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1.
N Engl J Med ; 384(17): 1601-1612, 2021 04 29.
Article in English | MEDLINE | ID: mdl-33913638

ABSTRACT

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, a class of compounds that stimulate endogenous erythropoietin production. METHODS: We conducted two randomized, open-label, noninferiority phase 3 trials to evaluate the safety and efficacy of vadadustat, as compared with darbepoetin alfa, in patients with anemia and incident or prevalent dialysis-dependent chronic kidney disease (DD-CKD). The primary safety end point, assessed in a time-to-event analysis, was the first occurrence of a major adverse cardiovascular event (MACE, a composite of death from any cause, a nonfatal myocardial infarction, or a nonfatal stroke), pooled across the trials (noninferiority margin, 1.25). A key secondary safety end point was the first occurrence of a MACE plus hospitalization for either heart failure or a thromboembolic event. The primary and key secondary efficacy end points were the mean change in hemoglobin from baseline to weeks 24 to 36 and from baseline to weeks 40 to 52, respectively, in each trial (noninferiority margin, -0.75 g per deciliter). RESULTS: A total of 3923 patients were randomly assigned in a 1:1 ratio to receive vadadustat or darbepoetin alfa: 369 in the incident DD-CKD trial and 3554 in the prevalent DD-CKD trial. In the pooled analysis, a first MACE occurred in 355 patients (18.2%) in the vadadustat group and in 377 patients (19.3%) in the darbepoetin alfa group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.11). The mean differences between the groups in the change in hemoglobin concentration were -0.31 g per deciliter (95% CI, -0.53 to -0.10) at weeks 24 to 36 and -0.07 g per deciliter (95% CI, -0.34 to 0.19) at weeks 40 to 52 in the incident DD-CKD trial and -0.17 g per deciliter (95% CI, -0.23 to -0.10) and -0.18 g per deciliter (95% CI, -0.25 to -0.12), respectively, in the prevalent DD-CKD trial. The incidence of serious adverse events in the vadadustat group was 49.7% in the incident DD-CKD trial and 55.0% in the prevalent DD-CKD trial, and the incidences in the darbepoetin alfa group were 56.5% and 58.3%, respectively. CONCLUSIONS: Among patients with anemia and CKD who were undergoing dialysis, vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and correction and maintenance of hemoglobin concentrations. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; INNO2VATE ClinicalTrials.gov numbers, NCT02865850 and NCT02892149.).


Subject(s)
Anemia/drug therapy , Darbepoetin alfa/therapeutic use , Glycine/analogs & derivatives , Hematinics/therapeutic use , Picolinic Acids/therapeutic use , Prolyl-Hydroxylase Inhibitors/therapeutic use , Renal Dialysis/adverse effects , Renal Insufficiency, Chronic/complications , Aged , Anemia/blood , Anemia/etiology , Cardiovascular Diseases/chemically induced , Darbepoetin alfa/adverse effects , Female , Glycine/adverse effects , Glycine/therapeutic use , Hematinics/adverse effects , Hemoglobins/analysis , Humans , Male , Middle Aged , Picolinic Acids/adverse effects , Prolyl-Hydroxylase Inhibitors/adverse effects , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/therapy
2.
N Engl J Med ; 384(17): 1589-1600, 2021 04 29.
Article in English | MEDLINE | ID: mdl-33913637

