Ultrahigh resolution CT enables coronary artery disease diagnosis in high-risk patients

29th June 2023

A study by German researchers has shown that an ultrahigh resolution coronary CT angiography can enable clinicians to diagnose coronary artery disease in high-risk patients prior to transcatheter aortic value replacement.

Patients with severe aortic stenosis and who are suitable for transcatheter aortic valve replacement (TAVR), often have co-existing coronary artery disease (CAD). Moreover, guidelines recommend that patients suitable for TAVR undergo an assessment for CAD. Although coronary CT angiography can be used to assess the whether a patient has CAD, it often overestimates the extent of disease in high-risk patients. With the introduction of ultrahigh resolution coronary CT angiography, it may be possible to identify CAD in these high-risk patients.

Writing in the journal Radiology, the German team set out to determine the diagnostic accuracy of the new ultrahigh resolution coronary CT angiography for the detection of CAD compared with the reference standard of invasive coronary angiography (ICA).

The team examined participants with severe aortic valve stenosis and who were clinically indicated for transcatheter aortic valve replacement. All participants underwent ultrahigh-resolution photon-counting CT angiography and invasive coronary angiography, with the latter being part of their clinical care. The image quality was assessed on a 5-point Likert scale, where one was excellent and five non-diagnostic.

In addition, clinicians, who were blind to the ICA findings, assessed for the presence of CAD, defined by a 50% or greater stenosis. The ultrahigh resolution CT and ICA findings were compared using area under the receiver operating characteristic curve (AUC).

Diagnostic accuracy of the ultrahigh resolution CT

A total of 68 patients (mean age 81 years, 52.9% female) with severe aortic valve stenosis and an indication for TAVR were included in the comparative analysis. The median image quality score was 1.5 with most segments rated as either good or excellent quality.

The ultrahigh resolution CT AUC for the detection of CAD was 0.93 (95% CI 0.86 – 0.99) at the participant level, 0.94 (95% CI 0.91 – 0.98) at the vessel level and 0.92 (95% CI 0.87 – 0.97) at the segment level. This gave rise to a 96% sensitivity, an 84% specificity and 88% accuracy for the detection of coronary artery disease.

Although seemingly impressive results, the researchers called for confirmatory research with more subjects to improve the generalisability of their findings, as well as larger trials with patient-related end points to determine the potential clinical benefits of photon-counting CT.

Molnupiravir treatment fails to reduce adverse outcomes among high-risk vaccinated patients

11th January 2023

Molnupiravir treatment failed to reduce both COVID-related hospitalisation and mortality among high-risk vaccinated adults in the community

Molnupiravir treatment in vaccinated, high-risk patients infected with COVID-19, failed to reduce both the rate of hospitalisation and death compared to usual care according to the results of a large, randomised trial by members of the PANORAMIC Trial collaborative group.

It is possible that the early treatment of COVID-19 infected patients with anti-viral agents, might prevent deterioration, speed up recovery and reduce the need for hospital admission. One such anti-viral is molnupiravir (EIDD-2801) and which was originally shown to be a potentially effective clinical candidate with high potential for monotherapy of seasonal and pandemic influenza virus infections.

Nevertheless, early molnupiravir treatment in patients infected with COVID-19 and at least one risk factor for severe illness, was subsequently shown to reduce the risk of hospitalisation or death in unvaccinated adults. But with millions of individuals now vaccinated against COVID-19, it remains uncertain whether molnupiravir treatment is still an effective option in such patients.

There is some evidence that molnupiravir has antiviral activity in vaccinated and unvaccinated individuals infected with a broad range of SARS-CoV-2 variants, although this is not conclusive. As a result, in the present study, researchers set out to establish the effectiveness of molnupiravir in vaccinated, high-risk, community patients at reducing hospital admission or death.

The study included community (i.e., non-hospitalised) patients aged 50 years and older, or 18 years and older with relevant comorbidities and who had COVID-19 symptoms within the previous 5 days, together with a positive PCR or rapid antigen test within the past 7 days. Eligible participants were randomly assigned (1:1) to receive molnupiravir 800 mg twice daily for 5 days plus usual care or usual care alone. The primary outcome was set as all-cause hospitalisation or death within 28 days of randomisation.

Molnupiravir treatment and adverse COVID-19 outcomes

A total of 25,783 individuals with a mean age of 56·6 years (58.5% female) were randomised to molnupiravir (12, 821) or usual care. Additionally, 69% of the whole cohort had comorbidities and 94% had received at least three doses of a COVID-19 vaccine.

Hospitalisations or deaths were recorded in 1% of both groups (adjusted odds ratio, aOR = 1·06, 95% CI 0·81 – 1·41, p = 0.33). Moreover, in subgroup analyses, there were no significant differences when assessed on several factors including the presence/absence of co-morbidities, age (< 65 vs > 65), or among those who were immunocompromised.

Despite no difference in the primary outcome, molnupiravir treatment was associated with a reduction in the median time from randomisation to first recovery (hazard ratio, HR = 1·36, 95% CI 1·32 – 1·40).

The authors concluded that in a highly vaccinated population at high risk of complications from COVID-19, the avoidance of hospitalisation and death was primarily achieved via extensive vaccination. They added that the benefits of molnupiravir in terms of a faster recovery time need to be considered in the context of several other relevant factors including the prevailing disease, burden on health-care services, drug-acquisition cost, social circumstances, cost-effectiveness, and opportunity costs.

Citation
Butler CC et al. Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet 2022.