Reduction Of Dietary Sodium to Less Than 100 Mmol in Heart Failure (SODIUM-HF): An International, Open-Label, Randomised, Controlled Trial

Ezekowitz JA, Colin-Ramirez E, Ross H, et al. Lancet. 2022 Apr 1:S0140-6736(22)00369-5. [CrossRef] [PubMed]

Dietary restriction of sodium has been a standard of care to prevent fluid overload and adverse outcomes for patients with heart failure. To test this hypothesis, the authors conducted the SODIUM-HF study which is an international, open-label, randomized, controlled trial that enrolled patients with chronic heart failure (New York Heart Association [NYHA] functional class 2-3), and receiving optimally tolerated guideline-directed medical treatment. Patients were randomly assigned to either usual care according to local guidelines or a low sodium diet of less than 100 mmol (ie, <1500 mg/day). The primary outcome was the composite of cardiovascular-related admission to hospital, cardiovascular-related emergency department visit, or all-cause death within 12 months in the intention-to-treat (ITT) population (ie, all randomly assigned patients). 806 patients were enrolled and randomly assigned to a low sodium diet (n=397) or usual care (n=409). There was no statistical difference in mortality, hospitalizations, or emergency room visits (p>0.05 all comparisons). In ambulatory patients with heart failure, a dietary intervention to reduce sodium intake did not reduce clinical events.

Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

REMAP-CAP Writing Committee for the REMAP-CAP Investigators, Bradbury CA, Lawler PR, Stanworth SJ, et al. JAMA. 2022 Mar 22. [CrossRef] [PubMed]

Anticoagulation has been proposed to benefit patients with COVID-19. The authors asked the question, “Does antiplatelet therapy administered to critically ill patients with COVID-19 improve organ support–free days (a composite end point of in-hospital mortality and duration of intensive care unit–based respiratory or cardiovascular support) up to day 21? In this bayesian randomized clinical trial that included 1557 patients, antiplatelet therapy with either aspirin or a P2Y12 inhibitor, compared with no antiplatelet therapy, resulted in a 95.7% posterior probability of futility with regard to the odds of improvement in organ support–free days within 21 days. The authors conclude that among critically ill patients with COVID-19, there was a low likelihood that treatment with an antiplatelet agent provided improvement in organ support–free days within 21 days.

Association Between Dexamethasone Treatment After Hospital Discharge for Patients With COVID-19 Infection and Rates of Hospital Readmission and Mortality

Huang CW, Yu AS, Song H, Park JS, Wu SS, Khang VK, Subject CC, Shen E. JAMA Netw Open. 2022 Mar 1;5(3):e221455. [CrossRef] [PubMed]

Current guidelines recommend use of dexamethasone, 6 mg/d, up to 10 days or until discharge for patients hospitalized with COVID-19. Whether patients who received less than 10 days of corticosteroids during hospitalization for COVID-19 benefit from continuing treatment at discharge has not been determined. The authors performed a retrospective cohort study at 15 medical centers within Kaiser Permanente Southern California. The population included adults who received less than 10 days of dexamethasone, 6 mg/d, until discharge during hospitalization for COVID-19 and were discharged alive between May 1 and September 30, 2020. A total of 1164 patients with a median age of 55 (IQR, 44-66) years were identified. Most patients were of Hispanic ethnicity (822 [70.6%]) and male (674 [57.9%]) and required oxygen support during hospitalization (1048 [90.0%]). Of the 1164 patients, 692 (59.5%) continued dexamethasone, 6 mg/d, at discharge. The adjusted odds ratio (OR) for readmissions or mortality within 14 days was 0.87 (95% CI, 0.58-1.30) for patients who continued dexamethasone therapy at discharge compared with those who did not. This finding suggests that dexamethasone should not be routinely prescribed beyond discharge for individuals with COVID-19.

