Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation

Impact of Modifiable Bleeding Risk Factors on Major Bleeding in Patients With Atrial Fibrillation Anticoagulated With Rivaroxaban.

Background Reducing major bleeding events is a challenge when managing anticoagulation in patients with atrial fibrillation. This study evaluated the impact of modifiable and nonmodifiable bleeding risk factors in patients with atrial fibrillation receiving rivaroxaban and estimated the impact of risk factor modification on major bleeding events. Methods and Results Modifiable and nonmodifiable risk factors associated with major bleeding events were identified from the XANTUS (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation) prospective registry data set (6784 rivaroxaban-treated patients). Parameters showing univariate association with bleeding were used to construct a multivariable model identifying independent risk factors. Modeling was used to estimate attributed weights to risk factors. Heavy alcohol use (hazard ratio [HR]=2.37; 95% CI 1.24-4.53); uncontrolled hypertension (HR after parameter-wise shrinkage=1.79; 95% CI 1.05-3.05); and concomitant treatment with antiplatelets, nonsteroidal anti-inflammatory drugs, or paracetamol (HR=1.80; 95% CI 1.24-2.61) were identified as modifiable, independent bleeding risk factors. Increasing age (HR=1.25 [per 5-year increment]; 95% CI 1.12-1.38); heart failure (HR=1.97; 95% CI 1.36-2.86); and vascular disease (HR=1.91; 95% CI 1.32-2.77) were identified as nonmodifiable bleeding risk factors. Overall, 128 (1.9%) patients experienced major bleeding events; of these, 11% had no identified bleeding risk factors, 50% had nonmodifiable bleeding risk factors only, and 39% had modifiable bleeding risk factors (with or without nonmodifiable risk factors). The presence of 1 modifiable bleeding risk factor doubled the risk of major bleeding. Conclusions Elimination of modifiable bleeding risk factors is a potentially effective strategy to reduce bleeding risk in atrial fibrillation patients receiving rivaroxaban. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01606995

Developing a complex intervention to improve prescribing safety in primary care:mixed methods feasibility and optimisation pilot study

Objectives (A) To measure the extent to which different candidate outcome measures identified high-risk prescribing that is potentially changeable by the data-driven quality improvement in primary care (DQIP) intervention.(B) To explore the value of reviewing identified high-risk prescribing to clinicians.(C) To optimise the components of the DQIP intervention.  Design Mixed method study.  Setting General practices in two Scottish Health boards.  Participants 4 purposively sampled general practices of varying size and socioeconomic deprivation.  Outcome measures Prescribing measures targeting (1) high-risk use of the non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelets; (2) ‘Asthma control’ and (3) ‘Antithrombotics in atrial fibrillation (AF)’.  Intervention The prescribing measures were used to identify patients for review by general practices. The ability of the measures to identify potentially changeable high-risk prescribing was measured as the proportion of patients reviewed where practices identified a need for action. Field notes were recorded from meetings between researchers and staff and key staff participated in semistructured interviews exploring their experience of the piloted intervention processes.  Results Practices identified a need for action in 68%, 25% and 18% of patients reviewed for prescribing measures (1), (2) and (3), respectively. General practitioners valued being prompted to review patients, and perceived that (1) ‘NSAID and antiplatelet’ and (2) ‘antithrombotics in AF’ were the most important to act on. Barriers to initial and ongoing engagement and to sustaining improvements in prescribing were identified.  Conclusions ‘NSAIDs and antiplatelets’ measures were selected as the most suitable outcome measures for the DQIP trial, based on evidence of this prescribing being more easily changeable. In response to the barriers identified, the intervention was designed to include a financial incentive, additional ongoing feedback on progress and reprompting review of patients, whose high-risk prescribing was restarted after a decision to stop.  Trial registration number Clinicaltrials.govNCT01425502

Association between patient outcomes and key performance indicators of stroke care quality: A systematic review and meta-analysis