ABSTRACT

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate erythropoietin and red-cell production. METHODS: In two phase 3, randomized, open-label, active-controlled, noninferiority trials, we compared vadadustat with the erythropoiesis-stimulating agent (ESA) darbepoetin alfa in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) not previously treated with an ESA who had a hemoglobin concentration of less than 10 g per deciliter and in patients with ESA-treated NDD-CKD and a hemoglobin concentration of 8 to 11 g per deciliter (in the United States) or 9 to 12 g per deciliter (in other countries). The primary safety end point, assessed in a time-to-event analysis, was the first major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), pooled across the two trials. Secondary safety end points included expanded MACE (MACE plus hospitalization for either heart failure or a thromboembolic event). The primary and key secondary efficacy end points in each trial were the mean change in hemoglobin concentration from baseline during two evaluation periods: weeks 24 through 36 and weeks 40 through 52. RESULTS: A total of 1751 patients with ESA-untreated NDD-CKD and 1725 with ESA-treated NDD-CKD underwent randomization in the two trials. In the pooled analysis, in which 1739 patients received vadadustat and 1732 received darbepoetin alfa, the hazard ratio for MACE was 1.17 (95% confidence interval [CI], 1.01 to 1.36), which did not meet the prespecified noninferiority margin of 1.25. The mean between-group differences in the change in the hemoglobin concentration at weeks 24 through 36 were 0.05 g per deciliter (95% CI, -0.04 to 0.15) in the trial involving ESA-untreated patients and -0.01 g per deciliter (95% CI, -0.09 to 0.07) in the trial involving ESA-treated patients, which met the prespecified noninferiority margin of -0.75 g per deciliter. CONCLUSIONS: Vadadustat, as compared with darbepoetin alfa, met the prespecified noninferiority criterion for hematologic efficacy but not the prespecified noninferiority criterion for cardiovascular safety in patients with NDD-CKD. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; PRO2TECT ClinicalTrials.gov numbers, NCT02648347 and NCT02680574.).


Subject(s)
Anemia/drug therapy , Darbepoetin alfa/therapeutic use , Glycine/analogs & derivatives , Hematinics/therapeutic use , Picolinic Acids/therapeutic use , Prolyl-Hydroxylase Inhibitors/therapeutic use , Renal Insufficiency, Chronic/complications , Administration, Oral , Aged , Anemia/blood , Anemia/etiology , Cardiovascular Diseases/chemically induced , Darbepoetin alfa/adverse effects , Female , Glycine/adverse effects , Glycine/therapeutic use , Hematinics/adverse effects , Hemoglobins/analysis , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Picolinic Acids/adverse effects , Prolyl-Hydroxylase Inhibitors/adverse effects , Renal Insufficiency, Chronic/mortality
3.
Rev Cardiovasc Med ; 24(4): 95, 2023 Apr.
Article in English | MEDLINE | ID: mdl-39076279

ABSTRACT

Patients with acromegaly carry a high risk of developing cardiovascular diseases (CVD). In fact, CVD is the leading cause of mortality among this group of patients. The most frequent cardiovascular complications are heart failure (HF), valvular disease, hypertension, arrhythmias, and coronary artery disease (CAD). The pathophysiology centers on the family of growth hormone (GH). These hormones are involved in normal cardiac development and function; however, excess of insulin-like growth factor-1 (IGF-1), the principally active hormone, can also cause negative effects on the cardiovascular system. HF in acromegaly usually presents with biventricular enlargement and diastolic dysfunction and is strongly associated with the duration of GH excess rather than the degree of hormone elevation. There is a high prevalence of valvular disease affecting aortic and mitral valves among patients with longer disease duration. The development of hypertension in acromegaly may be attributed to the effects of chronic GH/IGF-1 excess on different organ systems, which act via several mechanisms. The aspect of arrhythmia and CAD complicating acromegaly are currently not fully understood.

