Clinical study on the efficacy and safety of ketotifen in STEMI patients undergoing primary PCI
P Xie, Z Y Tian, H Liu, S J Peng, M CuiAbstract
Background
With the COLCOT study demonstrating that colchicine can improve prognosis in myocardial infarction (MI) patients, anti-inflammatory therapy has become a major focus of current research. Mast cells (MCs), as key inflammatory cells, play a critical role in MI. MCs are rapidly activated in the early phase of MI and release multiple effector molecules, amplifying the inflammatory cascade1. Previous studies have shown that tryptase levels in the acute phase of ST-segment elevation myocardial infarction (STEMI), a marker of mast cell activation, are an independent risk factor for long-term adverse outcomes2. Animal experiments suggest that stabilizing MCs or antagonizing their released products can alleviate I/R injury and reduce infarct size3. However, clinical evidence supporting this is still limited. Ketotifen, a classic mast cell stabilizer widely used in the treatment of allergic diseases, may have protective effects in myocardial infarction patients, which merits further investigation.
Purpose
This study aims to investigate the efficacy and safety of the mast cell stabilizer ketotifen in the treatment of STEMI patients.
Methods
This study enrolled STEMI patients undergoing primary PCI from September 2022 to September 2023, who were randomly assigned in a 1:1 ratio using block randomization: ① Control group: received standard treatment for STEMI; ② Ketotifen group: received standard treatment plus ketotifen (1 mg twice daily) for 3 months. Cardiac magnetic resonance imaging was performed at 3 months post-MI to assess infarct size as the primary endpoint.
Results
A total of 112 patients with STEMI were enrolled in this study and allocated to the ketotifen group (n = 56) and the control group (n = 56). The mean age was 56.74 ± 12.16 years, and 101 patients (90.18%) were male. At 3 months of follow-up, cardiac magnetic resonance imaging was performed to assess infarct size. The ketotifen group had a significantly smaller myocardial infarct size than the control group (12.86 ± 5.63 g VS. 15.87 ± 4.87 g, P = 0.003) (Figure 1). This effect was consistent across different age groups, CKMB peak levels (≥100 U/L VS. <100 U/L), and infarct locations (Figure 2). The ketotifen group had a lower extracellular volume fraction (27.27 ± 5.65% VS. 30.14 ± 5.14%, P = 0.006) and greater improvement in global longitudinal strain (3.24 ± 0.50% VS. 2.45 ± 0.73%, P < 0.001) compared to the control group. Five patients in the ketotifen group experienced mild drowsiness, which resolved within approximately one week without affecting treatment adherence.
Conclusion
The mast cell stabilizer ketotifen reduces myocardial infarct size and fibrosis while improving myocardial strain in STEMI patients undergoing primary PCI, with a favorable safety profile. We are currently conducting a multicenter, randomized, event-driven clinical trial to evaluate whether ketotifen can reduce the incidence of adverse outcomes.figure--1.jpgfigure--2.jpg