Antiplatelet Therapy in Patients with Abdominal Aortic Aneurysm Without Symptomatic Atherosclerotic Disease

Chalotte W. Nicolajsen; Mette Søgaard; Martin Jensen; Nikolaj Eldrup; Torben B. Larsen; Samuel Z. Goldhaber; Christian Alexander Behrendt; Peter Brønnum Nielsen

doi:10.1001/jamanetworkopen.2023.39715

Antiplatelet Therapy in Patients with Abdominal Aortic Aneurysm Without Symptomatic Atherosclerotic Disease

Chalotte W. Nicolajsen^*, Mette Søgaard, Martin Jensen, Nikolaj Eldrup, Torben B. Larsen, Samuel Z. Goldhaber, Christian Alexander Behrendt, Peter Brønnum Nielsen

^*Corresponding author for this work

Department of Clinical Medicine - Karkirurgi, Viborg

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Importance: Patients with abdominal aortic aneurysm have a high risk of ischemic events associated with concomitant atherosclerotic cardiovascular disease, and current clinical practice guidelines recommend antiplatelet therapy to mitigate this risk. However, in patients with aneurysms without symptomatic atherosclerosis, the benefit of antiplatelet therapy has been sparsely investigated. Objective: To estimate the effect of antiplatelets on the risk of ischemic events and bleeding in individuals with abdominal aneurysms with no symptomatic atherosclerotic vascular disease. Design, Setting, and Participants: A comparative effectiveness research study using a target trial emulation framework was performed. Population-based, cross-linked observational data from Danish national health registries containing comprehensive, individual-level information on all Danish citizens were used to evaluate patients who were antiplatelet-naive and diagnosed with abdominal aortic aneurysms, with no record of symptomatic atherosclerotic vascular disease, from January 1, 2010, through August 21, 2021. Exposure: Prescription filled for aspirin or clopidogrel. Main Outcomes and Measures: Risk of ischemic events (myocardial infarction and/or ischemic stroke) and risk of major bleeding. For target trial emulation, trials were emulated as sequential, contingent on patient eligibility at the time of inclusion, and were evaluated by means of pooled logistic regression models to estimate the intention-to-treat and as-treated effects, expressed as hazard ratio (HR) and event-free survival. Results: A total of 6344 patients (65.2% men; age, 72 [IQR, 64-78] years) provided 131047 trial cases; 3363 of these cases involved initiation of antiplatelet therapy and 127684 did not. A total of 182 ischemic events occurred among initiators and 5602 ischemic events occurred among noninitiators, corresponding to an intention-to-treat HR of 0.91 (95% CI, 0.73-1.17) and an estimated absolute event-free survival difference of -0.6% (95% CI, -1.7% to 0.5%). After censoring nonadherent person-time, the treatment HR was 0.90 (95% CI, 0.68-1.20), with similar risk difference. For bleeding, the intention-to-treat HR was 1.26 (95% CI, 0.97-1.58) and the event-free survival difference was 1.0%. The treatment HR was 1.21 (95% CI, 0.82-1.72); the risk difference was similar. Conclusions and Relevance: In this study, no evidence of effectiveness of antiplatelet therapy to lower the risk of ischemic events and a trend toward higher bleeding risk was noted. The observed differences between the treatment groups were minimal, suggesting limited clinical relevance of antiplatelet treatment.

Original language	English
Article number	e2339715
Journal	JAMA network open
Volume	6
Issue	10
ISSN	2574-3805
DOIs	https://doi.org/10.1001/jamanetworkopen.2023.39715
Publication status	Published - 25 Oct 2023

Keywords

Aged
Aortic Aneurysm, Abdominal/complications
Atherosclerosis/complications
Comparative Effectiveness Research
Female
Humans
Ischemic Stroke
Male
Myocardial Infarction
Platelet Aggregation Inhibitors/therapeutic use

Access to Document

10.1001/jamanetworkopen.2023.39715Licence: CC BY

Cite this

@article{f6f924accf8e4069a7830bbccec529fe,

title = "Antiplatelet Therapy in Patients with Abdominal Aortic Aneurysm Without Symptomatic Atherosclerotic Disease",

