Risk of hemorrhage among patients treated with warfarin much higher than expected from clinical trials: ICES study

The first large population-based study of its kind shows the rate of hemorrhage among Ontarians treated with warfarin therapy is substantially higher in routine clinical practice than that reported in clinical trials, and almost one in five of these hemorrhages ultimately leads to death.

Atrial fibrillation is a major risk factor for stroke and there is strong evidence that anticoagulation therapy with warfarin reduces this risk.

“Risk of hemorrhage is one of the major challenges to anticoagulation therapy, however, until now there have not been any large studies offering real-world, population-based estimates of this risk among warfarin users, ” says the study’s lead author, Tara Gomes, a scientist at the Institute for Clinical Evaluative Sciences (ICES). Gomes notes that these are all hemorrhages leading to hospitalization, not minor bruising.

This study examined 125,195 patients with atrial fibrillation who were 66 years or older and newly initiated on warfarin therapy between April 1, 1997 and March 31, 2008. The key findings of this study were:

• The overall rate of hemorrhage in routine clinical practice was higher than generally appreciated (3.8 per cent per person-year compared to one to three per cent per person-year reported in clinical trials).
• The risk was highest early in treatment. One per cent of patients had a hemorrhage in the first month following initiation of warfarin therapy, equivalent to 11.8 per cent per person-year.
• The consequences of hemorrhages were substantial. Over the five-year follow-up period, 10,840 patients (8.7 per cent) had a hospital visit for hemorrhage and of these, almost one in five (18.1 per cent) died in hospital or within seven days of hospital discharge.
• Patients at particular risk of hemorrhage over the study period were the elderly (aged less than 75) and those who suffered from a range of other chronic medical conditions.

“This study is the first large study to characterize these risks in an entire population receiving routine clinical care, and our findings indicate that the rate of hemorrhage among these patients may be higher than generally appreciated,” said Gomes, Scientific Lead of the Ontario Drug Policy Research Network. “Our study provides timely estimates of warfarin-related adverse events that are particularly important in light of recently emerging anticoagulant therapies that may be associated with different outcome profiles.”

The study “Hemorrhage rates during warfarin treatment for atrial fibrillation” was published in the CMAJ.

Author block: Tara Gomes, Muhammad M. Mamdani, Anne M. Holbrook, J. Michael Paterson, Chelsea Hellings, David N. Juurlink.

ICES is an independent, non-profit organization that uses population-based health information to produce knowledge on a broad range of health care issues. Our unbiased evidence provides measures of health system performance, a clearer understanding of the shifting health care needs of Ontarians, and a stimulus for discussion of practical solutions to optimize scarce resources. ICES knowledge is highly regarded in Canada and abroad, and is widely used by government, hospitals, planners, and practitioners to make decisions about care delivery and to develop policy.

This study was conducted by the Ontario Drug Policy Research Network (ODPRN), a province-wide network of researchers who provide timely, high quality, drug policy relevant research to decision makers. ODPRN researchers have expertise in pharmaceutical utilization, outcomes, economics, and policy research and leverage cutting-edge research methodology to generate and disseminate evidence on drug utilization, safety, effectiveness and costs in Ontario. The ODPRN is funded by the Ontario Ministry of Health and Long-Term Care. For more details visit ODPRN website.

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