From the Guidelines
The Acorns trial, also known as the TIMACS trial, suggests that an early invasive strategy within 12 to 24 hours is preferred in high-risk patients with unstable angina or non-ST-elevation myocardial infarction (UA/NSTEMI) 1. The trial, which randomized 3031 patients to early or delayed intervention, found that early intervention reduced the composite of death, MI, or refractory ischemia by 28% compared to delayed intervention 1. Key findings from the study include:
- Early intervention was associated with a reduced incidence of refractory ischemia, from 3.3% to 1.0% in the delayed versus early intervention arms, respectively 1.
- The trial was underpowered to discern a clinically meaningful 15% advantage to early invasive therapy for the primary end point, with recruitment stopped at 3000 because of recruitment and funding challenges 1.
- A prespecified analysis showed that early intervention improved the primary outcome in the one third of patients at highest risk, as determined by a GRACE risk score greater than 140, but not in the two thirds at low to intermediate risk 1. Other studies, such as the ISAR-COOL trial, have also compared early versus delayed intervention in patients with UA/NSTEMI, and found that early intervention was associated with a reduced incidence of death or large MI 1. However, the ABOARD trial found that an immediate invasive strategy was not associated with further incremental benefit compared to early intervention 1. Overall, the evidence suggests that an early invasive strategy within 12 to 24 hours is preferred in high-risk patients with UA/NSTEMI, but the optimal timing of intervention may depend on individual patient characteristics and risk factors 1.
From the Research
Acorns Trial Overview
- The ACORN trial is a randomized controlled trial that investigated the combination therapy of vancomycin and piperacillin-tazobactam and its potential increased risk for acute kidney injury 2.
- The trial found no association between receipt of cefepime or piperacillin-tazobactam and the primary outcome of acute kidney injury or death by day 14, despite the fact that >75% of the population received concomitant vancomycin 2.
Randomized Controlled Trials
- Randomized controlled trials (RCTs) are considered the most rigorous and robust research method for determining whether a cause-effect relation exists between an intervention and an outcome 3, 4.
- RCTs involve random allocation of interventions to comparison groups, and are often used to evaluate the effectiveness and safety of an intervention 3, 4.
- RCTs can be designed using a superiority, equivalency, or non-inferiority hypothesis, and are usually preceded by a pilot study 4.
Examples of Randomized Controlled Trials
- The EAGLE-1 trial was a phase 3, open-label, non-inferiority study that evaluated the efficacy and safety of gepotidacin for the treatment of uncomplicated urogenital gonorrhoea 5.
- The MATINEE trial was a phase 3, double-blind, randomized, placebo-controlled trial that investigated the use of mepolizumab to prevent exacerbations of COPD with an eosinophilic phenotype 6.