid during 2019. Percentage change during 2014–2019 and variation by health subgroups were assessed. Analyses were stratified by age.

Results: During 2014–2019, TCD screening increased 27% among children and adolescents aged 10–16 years; hydroxyurea use increased 27% among children aged 2–9 years and 23% among children and adolescents aged 10–16 years. However, in 2019, only 47% and 38% of children and adolescents aged 2–9 and 10–16 years, respectively, had received TCD screening and 38% and 53% of children and adolescents aged 2–9 years and 10–16 years, respectively, used hydroxyurea. For both prevention strategies, usage was highest among children and adolescents with high levels of health care utilization and evidence of previous complications indicative of severe disease.

Conclusion and Implications for Public Health Practice: Despite increases since 2014, TCD screening and hydroxyurea use remain low among children and adolescents with SCA. Health care providers should implement quality care strategies within their clinics and partner with patients, families, and community-based organizations to address barriers to delivering and receiving recommended care.

Keywords 
health personnel African Americans medicaid child blood cells

Final Report of a Trial of Intensive versus Standard Blood-Pressure Control

Author/s: 
Lewis, C. E., Fine, L. J., Beddhu, S., Cheung, A. K., Cushman, W. C., Cutler, J. A., Evans, G. W., Johnson, K. C., Kitzman, D. W., Oparil, S., Rahman, M., Reboussin, D. M., Rocco, M. V., Sink, K, M., Snyder, J. K., Whelton, P. K., Williamson, J. D., Wright Jr., J. T., Ambrosius, W. T.

Background: In a previously reported randomized trial of standard and intensive systolic blood-pressure control, data on some outcome events had yet to be adjudicated and post-trial follow-up data had not yet been collected.

Methods: We randomly assigned 9361 participants who were at increased risk for cardiovascular disease but did not have diabetes or previous stroke to adhere to an intensive treatment target (systolic blood pressure, <120 mm Hg) or a standard treatment target (systolic blood pressure, <140 mm Hg). The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes. Additional primary outcome events occurring through the end of the intervention period (August 20, 2015) were adjudicated after data lock for the primary analysis. We also analyzed post-trial observational follow-up data through July 29, 2016.

Results: At a median of 3.33 years of follow-up, the rate of the primary outcome and all-cause mortality during the trial were significantly lower in the intensive-treatment group than in the standard-treatment group (rate of the primary outcome, 1.77% per year vs. 2.40% per year; hazard ratio, 0.73; 95% confidence interval [CI], 0.63 to 0.86; all-cause mortality, 1.06% per year vs. 1.41% per year; hazard ratio, 0.75; 95% CI, 0.61 to 0.92). Serious adverse events of hypotension, electrolyte abnormalities, acute kidney injury or failure, and syncope were significantly more frequent in the intensive-treatment group. When trial and post-trial follow-up data were combined (3.88 years in total), similar patterns were found for treatment benefit and adverse events; however, rates of heart failure no longer differed between the groups.

Conclusions: Among patients who were at increased cardiovascular risk, targeting a systolic blood pressure of less than 120 mm Hg resulted in lower rates of major adverse cardiovascular events and lower all-cause mortality than targeting a systolic blood pressure of less than 140 mm Hg, both during receipt of the randomly assigned therapy and after the trial. Rates of some adverse events were higher in the intensive-treatment group. (Funded by the National Institutes of Health; SPRINT ClinicalTrials.gov number, NCT01206062.).

Keywords 
blood-pressure trial cardiovascular hypotension stroke
Subscribe to stroke