abstract = "Importance: Patients with abdominal aortic aneurysm have a high risk of ischemic events associated with concomitant atherosclerotic cardiovascular disease, and current clinical practice guidelines recommend antiplatelet therapy to mitigate this risk. However, in patients with aneurysms without symptomatic atherosclerosis, the benefit of antiplatelet therapy has been sparsely investigated. Objective: To estimate the effect of antiplatelets on the risk of ischemic events and bleeding in individuals with abdominal aneurysms with no symptomatic atherosclerotic vascular disease. Design, Setting, and Participants: A comparative effectiveness research study using a target trial emulation framework was performed. Population-based, cross-linked observational data from Danish national health registries containing comprehensive, individual-level information on all Danish citizens were used to evaluate patients who were antiplatelet-naive and diagnosed with abdominal aortic aneurysms, with no record of symptomatic atherosclerotic vascular disease, from January 1, 2010, through August 21, 2021. Exposure: Prescription filled for aspirin or clopidogrel. Main Outcomes and Measures: Risk of ischemic events (myocardial infarction and/or ischemic stroke) and risk of major bleeding. For target trial emulation, trials were emulated as sequential, contingent on patient eligibility at the time of inclusion, and were evaluated by means of pooled logistic regression models to estimate the intention-to-treat and as-treated effects, expressed as hazard ratio (HR) and event-free survival. Results: A total of 6344 patients (65.2% men; age, 72 [IQR, 64-78] years) provided 131047 trial cases; 3363 of these cases involved initiation of antiplatelet therapy and 127684 did not. A total of 182 ischemic events occurred among initiators and 5602 ischemic events occurred among noninitiators, corresponding to an intention-to-treat HR of 0.91 (95% CI, 0.73-1.17) and an estimated absolute event-free survival difference of -0.6% (95% CI, -1.7% to 0.5%). After censoring nonadherent person-time, the treatment HR was 0.90 (95% CI, 0.68-1.20), with similar risk difference. For bleeding, the intention-to-treat HR was 1.26 (95% CI, 0.97-1.58) and the event-free survival difference was 1.0%. The treatment HR was 1.21 (95% CI, 0.82-1.72); the risk difference was similar. Conclusions and Relevance: In this study, no evidence of effectiveness of antiplatelet therapy to lower the risk of ischemic events and a trend toward higher bleeding risk was noted. The observed differences between the treatment groups were minimal, suggesting limited clinical relevance of antiplatelet treatment.",

keywords = "Aged, Aortic Aneurysm, Abdominal/complications, Atherosclerosis/complications, Comparative Effectiveness Research, Female, Humans, Ischemic Stroke, Male, Myocardial Infarction, Platelet Aggregation Inhibitors/therapeutic use",

author = "Nicolajsen, {Chalotte W.} and Mette S{\o}gaard and Martin Jensen and Nikolaj Eldrup and Larsen, {Torben B.} and Goldhaber, {Samuel Z.} and Behrendt, {Christian Alexander} and Nielsen, {Peter Br{\o}nnum}",

year = "2023",

month = oct,

day = "25",

doi = "10.1001/jamanetworkopen.2023.39715",

language = "English",

volume = "6",

journal = "JAMA network open",

issn = "2574-3805",

publisher = "American Medical Association",

number = "10",

}

Antiplatelet Therapy in Patients with Abdominal Aortic Aneurysm Without Symptomatic Atherosclerotic Disease. / Nicolajsen, Chalotte W.; Søgaard, Mette; Jensen, Martin et al.
In: JAMA network open, Vol. 6, No. 10, e2339715, 25.10.2023.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Antiplatelet Therapy in Patients with Abdominal Aortic Aneurysm Without Symptomatic Atherosclerotic Disease

AU - Nicolajsen, Chalotte W.

AU - Søgaard, Mette

AU - Jensen, Martin

AU - Eldrup, Nikolaj

AU - Larsen, Torben B.

AU - Goldhaber, Samuel Z.