4.
Rev Cardiovasc Med ; 23(6): 218, 2022 Jun.
Article in English | MEDLINE | ID: mdl-39077163

ABSTRACT

The COVID pandemic has brought many new challenges worldwide, which has impacted on patients with chronic conditions. There is an increasing evidence base suggesting an interaction between chronic heart failure (HF) and COVID-19, and in turn the prognostic impact of co-existence of the two conditions. Patients with existing HF appear more prone to develop severe complications on contracting COVID-19, but the exact prevalence in patients with mild symptoms of COVID-19 not requiring hospital admission is poorly investigated. In addition, hospitalization rates for acute HF over the pandemic period appear reduced compared to previous periods. Several key issues remain rather unaddressed and, importantly, a specific algorithm focused on diagnostic differentiation between HF and acute respiratory distress syndrome, a severe complication of COVID-19, is still lacking. Furthermore, recent data suggests potential interaction existing between HF treatment and some anti-viral anti-inflammatory drugs prescribed during the infection, raising some doubts about a universal treatment strategy for all patients with COVID-19. With this manuscript, we aim to review the current literature in this field in light of growing understanding of COVID-19 in the setting of the HF population, its associated morbidity and mortality burden, and the impact on healthcare systems. We hope that this may stimulate a discussion to guarantee a better, more tailored delivery of care for patients with HF in the setting of concomitant COVID-19 infection.

5.
Circulation ; 142(17): e265-e286, 2020 10 27.
Article in English | MEDLINE | ID: mdl-32981345

ABSTRACT

Chronic kidney disease (CKD) with type 2 diabetes (T2D) is a major public health problem, resulting in significant cardiovascular and kidney adverse outcomes worldwide. Despite the widespread use of standard-of-care therapies for CKD with T2D over the past few decades, rates of progression to end-stage kidney disease remain high with no beneficial impact on its accompanying burden of cardiovascular disease. The advent of the newer classes of antihyperglycemic agents, including SGLT2 (sodium glucose cotransporter 2) inhibitors and GLP-1 (glucagon-like peptide-1) receptor agonists, has changed the landscape of therapeutic options for patients with CKD with T2D, with demonstration of significant reductions in cardiovascular adverse events and progression to end-stage kidney disease. Several potential mechanisms exist through which these beneficial effects are achieved in both drug classes, which may be independent of their antihyperglycemic effects. This scientific statement summarizes the current literature on the cardiorenal protective effects with SGLT2 inhibitors and GLP-1 receptor agonists in patients with CKD and T2D. It reviews potential mechanistic pathways that may drive these benefits and summarizes the literature on adverse effects in patients with CKD and T2D at risk for or with established cardiovascular disease. Last, it provides practical guidance on a proposed collaborative care model bridging cardiologists, nephrologists, endocrinologists, and primary care physicians to facilitate the prompt and appropriate integration of these therapeutic classes in the management of patients with T2D and CKD.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Renal Insufficiency, Chronic/drug therapy , American Heart Association , Humans , Hypoglycemic Agents/pharmacology , United States
6.
Am Heart J ; 235: 1-11, 2021 05.
Article in English | MEDLINE | ID: mdl-33129989

ABSTRACT

Current clinical practice guidelines for anemia management in non-dialysis-dependent chronic kidney disease (NDD-CKD) recommend the use of erythropoiesis-stimulating agents (ESAs) as standard of care. Vadadustat, an investigational oral hypoxia-inducible factor prolyl-hydroxylase inhibitor, stimulates endogenous erythropoietin production. The PRO2TECT program comprises 2 global, Phase 3, randomized, open-label, active-controlled, sponsor-blind clinical trials to evaluate safety and efficacy of vadadustat vs darbepoetin alfa in adult patients with anemia associated with NDD-CKD. Patients recruited into the ESA-untreated NDD-CKD trial (N = 1751) had hemoglobin <10 g/dL and had not received an ESA within 8 weeks prior to inclusion in the study. Patients recruited into the ESA-treated NDD-CKD trial (N = 1725) had hemoglobin between 8 and 11 g/dL (US) or 9 and 12 g/dL (non-US) and were actively treated with an ESA for anemia associated with CKD. Trial periods in both trials include (1) correction/conversion (weeks 0-23); (2) maintenance (weeks 24-52); (3) long-term treatment (week 53 to end of treatment); and (4) safety follow-up (end-of-treatment to 4 weeks later). The primary safety endpoint is time to first adjudicated major adverse cardiovascular event, defined as all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke, pooled across both trials. The primary efficacy endpoint in each trial is change in hemoglobin from baseline to primary evaluation period (weeks 24-36), comparing vadadustat vs darbepoetin alfa treatment groups. Demographics and baseline characteristics are similar among patients in both trials and broadly representative of the NDD-CKD population. These trials will help to evaluate the safety and efficacy of vadadustat for management of anemia associated with NDD-CKD.


