Influence of Low-Density Lipoprotein Cholesterol Levels on NSAID-Associated Cardiovascular Risks After Myocardial Infarction: A Population-Based Cohort Study

Mohab Basem; Kasper Bonnesen; Lars Pedersen; Henrik Toft Sørensen; Morten Schmidt

doi:10.2147/CLEP.S447451

Influence of Low-Density Lipoprotein Cholesterol Levels on NSAID-Associated Cardiovascular Risks After Myocardial Infarction: A Population-Based Cohort Study

Clin Epidemiol. 2024 Apr 22:16:281-291. doi: 10.2147/CLEP.S447451. eCollection 2024.

Authors

Mohab Basem¹, Kasper Bonnesen¹, Lars Pedersen¹, Henrik Toft Sørensen¹, Morten Schmidt^{1

2}

Affiliations

¹ Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark.
² Department of Cardiology, Gødstrup Regional Hospital, Herning, Denmark.

Abstract

Aim: To examine whether low-density lipoprotein cholesterol (LDL-C) levels influence the cardiovascular risk associated with non-aspirin non-steroidal anti-inflammatory drug (NSAID) use after myocardial infarction (MI).

Methods: Using Danish health registries, we conducted a population-based cohort study of all adult patients with first-time MI during 2010-2020 with an LDL-C value before discharge. Based on the latest LDL-C value, we categorized patients into a low and a high LDL-C group (<3.0 vs ≥3.0 mmol/L). We used time varying Cox regression to compute hazard ratios (HRs) with 95% confidence intervals of the association between NSAID use and a major adverse cardiovascular event (MACE: recurrent MI, ischemic stroke, and all-cause death).

Results: We followed 50,573 patients for a median of 3.1 years. While exposed, 521 patients experienced a MACE: 312 in the low LDL-C group and 209 in the high LDL-C group. The HRs for MACE comparing NSAID use with non-use were 1.21 (1.11-1.32) overall, 1.19 (1.06-1.33) in the low LDL-C group, and 1.23 (1.07-1.41) in the high LDL-group. The HRs for recurrent MI and ischemic stroke were comparable between the LDL-C subgroups. The HRs for all-cause death were 1.22 (1.07-1.39) in the low LDL-C group and 1.54 (1.30-1.83) in the high LDL-C group. Changing the cut-off value for LDL-C to 1.8 and 1.4 mmol/L showed consistent results.

Conclusion: In patients with MI, LDL-C levels did not influence the increased risk of MACE associated with NSAID use, but might influence the association between NSAID use and all-cause death.

Keywords: cardiovascular disease; cholesterol; effect modification; low-density lipoprotein cholesterol; myocardial infarction; non-steroidal anti-inflammatory drugs.

Grants and funding

The project was supported by the Novo Nordisk Foundation (grant NNF19OC0054908). The funding organization did not have any role in the design and conduct of the study; in the collection, management, and analysis of the data; or in the preparation, review and approval of the manuscript.