Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data

Rikke Sørensen; Morten L Hansen; Steen Z Abildstrom; Anders Hvelplund; Charlotte Andersson; Casper Jørgensen; Jan K Madsen; Peter R Hansen; Lars Køber; Christian Torp-Pedersen; Gunnar H Gislason; Rikke Sørensen; Morten L Hansen; Steen Z Abildstrom; Anders Hvelplund; Charlotte Andersson; Casper Jørgensen; Jan K Madsen; Peter R Hansen; Lars Køber; Christian Torp-Pedersen; Gunnar H Gislason

doi:10.1016/S0140-6736(09)61751-7

Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data

Rikke Sørensen, Morten L Hansen, Steen Z Abildstrom, Anders Hvelplund, Charlotte Andersson, Casper Jørgensen, Jan K Madsen, Peter R Hansen, Lars Køber, Christian Torp-Pedersen, Gunnar H Gislason, Rikke Sørensen, Morten L Hansen, Steen Z Abildstrom, Anders Hvelplund, Charlotte Andersson, Casper Jørgensen, Jan K Madsen, Peter R Hansen, Lars KøberChristian Torp-Pedersen, Gunnar H Gislason

448 Citations (Scopus)

Abstract

BACKGROUND: Combinations of aspirin, clopidogrel, and vitamin K antagonists are widely used in patients after myocardial infarction. However, data for the safety of combinations are sparse. We examined the risk of hospital admission for bleeding associated with different antithrombotic regimens. METHODS: By use of nationwide registers from Denmark, we identified 40 812 patients aged 30 years or older who had been admitted to hospital with first-time myocardial infarction between 2000 and 2005. Claimed prescriptions starting at hospital discharge were used to determine the regimen prescribed according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Risk of hospital admission for bleeding, recurrent myocardial infarction, and death were assessed by Cox proportional hazards models with the drug exposure groups as time-varying covariates. FINDINGS: During a mean follow-up of 476.5 days (SD 142.0), 1891 (4.6%) patients were admitted to hospital with bleeding. The yearly incidence of bleeding was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. With aspirin as reference, adjusted hazard ratios for bleeding were 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 antagonist, 3.52 (2.42-5.11) for clopidogrel plus vitamin K antagonist, and 4.05 (3.08-5.33) for triple therapy. Numbers needed to harm were 81.2 for aspirin plus clopidogrel, 45.4 for aspirin plus vitamin K antagonist, 15.2 for clopidogrel plus vitamin K antagonist, and 12.5 for triple therapy. 702 (37.9%) of 1852 patients with non-fatal bleeding had recurrent myocardial infarction or died during the study period compared with 7178 (18.4%) of 38 960 patients without non-fatal bleeding (HR 3.00, 2.75-3.27, p<0.0001). INTERPRETATION: In patients with myocardial infarction, risk of hospital admission for bleeding increased with the number of antithrombotic drugs used. Treatment with triple therapy or dual therapy with clopidogrel plus vitamin K antagonist should be prescribed only after thorough individual risk assessment. FUNDING: Danish Heart Foundation and the Danish Medical Research Council.

Original language	English
Journal	Lancet
Volume	374
Issue number	9706
Pages (from-to)	1967-74
Number of pages	7
ISSN	0140-6736
DOIs	https://doi.org/10.1016/S0140-6736(09)61751-7 https://doi.org/10.1016/S0140-6736(09)61751-7
Publication status	Published - 2009

Access to Document

Fingerprint

Dive into the research topics of 'Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data'. Together they form a unique fingerprint.

Cite this

Sørensen, R., Hansen, M. L., Abildstrom, S. Z., Hvelplund, A., Andersson, C., Jørgensen, C., Madsen, J. K., Hansen, P. R., Køber, L., Torp-Pedersen, C., Gislason, G. H., Sørensen, R., Hansen, M. L., Abildstrom, S. Z., Hvelplund, A., Andersson, C., Jørgensen, C., Madsen, J. K., Hansen, P. R., ... Gislason, G. H. (2009). Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data. Lancet, 374(9706), 1967-74. https://doi.org/10.1016/S0140-6736(09)61751-7, https://doi.org/10.1016/S0140-6736(09)61751-7

Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data. / Sørensen, Rikke; Hansen, Morten L; Abildstrom, Steen Z et al.

In: Lancet, Vol. 374, No. 9706, 2009, p. 1967-74.

