A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study.

The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far. We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-ischemic benefit may also be expected with additional acetylsalicylic acid (ASA) withdrawal. To evaluate these hypotheses, we designed the Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome - a randomized clinical trial (ELECTRA-SIRIO 2), to assess the influence of ticagrelor dose reduction with or without continuation of ASA versus DAPT with standard dose ticagrelor in reducing clinically relevant bleeding and maintaining anti-ischemic efficacy in ACS patients. The study was designed as a phase III, randomized, multicenter, double-blind, investigator-initiated clinical study with a 12-month follow-up (ClinicalTrials.gov Identifier: NCT04718025; EudraCT number: 2020-005130-15).

Antioxidant effects of combined vitamins C and E in acute myocardial infarction. The randomized, double-blind, placebo controlled, multicenter pilot Myocardial Infarction and VITamins (MIVIT) trial.

AIMS: There is a large body of evidence that reactive oxygen species (ROS) produced during myocardial ischemia and reperfusion play a crucial role in myocardial damage and endothelial dysfunction. The MIVIT pilot trial was designed to test the effects of antioxidant vitamins C and E on the clinical outcome of patients with AMI. METHODS AND RESULTS: In this randomized, double-blind, multicenter trial, 800 patients (mean age 62) with AMI were randomly allocated to receive, on top of routine medication, one of two treatments: vitamin C (1000 mg/12 h infusion) followed by 1200 mg/24 h orally and vitamin E (600 mg/24 h) or matching placebo for 30 days. Primary end point (composite of in-hospital cardiac mortality, non-fatal new myocardial infarction, VT/VF/asystole, shock/pulmonary edema) occurred less frequently in patients treated with antioxidants (55 [14%] vs 75 [19%], OR 0.82 [95% CI, 0.68-1.00], p=0.048). CONCLUSIONS: This randomized pilot trial shows that supplementation with antioxidant vitamins is safe and seems to positively influence the clinical outcome of patients with AMI. A larger study is warranted to provide further evidence of this promising and inexpensive regimen.

Efficacy and safety of oral l-arginine in acute myocardial infarction. Results of the multicenter, randomized, double-blind, placebo-controlled ARAMI pilot trial.

AIMS: L-arginine is a substrate for nitric oxide (NO) synthesis in vascular endothelial cells. NO bioavailability is decreased during myocardial infarction (MI). It might be expected that administration of L-arginine may maintain NO production and alleviate the course of MI. The aim of the study was to assess safety and effects of treatment with L-arginine on the clinical course of MI. METHODS AND RESULTS: 792 patients (mean age 64 years, 551 men) with ST segment elevation MI admitted within 24h after the onset of symptoms were randomized to oral L-arginine (3.0 t.i.d p.o. for 30 days) or placebo on top of routine therapy. The end point which was the composite of 30 day cardiovascular death, reinfarction, successful resuscitation, shock/pulmonary edema or recurrent myocardial ischemia occurred in 24% patients treated with L-arginine and 27% with placebo (OR 0.63, 95% CI 0.39-1.02, p=0.06). The end point was observed less frequently in 226 patients with hyperlipidemia (19 vs 31, p<0.05). No serious adverse effects were observed during L-arginine supplementation. CONCLUSIONS: This study, which is the first attempt to use L-arginine in MI, showed that oral L-arginine supplementation was well tolerated. Beneficial nonsignificant trend was observed towards reduction of major clinical events.