AU - Behrendt, Christian Alexander

AU - Nielsen, Peter Brønnum

PY - 2023/10/25

Y1 - 2023/10/25

N2 - Importance: Patients with abdominal aortic aneurysm have a high risk of ischemic events associated with concomitant atherosclerotic cardiovascular disease, and current clinical practice guidelines recommend antiplatelet therapy to mitigate this risk. However, in patients with aneurysms without symptomatic atherosclerosis, the benefit of antiplatelet therapy has been sparsely investigated. Objective: To estimate the effect of antiplatelets on the risk of ischemic events and bleeding in individuals with abdominal aneurysms with no symptomatic atherosclerotic vascular disease. Design, Setting, and Participants: A comparative effectiveness research study using a target trial emulation framework was performed. Population-based, cross-linked observational data from Danish national health registries containing comprehensive, individual-level information on all Danish citizens were used to evaluate patients who were antiplatelet-naive and diagnosed with abdominal aortic aneurysms, with no record of symptomatic atherosclerotic vascular disease, from January 1, 2010, through August 21, 2021. Exposure: Prescription filled for aspirin or clopidogrel. Main Outcomes and Measures: Risk of ischemic events (myocardial infarction and/or ischemic stroke) and risk of major bleeding. For target trial emulation, trials were emulated as sequential, contingent on patient eligibility at the time of inclusion, and were evaluated by means of pooled logistic regression models to estimate the intention-to-treat and as-treated effects, expressed as hazard ratio (HR) and event-free survival. Results: A total of 6344 patients (65.2% men; age, 72 [IQR, 64-78] years) provided 131047 trial cases; 3363 of these cases involved initiation of antiplatelet therapy and 127684 did not. A total of 182 ischemic events occurred among initiators and 5602 ischemic events occurred among noninitiators, corresponding to an intention-to-treat HR of 0.91 (95% CI, 0.73-1.17) and an estimated absolute event-free survival difference of -0.6% (95% CI, -1.7% to 0.5%). After censoring nonadherent person-time, the treatment HR was 0.90 (95% CI, 0.68-1.20), with similar risk difference. For bleeding, the intention-to-treat HR was 1.26 (95% CI, 0.97-1.58) and the event-free survival difference was 1.0%. The treatment HR was 1.21 (95% CI, 0.82-1.72); the risk difference was similar. Conclusions and Relevance: In this study, no evidence of effectiveness of antiplatelet therapy to lower the risk of ischemic events and a trend toward higher bleeding risk was noted. The observed differences between the treatment groups were minimal, suggesting limited clinical relevance of antiplatelet treatment.

AB - Importance: Patients with abdominal aortic aneurysm have a high risk of ischemic events associated with concomitant atherosclerotic cardiovascular disease, and current clinical practice guidelines recommend antiplatelet therapy to mitigate this risk. However, in patients with aneurysms without symptomatic atherosclerosis, the benefit of antiplatelet therapy has been sparsely investigated. Objective: To estimate the effect of antiplatelets on the risk of ischemic events and bleeding in individuals with abdominal aneurysms with no symptomatic atherosclerotic vascular disease. Design, Setting, and Participants: A comparative effectiveness research study using a target trial emulation framework was performed. Population-based, cross-linked observational data from Danish national health registries containing comprehensive, individual-level information on all Danish citizens were used to evaluate patients who were antiplatelet-naive and diagnosed with abdominal aortic aneurysms, with no record of symptomatic atherosclerotic vascular disease, from January 1, 2010, through August 21, 2021. Exposure: Prescription filled for aspirin or clopidogrel. Main Outcomes and Measures: Risk of ischemic events (myocardial infarction and/or ischemic stroke) and risk of major bleeding. For target trial emulation, trials were emulated as sequential, contingent on patient eligibility at the time of inclusion, and were evaluated by means of pooled logistic regression models to estimate the intention-to-treat and as-treated effects, expressed as hazard ratio (HR) and event-free survival. Results: A total of 6344 patients (65.2% men; age, 72 [IQR, 64-78] years) provided 131047 trial cases; 3363 of these cases involved initiation of antiplatelet therapy and 127684 did not. A total of 182 ischemic events occurred among initiators and 5602 ischemic events occurred among noninitiators, corresponding to an intention-to-treat HR of 0.91 (95% CI, 0.73-1.17) and an estimated absolute event-free survival difference of -0.6% (95% CI, -1.7% to 0.5%). After censoring nonadherent person-time, the treatment HR was 0.90 (95% CI, 0.68-1.20), with similar risk difference. For bleeding, the intention-to-treat HR was 1.26 (95% CI, 0.97-1.58) and the event-free survival difference was 1.0%. The treatment HR was 1.21 (95% CI, 0.82-1.72); the risk difference was similar. Conclusions and Relevance: In this study, no evidence of effectiveness of antiplatelet therapy to lower the risk of ischemic events and a trend toward higher bleeding risk was noted. The observed differences between the treatment groups were minimal, suggesting limited clinical relevance of antiplatelet treatment.

KW - Aged

KW - Aortic Aneurysm, Abdominal/complications

KW - Atherosclerosis/complications

KW - Comparative Effectiveness Research

KW - Female

KW - Humans

KW - Ischemic Stroke

KW - Male

KW - Myocardial Infarction

KW - Platelet Aggregation Inhibitors/therapeutic use

U2 - 10.1001/jamanetworkopen.2023.39715

DO - 10.1001/jamanetworkopen.2023.39715

M3 - Journal article

C2 - 37878310

AN - SCOPUS:85175269601

SN - 2574-3805

VL - 6

JO - JAMA network open

JF - JAMA network open

IS - 10

M1 - e2339715

ER -

Antiplatelet Therapy in Patients with Abdominal Aortic Aneurysm Without Symptomatic Atherosclerotic Disease

Abstract

Keywords

Access to Document

Fingerprint

Cite this