Subject(s)
Anemia/drug therapy , Glycine/analogs & derivatives , Picolinic Acids/administration & dosage , Renal Insufficiency, Chronic/complications , Administration, Oral , Aged , Anemia/etiology , Female , Follow-Up Studies , Glycine/administration & dosage , Humans , Male , Middle Aged , Renal Dialysis , Treatment Outcome
7.
Heart Fail Rev ; 26(4): 973-979, 2021 07.
Article in English | MEDLINE | ID: mdl-33405001

ABSTRACT

Observational studies suggest that a heart failure (HF) diagnosis carries a poor prognosis in subjects with severe SARS-CoV2 (COVID-19) infection, but it is unknown whether this association reflects direct myocardial damage due to COVID-19 or the consequence of preexisting cardiac defects and related cardiovascular disease (CVD) risk burden. Although the close relation between CVD and COVID-19 outcomes is well established, contrasting data exists about the occurrence of HF complications during COVID-19 infection. Therefore, a specific algorithm focused on diagnostic differentiation in acute patients distinguishing between acute HF and acute respiratory distress syndrome related to COVID-19 is needed. Further, several concerns exist for the management of patients with an uncertain diagnosis and acute dyspnea, the exact relationship existing between COVID-19 and HF. Therefore, the treatment for subjects with both COVID-19 and HF and which criteria may be defined for domiciliary or hospital management, remain poorly defined. Herein, we describe practices to be adopted in order to address these concerns and avoid further virus spread among patients, l and their familiars involved in such patients' care.


Subject(s)
COVID-19/diagnosis , COVID-19/therapy , Heart Failure/diagnosis , Heart Failure/therapy , COVID-19 Testing , Disease Management , Dyspnea/etiology , Hospitalization , Humans , Myocardium/pathology
10.
Rev Cardiovasc Med ; 22(1): 199-206, 2021 Mar 30.
Article in English | MEDLINE | ID: mdl-33792263

ABSTRACT

There are limited data regarding the use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) in acute heart failure (AHF). The purpose is to determine the patterns of ACEi/ARB use at the time of admission and discharge in relation to invasive hemodynamic data, mortality, and heart failure (HF) readmissions. This is a retrospective single-center study in patients with AHF who underwent right heart catheterization between January 2010 and December 2016. Patients on dialysis, evidence of shock, or incomplete follow up were excluded. Multivariate logistic regression analysis was used to analyze the factors associated with continuation of ACEi/ARB use on discharge and its relation to mortality and HF readmissions. The final sample was 626 patients. Patients on ACEi/ARB on admission were most likely continued on discharge. The most common reasons for stopping ACEi/ARB were worsening renal function (WRF), hypotension, and hyperkalemia. Patients with ACEi/ARB use on admission had a significantly higher systemic vascular resistance (SVR) and mean arterial pressure (MAP), but lower cardiac index (CI). Patients with RA pressures above the median received less ACEi/ARB (P = 0.025) and had significantly higher inpatient mortality (P = 0.048). After multivariate logistic regression, ACEi/ARB use at admission was associated with less inpatient mortality; OR 0.32 95% CI (0.11 to 0.93), and this effect extended to the subgroup of patients with HFpEF. Patients discharged on ACEi/ARB had significantly less 6-month HF readmissions OR 0.69 95% CI (0.48 to 0.98). ACEi/ARB use on admission for AHF was associated with less inpatient mortality including in those with HFpEF.


