Clopidogrel discontinuation within the first year after coronary drug-eluting stent implantation: an observational study
BMC Cardiovascular Disorders
Clopidogrel discontinuation within the first year after coronary drug-eluting stent implantation: an observational study
Troels Thim 0
Martin Berg Johansen 2
Gro Egholm Chisholm 0
Morten Schmidt 2
Anne Kaltoft 0
Henrik Toft Srensen 2
Leif Thuesen 0
Steen Dalby Kristensen 0
Hans Erik Btker 2
Lars Romer Krusell 0
Jens Flensted Lassen 0
Per Thayssen 1
Lisette Okkels Jensen 1
Hans-Henrik Tilsted 3
Michael Maeng 0
0 Department of Cardiology, Aarhus University Hospital , Aarhus , Denmark
1 Department of Cardiology, Odense University Hospital , Odense , Denmark
2 Department of Clinical Epidemiology, Aarhus University Hospital , Brendstrupgaardsvej 100, Aarhus, N 8200 , Denmark
3 Department of Cardiology, Aalborg University Hospital , Aalborg , Denmark
Background: The impact of adherence to the recommended duration of dual antiplatelet therapy after first generation drug-eluting stent implantation is difficult to assess in real-world settings and limited data are available. Methods: We followed 4,154 patients treated with coronary drug-eluting stents in Western Denmark for 1 year and obtained data on redeemed clopidogrel prescriptions and major adverse cardiovascular events (MACE, i.e., cardiac death, myocardial infarction, or stent thrombosis) from medical databases. Results: Discontinuation of clopidogrel within the first 3 months after stent implantation was associated with a significantly increased rate of MACE at 1-year follow-up (hazard ratio (HR) 2.06; 95% confidence interval (CI): 1.08-3.93). Discontinuation 3-6 months (HR 1.29; 95% CI: 0.70-2.41) and 6-12 months (HR 1.29; 95% CI: 0.54-3.07) after stent implantation were associated with smaller, not statistically significant, increases in MACE rates. Among patients who discontinued clopidogrel, MACE rates were highest within the first 2 months after discontinuation. Conclusions: Discontinuation of clopidogrel was associated with an increased rate of MACE among patients treated with drug-eluting stents. The increase was statistically significant within the first 3 months after drug-eluting stent implantation but not after 3 to 12 months.
Percutaneous coronary intervention; Dual antiplatelet therapy; Drug-eluting stent; Clopidogrel
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Background
Dual antiplatelet therapy (DAPT), i.e., aspirin in
combination with a P2Y12 antagonist, has been shown to
reduce occurrence of ischemic events after coronary
stent implantation in randomized clinical trials [1,2]. In
real-world settings, however, the level of adherence to
recommended DAPT is difficult to assess and its
influence on outcomes is less well known. Moreover, the
optimal duration of DAPT after coronary stent
implantation is disputed [3].
Twelve months of DAPT after percutaneous coronary
intervention (PCI) with coronary stent implantation
has been recommended in Denmark since November
2002. This recommendation is based on interpretation
of results of existing randomized clinical trials [1,2]. In
such trials, we expect adherence to treatment to be high
owing to patient selection, trial-related follow-up, and
cost-free provision of the platelet inhibitor. Adherence
to DAPT in real-world settings is most likely lower than
in these randomized trials. Assessment of adherence
levels and risks associated with discontinuation of DAPT
within the first year after coronary stent implantation is
needed in real-world settings.
Danish medical registries allow validated monitoring of
coronary interventions, prescription redemption, and
clinical outcomes [4-9]. Based on data from these registries,
we report rates of discontinuation of clopidogrel treatment
after coronary drug-eluting stent (DES) implantation and
assess the risk of associated adverse events.
Methods
According to the Central Denmark Region Committees on
Health Research Ethics, this study could be conducted
without an approval from the Committees.
Setting
We conducted this population-based cohort study,
retrospectively, using medical registries in Western Denmark,
which has approximately three million inhabitants (55% of
the Danish population). The Danish National Health
Service provides universal tax-supported health care,
guaranteeing unfettered access to general practitioners and
hospitals. Costs of prescription medications, including
clopidogrel, are partially reimbursed. Accurate and
unambiguous linkage of data from all registries at the
individual level is possible in Denmark using the unique central
personal registry number assigned to every Danish citizen
at birth or upon immigration [9].
Patients and procedures
We used the Western Denmark Heart Registry (WDHR)
[10] to identify all PCI procedures performed between 1
January 2003 and 30 June 2005 [11-13]. For each patient,
the first PCI procedure with implantation of one or
more coronary DES during the inclusion period was
defined as the index PCI procedure and the date of
that procedure as the index date. Patients treated with
balloon angioplasty without stenting o (...truncated)