Citation: Perry JJ, Stiell IG, Sivilotti ML, et al. Sensitivity of computed tomography performed within six hours of onset of headache for diagnosis of subarachnoid haemorrhage: prospective cohort study. Br Med J. 2011;343:d4277.
Improved Model Stratifies Risk of Warfarin-Associated Bleeding in Patients with Atrial Fibrillation
Clinical question: Can a simple scoring model accurately assess the risk of warfarin-associated bleeding in a cohort of patients with atrial fibrillation?
Background: It is well known that anticoagulants, such as warfarin, dramatically reduce the risk of thromboembolic events in patients with atrial fibrillation. Despite this, clinicians often find themselves weighing the risks and benefits of anticoagulation in this cohort of patients, and improved models to assess those risks are needed.
Study design: Retrospective cohort study.
Setting: Kaiser Permanente of Northern California.
Synopsis: From a cohort of 13,559 adult patients with atrial fibrillation, the investigators used chart review to determine hemorrhagic events in this population and developed a model using Cox regression to assess hemorrhagic risk in certain patient populations. Final input variables for the model included anemia, severe renal disease, age ≥75, prior hemorrhage, and hypertension. When collapsed into three risk tiers (low, intermediate, and high), the scoring model nicely differentiated low (<1% annual) from high (5.8% annual) bleeding risk.
This study is limited by the lack of information on concomitant use of NSAIDs or aspirin in these patients and the lack of external validation of the model. Despite those limitations, it may serve as a valuable tool for clinicians. As the number of alternatives to warfarin rise and as those agents become more familiar, it will become increasingly important to accurately assess hemorrhage risk with various anticoagulants.
Bottom line: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) risk scoring system is a reliable and easy way for clinicians to estimate the degree of bleeding risk in patients anticoagulated with warfarin for atrial fibrillation.
Citation: Fang MC, Go AS, Chang Y, et al. A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (anticoagulation and risk factors in atrial fibrillation) study. J Am Coll Cardiol. 2011;58:395-401.
Tiotropium Mist Inhaler Associated with Increased Mortality
Clinical question: Does the mist-inhaler formulation of tiotropium increase mortality in patients with chronic obstructive pulmonary disease (COPD) when compared with placebo?
Background: Tiotropium is used in patients with COPD to reduce both symptoms of dyspnea and exacerbations of COPD. Tiotropium comes in two formulations: a powder (approved in the U.S.) and the mist inhaler (not approved in the U.S. but approved in 55 other countries). There are concerns based on recent studies that tiotropium may increase cardiovascular events and death.
Study design: Meta-analysis of five randomized controlled trials (RCTs) comparing tiotropium mist inhaler with a placebo.
Setting: Multinational studies.
Synopsis: This study of 6,522 patients with COPD showed a 52% increased risk of all-cause mortality with the use of the tiotropium mist inhaler when compared with placebo. It is important to note that there are data showing higher plasma concentrations with the approved mist-inhaler doses when compared with the powder formulation doses. Further, a possible dose effect was seen in this study (though not statistically significant), with higher tiotropium doses associated with a high-risk ratio for the mortality endpoint.
Limitations of this study include the fact that the dosage of the tiotropium varied, as did the length of follow-up for patients. Given that death was a relatively rare event (<1%), estimates are imprecise. Even given these limitations, this study sheds light on the debate over the safety of tiotropium, specifically the mist-inhaler formulation. Caution should be used when prescribing the mist-inhaler formulation of tiotropium, and an understanding of the potential cardiovascular risks should be communicated to patients prior to initiating therapy.