Subject(s)
Angiotensin Receptor Antagonists , Heart Failure , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Heart Failure/diagnosis , Heart Failure/drug therapy , Humans , Retrospective Studies , Stroke Volume
11.
Nephrol Dial Transplant ; 36(1): 137-150, 2021 01 01.
Article in English | MEDLINE | ID: mdl-32030422

ABSTRACT

BACKGROUND: Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for the treatment of adults with hyperkalaemia. This post hoc analysis of an open-label, single-arm trial (NCT02163499) compared SZC efficacy and safety >12 months among outpatients with hyperkalaemia and Stages 4 and 5 chronic kidney disease (CKD) versus those with Stages 1-3 CKD. METHODS: Adults with serum K+ ≥5.1 mmol/L (measured by point-of-care i-STAT device) received SZC 10 g three times daily for 24-72 h until normokalaemia (i-STAT K+ 3.5-5.0 mmol/L) was achieved [correction phase (CP)], followed by once daily SZC 5 g for ≤12 months [maintenance phase (MP)]. Here, patients were stratified by baseline estimated glomerular filtration rate (eGFR <30 or ≥30 mL/min/1.73 m2). Study endpoints included percent achieving normokalaemia during CP and MP, mean serum K+ and bicarbonate during MP, and adverse events (AEs). RESULTS: Of 751 patients enrolled, 289 (39%), 453 (60%) and 9 (1%) had baseline eGFR values of <30, ≥30 mL/min/1.73 m2 or missing, respectively. During the CP, 82% of patients achieved normokalaemia in both eGFR subgroups within 24 h, and 100 and 95% with baseline eGFR <30 and ≥30 mL/min/1.73 m2, respectively, within 72 h. Corresponding proportions with normokalaemia during the MP were 82 and 90% at Day 365, respectively. Mean serum K+ reduction from baseline during the CP was sustained throughout the MP and serum bicarbonate increased. AEs during the MP were more common in the eGFR <30 ≥30 mL/min/1.73 m2 subgroup. CONCLUSIONS: SZC corrects hyperkalaemia and maintains normokalaemia among outpatients regardless of the CKD stage.


Subject(s)
Biomarkers/blood , Hyperkalemia/drug therapy , Kidney Failure, Chronic/complications , Potassium/blood , Renal Insufficiency, Chronic/complications , Severity of Illness Index , Silicates/therapeutic use , Aged , Female , Humans , Hyperkalemia/blood , Hyperkalemia/etiology , Hyperkalemia/pathology , Male , Middle Aged , Prognosis , Prospective Studies
12.
Nephrol Dial Transplant ; 36(11): 2039-2048, 2021 11 09.
Article in English | MEDLINE | ID: mdl-33188693

ABSTRACT

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are currently the mainstay of treatment for anaemia of chronic kidney disease (CKD). Vadadustat is an investigational oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that stimulates endogenous erythropoietin formation. The INNO2VATE programme comprises two studies designed to evaluate the safety and efficacy of vadadustat versus the ESA darbepoetin alfa in ameliorating anaemia in patients with dialysis-dependent CKD (DD-CKD). Here we describe the trial design along with patient demographics and baseline characteristics. METHODS: Two Phase 3, open-label, sponsor-blind, active-controlled trials enrolled adults with anaemia of CKD who recently initiated dialysis and had limited ESA exposure (incident DD-CKD trial) or were receiving maintenance dialysis with ESA treatment (prevalent DD-CKD trial). Study periods include correction/conversion (Weeks 0-23), maintenance (Weeks 24-52), long-term treatment (Weeks 53 to end of treatment) and safety follow-up. The primary safety endpoint is the time to the first major adverse cardiovascular event and the primary efficacy endpoint is the change in haemoglobin (baseline to Weeks 24-36). RESULTS: A total of 369 and 3554 patients were randomized in the incident DD-CKD and prevalent DD-CKD trials, respectively. Demographics and baseline characteristics were similar among patients in both trials and comparable to those typically observed in DD-CKD. CONCLUSIONS: The two INNO2VATE trials will provide important information on the safety and efficacy of a novel approach for anaemia management in a diverse DD-CKD population. Demographics and baseline characteristics of enrolled patients suggest that study results will be representative for a large proportion of the DD-CKD population.


