Acute myocardial infarction (AMI) is one of the most common causes of death in both the developed and developing world. It has high associated morbidity despite prompt institution of recommended therapy. The focus over the last few decades in ST-segment elevation AMI has been on timely reperfusion of the epicardial vessel. However, microvascular consequences after reperfusion, such as microvascular obstruction (MVO), are equally reliable predictors of outcome. The attention on the microcirculation has meant that traditional angiographic/anatomic methods are insufficient. We searched PubMed and the Cochrane database for English-language studies published between January 2000 and November 2019 that investigated the use of invasive physiologic tools in AMI. Based on these results, we provide a comprehensive review regarding the role for the invasive evaluation of the microcirculation in AMI, with specific emphasis on coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR).
Background
Despite improvement in the standard of care (SOC) for hospitalized COVID-19 patients, rates of morbidity and mortality remain high. There continues to be a need for easily available and cost-effective treatments. Colchicine and rosuvastatin are both safe and well-studied medications with anti-inflammatory and other pleiotropic effects that may provide additional benefits to hospitalized COVID-19 patients.
Methods and results
The Colchicine/Statin for the Prevention of COVID-19 Complications (COLSTAT) Trial is a pragmatic, open-label, multicenter, randomized trial comparing the combination of colchicine and rosuvastatin in addition to SOC to SOC alone in hospitalized COVID-19 patients. Four centers in the Yale New Haven Health network will enroll a total of 466 patients with 1:1 randomization. The trial will utilize the electronic health record (Epic® Systems, Verona, Wisconsin, USA) at all stages including screening, randomization, intervention, event ascertainment, and follow-up. The primary endpoint is the 30-day composite of progression to severe COVID-19 disease as defined by the World Health Organization ordinal scale of clinical improvement and arterial/venous thromboembolic events. The secondary powered endpoint is the 30-day composite of death, respiratory failure requiring intubation, and myocardial injury.
Conclusions
The COLSTAT trial will provide evidence on the efficacy of repurposing colchicine and rosuvastatin for the treatment of hospitalized COVID-19 patients. Moreover, it is designed to be a pragmatic trial that will demonstrate the power of using electronic health records to improve efficiency and enrollment in clinical trials in an adapting landscape.
Clinical Trial Registration:
NCT04472611
(
https://clinicaltrials.gov/ct2/show/NCT04472611
).
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