Research output: Contribution to journal › Journal article › Research › peer-review

Sørensen, R, Hansen, ML, Abildstrom, SZ, Hvelplund, A, Andersson, C, Jørgensen, C, Madsen, JK, Hansen, PR, Køber, L , Torp-Pedersen, C , Gislason, GH, Sørensen, R, Hansen, ML, Abildstrom, SZ, Hvelplund, A, Andersson, C, Jørgensen, C, Madsen, JK, Hansen, PR , Køber, L , Torp-Pedersen, C & Gislason, GH 2009, 'Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data', Lancet, vol. 374, no. 9706, pp. 1967-74. https://doi.org/10.1016/S0140-6736(09)61751-7, https://doi.org/10.1016/S0140-6736(09)61751-7

Sørensen R, Hansen ML, Abildstrom SZ, Hvelplund A, Andersson C, Jørgensen C et al. Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data. Lancet. 2009;374(9706):1967-74. doi: 10.1016/S0140-6736(09)61751-7, http://dx.doi.org/10.1016/S0140-6736(09)61751-7

@article{9825e080117111df803f000ea68e967b,

title = "Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data",

abstract = "BACKGROUND: Combinations of aspirin, clopidogrel, and vitamin K antagonists are widely used in patients after myocardial infarction. However, data for the safety of combinations are sparse. We examined the risk of hospital admission for bleeding associated with different antithrombotic regimens. METHODS: By use of nationwide registers from Denmark, we identified 40 812 patients aged 30 years or older who had been admitted to hospital with first-time myocardial infarction between 2000 and 2005. Claimed prescriptions starting at hospital discharge were used to determine the regimen prescribed according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Risk of hospital admission for bleeding, recurrent myocardial infarction, and death were assessed by Cox proportional hazards models with the drug exposure groups as time-varying covariates. FINDINGS: During a mean follow-up of 476.5 days (SD 142.0), 1891 (4.6%) patients were admitted to hospital with bleeding. The yearly incidence of bleeding was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. With aspirin as reference, adjusted hazard ratios for bleeding were 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 antagonist, 3.52 (2.42-5.11) for clopidogrel plus vitamin K antagonist, and 4.05 (3.08-5.33) for triple therapy. Numbers needed to harm were 81.2 for aspirin plus clopidogrel, 45.4 for aspirin plus vitamin K antagonist, 15.2 for clopidogrel plus vitamin K antagonist, and 12.5 for triple therapy. 702 (37.9%) of 1852 patients with non-fatal bleeding had recurrent myocardial infarction or died during the study period compared with 7178 (18.4%) of 38 960 patients without non-fatal bleeding (HR 3.00, 2.75-3.27, p<0.0001). INTERPRETATION: In patients with myocardial infarction, risk of hospital admission for bleeding increased with the number of antithrombotic drugs used. Treatment with triple therapy or dual therapy with clopidogrel plus vitamin K antagonist should be prescribed only after thorough individual risk assessment. FUNDING: Danish Heart Foundation and the Danish Medical Research Council.",

author = "Rikke S{\o}rensen and Hansen, {Morten L} and Abildstrom, {Steen Z} and Anders Hvelplund and Charlotte Andersson and Casper J{\o}rgensen and Madsen, {Jan K} and Hansen, {Peter R} and Lars K{\o}ber and Christian Torp-Pedersen and Gislason, {Gunnar H} and Rikke S{\o}rensen and Hansen, {Morten L} and Abildstrom, {Steen Z} and Anders Hvelplund and Charlotte Andersson and Casper J{\o}rgensen and Madsen, {Jan K} and Hansen, {Peter R} and Lars K{\o}ber and Christian Torp-Pedersen and Gislason, {Gunnar H}",

note = "Keywords: Adult; Aged; Aspirin; Denmark; Drug Therapy, Combination; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Patient Admission; Proportional Hazards Models; Recurrence; Registries; Retrospective Studies; Risk Factors; Ticlopidine; Vitamin K",

year = "2009",

doi = "10.1016/S0140-6736(09)61751-7",

language = "English",

volume = "374",

pages = "1967--74",

journal = "Lancet",

issn = "0140-6736",

publisher = "TheLancet Publishing Group",

number = "9706",

}

TY - JOUR

T1 - Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data

AU - Sørensen, Rikke

AU - Hansen, Morten L

AU - Abildstrom, Steen Z

AU - Hvelplund, Anders

AU - Andersson, Charlotte

AU - Jørgensen, Casper

AU - Madsen, Jan K

AU - Hansen, Peter R

AU - Køber, Lars

AU - Torp-Pedersen, Christian

AU - Gislason, Gunnar H

AU - Sørensen, Rikke

AU - Hansen, Morten L

AU - Abildstrom, Steen Z

AU - Hvelplund, Anders

AU - Andersson, Charlotte

AU - Jørgensen, Casper

AU - Madsen, Jan K

AU - Hansen, Peter R

AU - Køber, Lars

AU - Torp-Pedersen, Christian

AU - Gislason, Gunnar H

N1 - Keywords: Adult; Aged; Aspirin; Denmark; Drug Therapy, Combination; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Patient Admission; Proportional Hazards Models; Recurrence; Registries; Retrospective Studies; Risk Factors; Ticlopidine; Vitamin K

