VTE treatment regimens have similar outcomes

Historically, unfractionated heparin (UFH) with a vitamin K antagonist has been the standard treatment for deep venous thrombosis (DVT) or pulmonary embolism. More recently, low-molecular-weight heparin (LMWH) combined with vitamin K antagonists has become the most common choice, but newer target-specific oral anticoagulants have widened the range of treatment options.

In a systematic review, researchers examined the safety and efficacy of these treatment strategies in 45 randomized controlled trials with nearly 45,000 patients. Meta-analysis techniques were used to compare all regimens with the LMWH–vitamin K antagonist combination. All treatment options, except the UFH–vitamin K antagonist combination, were similarly effective. The UFH–vitamin K antagonist combination was associated with about 40% greater relative risk for VTE recurrence (1.8% vs. 1.3%). Incidences of major bleeding were 0.5% and 0.3% with rivaroxaban and apixaban, respectively, compared with 0.9% for the LMWH–vitamin K antagonist combination.

Source: Castellucci LA, Cameron C, Le Gal G, et al. Clinical and safety outcomes associated with treatment of acute venous thromboembolism: A systematic review and meta-analysis. JAMA. 2014 Sep 17;312(11):1122–1135.

AF pattern predicts stroke risk

The pattern of atrial fibrillation (AF) - paroxysmal, persistent, or permanent - is associated with progressive stages of atrial dysfunction and presumably higher stroke risk. Results of previous studies examining this relationship have been inconsistent, and study designs have been flawed.

In a newly published study, investigators analyzed the rates of stroke and systemic embolism in more than 6,500 aspirin-treated patients with AF from the ACTIVE-A/AVERROES databases. Mean age of patients with paroxysmal, persistent, and permanent AF was 69.0 ± 9.9, 68.6 ± 10.2, and 71.9 ± 9.8 years. The CHA₂DS₂-VASc score was similar in patients with paroxysmal and persistent AF (3.1 ± 1.4), but was higher in patients with permanent AF (3.6 ± 1.5). Yearly ischemic stroke rates were 2.1%, 3.0%, and 4.2% for paroxysmal, persistent, and permanent AF, respectively, with adjusted hazard ratio of 1.83 for permanent vs. paroxysmal and 1.44 for persistent vs. paroxysmal. Multivariable analysis identified age ≥75 years, sex, history of stroke or TIA, and AF pattern as independent predictors of stroke, with AF pattern being the second-strongest predictor after previous stroke or TIA.

Source: Vanassche T, Lauw MN, Eikelboom JW, et al. Risk of ischaemic stroke according to pattern of atrial fibrillation: Analysis of 6,563 aspirin-treated patients in ACTIVE-A and AVERROES. Eur Heart J. 2014 Sep 3. [Epub ahead of print]

NSAIDS increase risk of VTE

Nonsteroidal anti-inflammatory drugs (NSAIDs) may almost double VTE risk, according to an article published online in Rheumatology.

This is the first systematic review and meta-analysis of published observational studies to examine the association between NSAID use and VTE. The authors included six studies, representing 21,401 VTE events, in their final analysis. The studies, one cohort study (n= 19,293; 215 events) and five case-control studies (cases, 21,186; controls, 110,824), were conducted in the U.K. and Europe between 2007 and 2013.

The pooled risk ratio among NSAID users was 1.8-fold for VTE (95% confidence interval, 1.28–2.52). Among participants who used selective cyclooxygenase 2 (COX-2) inhibitors, the pooled risk ratio was 1.99 (95% confidence interval, 1.44–2.75). Both measures reached statistical significance.

The mechanism for increased risk of VTE is not clear, however, for the COX-2 inhibitors. The authors suggested that inhibition of the COX-2 enzyme may inhibit synthesis of prostacyclins, which are potent platelet activation inhibitors, while stimulating the release of thromboxane, a potent platelet aggregation facilitator, from the activated platelets. The activation and aggregation of platelets might, in turn, induce a coagulation cascade and clotting.

NSAIDs are widely used, and although this study was small, relative to the number of users of these medications, healthcare providers should be aware of this potential problem and advise patients who use NSAIDs and are at high risk of VTE accordingly.

Source: Ungprasert P, Srivali N, Wijarnpreecha K, et al. Non-steroidal anti-inflammatory drugs and risk of venous thromboembolism: A systematic review and meta-analysis. Rheumatology 2014. Published online September 24, 2014.