Dose-Dependent Inhibitory Effect of Rosuvastatin in Japanese Patients with Acute Myocardial Infarction on Serum Concentration of Matrix Metalloproteinases–INVITATION Trial–

Abstract

Aim: Matrix metalloproteinases (MMPs) play critical roles in acute myocardial infarction (AMI). This trial was conducted to determine the potential effects of higher-dose rosuvastatin on circulating MMP levels in patients with AMI. Methods: This was a multicenter, open-label, 1:1 randomized, parallel-group study. Patients with AMI were randomly assigned to the appropriate-dose group (10 mg rosuvastatin once daily) or the low-dose group (2.5 mg rosuvastatin once daily) within 24 hours after percutaneous coronary intervention. MMP-2 and MMP-9 levels were measured on day 1 and at week 4, 12, and 24 after enrollment. The primary endpoint was the change in MMP levels at 24 weeks after enrollment. The secondary endpoints were change in MMP levels at day 1 and weeks 4 and 12 after enrollment. Results: Between August 2017 and October 2018, 120 patients with AMI from 19 institutions were randomly assigned to either the appropriate-dose or the low-dose group. There were 109 patients who completed the 24-week follow-up. The primary endpoint for both MMP-2 and MMP-9 was not significantly different between the two groups. The change in the active/total ratio of MMP-9 at week 12 after baseline was significantly lower in the appropriate-dose group compared with the low-dose group (0.81 [−52.8–60.1]% vs. 70.1 [−14.5–214.2]%, P=0.004), while the changes in MMP-2 were not significantly different between the two groups during the study period. Conclusions: This study could not demonstrate the superiority of appropriate-dose of rosuvastatin in inhibiting serum MMPs levels in patients with AMI.