By Victoria Gore, MD
Peer Reviewed
With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature. This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature firehose.
Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes [1]
Finerenone is a nonsteroidal, selective mineralocorticoid receptor antagonist that blocks overactivation of the mineralocorticoid receptor in cardiorenal disease. This potentially reduces the inflammation and fibrosis that contribute to kidney and heart disease in type 2 diabetes mellitus [2].
Bakris et al conducted a double-blind, multi-center, randomized, placebo-controlled trial examining finerenone. They recruited 5734 patients with CKD and type 2 diabetes who were already on a maximally tolerated ACEI or ARB. The primary outcome was a composite of kidney failure, a sustained decrease in GFR (more than 40% from baseline), and death from kidney-related causes. The secondary outcome was cardiovascular events. Researchers found the primary outcome occurred significantly less with finerenone than placebo, with a hazard ratio of 0.82 (95% CI 0.73-0.93; p=0.001). The number needed to treat and prevent one primary outcome event was 29 (95% CI 16 to 166). Patients in the finerenone group also had a significantly lower risk of cardiovascular events, with a hazard ratio of 0.86 (95% CI 0.75 to 0.99; p=0.03). Hyperkalemia-related events were more frequent with finerenone, and more frequently led to stopping the trial regimen with finerenone (2.3%) vs placebo (0.9%).
The reported magnitude of benefit in slowing kidney disease progression is less than that reported with SGLT2 inhibitors [3]. Nonetheless, the addition of finerenone as a way to decrease mineralocorticoid receptor activity in patients with CKD and diabetes remains promising.
Association of Physical Activity Intensity With Mortality [4]
We have all counseled our patients on the 2018 Physical Activity Guidelines for America, which recommends 150-300 minutes of moderate exercise per week, or 75-100 minutes of vigorous exercise [5]. The question remains, though, whether performing more intense physical activity confers more benefit.
This study took data from the annual National Health Interview Survey from 1997 to 2013. Participants self-reported on their lifestyles, including how often they exercised, and how much of it was vigorous (defined as heavy sweating or a large increase in heart rate or breathing) or moderate (light sweating, mild increase in heart rate or breathing). The study took a group of 403,681 participants without cardiovascular disease, stroke or cancer and looked at all-cause mortality. They found that for the same amount of total physical activity, a greater proportion of vigorous physical activity was associated with lower all-cause mortality. Compared with participants who did 0% vigorous physical activity, participants with >50% and <75% vigorous physical activity had 17% lower all-cause mortality (HR, 0.83; 95% CI 0.78-0.88). This effect was also present after adjusting for the total amount of time spent on physical activity.
Notably, a potential confounder is diet, for which the researchers did not fully control. This study still helps us answer an important question for our patients. Though most of the health benefit of exercise can be reaped through moderate physical activity, increasing the proportion of vigorous physical activity is associated with additional benefits.
Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results [6]
In March 2020, the World Health Organization began the Solidarity trial, a large, open-label randomized trial of patients hospitalized with COVID-19. Four repurposed anti-viral drugs were evaluated: remdesivir, hydroxychloroquine, lopinavir and interferon beta-1a.
Participants were randomly assigned to receive one of the trial drugs or, as a control, the local standard of care without a trial drug. Intention-to-treat analyses examined the primary outcome of in-hospital mortality. Secondary outcomes were initiation of mechanical ventilation and duration of hospitalization. Unfortunately, no trial drug had any significant effect on mortality (each p > 0.10). Deaths occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving the control (rate ratio, 0.95; 95% CI 0.81 to 1.1), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving the control (rate ratio, 1.19; 95% CI 0.89 to 1.59), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving the control (rate ratio, 1.00; 95% CI 0.79 to 1.25), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving the control (rate ratio, 1.16; 95% CI 0.96 to 1.39). Similarly, no trial drug reduced the initiation of ventilation or accelerated discharge from the hospital.
The presence of narrower confidence intervals would be helpful, especially for remdesivir, a drug studied in multiple clinical trials [7]. More pressingly, we need better treatments for COVID-19.
Minicuts:
Effect of Cannabidiol and Δ9-Tetrahydrocannabinol on Driving Performance [8]
This was a crossover, randomized clinical trial of 26 healthy participants who underwent a driving test after vaping THC, CBD, THC/CBD equivalent cannabis or placebo. Drivers were observed to swerve and lane weave more after vaping THC or THC/CBD equivalent cannabis. There were no significant driving differences after vaping CBD cannabis, possibly due to effect size.
Most studies of sex differences after myocardial infarction (MI) focus on mortality. This retrospective cohort study of 45,064 patients with MI found the risk of developing heart failure either in-hospital or after discharge was higher for women compared with men (23% vs 15%) after a STEMI or NSTEMI.
Association of Lumbar Puncture With Spinal Hematoma in Patients With and Without Coagulopathy [10]
This cohort study of 64,730 persons undergoing lumbar puncture found the risk of spinal hematoma after lumbar puncture was 0.20% (95% CI 0.16%-0.24%) in those without coagulopathy vs 0.23% (95% CI 0.15%-0.34%) in those with coagulopathy. Though potentially limited by bias from physicians selectively choosing lower-risk patients, this study provides an estimate of risk that may help inform decision-making.
Dr. Victoria Gore is a third-year resident at NYU Langone Health
Peer reviewed by Christian Torres, MD, editor-in-chief, Clinical Correlations
Image courtesy of Wikimedia Commons
References
- Bakris, George, et al. “Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes.” New England Journal of Medicine, Dec. 2020, doi: 10.1056/NEJMoa2025845.
- Barrera-Chimal, Jonatan, et al. “Mineralocorticoid Receptor Antagonists and Kidney Diseases: Pathophysiological Basis.”Kidney International, ScienceDirect, Aug. 2019, doi:https://doi.org/10.1016/j.kint.2019.02.030.
- Perkovic, Vlado et al. “Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy.” New England Journal of Medicine, 13 June 2019, doi: 10.1056/NEJMoa1811744.
- Wang Yafeng, et al. “Association of Physical Activity Intensity With Mortality: A National Cohort Study of 403 681 US Adults”. JAMA Intern Med. Nov 2020, doi:10.1001/jamainternmed.2020.6331
- Piercy, Katrina et al. “The Physical Activity Guidelines for Americans.”JAMA, Nov. 2018, doi:10.1001/jama.2018.14854.
- WHO Solidarity Trial Consortium. “Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results.” New England Journal of Medicine, Dec. 2020, doi: 10.1056/NEJMoa2023184.
- Beigel, John et al. “Remdesivir for the Treatment of Covid-19 — Final Report.” New England Journal of Medicine, Nov. 2020, doi: 10.1056/NEJMoa2007764.
- Arkell TR, et al. “Effect of Cannabidiol and Δ9-Tetrahydrocannabinol on Driving Performance: A Randomized Clinical Trial.” 2020;324(21):2177–2186. doi:10.1001/jama.2020.21218
- Ezekowitz, Justin et al. “Is There a Sex Gap in Surviving an Acute Coronary Syndrome or Subsequent Development of Heart Failure?” Circulation, Nov. 2020, doi: 10.1161/CIRCULATIONAHA.120.048015.
- Bodilsen, Jacob, and Theis Mariager. “Association of Lumbar Puncture With Spinal Hematoma in Patients With and Without Coagulopathy.” JAMA, Oct. 2020, doi:10.1001/jama.2020.14895.