PY - 2009

Y1 - 2009

N2 - BACKGROUND: Combinations of aspirin, clopidogrel, and vitamin K antagonists are widely used in patients after myocardial infarction. However, data for the safety of combinations are sparse. We examined the risk of hospital admission for bleeding associated with different antithrombotic regimens. METHODS: By use of nationwide registers from Denmark, we identified 40 812 patients aged 30 years or older who had been admitted to hospital with first-time myocardial infarction between 2000 and 2005. Claimed prescriptions starting at hospital discharge were used to determine the regimen prescribed according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Risk of hospital admission for bleeding, recurrent myocardial infarction, and death were assessed by Cox proportional hazards models with the drug exposure groups as time-varying covariates. FINDINGS: During a mean follow-up of 476.5 days (SD 142.0), 1891 (4.6%) patients were admitted to hospital with bleeding. The yearly incidence of bleeding was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. With aspirin as reference, adjusted hazard ratios for bleeding were 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 antagonist, 3.52 (2.42-5.11) for clopidogrel plus vitamin K antagonist, and 4.05 (3.08-5.33) for triple therapy. Numbers needed to harm were 81.2 for aspirin plus clopidogrel, 45.4 for aspirin plus vitamin K antagonist, 15.2 for clopidogrel plus vitamin K antagonist, and 12.5 for triple therapy. 702 (37.9%) of 1852 patients with non-fatal bleeding had recurrent myocardial infarction or died during the study period compared with 7178 (18.4%) of 38 960 patients without non-fatal bleeding (HR 3.00, 2.75-3.27, p<0.0001). INTERPRETATION: In patients with myocardial infarction, risk of hospital admission for bleeding increased with the number of antithrombotic drugs used. Treatment with triple therapy or dual therapy with clopidogrel plus vitamin K antagonist should be prescribed only after thorough individual risk assessment. FUNDING: Danish Heart Foundation and the Danish Medical Research Council.

AB - BACKGROUND: Combinations of aspirin, clopidogrel, and vitamin K antagonists are widely used in patients after myocardial infarction. However, data for the safety of combinations are sparse. We examined the risk of hospital admission for bleeding associated with different antithrombotic regimens. METHODS: By use of nationwide registers from Denmark, we identified 40 812 patients aged 30 years or older who had been admitted to hospital with first-time myocardial infarction between 2000 and 2005. Claimed prescriptions starting at hospital discharge were used to determine the regimen prescribed according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Risk of hospital admission for bleeding, recurrent myocardial infarction, and death were assessed by Cox proportional hazards models with the drug exposure groups as time-varying covariates. FINDINGS: During a mean follow-up of 476.5 days (SD 142.0), 1891 (4.6%) patients were admitted to hospital with bleeding. The yearly incidence of bleeding was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. With aspirin as reference, adjusted hazard ratios for bleeding were 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 antagonist, 3.52 (2.42-5.11) for clopidogrel plus vitamin K antagonist, and 4.05 (3.08-5.33) for triple therapy. Numbers needed to harm were 81.2 for aspirin plus clopidogrel, 45.4 for aspirin plus vitamin K antagonist, 15.2 for clopidogrel plus vitamin K antagonist, and 12.5 for triple therapy. 702 (37.9%) of 1852 patients with non-fatal bleeding had recurrent myocardial infarction or died during the study period compared with 7178 (18.4%) of 38 960 patients without non-fatal bleeding (HR 3.00, 2.75-3.27, p<0.0001). INTERPRETATION: In patients with myocardial infarction, risk of hospital admission for bleeding increased with the number of antithrombotic drugs used. Treatment with triple therapy or dual therapy with clopidogrel plus vitamin K antagonist should be prescribed only after thorough individual risk assessment. FUNDING: Danish Heart Foundation and the Danish Medical Research Council.

U2 - 10.1016/S0140-6736(09)61751-7

DO - 10.1016/S0140-6736(09)61751-7

M3 - Journal article

SN - 0140-6736

VL - 374

SP - 1967

EP - 1974

JO - Lancet

JF - Lancet

IS - 9706

ER -