Alex Nowbar’s research reviews—29 January 2021

Alex Nowbar reviews the latest research from the top medical journals

ACE-inhibitor continuation in covid

There was a time when it was cool to talk about the relation between the virus and the renin-angiotensin-aldosterone system because the virus attaches to the ACE2 receptor on human cells. It was the sort of thing that sounded a bit clever. The actual clever ones were Lopes et al who cracked on with a randomised controlled trial to establish whether continuing or discontinuing ACE-inhibitors and angiotensin-receptor blockers improved outcomes in people admitted to hospital with covid-19. They randomised 659 people in Brazil and assessed days alive and out of hospital at 30 days as the primary outcome. They excluded people with a clinical indication to stop ACEI or ARB treatment e.g. acute kidney injury. They found no difference between the continuing and discontinuing groups.

JAMA. doi:10.1001/jama.2020.25864

Adherence survey on nonpharmacological interventions in covid 

Crane et al looked at changes in adherence to protective behaviours like mask-wearing through the US Coronavirus Tracking Survey. The survey repeatedly surveyed the same group of people between April and November 2020 about various behaviours in the preceding 7 days e.g. have you remained in your residence at all times except for essential activities or exercise, to form an index of non-pharmaceutical intervention adherence. This index started at 70 in early April, plateaued in the high 50s in June, and then in November rose again to 60. Regional differences were also seen across the US: the South, West and Northeast having higher adherence index compared to the Midwest. Things that appear to be harder to adhere to were staying at home, staying 6 feet away from non-household members, and avoiding restaurants. But mask-wearing increased which I supposed we should applaud, but otherwise these data support the sad reality of so called pandemic fatigue.

JAMA. doi:10.1001/jama.2021.0286

Following lung nodules

Incidentally discovered lung nodules are a bane of modern day imaging practice. Are they life-threatening lung cancer, lung cancer that may not cause issues, or not cancer at all— it is hard to tell and yet vitally important! The question is how intensively to pursue investigation. It’s a difficult area to do a randomised study because there is such heterogeneity in patients and their lesions and it would have to be a large study with long follow-up. Instead guidelines are based on biological features and other evidence. Farjah et al’s cohort study of 5057 US patients compared outcomes between 3 levels diagnostic evaluation (guideline-concordant, less-intensive, and more-intensive). Less-intensive evaluation was associated with fewer adverse events, less radiation, lower costs, and there was no association with a more advanced stage at lung cancer diagnosis. Unfortunately, due to the observational nature of this work, we cannot simply dismiss more intense evaluation. There may have been unmeasured factors associated with people at lower risk causing them to be investigated less intensely. I’m not sure how reassured patients can be by this information. The authors wisely conclude, “These findings underscore the need for more evidence on better ways to evaluate lung nodules and to avoid unnecessarily intensive diagnostic evaluations of lung nodules.”

JAMA Intern Med. doi:10.1001/jamainternmed.2020.8250

Oxygen targets in acute hypoxaemic respiratory failure

HOT-ICU is a timely study given the recent scandal with UK hospitals “running out of oxygen” in relation to covid-19. Of course, this study wasn’t done to save on oxygen stores – that’s a separate issue. And this study isn’t about covid-19 either. The study was done to test the hypothesis that a lower oxygen target would be beneficial for patients’ outcomes in acute hypoxaemic respiratory failure on ICU. There has been concern that high partial pressures of oxygen increase mortality. 2928 people in ICUs across seven European countries were randomised to a target of 60mmHg or a target of 90mmHg. There was no difference in 90-day mortality between the two groups. Secondary outcomes that might be expected from oxygen deprivation like myocardial ischaemia, ischemic stroke, or intestinal ischaemia were also similar between the two groups. These data do not support the concept that high partial pressures of oxygen increase mortality. It is useful to be able to fear over-oxygenation a little less (assuming we live in a world without oxygen shortages as we usually do).

NEJM. doi:10.1056/NEJMoa2032510

That old chestnut – the polypill

TIPS-3 involved 5718 people without cardiovascular disease, but at high or intermediate risk (according to the INTERHEART score) in nine countries (primarily India and the Philippines). Participants were randomised to a polypill or placebo, and also to aspirin or placebo, and to vitamin D or placebo in a 2 by 2 by 2 factorial design. This design has the advantage of efficiency by gleaning as much information as possible from one group of patients. This paper looks at the first two treatments; polypill, does it reduce major cardiovascular events, and aspirin, does it reduce cardiovascular death, stroke and myocardial infarction? The polypill contained simvastatin and 3 anti-hypertensives. Unsurprisingly the primary outcome was reduced with polypill plus aspirin, but not with polypill alone, or aspirin alone. There was more hypotension or dizziness in those that received the polypill compared to the respective placebo groups. It is also worth mentioning that many people entered the run-in phase, but then did not take part due to side effects related to the polypill or aspirin. The primary findings will be a slightly disappointing result for polypill proponents, but is a chance to try and improve upon the strategy. 

NEJM. doi:10.1056/NEJMoa2028220

Alex Nowbar is a clinical research fellow at Imperial College London, UK.

Competing interests: None declared