Patients taking dual antiplatelet therapy have a high frequency of minor hemorrhage and should be taught to anticipate and recognize such events, according to the results of a large, retrospective analysis reported in the Nov. 22 issue of Archives of Internal Medicine.
Otherwise, patients caught unawares may overreact to minor hemorrhage and discontinue the antiplatelet therapy abruptly, jeopardizing their health, wrote Nadine Shehab, Pharm.D., of the Centers for Disease Control and Prevention, Atlanta, and her associates.
Until now there have been few data on the real-world risks of dual antiplatelet therapy "outside the rigorous controlled settings of clinical trials," the researchers said. So their finding that patients on dual antiplatelet therapy visit an emergency department for acute hemorrhage with a similar frequency as that of patients on warfarin will likely come as a surprise to many clinicians.
"We used nationally representative surveillance data ... to describe the frequency, rates, and nature of emergency department (ED) visits for hemorrhagic and other related adverse events attributed to clopidogrel plus aspirin therapy. To gain a better understanding of the magnitude and scope of these types of adverse events, we placed these data in the context of similar data for warfarin, an agent with a related adverse-event profile," they said.
Based on data from adult ED visits to a probability sample of 63 hospitals across the United States between 2006 and 2009, the investigators estimated that there are 7,654 visits every year for hemorrhage-related adverse events among patients taking dual antiplatelet therapy, and that almost all of these involve acute hemorrhage.
In comparison, the number of ED visits for hemorrhage-related adverse events among patients taking warfarin was estimated to be nearly 8 times higher (60,575) – a reasonable difference given that warfarin is prescribed so much more often than is dual antiplatelet therapy. However, ED visits for patients on warfarin often did not involve acute hemorrhage; rather, these patients often visited the ED because of abnormalities in laboratory coagulation variables such as an elevated INR, or for evaluation of potential hemorrhage from a fall or injury, or for toxic effects unrelated to hemorrhage.
"When only ED visits involving acute hemorrhages were considered, the difference [between dual antiplatelet therapy users and warfarin users] was not statistically significant," Dr. Shehab and her colleagues said.
An estimated 60% of ED visits for dual-antiplatelet users involved only epistaxis, skin, or other minor hemorrhages, such as bleeding from the mouth, small cuts, bruising, petechiae, and ecchymosis. Even though the immediate harm from such adverse events is not severe, patients find it very concerning and have been shown to discontinue antiplatelet therapy prematurely after such "nuisance" bleeding.
In contrast, warfarin users tend to be more familiar with minor hemorrhages and less likely to seek ED treatment for them.
Clinicians should be made aware of the large number of patients on dual antiplatelet therapy who mistakenly consider such events to be emergencies. Clinicians also should provide patients with both avoidance and management strategies for such hemorrhages. And they should make sure patients know to anticipate these events, recognize them, seek more appropriate treatment, and, most importantly, not stop antiplatelet therapy abruptly, Dr. Shehab and her associates said (Arch. Intern. Med. 2010;170:1926-33).
Even though most of the ED visits for dual-antiplatelet users involved only minor hemorrhage, a substantial portion – nearly one-third – of visits did involve bleeding severe enough to require hospitalization, including life-threatening pulmonary or CNS hemorrhages, the investigators noted.
When the analysis was restricted only to ED visits for acute hemorrhage, "the risk of clopidogrel plus aspirin-related ED visits resulting in hospitalization was not significantly different from that for warfarin." In addition, almost one-third of clopidogrel plus aspirin-related ED visits were for gastrointestinal tract hemorrhages, and the proportion of patients hospitalized for such bleeding was similar between antiplatelet users and warfarin users.
This is particularly concerning because there are several strategies for managing GI hemorrhages in warfarin users (including careful dose titration, INR monitoring, and patient education) but "few similar interventions for mitigating bleeding harm from antiplatelet medication," Dr. Shehab and her colleagues said.
Overall, the study findings indicate that the hemorrhagic risks with dual antiplatelet therapy are substantial, and that both clinicians and patients "need to approach that risk with vigilance," they added.
This study was supported by the Centers for Disease Control and Prevention. No financial conflicts of interest were reported.