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Triglyceride reduction after MI and major adverse outcomes in SWEDEHEART-insights for future trials
Jessica Schubert1, Emil Hagström1,2, Johan Westerbergh2
1Department of Medical Sciences, Cardiology, Uppsala University, Entrance 40, 5tr, Uppsala 751 85, Sweden.
Insights
Achieving triglyceride reductions of approximately 1.0 mmol/L after myocardial infarction (MI) is linked to lower cardiovascular risk. Future trials should target patients with high baseline triglycerides (≥2.2 mmol/L) for significant benefit.
Area of Science:
- Cardiology
- Biochemistry
- Clinical Trials
Background:
- Genetically higher triglyceride levels are linked to cardiovascular risk, but triglyceride-lowering therapies haven't shown clear cardiovascular benefits.
- Understanding the necessary treatment effect magnitude and identifying patient subgroups who may benefit is crucial for effective cardiovascular risk management.
Purpose of the Study:
- To assess the relationship between triglyceride levels and cardiovascular events following myocardial infarction (MI).
- To provide insights into the magnitude of treatment effect needed for cardiovascular risk reduction.
- To identify patient profiles that might benefit from triglyceride-lowering interventions.
Main Methods:
- Utilized data from 51,719 MI patients in the Swedish SWEDEHEART registry (2005-2022).
- Evaluated triglyceride changes from admission to 1-year post-MI and 1-year triglyceride levels using adjusted Cox models.
- Assessed outcomes including Major Adverse Cardiovascular Events (MACE), all-cause mortality, and non-fatal MI over a median follow-up of 5.6 years.
Main Results:
- Patients achieving the top quartile of triglyceride reduction (≥0.6 mmol/L, median 1.0 mmol/L) had the lowest risk of MACE (HR 0.85), all-cause mortality (HR 0.90), and non-fatal MI (HR 0.83) compared to those with minimal change.
- The quartile with significant triglyceride reduction had higher baseline triglycerides (median 2.2 mmol/L).
- Patients with the lowest 1-year triglyceride levels (<0.9 mmol/L) exhibited the lowest cardiovascular risk.
Conclusions:
- Triglyceride reductions of approximately 1.0 mmol/L were associated with the lowest cardiovascular risk in MI patients.
- Only 27% of patients achieved this target reduction, potentially explaining neutral results in previous triglyceride-lowering trials.
- Future trials should focus on patients with baseline triglycerides ≥2.2 mmol/L, targeting reductions of ≥1.0 mmol/L for optimal cardiovascular risk management.
Aims:
Despite causal inference from genetically higher triglyceride levels and cardiovascular risk, therapeutic triglyceride lowering has yet to demonstrate cardiovascular benefits. Providing insights into the magnitude of treatment effect needed and the type of patients who might benefit, we assessed the relationship between triglyceride levels and cardiovascular events following myocardial infarction (MI).
Methods And Results:
Between 2005 and 2022, 51,719 MI patients in the Swedish MI registry SWEDEHEART were studied. Triglyceride change from admission to 1-year and 1-year levels was evaluated in adjusted Cox models. Outcomes were MACE (all-cause mortality, non-fatal MI, and non-fatal ischaemic stroke), all-cause mortality, and non-fatal MI. Over 5.6 years, 9008 patients experienced an MACE, and 5148 died. Median triglycerides were 1.4 mmol/L (interquartile range IQR 1.0-2.0) at MI admission and 1.2 mmol/L (0.9-1.6) at 1 year. Patients in the top quartile of triglyceride reduction (≥0.6 mmol/L, median 1.0 mmol/L) had the highest baseline triglycerides of 2.2 mmol/L (1.8-2.9). Compared to patients with minimal change, this quartile had the lowest risk of MACE (HR 0.85 95% CI 0.79-0.92), all-cause mortality (HR 0.90, 0.81-0.99), and non-fatal MI (HR 0.83, 0.74-0.94). Patients in the lowest quartile at 1-year (<0.9 mmol/L) had the lowest cardiovascular risk.
Conclusion:
Among MI patients, triglyceride reductions of ∼1.0 mmol/L were associated with the lowest cardiovascular risk. Only 27% of patients achieved this reduction with baseline triglycerides ∼2.2 mmol/L. These findings may explain neutral results in prior triglyceride-lowering trials and suggest future trials should enrol patients with baseline triglycerides ≥2.2 mmol/L and target reductions ≥1.0 mmol/L.
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