Research Spotlight

Goyal, A., Lo, K.B., Chatterjee, K., Mathew, R.O., McCullough, P.A., Bangalore, S. and Rangaswami, J. (2020). “Acute coronary syndromes in the peri-operative period after kidney transplantation in United States.” Clin Transplant Sep 18;e14083. [Epub ahead of print.].

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INTRODUCTION: Chronic kidney disease is an independent risk factor for cardiovascular disease. Despite careful preoperative evaluation, there is a risk of acute coronary syndromes after kidney transplant. METHODS: The National Inpatient Sample for the years 2004-2013 was used for this retrospective cohort study. All adult patients undergoing kidney transplantation were identified using the appropriate ICD-9-CM codes. Multivariate logistic regression was used to identify predictors of acute coronary syndromes in the peri-operative period after kidney transplantation. RESULTS: A total of 147 431 kidney transplants were performed from 2004 through 2013 in the United States. The average peri-operative in-hospital mortality was 0.5%. Acute coronary syndrome occurred in 1.3% patients in the peri-operative period. Half of patients with acute coronary syndromes had pre-existing coronary artery disease. The strongest predictors of acute coronary syndromes included older age: 45-64 years. OR 3.28 95% CI (1.85-5.83), ≥65 years. OR 4.84 (2.59-9.05), race: African American, OR 0.66 (0.47-0.93) and pre-existing coronary artery disease OR 3.83 (2.84-5.15). The case fatality rates were 16.9% and 5.3% for STEMI and NSTEMI, respectively. The overall mortality for any ACS event was 7.1%. CONCLUSION: Acute coronary syndrome in the immediate peri-operative period after kidney transplantation is rare but is associated with high rates of mortality.

Lo, K.B., Bhargav, R., Salacup, G., Pelayo, J., Albano, J., McCullough, P.A. and Rangaswami, J. (2020). “Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers and outcomes in patients with COVID-19: a systematic review and meta-analysis.” Expert Rev Cardiovasc Ther Oct 5;1-12. [Epub ahead of print.].

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BACKGROUND: The use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in patients with coronavirus disease 2019 (COVID-19) given their interaction with the angiotensin-converting enzyme-2 (ACE-2) receptor remains controversial. . OBJECTIVE: To investigate the impact of ACEI/ARB on COVID-19 disease severity and mortality through a systematic review and meta-analysis. METHODS: We searched PubMed and CINAHL databases as well as pre-print servers for studies investigating usage of ACEIs/ARBs in patients with COVID-19 compared to a control group of COVID-19 patients without ACEI/ARB use. COVID-19 related severity of disease, and death were identified as end points. Pooled odds ratios (OR) and their 95% confidence intervals (CI) were calculated using random-effects model. RESULTS: 21 studies were included in the meta-analysis. For mortality with ACEI/ARB use, the pooled odds ratio was 1.29 [0.89-1.87] p = 0.18 with heterogeneity of 91%, while the pooled OR for COVID-19 severity was 0.94 [0.59-1.50] p = 0.81 with heterogeneity of 89% (Figure 2). In combining both mortality and severe disease outcomes, the pooled odds ratio was 1.09 [0.80-1.48] p = 0.58 but with heterogeneity of 92%. EXPERT OPINION: Even on pooled analysis of both un-adjusted data, adjusted data(studies with matched controls) and taking into account factors such as risk of bias of studies via meta regression and sensitivity analyses, the results hold true that ACEI/ARB use is not associated with COVID-19 disease severity or mortality. To look for any potential beneficial effects, randomized controlled trials are needed. CONCLUSION: use of ACEI/ARB was not associated with increased mortality or severe COVID-19.

Singhania, N., Bansal, S., Nimmatoori, D.P., Ejaz, A.A., McCullough, P.A. and Singhania, G. (2020). “Current Overview on Hypercoagulability in COVID-19.” Am J Cardiovasc Drugs 20(5): 393-403.