Subject(s)
Anemia , Glycine/therapeutic use , Hematinics , Picolinic Acids/therapeutic use , Renal Insufficiency, Chronic , Adult , Anemia/drug therapy , Anemia/etiology , Erythropoietin , Glycine/analogs & derivatives , Hematinics/therapeutic use , Hemoglobins/analysis , Humans , Renal Dialysis , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/therapy
13.
Med Sci Monit ; 27: e935379, 2021 Dec 30.
Article in English | MEDLINE | ID: mdl-34966165

ABSTRACT

BACKGROUND This retrospective study aimed to investigate outcomes and hospitalization rates in patients with a confirmed diagnosis of early COVID-19 treated at home with prescribed and non-prescribed treatments. MATERIAL AND METHODS The medical records of a cohort of 158 Italian patients with early COVID-19 treated at home were analyzed. Treatments consisted of indomethacin, low-dose aspirin, omeprazole, and a flavonoid-based food supplement, plus azithromycin, low-molecular-weight heparin, and betamethasone as needed. The association of treatment timeliness and of clinical variables with the duration of symptoms and with the risk of hospitalization was evaluated by logistic regression. RESULTS Patients were divided into 2 groups: group 1 (n=85) was treated at the earliest possible time (<72 h from onset of symptoms), and group 2 (n=73) was treated >72 h after the onset of symptoms. Clinical severity at the beginning of treatment was similar in the 2 groups. In group 1, symptom duration was shorter than in group 2 (median 6.0 days vs 13.0 days, P<0.001) and no hospitalizations occurred, compared with 19.18% hospitalizations in group 2. One patient in group 1 developed chest X-ray alterations and 2 patients experienced an increase in D-dimer levels, compared with 30 and 22 patients, respectively, in group 2. The main factor determining the duration of symptoms and the risk of hospitalization was the delay in starting therapy (P<0.001). CONCLUSIONS This real-world study of patients in the community showed that early diagnosis and early supportive patient management reduced the severity of COVID-19 and reduced the rate of hospitalization.


Subject(s)
COVID-19 Drug Treatment , COVID-19/diagnosis , Hospitalization/statistics & numerical data , Time-to-Treatment/statistics & numerical data , Aged , Aged, 80 and over , Aspirin/therapeutic use , Betamethasone/therapeutic use , Cohort Studies , Dietary Supplements , Early Diagnosis , Female , Flavonoids/therapeutic use , Follow-Up Studies , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Indomethacin/therapeutic use , Italy , Male , Middle Aged , Omeprazole/therapeutic use , Patient Acuity , Retrospective Studies , Risk Assessment , SARS-CoV-2 , Time , Treatment Outcome
14.
Circulation ; 139(16): e840-e878, 2019 04 16.
Article in English | MEDLINE | ID: mdl-30852913

ABSTRACT

Cardiorenal syndrome encompasses a spectrum of disorders involving both the heart and kidneys in which acute or chronic dysfunction in 1 organ may induce acute or chronic dysfunction in the other organ. It represents the confluence of heart-kidney interactions across several interfaces. These include the hemodynamic cross-talk between the failing heart and the response of the kidneys and vice versa, as well as alterations in neurohormonal markers and inflammatory molecular signatures characteristic of its clinical phenotypes. The mission of this scientific statement is to describe the epidemiology and pathogenesis of cardiorenal syndrome in the context of the continuously evolving nature of its clinicopathological description over the past decade. It also describes diagnostic and therapeutic strategies applicable to cardiorenal syndrome, summarizes cardiac-kidney interactions in special populations such as patients with diabetes mellitus and kidney transplant recipients, and emphasizes the role of palliative care in patients with cardiorenal syndrome. Finally, it outlines the need for a cardiorenal education track that will guide future cardiorenal trials and integrate the clinical and research needs of this important field in the future.


