Long-Term Cardiovascular Mortality After Procedure-Related or Spontaneous Myocardial Infarction in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: A Collaborative Analysis of Individual Patient Data From the FRISC II, ICTUS, and RITA-3 Trials (FIR)

Study Questions:

What is the long-term prognostic impact of procedure-related and spontaneous myocardial infarction (MI) on cardiovascular mortality in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS)?


Five-year follow-up after procedure-related or spontaneous MI was investigated in the individual patient-pooled data set of the FRISC-II, ICTUS, and RITA-3 (FIR) NSTE-ACS trials. The principal outcome was cardiovascular death up to 5 years of follow-up. Cumulative event rates were estimated with the Kaplan-Meier method, and hazard ratios (HRs) were calculated with time-dependent Cox proportional-hazards models. Adjustments were made for the variables associated with long-term outcomes.


Of the 5,467 patients, 212 endured a procedure-related MI within 6 months after enrollment. A spontaneous MI occurred in 236 patients within 6 months. The cumulative cardiovascular death rate was 5.2% in patients who endured a procedure-related MI and comparable to patients without a procedure-related MI (HR, 0.66; 95% confidence interval [CI], 0.36-1.20; p = 0.17). In patients who endured a spontaneous MI within 6 months, the cumulative cardiovascular death rate was 22.2% and higher than patients without a spontaneous MI (HR, 4.52; 95% CI, 3.37-6.06; p < 0.001). These HRs did not materially alter after risk adjustments.


The authors concluded that 5-year follow-up of NSTE-ACS patients from the three trials showed no association between a procedure-related MI and long-term cardiovascular mortality.


This analysis of the individual patient-pooled FIR data set did not show any association between procedure-related MIs, occurring at procedures within 6 months of presentation with NSTE-ACS, and long-term cardiovascular mortality. In contrast, the occurrence of a spontaneous MI in the same time frame, as expected, was associated with a substantial increase in cardiovascular mortality at long-term follow-up. These findings emphasize the importance of differentiating effects on different types of MI when evaluating the efficacy and safety of new medical and interventional treatments and translating these findings for treatment recommendations. The study also raises the question of whether procedure-related MI is a valid outcome for clinical trials.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Pyrrolidinones, Myocardial Infarction, Acute Coronary Syndrome, Death, Coronary Angiography, Cardiology, Confidence Intervals, Kainic Acid

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