Purpose: Translating research evidence into clinical practice often uses key performance indicators to monitor quality of care. We conducted a systematic review to identify the stroke key performance indicators used in large registries, and to estimate their association with patient outcomes. Method: We sought publications of recent (January 2000–May 2017) national or regional stroke registers reporting the association of key performance indicators with patient outcome (adjusting for age and stroke severity). We searched Ovid Medline, EMBASE and PubMed and screened references from bibliographies. We used an inverse variance random effects meta-analysis to estimate associations (odds ratio; 95% confidence interval) with death or poor outcome (death or disability) at the end of follow-up. Findings: We identified 30 eligible studies (324,409 patients). The commonest key performance indicators were swallowing/nutritional assessment, stroke unit admission, antiplatelet use for ischaemic stroke, brain imaging and anticoagulant use for ischaemic stroke with atrial fibrillation, lipid management, deep vein thrombosis prophylaxis and early physiotherapy/mobilisation. Lower case fatality was associated with stroke unit admission (odds ratio 0.79; 0.72–0.87), swallow/nutritional assessment (odds ratio 0.78; 0.66–0.92) and antiplatelet use for ischaemic stroke (odds ratio 0.61; 0.50–0.74) or anticoagulant use for ischaemic stroke with atrial fibrillation (odds ratio 0.51; 0.43–0.64), lipid management (odds ratio 0.52; 0.38–0.71) and early physiotherapy or mobilisation (odds ratio 0.78; 0.67–0.91). Reduced poor outcome was associated with adherence to swallowing/nutritional assessment (odds ratio 0.58; 0.43–0.78) and stroke unit admission (odds ratio 0.83; 0.77–0.89). Adherence with several key performance indicators appeared to have an additive benefit. Discussion: Adherence with common key performance indicators was consistently associated with a lower risk of death or disability after stroke. Conclusion: Policy makers and health care professionals should implement and monitor those key performance indicators supported by good evidence

Gender differences in the implementation of cardiovascular prevention measures after an acute coronary event

Objective To compare gender-related lifestyle changes and risk factor management after hospitalisation for a coronary event or revascularisation intervention in Europe. Method The EUROASPIRE III survey was carried out in 22 European countries in 2006-2007. Consecutive patients having had a coronary event or revascularisation before the age of 80 were identified. A total of 8966 patients (25.3% women) were interviewed and underwent clinical and biochemical tests at least 6 months after hospital admission. Trends in cardiovascular risk management were assessed on the basis of the 1994-1995, 1999-2000 and 2006-2007 EUROASPIRE surveys. Results Female survey participants were generally older and had a lower educational level than male participants (p<0.0001). The prevalences of obesity (p<0.0001), high blood pressure (BP) (p=0.001), elevated low-density lipoprotein (LDL)-cholesterol (p<0.0001) and diabetes (p<0.0001) were significantly higher in women than in men, whereas current smoking (p<0.0001) was significantly more common in men. The use of antihypertensive and antidiabetic drugs (but not that of other drugs) was more common in women than in men. However, BP (p<0.0001), LDL-cholesterol (p<0.0001) and HbA1c (p<0.0001) targets were less often achieved in women than in men. Between 1994 and 2007, cholesterol control improved less in women than in men (interaction: p=0.009), whereas trends in BP control (p=0.32) and glycaemia (p=0.36) were similar for both genders. Conclusion The EUROASPIRE III results show that despite similarities in medication exposure, women are less likely than men to achieve BP, LDL-cholesterol and HbA1c targets after a coronary event. This gap did not appear to narrow between 1994 and 2007

Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p &lt; 0.001) and younger (p &lt; 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 ± 11.7 days for men versus 6.5 ± 12.4 days for women, p = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 ± 6.9 versus 8.1 ± 7.5, p &lt; 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p = 0.28 and p = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p &lt; 0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes

Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388)

RATIONALE: The risk of recurrence following a stroke or transient ischemic attack is high, especially immediately after the event. HYPOTHESIS: Because two antiplatelet agents are superior to one in patients with non-cardioembolic events, more intensive treatment might be even more effective. SAMPLE SIZE ESTIMATES: The sample size of 4100 patients will allow a shift to less recurrence, and less severe recurrence, to be detected (odds ratio 0·68) with 90% power at 5% significance. METHODS AND DESIGN: Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (ISRCTN47823388) is comparing the safety and efficacy of intensive (combined aspirin, clopidogrel, and dipyridamole) vs. guideline antiplatelet therapy, both given for one-month. This international collaborative parallel-group prospective randomized open-label blinded-end-point phase III trial plans to recruit 4100 patients with acute ischemic stroke or transient ischemic attack. Randomization and data collection are performed over a secure Internet site with real-time data validation and concealment of allocation. Outcomes, serious adverse events, and neuroimaging are adjudicated centrally with blinding to treatment allocation. STUDY OUTCOME: The primary outcome is stroke recurrence and its severity ('ordinal recurrence' based on modified Rankin Scale) at 90 days, with masked assessment centrally by telephone. Secondary outcomes include vascular events, functional measures (disability, mood, cognition, quality of life), and safety (bleeding, death, serious adverse events). DISCUSSION: The trial has recruited more than 50% of its target sample size (latest number: 2399) and is running in 104 sites in 4 countries. One-third of patients presented with a transient ischemic attack