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According to a recent report from the Institute of Safe Medication practices (ISMP), FDA received 34,765 adverse drug event reports for oral anticoagulants in 2015.
Oral Anticoagulant Use and Injuries Increase
Anna D. GarrettAccording to a recent report from the Institute of Safe Medication practices (ISMP), FDA received 34,765 adverse drug event reports for oral anticoagulants in 2015. These included 2,997 patient deaths and 9,523 adverse events severe enough to require hospitalization. The major problem reported was hemorrhage (n=16,222; 47%), most frequently in the GI tract and CNS.
The median age of patients in the reports was 73 years, which underscores that anticoagulants are among the highest risk outpatient drug treatments in older adults. The actual numbers of deaths and injuries associated with anticoagulant therapy are unknown, but thought to be 10 to 100 times higher than those reported.
In 2015, important changes in prescribing patterns could also be seen. Dispensed prescriptions for novel oral anticoagulants rose 73.6% from early 2014 through 2015, while warfarin use decreased by 10.9% during the same time period.
Clinical trial data and post-market surveillance indicate that the novel oral anticoagulants have about the same benefits and risks as warfarin in most settings. The clinical trials that compared warfarin to the new agents had numerous flaws including unreported cases of major bleeding and acute myocardial infarction, problems with point-of-care testing devices, and fabricated data.
Apixaban Appears Safe in Patients with Worsening Renal Function
A sub-analysis of the ARISTOTLE trial raises questions about how direct oral anticoagulants (DOACs) should be monitored in atrial fibrillation.
The purpose of the sub-analysis was to assess the efficacy and safety outcomes over 12 months of follow-up in patients with renal dysfunction.
Using serial blood samples available in 16,869 patients, researchers found that 13.6% had worsening renal function, defined as a decline of more than 20% in estimated glomerular filtration rate (eGFR). The rate of eGFR deterioration was variable but dropped more rapidly in older patients and those with low hematocrit, heart failure, vascular disease, or diabetes.
Patients with worsening renal function had consistently higher rates of stroke or systemic embolism, major bleeding, and all-cause mortality. This was true regardless of baseline renal function and using either the Cockcroft-Gault or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to estimate renal function.
However, when randomized to apixaban rather than warfarin, these patients had a lower relative risk of stroke or systemic embolism and major bleeding. The beneficial effects of apixaban on these primary efficacy and safety outcomes were also consistent in patients with normal or stable poor renal function (<50 mL/min) over time.
Hijazi, Z, Hohnloser SH, Andersson U, et al. Efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation in relation to renal function over time: insights from the ARISTOTLE randomized clinical trial. JAMA Cardiol. 2016; DOI:10.1001/jamacardio.2016.1170.
Statin Therapy Decreases Risk of Recurrent VTE
Meta-analyses of randomized controlled trials suggest that treatment with HMG co-A reductase inhibitors (statins) lowers the risk of incident venous thromboembolism (VTE)-particularly among those without prevalent clinical cardiovascular disease (CVD). It is not clear whether this is true for the prevention of recurrent VT.
A recent study of 2798 subjects who experienced an initial validated VTE between January 1, 2002, and December 31, 2010 suggests that statins may offer protection against recurrence. During follow-up, 457 (16%) developed a first recurrent VT. In time-to-event models incorporating time-varying statin use and adjusting for potential confounders, current statin use was associated with a 26% lower risk of recurrent VT. Among subjects without CVD (n = 2134), current statin use was also associated with a lower risk (38%) of recurrent VT. The results were similar for new users of statins and in subgroups of different statin types and doses.
These findings suggest a potential secondary benefit of statins among patients who have experienced VTE.
Smith NL, Harrington LB, Blondon M et al. The association of statin therapy with the risk of recurrent venous thrombosis. J Thromb Haemost. 2016;14:1384-1392.