By Susan Mirabal, 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.
Apixaban to Prevent Venous Thromboembolism in Patients with Cancer [1]
Patients with cancer are at an increased risk of venous thromboembolism (VTE). This randomized, placebo-controlled, double-blind clinical trial suggests that prophylactic apixaban can help lower the rate of VTE among patients with cancer at an intermediate-to-high risk (hazard ratio 0.14; 95% CI, 0.05 to 0.42; NNT 17).
After excluding patients with a higher risk of bleeding or with life expectancy less than 6 months, researchers randomized 574 patients to 2.5 mg twice-daily apixaban or placebo for 180 days. These adults had a new cancer diagnosis, or progression of cancer after complete or partial remission, along with Khorana scores greater than or equal to 2, indicative of an intermediate-to-high risk of VTE.
The trial found that the rate of major bleeding episodes (which included gastrointestinal bleeding, hematuria and gynecological bleeding) was significantly higher with apixaban than placebo in the modified intention-to-treat analysis (3.5% and 1.8% respectively; hazard ratio 2.00; 95% CI 1.01-3.95; NNH 59), but the rate was not significant in the analysis of outcomes during treatment (2.1% and 1.1% respectively; hazard ratio, 1.89; 95% CI 0.39-9.24).
It remains crucial that we identify patients who would benefit from thromboprophylaxis, yet given these findings, one cannot help but advocate for further in-depth discussions between patients and providers, regarding the risks and benefits of anticoagulation.
A large, nationwide cohort study in Taiwan assessed whether the CHA2DS2-VASc score, traditionally used to assess stroke risk among patients with atrial fibrillation (AF), may be a useful tool for identifying patients at risk of sudden cardiac death (SCD) and ventricular arrhythmias (VA).
288,181 patients with newly diagnosed AF, and without previous VAs/SCD, were followed until endpoint mortality or 11 years and were risk-stratified according to their CHA2DS2-VASc score. During the follow-up of 1,065,751 person-years, 11,166 patients experienced SCD/VA, with an annual risk of 1.05%. This risk increased from 0.34% for patients with a CHA2DS2-VASc score of 0 to 2.63% for those with a score of 9. Per one-point increase in score, there was a hazard ratio of 1.21; 95% CI 1.20-1.22.
Limitations of this study included likely erroneous classification of AF with aberrancy as VA and a lack of assessment of the use of non-vitamin K antagonist anticoagulants. Still, the CHA2DS2-VASc score remains a convenient scoring system that may be used to predict not only stroke risk, but also the risk of SCD/VA in patients with AF. It’s another win for easy risk assessment available to physicians.
In this randomized, double-blind, prospective, proof-of-mechanism study, 81 asymptomatic patients who were seropositive for both anti-citrullinated peptide antibodies and rheumatoid factor were treated with a single dose of rituximab. They were then followed for a median of 29 months to assess their risk of developing symptomatic rheumatoid arthritis (RA).
Results showed that one infusion of 1 g rituximab delayed the onset of arthritic symptoms by up to 12 months compared to placebo, when looking at the point at which 25% of subjects in both groups became symptomatic. Specifically, treatment with rituximab decreased the risk of developing RA by 55% (HR 0.45, 95% CI 0.154-1.322) at 12 months.
Strict inclusion and exclusion criteria limited the sample size in this study by including only adults 18-80 years of age with positive IgM-RF and anti-CCP antibody, without signs or symptoms of inflammatory arthritis, nor previous treatment with disease-modifying drugs, among other criteria.
These results argue that early intervention may temporarily alter the disease process by delaying B-cell activation and thereby reducing the rate of antigen presentation and activation of T cells. It’s a rather fascinating thought given that RA remains one of the most common rheumatologic diseases, and there is a 40% risk of developing arthritis within two years among asymptomatic, seropositive patients.
Traditionally, lifestyle modification is the mainstay of primary prevention. These results suggest an earlier potential therapeutic window for RA, but we must be cautious not to overzealously treat.
Minicuts:
In a pilot trial, the nutritional supplement spermidine was associated with moderately enhanced memory performance in older patients at risk of developing Alzheimer’s disease. While only a significant improvement in mnemonic discrimination was noted, a study like this serves to open doors to think broadly about treatment options for dementia and Alzheimer’s disease.
This large observational study of patients with end-stage renal disease requiring dialysis compared mortality between the pre- and post-Affordable Care Act (ACA) Medicaid expansion periods. It concluded that, for patients living in a state that expanded Medicaid under the ACA, there was a significant improvement in one-year survival, particularly for black patients and those aged 19 to 44 years. It would be interesting to see what, if any, long-term effects arise as more and more states choose to expand Medicaid coverage.
Using transcranial Doppler ultrasound, this prospective observational cohort study showed that cerebral arterial mean flow velocity (MFV) declines during dialysis. Moreover, MFV decline correlated with intradialytic decline in cognitive, global and executive function and verbal fluency in adult patients on chronic hemodialysis. Patients were found to improve, however, only after renal transplant. While insightful, observational studies such as this cannot prove causality. More importantly, this potential complication of dialysis poses an important ethical question regarding informed consent: When and how should physicians inform patients undergoing dialysis of the likelihood of cognitive decline?
Dr. Susan Mirabal is a 1st year resident in internal medicine, Community Health, NYU Langone – Brooklyn
Peer reviewed by Christian Torres, resident, internal medicine, NYU Langone Health
Image courtesy of Wikimedia Commons
References
- Carrier M, Abou-Nassar K, Mallick R, et al. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med. 2018. DOI 10.1056/NEJMoa1814468. https://www.nejm.org/doi/pdf/10.1056/NEJMoa1814468
- Kuo L, Chao TF, Liu CJ, et al. Usefulness of CHA2DS2-VaSc score to predict risk of sudden cardiac death and ventricular arrhythmia in patients with atrial fibrillation. Am J Cardiol. 2018; 122(12):2049-2054. DOI: 10.1016/j.amjcard.2018.08.056. https://www.ajconline.org/article/S0002-9149(18)31761-2/fulltext
- Gerlag DM, Safy M, Maijer KI, et al. Effects of B-cell Directed Therapy on the Preclinical Stage of Rheumatoid Arthritis: the PRAIRI study. Ann Rheum Dis. 2018;0:1-7. DOI: 10.1136/annrheumdis-2017-212763. https://ard.bmj.com/content/early/2018/12/01/annrheumdis-2017-212763
- Wirth M, Benson G, Schwarz C, et. al. The Effect of Spermidine on Memory Performance in Older Adults at Risk for Dementia. A Randomized Control Trial. Cortex. 2018;19: 181-188. DOI: https://doi.org/10.1016/j.cortex.2018.09.014
- Swaminathan S, Sommers BD, Thorsness R, et al. Association of Medicaid Expansion with 1-Year Mortality Among Patients with End-Stage Renal Disease. JAMA. 2018;320(21):2242-2250. DOI: 10.1001/jama.2018.16504. https://jamanetwork.com/journals/jama/article-abstract/2710505
- Findlay MD, Dawson J, Dickie DA, et al. Investigating the Relationship between Cerebral Blood Flow and Cognitive Function in Hemodialysis Patients. JASN. 2018. DOI: https://doi.org/10.1681/ASN.2018050462.