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Clopidogrel treatment after acute myocardial infarction: a pharmacoepidemiological survey of use, efficacy and adverse effects

Rikke Sørensen

Summary

Background and objectives

Clopidogrel has been recommended for patients with myocardial infarction (MI) or percutaneouscoronary intervention (PCI) since 2000 to prevent recurrent thrombotic events. Several clinicaldilemmas have been tied to clopidogrel treatment, for instance, variability in response to treatment,increased risk of bleeding with the optimal duration of treatment being largely unknown. Toexamine different aspects of clopidogrel treatment in MI patients, the following objectives wereestablished:1) to investigate the initiation and persistence with clopidogrel treatment; 2) to analyse the risk ofrecurrent MI or death related to different durations of clopidogrel treatment among MI patients withPCI; and 3) to assess the risk of non-fatal and fatal bleedings related to different combinations ofacetylsalicylic acid (ASA), clopidogrel and vitamin K antagonists treatment.

Methods

By linkage of nationwide registers, we identified patients admitted with first-time MI between 2000and 2005. Dispensed prescriptions were used to obtain information on antithrombotic use.Endpoints were assessed using the Danish National Prescription Registry, the National PatientRegister, the Civil Register, and the Register of Causes of Death. Several statistical methods wereapplied: multivariable logistic regression analysis (initiation of clopidogrel), the Kaplan MeierMethod (estimation of the risk of recurrent MI or death), cumulative incidences (estimation of therisk of non-fatal bleeding, death from bleeding or other causes), Cox proportional Hazard Model(estimation of the risk of non-persistence, MI or death, non-fatal and fatal bleedings).

Results

The initiation of clopidogrel in MI patients treated with PCI was high, 93.7% initiated treatment in2004–2005, whereas this applied to only 39.3% of MI patients without PCI. During the study periodduration of clopidogrel treatment increased in accordance with changes in guidelines. Persistencewith treatment was good, 82.1% of MI patients with PCI continued treatment for 180 days in 2004–2005. Treatment with 6 months’ and 12 months’ clopidogrel was associated with comparable risksof recurrent MI or death in MI patients treated with PCI. Combinations of ASA, clopidogrel andvitamin K antagonists were widely used in MI patients. The risk of non-fatal and fatal bleedingincreased with the number of drugs used, but the combination of clopidogrel + vitamin K antagonistwas associated with nearly the same risk as that of triple therapy. Patients with a non-fatal bleedinghad a 3-fold risk increase of recurrent MI or death after the bleeding.

Conclusions

A high initiation rate of clopidogrel and good persistence with treatment among MI patients treatedwith PCI was found. The risk of recurrent MI or death was comparable in patients treated with 6and 12 months’ clopidogrel. The risk of bleeding increased with the number of antithromboticsused, but a combination of clopidogrel + vitamin K antagonist gave nearly the same risk as that oftriple therapy.