Single Stroke Risk Factor Research Articles

Should oral anticoagulants still be prescribed to patients with atrial fibrillation with a single stroke risk factor but at high bleeding risk? A nationwide cohort study.

To investigate the co-distributions of stroke and bleeding risks in Asian patients with atrial fibrillation (AF) and the clinical benefits of oral anticoagulants (OACs) among AF patients with a single stroke risk factor but at high bleeding risk. From 1 January 2001 to 31 December 2016, a total of 404949 AF patients were retrospectively identified from Taiwan National Health Insurance Research Database. Stroke risk was assessed using the CHA2DS2-VASc score and was categorized into low risk (score=0 for males and 1 for females), intermediate risk (i.e. a single non-sex stroke risk factor; score=1 for males and 2 for females), and high risk (score ≥2 for males and ≥3 for females). A high risk of bleeding was defined as a HAS-BLED score ≥3. Around 57.5% of AF patients were at high risk for both stroke and bleeding, and most patients (97.6%) with a low stroke risk were also at low risk for bleeding. Around 18.3% of patients with a CHA2DS2-VASc score of 1 (males) or 2 (females) were at high bleeding risk, and the use of OACs in such patients was associated with a lower risk of composite adverse events of ischaemic stroke, intracranial haemorrhage, or mortality (4.19/100 person-years vs. 5.22/100 person-years, adjusted hazard ratio=0.781, P=0.04). For AF patients with an intermediate risk of stroke (i.e. a single non-sex stroke risk factor) but at high bleeding risk, the use of OACs was still significantly associated with a better overall clinical outcome.

Voorkamerfibrillatie en niet-vitamine K-antagonist orale anticoagulantia: van klinische studies tot gebruik in de dagelijkse praktijk

Atrial fibrillation and non-vitamin K antagonist oral anticoagulants: from clinical trials to real-world clinical practice. For decades, vitamin K antagonists (VKAs) were the only oral anticoagulants available for the prevention of thromboembolism in patients with atrial fibrillation (AF). Since 2012, non-vitamin K antagonist oral anticoagulants (NOACs) are available for this indication, which have proven to be at least as effective and safe as VKAs in randomized controlled trials (RCTs). NOACs have additional benefits, such as a fast onset of action, a fixed-dose regimen without requiring regular monitoring, less interactions and less intracranial bleeding. Their emergence has caused a paradigm shift in anticoagulation therapy, with NOACs being the anticoagulant of choice compared to VKAs. Since strict in- and exclusion criteria were used in the pivotal RCTs, concerns have risen regarding the generalizability of these results to real-life clinical practice in patients with multiple comorbidities. In this manuscript, this extrapolation is discussed, focusing on 4 different topics regarding appropriate NOAC use: the management of AF patients with a single stroke risk factor, the importance of an optimal therapy adherence, potential drug-drug interactions with NOACs and addressing a geriatric AF patient after a fall. Hopefully, this manuscript will help guide clinicians in the optimal use of NOACs in their daily clinical practice.

Effectiveness and Safety of Standard-Dose Nonvitamin K Antagonist Oral Anticoagulants and Warfarin Among Patients With Atrial Fibrillation With a Single Stroke Risk Factor

The randomized clinical trials comparing nonvitamin K antagonist oral anticoagulants (NOACs) vs warfarin largely focused on recruiting high-risk patients with atrial fibrillation with more than 2 stroke risk factors, with only the trials testing dabigatran or apixaban including few patients with 1 stroke risk factor. Despite this, regulatory approvals of all NOACs have been based on stroke prevention for patients with atrial fibrillation with 1 or more stroke risk factors. To compare the effectiveness and safety study of standard-dose NOACs (dabigatran at 150 mg twice daily, rivaroxaban at 20 mg once daily, and apixaban at 5 mg twice daily) and warfarin in patients with atrial fibrillation with 1 low-risk, nonsex-related stroke risk factor. This nationwide observational cohort study used data from Danish registries to determine the inverse probability of treatment-weighted comparative effectiveness and safety of standard-dose NOACs (dabigatran at 150 mg twice daily, rivaroxaban at 20 mg once daily, and apixaban at 5 mg twice daily) compared with treatment with warfarin among 14 020 patients with atrial fibrillation with 1 low-risk, nonsex- related stroke risk factor. Rates of ischemic stroke/systemic embolism, death, and bleeding. Of 14 020 participants, 5151 (36.7%) were women, and the median age for participants was 66.5 years. For the principal effectiveness end point of ischemic stroke/systemic embolism, no significant differences of the NOACs compared with treatment with warfarin across strata were evident. For the end point of "any bleeding," this was significantly lower for treatment with apixaban (hazard ratio [HR], 0.35; 95% CI, 0.17-0.72) and dabigatran (HR, 0.48; 95% CI, 0.30-0.77) compared with warfarin in the main analysis, and was not significantly different for treatment with rivaroxaban vs warfarin (HR, 0.84; 95% CI, 0.49-1.44). There was broad consistency across most subgroups in the sensitivity analyses and whether 1- or 2.5-year follow-up periods were analyzed. However, falsification end points generally did not falsify, indicating the possible presence of residual confounding across these comparisons, presumably related to selective prescribing and unobserved covariates. In this Danish cohort study of patients with atrial fibrillation and a single stroke risk factor, there was no difference between NOACs compared with treatment with warfarin in terms of the risk of having an ischemic stroke/systemic embolism. For "any bleeding," this was lower for treatment with apixaban and dabigatran compared with warfarin. These data do not allow for a definitive statement of the comparative effectiveness or safety of NOACs because of the possible residual confounding that was unmasked with falsification outcomes.

Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 1.

Patients with atrial fibrillation (AF) have a high risk of stroke and mortality, which can be considerably reduced by oral anticoagulants (OAC). Recently, four non-vitamin-K oral anticoagulants (NOACs) were compared with warfarin in large randomized trials for the prevention of stroke and systemic embolism. Today's clinician is faced with the difficult task of selecting a suitable OAC for a patient with a particular clinical profile or a particular pattern of risk factors and concomitant diseases. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. NOACs for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In the first of a two-part review, we discuss the choice of NOAC for stroke prevention in the following subgroups of patients with AF: (i) stable coronary artery disease or peripheral artery disease, including percutaneous coronary intervention with stenting and triple therapy; (ii) cardioversion, ablation and anti-arrhythmic drug therapy; (iii) mechanical valves and rheumatic valve disease, (iv) patients with time in therapeutic range of >70% on warfarin; (v) patients with a single stroke risk factor (CHA2DS2VASc score of 1 in males, 2 in females); and (vi) patients with a single first episode of paroxysmal AF. Although there are no major differences in terms of efficacy and safety between the NOACs for some clinical scenarios, in others we are able to suggest that particular drugs and/or doses be prioritized for anticoagulation.

Stroke prevention in atrial fibrillation patients with a single stroke risk factor: Clinical decision-making and guideline recommendations: A case report and comparative analysis of the European Society of Cardiology (ESC) and American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines on the management of atrial fibrillation

Stroke prevention in atrial fibrillation patients with a single stroke risk factor: Clinical decision-making and guideline recommendations: A case report and comparative analysis of the European Society of Cardiology (ESC) and American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines on the management of atrial fibrillation

Stroke-Related Knowledge among Uninsured Latino Immigrants in Durham County, North Carolina

Knowledge of stroke risk factors and symptoms is a necessary prerequisite for improving prevention and reducing treatment delays. Little is known about stroke-related knowledge among the US immigrant Latino population. A previously published stroke knowledge survey was translated into Spanish and administered orally to a convenience sample of 76 Latino Spanish-speaking clients of a community-based health care management program for uninsured residents of Durham County, North Carolina, between January and March 2007. Of respondents, 81% could not correctly name a single stroke risk factor, 57% could not correctly identify a stroke symptom, and only 45% said they would telephone emergency services (dial 9-1-1), call an ambulance, or go to a hospital if they or a family member were having a stroke. However, 80% of respondents knew that a stroke could be prevented, and 86% knew that a stroke could be treated. Stroke-related knowledge may be particularly poor in the uninsured Latino immigrant population. Novel approaches will be needed to improve awareness and prevention in this high-risk group.

