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FOCUS ON DRUG INTERACTIONS
CORNER Daniel S. Streetman, Section
Advisor
Antithrombotic polypharmacy increases bleeding complications after
first myocardial infarction
Key point: According to a study recently published
in Lancet, patients who have suffered a first-time myocardial
infarction are more likely to be readmitted to the hospital with a
bleeding complication when they are prescribed triple therapy (aspirin,
clopidogrel, and vitamin K antagonist) or dual therapy with clopidogrel
plus vitamin K antagonist than when they receive monotherapy with either
aspirin, clopidogrel, or a vitamin K antagonist.
Finer points: The investigators used a Danish
nationwide registry to identify patients aged 30 years or older who had
been hospitalized because of a first-time myocardial infarction between
2000 and 2005. Patients had been started on various combinations of
aspirin, clopidogrel, and vitamin K antagonists. The investigators
assessed the risks of nonfatal and fatal bleeding events in the patients
in order to identify the safest combinations of antithrombotic
drugs.
A total of 40,812 patients were included in the study. After a mean
follow-up of 476.5 days, 4.6% of patients (n = 1891) were readmitted to
the hospital with bleeding complications. Annual incidences of bleeding
complications were 2.6% for patients who received aspirin monotherapy,
4.6% for clopidogrel monotherapy, 4.3% for vitamin K antagonist
monotherapy, 3.7% for aspirin–clopidogrel dual therapy, 5.1% for
aspirin–vitamin K antagonist dual therapy, 12.3% for
clopidogrel–vitamin K antagonist dual therapy, and , 3.52
(2.42–5.11) for clopidogrel plus vitamin K antagonist, and 4.05
(3.08–5.33) for triple therapy. Of patients who suffered a
nonfatal bleeding event, 37.9% had a recurrent myocardial infarction or
died during the study, compared with 18.4% of patients who did not
experience such a bleeding event (HR 3.00 [2.75–3.27], P
< 0.001). While bleeding risks were increased, all-cause mortality
for all of the combin12% for triple therapy. Using aspirin as a
reference, the investigators calculated adjusted hazard ratios (HR) for
bleeding: 1.33 (95% CI 1.11–1.59) for clopidogrel, 1.23
(0.94–1.61) for vitamin K antagonist, 1.47 (1.28–1.69) for
aspirin plus clopidogrel, 1.84 (1.51–2.23) for aspirin plus
vitamin K antagonistations was not increased compared with aspirin
monotherapy.
What you need to know: According to a comment
published in the same issue of Lancet, dual therapy with
clopidogrel plus vitamin K antagonist was associated with an almost four
times increased risk of bleeding. The writers explained that this risk
was similar to that of triple therapy, noting, “These drug
combinations lead to high rates of bleeding with an apparent loss of
protection against death, possibly because the reduction in ischemic
events is offset by an increased risk of death associated with
bleeding.” The editors commented that new stent technologies,
medications, and equipment capable of assessing platelet reactivity may
assist in developing antiplatelet therapies that are both efficacious
and safe.
What your patients need to know: Antithrombotic
pharmacotherapy decreases the incidence of future ischemic events in
people who have had a myocardial infarction. Bleeding complications
increase with the number of antithrombotics prescribed, and patients who
experience bleeding complications are more likely to have a recurrent
myocardial infarction or die. Encourage patients who are prescribed more
than one antithrombotic agent to speak with their prescribers about the
risks and benefits.
Sources:
Related resources on www.pharmacist.com
Posted by Beth Farnstrom (bfarnstrom@aphanet.org)
January 29, 2010
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