Triglyceride reduction after MI and major adverse outcomes in SWEDEHEART—insights for future trials

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.