Subject(s)
Cardio-Renal Syndrome/epidemiology , Diabetes Mellitus/epidemiology , Graft Rejection/epidemiology , Heart/physiology , Kidney Transplantation , Kidney/physiology , Neurotransmitter Agents/metabolism , American Heart Association , Biomarkers , Cardio-Renal Syndrome/diagnosis , Cardio-Renal Syndrome/therapy , Education, Medical , Expert Testimony , Humans , Prognosis , Translational Research, Biomedical , United States/epidemiology
15.
Antimicrob Agents Chemother ; 64(12)2020 11 17.
Article in English | MEDLINE | ID: mdl-32967849

ABSTRACT

It is becoming increasingly clear that severe acute respiratory syndrome coronavirus 2 (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 describe successful treatment of 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, or ivermectin) followed by corticosteroids and antithrombotics to prevent COVID-19 hospitalization and death in those over age 50 and/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.


Subject(s)
Antiviral Agents , Coronavirus Infections , Pandemics , Pneumonia, Viral , Severe Acute Respiratory Syndrome , Amides , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/drug therapy , Humans , Pneumonia, Viral/drug therapy , Prospective Studies , Pyrazines , SARS-CoV-2 , Severe Acute Respiratory Syndrome/drug therapy
16.
Rev Cardiovasc Med ; 21(1): 9-23, 2020 Mar 30.
Article in English | MEDLINE | ID: mdl-32259900

ABSTRACT

Contrast-induced acute kidney injury (CI-AKI) is a serious complication that can affect outcome and prognosis of patients undergoing percutaneous diagnostic and interventional procedures in catheterization laboratories. There have been advancements in case definition and epidemiology. Additionally strategies have emerged that are positioned to have impact in the catheterization laboratory for patients undergoing cardiovascular procedures. The aim of this review is to provide the state-of-the-art of diagnosis, prevention and management of CI-AKI in interventional cardiology.


Subject(s)
Acute Kidney Injury/chemically induced , Contrast Media/adverse effects , Coronary Angiography/adverse effects , Percutaneous Coronary Intervention/adverse effects , Radiography, Interventional/adverse effects , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Acute Kidney Injury/therapy , Animals , Contrast Media/administration & dosage , Humans , Predictive Value of Tests , Prognosis , Risk Assessment , Risk Factors
17.
Rev Cardiovasc Med ; 21(3): 315-319, 2020 09 30.
Article in English | MEDLINE | ID: mdl-33070537

ABSTRACT

Great attention has been paid to endothelial dysfunction (ED) in coronavirus disease 2019 (COVID-19). There is growing evidence to suggest that the angiotensin converting enzyme 2 receptor (ACE2 receptor) is expressed on endothelial cells (ECs) in the lung, heart, kidney, and intestine, particularly in systemic vessels (small and large arteries, veins, venules, and capillaries). Upon viral infection of ECs by severe acute respiratory syndrome coronarvirus 2 (SARS-CoV-2), ECs become activated and dysfunctional. As a result of endothelial activation and ED, the levels of pro-inflammatory cytokines (interleukin -1, interleukin-6 (IL-6), and tumor necrosis factor-α), chemokines (monocyte chemoattractant protein-1), von Willebrand factor (vWF) antigen, vWF activity, and factor VIII are elevated. Higher levels of acute phase reactants (IL-6, C-reactive protein, and D-dimer) are also associated with SARS-CoV-2 infection. Therefore, it is reasonable to assume that ED contributes to COVID-19-associated vascular inflammation, particularly endotheliitis, in the lung, heart, and kidney, as well as COVID-19-associated coagulopathy, particularly pulmonary fibrinous microthrombi in the alveolar capillaries. Here we present an update on ED-relevant vasculopathy in COVID-19. Further research for ED in COVID-19 patients is warranted to understand therapeutic opportunities.


