Their findings show that the higher the dose of statin therapy, the greater the attenuation of oxidative stress and inflammatory activity after MI, and the larger the improvement of nitric oxide production and endothelial vasomotor function.
Furthermore, the team says that to achieve maximum benefits with statin therapy, its initiation should occur in the acute phase of MI.
In the first treatment phase, 125 ST-elevation MI (STEMI) patients were randomly assigned to one of five treatment groups: no statin, simvastatin 20, 40, or 80 mg/day starting at admission, or simvastatin 80 mg/day starting 48 hours after admission.
After 7 days, all patients switched treatment plan to receive simvastatin 20 mg/day for 3 weeks (second phase), and underwent assessment of flow-mediated dilation (FMD) in the brachial artery.
Andrei Sposito (State University of Campinas, Sao Paulo) and colleagues found that within the first 24 hours post-MI, there was a rapid rise in C-reactive protein (CRP) levels for all treatment groups during the first phase.
By the second day, these levels differed significantly between nonstatin users and patients treated with simvastatin 20, 40 and 80 mg/day, at 12.6 versus 8.1, 3.4, and 1.2 mg/l, respectively, and these daily differences remained significant until the seventh day.
Furthermore, during the first 5 days of treatment, the higher the statin dose, the lower the elevation of the inflammatory cytokines interleukin-2 and tumor necrosis factor-?, and the greater the reduction of two indicators of oxidative stress - 8-isoprostane and low-density lipoprotein cholesterol. Nitric oxide levels also increased in proportion to the dose of simvastatin received.
At the end of the second phase of treatment, there were no longer significant differences in lipid profiles or CRP levels between treatment groups. However, changes in FMD values were proportional to the initial statin dose, at 3.6%, 7.0%, and 12.4% for patients treated with simvastatin 20, 40, and 80 mg/day, respectively.
Delaying simvastatin treatment by 48 hours reduced the anti-inflammatory effect by approximately one third compared with initiating statin administration at admission, which the researchers say indicates that the timing of treatment is key to its main beneficial mechanisms.
"It is plausible that statin effect on inflammation or on the source of inflammation itself has contributed to the improvement or preservation of the endothelial function in the present study," write the authors in the journal Arteriosclerosis, Thrombosis and Vascular Biology.
They conclude that to achieve maximum benefit with statin therapy, its initiation is mandatory in the first hours after onset of MI.