Atrial fibrillation and stroke risk prevention in real-life clinical practice

Thromb Haemost 2009; 101: 415–416 Patients with atrial fibrillation (AF) have a substantial risk of stroke and thromboembolism compared with age-matched people in sinus rhythm, which varies with associated comorbidities and risk factors (1, 2). When a stroke occurs in patients with AF, the severity of the stroke is much greater, as is mortality and disability compared to those in sinus rhythm (3). Unsurprisingly, the biggest challenge facing physicians caring for patients with AF is the prevention of stroke and thromboembolism, whether as primary or secondary prevention. Examination of stroke rates from the non-warfarin arms of trial cohorts and one epidemiological study have informed the development of stroke risk stratification schema for AF (4). More than a dozen stroke risk stratification schemes for AF patients have been proposed, but all have modest predictive value for stroke (1, 5). These risk stratification schemes are used in many guidelines, which generally recommend anti-thrombotic therapy with warfarin for AF patients at ‘high-risk’ of stroke and aspirin for those at ‘low-risk’. For those patients who fall into the ‘moderate-risk’ category (usually those with one single stroke risk factor), either aspirin or warfarin is recommended, due to the lack of evidence in favour of either drug, as well as the close margin between stroke reduction and bleeding risk of anticoagulation with warfarin. Thus, many guidelines recommend that anti-thrombotic therapy is decided on an individual basis. However, such an approach is confounded by new trial evidence from the Birmingham Atrial Fibrillation Treatment of the Aged Study (BAFTA) showing the substantial benefits – even in subjects aged >75 – of warfarin over aspirin for stroke prevention (1.8% vs. 3.8% events per year, respectively: relative risk [RR] 0.48, 95% confidence interval [CI] 0.28–0.80), with no difference in rates of major haemorrhage between warfarin or aspirin (6). The merits or otherwise of why warfarin should really be the drug of choice for stroke prevention in elderly patients with AF have recently been debated in this journal (7, 8). It is said that guidelines begat guidelines, and in real-life clinical practice, such guidelines on anti-thrombotic therapy for AF are often not adhered to (9). In the Euro Heart Survey, prescription of antithrombotic therapy was based on the type of AF and availability of warfarin monitoring clinic, rather than the stroke risk profile per se (9). The type of AF should not be a consideration, given that paroxysmal AF has a similar stroke risk to persistent or permanent AF, in the presence of risk factors, and such patients would derive much benefit from anticoagulation (10). In the current issue of Thrombosis and Haemostasis, Rietbrock et al. (11) evaluate the incidence of stroke in routine clinical practice among >51,000 chronic AF patients aged ≥40 years taking either aspirin or warfarin, by examining the United Kingdom General Practice Research Database from 1987 onwards. Virtually all the patients had been treated with warfarin or aspirin, with almost 10,000 patients who had received both (either concomitantly or separately). They compared non-use (never) with both ‘current use’ (defined as the time from the prescription date until three months after the expected duration of use) and ‘past use’ (defined as the period of time starting three months after the expected end of a prescription) and found that current use of warfarin was associated with a 38% (RR 0.62, 95% CI 0.54–0.71) reduction in stroke compared to past use after adjustment for age, sex, and stroke risk profile. Compared to no warfarin use, current and past use were both associated with a significant reduction in stroke rate, by 67% (RR 0.33, 95% CI 0.30–0.35) and 44% (RR 0.56, 95% CI 0.50–0.63), respectively. The benefits were more evident amongst the elderly, whereby the risk of stroke was reduced by 45% in elderly warfarin users (aged 75 years or older) and by 14% in younger users. As emphasised by the BAFTA trial (6), elderly patients with AF should not be denied warfarin thromboprophylaxis, given the impressive benefits of stroke prevention with anticoagulation in elderly AF patients. In contrast, there was no difference in the rate of stroke between current and past use of aspirin (RR 1.04, 95% CI 0.94 – 1.15). Thus, the stroke risk reduction with warfarin in routine clinical practice is similar to that achieved in clinical trials, in a UK general practice cohort involving >30,000 elderly AF patients, demonstrating that the evidence from clinical trials can translate into real-life clinical practice. Indeed, current or past use of aspirin did not seem to matter, and in fact, there were no significant changes in the rates of stroke were observed with dis© 2009 Schattauer GmbH, Stuttgart

Stroke: Putting Assessment and Primary Prevention Strategies into Practice

Stroke is the third leading cause of death in the United States and the leading cause of serious disability. The economic burden of first strokes occurring in 1990 was estimated to be $40.6 billion. In one survey, 42% of Americans were u nable to identify a single stroke risk factor, and two-thirds were unable to id entify a stroke warning sign.1 Primary care practitioners need to assess patien ts risk factors for stroke and work with patients to modify the risk factors th rough lifestyle changes and pharmacological therapy. Primary care practitioners also need to educate patients of the warning signs of stroke thereby expeditin g treatment of stroke to decrease disability. Several new therapies for stroke treatment are available but some, such as thrombolysis, have a limited window o f opportunity. Education of the public and health professionals is needed to im prove the treatment of patients at risk for stroke.