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VTE risk elevated among glucocorticoid users
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Glucocorticoid users exhibited an increased risk for venous thromboembolism, particularly pulmonary embolism, according to results of a population-based case-control study conducted in Denmark.
Systemic glucocorticoids were associated with the greatest risk.
“Experimental studies show that glucocorticoids increase levels of clotting factors and fibrinogen,” the researchers wrote. “Also, Cushing’s syndrome has been linked to an increased VTE risk, possibly resulting from high endogenous glucocorticoid levels in these patients. Nevertheless, clinical data on the association between exogenous glucocorticoids and VTE are sparse, and comparison of available studies is hampered by their focus on specific patient populations.”
To determine the association between glucocorticoid use and VTE, the researchers examined 38,765 VTE cases diagnosed from 2005 to 2011 and 387,650 controls included through risk-set sampling and matched by birth year and sex.
The researchers used the Danish National Registry of Patients to identify all first-time primary and secondary inpatient and outpatient diagnoses of deep vein thrombosis or PE embolism. Patients with both PE and DVT diagnoses were included in the PE group only.
Patients who filled their most recent glucocorticoid prescription within 90 days or less were classified as present users. Those who filled their most recent prescription within 91 to 365 days were classified as recent users, and those who did so more than 365 days before the index date were classified as former users.
The researchers then subdivided present users into new (first-time prescription 90 days or less before the index date) and continuing users.
According to study results, systemic glucocorticoids increased VTE risk among present (adjusted incidence rate ratio [IRR]=2.31; 95% CI, 2.18-2.45), new (adjusted IRR=3.06; 95% CI, 2.77-3.38), continuing (adjusted IRR=2.02; 95% CI, 1.88-2.17) and recent users (adjusted IRR=1.18; 95% CI, 1.10-1.26) but not among former users (adjusted IRR=0.94; 95% CI, 0.90-0.99).
The adjusted IRR increased from 1.0 (95% CI, 0.93-1.07) for a prednisolone-equivalent cumulative dose of 10 mg or less to 1.98 (95% CI, 1.78-2.20) for 1,000 mg to 2,000 mg, and to 1.6 (95% CI, 1.49-1.71) for doses of at least 2,000 mg. New use of inhaled (adjusted IRR=2.21; 95% CI, 1.72-2.86) and intestinal-acting (adjusted IRR=2.17; 95% CI, 1.27-3.71) glucocorticoids also elevated VTE risk.
“Glucocorticoid users had an increased risk of VTE, especially [PE],” the researchers wrote. “The effect was strongest for new users of systemic glucocorticoids but persisted (albeit less prominently) among users of inhaled glucocorticoids and glucocorticoids acting on the intestines. Although residual confounding might partially explain the results, clinicians should be aware of this association.”
Disclosure: The researchers report no relevant financial disclosures.
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Harry S. Jacob, MD, FRCPath(Hon)
I wonder if we don’t have a horse-vs.-cart phenomenon here. Corticosteroids are generally used for inflammatory conditions that, per se, increase clotting propensity. Nevertheless, the slight (if any) hypercoagulability in Cushing’s syndrome, and the definite steroid-associated risk of femoral head necrosis — if vascular at all — that presumably involves arterial rather than venous occlusions, may support somewhat the findings in this report.
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