Aspirin Use Is Associated with Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients with Coronavirus Disease 2019

Chow JH, Khanna AK, Kethireddy S, et al. Anesth Analg. 2021 Apr 1;132(4):930-941. [CrossRef] [PubMed]

Coronavirus disease-2019 (COVID-19) is associated with hypercoagulability and increased thrombotic risk in critically ill patients. The authors conducted a retrospective, observational cohort study of adult patients admitted with COVID-19 to multiple hospitals in the United States between March 2020 and July 2020 was performed. The primary outcome was the need for mechanical ventilation. Secondary outcomes were ICU admission and in-hospital mortality. Adjusted hazard ratios (HRs) for study outcomes were calculated using Cox-proportional hazards models after adjustment for the effects of demographics and comorbid conditions. Four hundred twelve patients were included in the study. Three hundred fourteen patients (76.3%) did not receive aspirin, while 98 patients (23.7%) received aspirin within 24 hours of admission or 7 days before admission. Aspirin use had a crude association with less mechanical ventilation (35.7% aspirin versus 48.4% nonaspirin, P = .03) and ICU admission (38.8% aspirin versus 51.0% nonaspirin, P = .04), but no crude association with in-hospital mortality (26.5% aspirin versus 23.2% nonaspirin, P = .51). After adjusting for 8 confounding variables, aspirin use was independently associated with decreased risk of mechanical ventilation (adjusted HR, 0.56, 95% confidence interval [CI], 0.37-0.85, P = .007), ICU admission (adjusted HR, 0.57, 95% CI, 0.38-0.85, P = .005), and in-hospital mortality (adjusted HR, 0.53, 95% CI, 0.31-0.90, P = .02). There were no differences in major bleeding (P = .69) or overt thrombosis (P = .82) between aspirin users and nonaspirin users. A sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients.

Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants

Oskotsky T, Maric I, Tang A, Oskotsky B, Wong RJ, Aghaeepour N, Sirota M, Stevenson DK. JAMA Netw Open. 2021 Nov 1;4(11):e2133090. [CrossRef] [PubMed]

Importance: Antidepressant use may be associated with reduced levels of several proinflammatory cytokines suggested to be involved with the development of severe COVID-19. An association between the use of selective serotonin reuptake inhibitors (SSRIs)—specifically fluoxetine hydrochloride and fluvoxamine maleate—with decreased mortality among patients with COVID-19 has been reported in recent studies; however, these studies had limited power due to their small size.

Objective: The authors investigated the association of SSRIs with outcomes in patients with COVID-19 by analyzing electronic health records (EHRs).

Design, setting, and participants: This retrospective cohort study used propensity score matching by demographic characteristics, comorbidities, and medication indication to compare SSRI-treated patients with matched control patients not treated with SSRIs within a large EHR database representing a diverse population of 83 584 patients diagnosed with COVID-19 from January to September 2020 and with a duration of follow-up of as long as 8 months in 87 health care centers across the US. A total of 3401 adult patients with COVID-19 prescribed SSRIs were identified. When compared with matched untreated control patients, relative risk (RR) of mortality was reduced among patients prescribed any SSRI (497 of 3401 [14.6%] vs 1130 of 6802 [16.6%]; RR, 0.92 [95% CI, 0.85-0.99]; adjusted P = .03); fluoxetine (46 of 470 [9.8%] vs 937 of 7050 [13.3%]; RR, 0.72 [95% CI, 0.54-0.97]; adjusted P = .03); and fluoxetine or fluvoxamine (48 of 481 [10.0%] vs 956 of 7215 [13.3%]; RR, 0.74 [95% CI, 0.55-0.99]; adjusted P = .04). The association between receiving any SSRI that is not fluoxetine or fluvoxamine and risk of death was not statistically significant (447 of 2898 [15.4%] vs 1474 of 8694 [17.0%]; RR, 0.92 [95% CI, 0.84-1.00]; adjusted P = .06).

Conclusions and Relevance:  These results support evidence that SSRIs may be associated with reduced severity of COVID-19 reflected in the reduced RR of mortality. Further research and randomized clinical trials are needed to elucidate the effect of SSRIs generally, or more specifically of fluoxetine and fluvoxamine, on the severity of COVID-19 outcomes.