Relationship Between Therapeutic Effects on Infarct Size in Acute MI and One-year Outcomes: Patient-Level Analysis of Randomized Clinical Trials

James Udelson, Harry P. Selker, Robin Ruthazer, Holger Thiele, Manesh R Patel, E. Magnus Ohman, Akiko Maehara, Paul L. Jenkins, Melissa Nichols, Ori Ben-Yehuda, Gregg W. Stone


Infarct size (IS) after MI is related to long-term outcomes. Whether a change in IS from an intervention is related to the intervention’s effect on outcomes is unknown. A therapy-induced change in IS is related in direction and/or magnitude to the outcome effect of that therapy. We combined patient-level data from 10 randomized clinical trials of therapies for STEMI. IS was assessed by sestamibi imaging or cardiac MR with analysis in core labs. Each patient within a trial was assigned a variable to represent a treatment’s mean effect on IS. Cox proportional hazards models estimated the association of treatment-related IS to one-year adjudicated clinical outcomes of hospitalization for HF and all-cause mortality. The 10 trials included 2,458 patients, 24% women. IS was measured at median 5 days post-MI. Mean trial IS in the control groups in the 10 trials ranged from 12% – 35% of the LV, and from 12% – 40% among treatment groups. There was a significant relation of treatment effect on IS to treatment effect on one-year HF hospitalization (HR 0.83, 95% CI 0.75 to 0.93, p<0.001). There was no significant relation between treatment effect on IS to treatment effect on one-year mortality (HR 1.04, 95% CI 0.94 to 1.15). The relation to HF hospitalization was stable in sensitivity analyses adjusting for time from MI to IS assessment, and for considering HF as the main outcome and death as a competing risk. This patient-level analysis of randomized placebo-controlled trials of multiple therapeutics for STEMI suggests that a treatment-induced effect on IS is related in direction and quantifiable magnitude to a treatment effect on HF hospitalizations. The data enable the consideration of incorporating infarct size assessment into novel trial analytic approaches as a surrogate endpoint to assess new therapeutics.

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