Individual patient data meta-analysis links myocardial injury categories to cardiovascular event risk

This is an individual patient-level data meta-analysis of prospective studies from 9 countries, synthesizing data from 120,734 patients with myocardial injury and infarction classified according to the Universal Definition. The population included patients across the spectrum of myocardial injury, categorized into Type 1 MI, Type 2 MI, Acute Myocardial Injury, and Chronic Myocardial Injury. The comparator was patients without myocardial injury. The analysis had a minimum follow-up of 1 year.

The intervention or exposure was the classification into specific myocardial injury and infarction categories. The primary outcome was major adverse cardiovascular events (MACE), defined as MI or cardiovascular death. Key secondary outcomes included noncardiovascular death.

For the primary outcome, the MACE rate was 55.2 per 1,000 patient-years for Type 1 MI (n=11,298) versus 51.7 per 1,000 patient-years for Type 2 MI (n=3,609). The risk of MACE for Type 1 MI versus no MI was a subdistribution HR of 4.82 (95% CI: 3.55-6.57), indicating increased risk. The risk of MACE for Type 2 MI versus no MI was a subdistribution HR of 3.36 (95% CI: 2.92-3.86), also indicating increased risk. The MACE rate for Acute Myocardial Injury was 47.1 per 1,000 patient-years (n=5,864) versus 44.9 per 1,000 patient-years for Chronic Myocardial Injury (n=5,625). The risk of MACE for Acute Myocardial Injury versus no MI was a subdistribution HR of 3.24 (95% CI: 2.41-4.36), and for Chronic Myocardial Injury versus no MI, it was a subdistribution HR of 3.03 (95% CI: 2.53-3.62), both indicating increased risk.

For key secondary outcomes, the noncardiovascular death rate was 25.7 per 1,000 patient-years for Type 1 MI versus 60.1 per 1,000 patient-years for Type 2 MI. The noncardiovascular death rate for Acute Myocardial Injury was 67.0 per 1,000 patient-years versus 46.9 per 1,000 patient-years for Chronic Myocardial Injury.

Safety and tolerability findings were not reported in the input data, including adverse events, serious adverse events, and discontinuations.

These results can be compared to prior landmark studies in this therapeutic area, which have generally shown that myocardial injury is associated with adverse outcomes. This meta-analysis provides individual patient-level data across multiple prospective studies, offering a more granular view of risk by injury category. The finding of a substantially greater competing risk of noncardiovascular death in Type 2 MI is a key distinction from some prior analyses.

Key methodological limitations include the competing risk of noncardiovascular death, which affects risk interpretation in Type 2 MI, as noted in the limitations. The analysis is observational, and the authors caution against inferring causation from association. Potential biases inherent in meta-analyses of prospective studies, such as heterogeneity in study protocols and definitions, are not detailed but should be considered.

Clinically, these results imply that all patients with myocardial injury and infarction are at increased risk of future cardiovascular events. For Type 2 MI, the apparent risk is reduced by a substantially greater competing risk of noncardiovascular death, which should inform risk stratification and management decisions. Practice relevance emphasizes that clinicians should consider the full risk profile, including noncardiovascular mortality.

Unanswered questions remain regarding the mechanisms driving the increased risk in different injury categories, optimal management strategies tailored to each category, and the impact of interventions on these outcomes. Further research is needed to address these gaps.