JAMA Internal Medicine: Thromboembolism/Anticoagulation Topic Collection

Use of Glucocorticoids and Risk of Venous Thromboembolism A Nationwide Population-Based Case-Control Study Glucocorticoids and Risk of Venous Thromboembolism

Johannesdottir SA, Horváth-Puhó E, Dekkers OM, et al. — Mon, 13 May 2013 00:00:00 GMT

Importance

Excess endogenous cortisol has been linked to venous thromboembolism (VTE) risk, but whether this relationship applies to exogenous glucocorticoids remains uncertain. Because the prevalence of glucocorticoid use and the incidence of VTE are high, an increased risk of VTE associated with glucocorticoid use would have important implications.

Background

To examine the association between glucocorticoid use and VTE.

Design

Population-based case-control study using nationwide databases.

Setting

Denmark (population 5.6 million).

Participants

We identified 38 765 VTE cases diagnosed from January 1, 2005, through December 31, 2011, and 387 650 population controls included through risk-set sampling and matched by birth year and sex. The VTE diagnosis date for the case was the index date for cases and matched controls.

Exposure

We classified individuals who filled their most recent glucocorticoid prescription 90 days or less, 91 to 365 days, and more than 365 days before the index date as present, recent, and former users, respectively. Present users were subdivided into new (first-ever prescription 90 days or less before the index date) and continuing users (others).

Main Outcomes and Measures

We used conditional logistic regression adjusted for VTE risk factors to estimate incidence rate ratios (IRRs) and 95% CIs for glucocorticoid users vs nonusers.

Results

Systemic glucocorticoids increased VTE risk among present (adjusted IRR, 2.31; 95% CI, 2.18-2.45), new (3.06; 2.77-3.38), continuing (2.02; 1.88-2.17), and recent (1.18; 1.10-1.26) users but not among former users (0.94; 0.90-0.99). The adjusted IRR increased from 1.00 (95% CI, 0.93-1.07) for a prednisolone-equivalent cumulative dose of 10 mg or less to 1.98 (1.78-2.20) for more than 1000 to 2000 mg, and to 1.60 (1.49-1.71) for doses higher than 2000 mg. New use of inhaled (adjusted IRR, 2.21; 95% CI, 1.72-2.86) and intestinal-acting (2.17; 1.27-3.71) glucocorticoids also increased VTE risk.

Conclusions and Relevance

The risk of VTE is increased among glucocorticoid users. Although residual confounding may partly explain this finding, we consider a biological mechanism likely because the association followed a clear temporal gradient, persisted after adjustment for indicators of severity of underlying disease, and existed also for noninflammatory conditions. Hence, our observations merit clinical attention.

In This Issue of JAMA Internal Medicine

Mon, 13 May 2013 00:00:00 GMT

Resumption of Warfarin Therapy After Gastrointestinal Tract Bleeding: Benefit or Bias?

Filion KB, Assayag J, Azoulay L. — Mon, 13 May 2013 00:00:00 GMT

It is with great interest that we read the article by Witt and colleagues, who examined the risk of thromboembolism, recurrent hemorrhage, and death in a retrospective cohort of warfarin users with gastrointestinal tract bleeding. Although no difference was observed in recurrent hemorrhage, the authors found that warfarin therapy resumption after gastrointestinal tract bleeding resulted in substantial decreases in thrombosis (adjusted hazard ratio [HR], 0.05; 95% CI, 0.01-0.58) and death (adjusted HR, 0.31; 95% CI, 0.15-0.62). In contrast, a participant-level meta-analysis estimated that oral anticoagulants reduce the rate of ischemic stroke in patients with atrial fibrillation by 52% (HR, 0.48; 95% CI, 0.37-0.63) but not death (HR, 0.93; 95% CI, 0.76-1.13) relative to aspirin.

Resumption of Warfarin Therapy After Gastrointestinal Tract Bleeding: Benefit or Bias?—Reply

Witt DM, Delate T, Crowther MA. — Mon, 13 May 2013 00:00:00 GMT

In reply

New Oral Anticoagulants in Acute Coronary Syndromes: What Does a Meta-analysis Tell Us?

Kwong JW, Yu C. — Mon, 13 May 2013 00:00:00 GMT

We read with interest the meta-analysis by Komócsi et al, which reported that the use of factor Xa and direct thrombin inhibitors in patients receiving antiplatelet therapy after an acute coronary syndrome (ACS) was associated with a substantial increase in major bleeding and moderate reduction in ischemic events. However, there are a few issues we would like to highlight.

New Oral Anticoagulants in Acute Coronary Syndromes: What Does a Meta-analysis Tell Us?—Reply

Komócsi A, Vorobcsuk A, Aradi D. — Mon, 13 May 2013 00:00:00 GMT

In reply