Vitamin K antagonists versus antiplatelet therapy after transient ischaemic attack or minor ischaemic stroke of presumed arterial origin
ABSTRACT People who have had a transient ischaemic attack (TIA) or non-disabling ischaemic stroke have an annual risk of major vascular events of between 4% and 11%. Aspirin reduces this risk by 20% at most. Secondary prevention trials after myocardial infarction indicate that treatment with vitamin K antagonists is associated with a risk reduction approximately twice that of treatment with antiplatelet therapy.
To compare the efficacy and safety of vitamin K antagonists and antiplatelet therapy in the secondary prevention of vascular events after cerebral ischaemia of presumed arterial origin.
We searched the Cochrane Stroke Group Trials Register (last searched 15 September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (2008 to September 2011) and EMBASE (2008 to September 2011). In an effort to identify further relevant trials we searched ongoing trials registers and reference lists. We also contacted authors of published trials for further information and unpublished data.
Randomised trials of oral anticoagulant therapy with vitamin K antagonists (warfarin, phenprocoumon or acenocoumarol) versus antiplatelet therapy for long-term secondary prevention after recent transient ischaemic attack or minor ischaemic stroke of presumed arterial origin.
Two review authors independently selected trials, assessed trial quality and extracted data.
We included eight trials with a total of 5762 participants. The data showed that anticoagulants (in any intensity) are not more efficacious in the prevention of vascular events than antiplatelet therapy (medium intensity anticoagulation: relative risk (RR) 0.80, 95% confidence interval (CI) 0.56 to 1.14; high intensity anticoagulation: RR 1.02, 95% CI 0.49 to 2.13). There is no evidence that treatment with low intensity anticoagulation gives a higher bleeding risk than treatment with antiplatelet agents: RR 1.27 (95% CI 0.79 to 2.03). However, it was clear that medium and high intensity anticoagulation with vitamin K antagonists, with an INR of 2.0 to 4.5, were not safe because they yielded a higher risk of major bleeding complications (medium intensity anticoagulation: RR 1.93, 95% CI 1.27 to 2.94; high intensity anticoagulation: RR 9.0, 95% CI 3.9 to 21).
For the secondary prevention of further vascular events after TIA or minor stroke of presumed arterial origin, there is sufficient evidence to conclude that vitamin K antagonists in any dose are not more efficacious than antiplatelet therapy and that medium and high intensity anticoagulation leads to a significant increase in major bleeding complications.
- [Show abstract] [Hide abstract]
ABSTRACT: Vitamin K antagonists are widely used for the prevention of stroke due to atrial fibrillation, treatment and secondary prevention of venous thromboembolism, prevention of valvular thromboembolism in patients with prosthetic heart valves, and secondary prevention of acute myocardial infarction. The most common adverse event experienced by patients receiving anticoagulant therapy is major bleeding. The incidence of major bleeding in patients receiving long-term anticoagulation with a vitamin K antagonist in contemporary studies is 1-3% per year. To determine if the benefits of anticoagulant therapy outweigh the risk of bleeding in an individual patient, physicians must be aware of the risk factors associated with major bleeding. This narrative review will provide an overview of the incidence of major bleeding in patients receiving therapeutic anticoagulant therapy with vitamin K antagonists, discuss the risk factors for bleeding, and outline the most commonly used clinical prediction rules for bleeding.Blood reviews 03/2013; 27. DOI:10.1016/j.blre.2013.02.004 · 5.45 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowing glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA). We searched the Cochrane Stroke Group Trials Register (August 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE (1949 to October 2013), EMBASE (1980 to October 2013), CINAHL (1982 to October 2013), AMED (1985 to October 2013) and 11 Chinese databases (October 2013). In an effort to identify further published, unpublished and ongoing trials we searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical companies. There were no language restrictions. We included randomised controlled trials (RCTs) evaluating PPAR-γ agonists versus placebo for the secondary prevention of stroke and related vascular events in people with stroke or TIA, with the outcomes of recurrent stroke, vascular events and adverse events. Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy and assessed the methodological quality. We identified four eligible studies with 1163 participants; only one study had a low risk of bias for all domains. The participants in different studies were heterogeneous. The number of participants with recurrent stroke was evaluated in two studies, where PPAR-γ agonists reduced the recurrence of stroke compared with placebo (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.34 to 0.80). PPAR-γ agonists given over a mean duration of 34.5 months in a single trial were found to reduce a composite outcome of total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (RR 0.73, 95% CI 0.54 to 0.99). Data on additional composite outcomes reflecting serious adverse events (all-cause death and other major vascular events; all-cause mortality, non-fatal myocardial infarction or non-fatal stroke) were similar although the confidence intervals were wider and the effects were not statistically significant. In addition, two studies respectively measured insulin sensitivity and the ubiquitin-proteasome activity in carotid plaques with significant differences in these outcomes between PPAR-γ agonists and placebo. None of the studies reported the number of participants with disability due to vascular events or improvement in quality of life. Three RCTs reported information about adverse events. Frequent adverse events included oedema, cardiac failure and anaemia. Evidence that adverse events occurred more frequently in participants treated with PPAR-γ agonists when compared with placebo was imprecise and inconsistent (risk difference (RD) 10%, 95% CI -8% to 28%, I² = 86%). PPAR-γ agonists were demonstrated to reduce recurrent stroke and total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, and improve insulin sensitivity and the stabilisation of carotid plaques. There is evidence of limited quality that they are well-tolerated. However, the conclusions should be interpreted with caution considering the small number and the quality of the included studies. In future, well-designed, double-blind RCTs with large samples are required to test the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events in people with stroke or TIA.Cochrane database of systematic reviews (Online) 01/2014; 1(1):CD010693. DOI:10.1002/14651858.CD010693.pub2 · 5.94 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: In patients with non-valvular atrial fibrillation (NVAF) and history of transient ischemic attack (TIA) or stroke, the rate of vascular events is higher in comparison to patients without history of stroke or TIA. A meta-analysis of direct oral anticoagulants (DOACs) studies, including only patients with history of stroke or TIA, report a significant reduction of 15 % in the rates of composite of stroke and systemic embolism in patients treated with DOACs, compared to those treated with warfarin. Furthermore, a reduction of 14 % for major bleeding, as well as a 56 % reduction for hemorrhagic stroke over a median follow-up of 1.8-2.0 years is reported. The combination of DOACs and antiplatelet agents carries the potential of additive benefits in patients with NVAF and other vascular diseases. However, the rate of major bleeding is higher among patients who receive concomitantly antiplatelet agents, compared to those taking only a single drug category. The risk of major bleeding seems to be higher among patients receiving dual antiplatelet agents, compared to those receiving a single antiplatelet drug. When NVAF is associated with an acute coronary syndrome requiring dual antiplatelet therapy (e.g. coronary angioplasty and stenting), DOACs plus this therapy should be considered. However, this therapy has to be administered for the shortest possible time, according to the patient's haemorrhagic and thrombotic risks, and stent type. When NVAF is associated with carotid stenosis, a single antiplatelet therapy should be considered. Regarding carotid revascularization, it seems preferable to treat these patients with endarterectomy, so to avoid dual antiplatelet therapy, which is generally administered after stenting.Internal and Emergency Medicine 04/2015; 10(5). DOI:10.1007/s11739-015-1226-4 · 2.41 Impact Factor