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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought many unique pathologies, such as coagulopathy, prompting a desperate need for effective management. COVID-19-associated coagulopathy (CAC) can cause various thromboembolic complications, especially in critically ill patients. The pathogenesis is likely due to endothelial injury, immobilization, and an increase in circulating prothrombotic factors. Data on treatment are limited, although prophylactic anticoagulation is advised in all hospitalized patients. Herein, we have comprehensively reviewed the current literature available on CAC and highlight the pathogenesis, clinical features, and management of CAC.

Ruocco, G., McCullough, P.A., Tecson, K.M., Mancone, M., De Ferrari, G.M., D’Ascenzo, F., De Rosa, F.G., Paggi, A., Forleo, G., Secco, G.G., Pistis, G., Monticone, S., Vicenzi, M., Rota, I., Blasi, F., Pugliese, F., Fedele, F. and Palazzuoli, A. (2020). “Mortality Risk Assessment Using CHA(2)DS(2)-VASc Scores in Patients Hospitalized With Coronavirus Disease 2019 Infection.” Am J Cardiol Sep 28;S0002-9149(20)31004-3. [Epub ahead of print.].

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Early risk stratification for complications and death related to Coronavirus disease 2019 (COVID-19) infection is needed. Because many patients with COVID-19 who developed acute respiratory distress syndrome have diffuse alveolar inflammatory damage associated with microvessel thrombosis, we aimed to investigate a common clinical tool, the CHA(2)DS(2)-VASc, to aid in the prognostication of outcomes for COVID-19 patients. We analyzed consecutive patients from the multicenter observational CORACLE registry, which contains data of patients hospitalized for COVID-19 infection in 4 regions of Italy, according to data-driven tertiles of CHA(2)DS(2)-VASc score. The primary outcomes were inpatient death and a composite of inpatient death or invasive ventilation. Of 1045 patients in the registry, 864 (82.7%) had data available to calculate CHA(2)DS(2)-VASc score and were included in the analysis. Of these, 167 (19.3%) died, 123 (14.2%) received invasive ventilation, and 249 (28.8%) had the composite outcome. Stratification by CHA(2)DS(2)-VASc tertiles (T1: ≤1; T2: 2 to 3; T3: ≥4) revealed increases in both death (8.1%, 24.3%, 33.3%, respectively; p <0.001) and the composite end point (18.6%, 31.9%, 43.5%, respectively; p <0.001). The odds ratios for mortality and the composite end point for T2 patients versus T1 CHA(2)DS(2)-VASc score were 3.62 (95% CI:2.29 to 5.73,p <0.001) and 2.04 (95% CI:1.42 to 2.93, p <0.001), respectively. Similarly, the odds ratios for mortality and the composite end point for T3 patients versus T1 were 5.65 (95% CI:3.54 to 9.01, p <0.001) and 3.36 (95% CI:2.30 to 4.90,p <0.001), respectively. In conclusion, among Italian patients hospitalized for COVID-19 infection, the CHA(2)DS(2)-VASc risk score for thromboembolic events enhanced the ability to achieve risk stratification for complications and death.

McCullough, P.A. (2020). “Favipiravir and the Need for Early Ambulatory Treatment of SARS-CoV2 Infection (COVID-19).” Antimicrob Agents Chemother Sep 23;AAC.02017-20. [Epub ahead of print.].

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It is becoming increasingly clear that SARS-CoV-2 like most human viral infections will require multiple drugs in combination to treat COVID-19 illness. In this issue of the Journal, Doi and colleagues successfully treated patients with early COVID-19 with favipiravir, an oral polymerase inhibitor to rapidly and substantially clear SARS-CoV-2 from nasal secretions irrespective if it was started relatively early or later within the first week of infection. These data support the concept that favipiravir could be paired with at least one more off-target antiviral agent (doxycycline, azithromycin, ivermectin) followed by corticosteroids and antithrombotics to prevent COVID-19 hospitalization and death in those over age 50 an or those with one or more comorbidities. Clinical trials and advanced practice should immediately pivot to combination/sequential drug therapy for ambulatory COVID-19 illness.