Subject(s)
Betacoronavirus , Blood Coagulation Disorders/etiology , Coronavirus Infections/complications , Endothelium, Vascular/physiopathology , Pneumonia, Viral/complications , Vascular Diseases/etiology , Vasodilation/physiology , Blood Coagulation Disorders/physiopathology , COVID-19 , Coronavirus Infections/epidemiology , Humans , Inflammation/etiology , Inflammation/physiopathology , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Vascular Diseases/physiopathology
18.
Rev Cardiovasc Med ; 21(3): 339-344, 2020 09 30.
Article in English | MEDLINE | ID: mdl-33070539

ABSTRACT

There is emerging evidence to suggest that vitamin D deficiency is associated with adverse outcomes in COVID-19 patients. Conversely, vitamin D supplementation protects against an initial alveolar diffuse damage of COVID-19 becoming progressively worse. The mechanisms by which vitamin D deficiency exacerbates COVID-19 pneumonia remain poorly understood. In this review we describe the rationale of the putative role of endothelial dysfunction in this event. Herein, we will briefly review (1) anti-inflammatory and anti-thrombotic effects of vitamin D, (2) vitamin D receptor and vitamin D receptor ligand, (3) protective role of vitamin D against endothelial dysfunction, (4) risk of vitamin D deficiency, (5) vitamin D deficiency in association with endothelial dysfunction, (6) the characteristics of vitamin D relevant to COVID-19, (7) the role of vitamin D on innate and adaptive response, (8) biomarkers of endothelial cell activation contributing to cytokine storm, and (9) the bidirectional relationship between inflammation and homeostasis. Finally, we hypothesize that endothelial dysfunction relevant to vitamin D deficiency results from decreased binding of the vitamin D receptor with its ligand on the vascular endothelium and that it may be immune-mediated via increased interferon 1 α. A possible sequence of events may be described as (1) angiotensin II converting enzyme-related initial endothelial injury followed by vitamin D receptor-related endothelial dysfunction, (2) endothelial lesions deteriorating to endothelialitis, coagulopathy and thrombosis, and (3) vascular damage exacerbating pulmonary pathology and making patients with vitamin D deficiency vulnerable to death.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Endothelium, Vascular/physiopathology , Pneumonia, Viral/epidemiology , Vasodilation/physiology , Vitamin D Deficiency/epidemiology , COVID-19 , Comorbidity , Coronavirus Infections/physiopathology , Humans , Pandemics , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Vitamin D Deficiency/physiopathology
19.
Rev Cardiovasc Med ; 21(4): 611-614, 2020 12 30.
Article in English | MEDLINE | ID: mdl-33388006

ABSTRACT

There is an emergency need for early ambulatory treatment of Coronavirus Disease 2019 (COVID-19) in acutely ill patients in an attempt to reduce disease progression and the risks of hospitalization and death. Such management should be applied in high-risk patients age > 50 years or with one or more medical problems including cardiovascular disease. We evaluated a total of 922 outpatients from March to September 2020. All patients underwent contemporary real-time polymerase chain reaction (PCR) assay tests from anterior nasal swab samples. Patients age 50.5 ± 13.7 years (range 12 to 89), 61.6% women, at moderate or high risk for COVID-19 received empiric management via telemedicine. At least two agents with antiviral activity against SARS-CoV-2 (zinc, hydroxychloroquine, ivermectin) and one antibiotic (azithromycin, doxycycline, ceftriaxone) were used along with inhaled budesonide and/or intramuscular dexamethasone consistent with the emergent science on early COVID-19 treatment. For patients with high severity of symptoms, urgent in-clinic administration of albuterol nebulizer, inhaled budesonide, and intravenous volume expansion with supplemental parenteral thiamine 500 mg, magnesium sulfate 4 grams, folic acid 1 gram, vitamin B12 1 mg. A total of 320/922 (34.7%) were treated resulting in 6/320 (1.9%) and 1/320 (0.3%) patients that were hospitalized and died, respectively. We conclude that early ambulatory (not hospitalized, treated at home), multidrug therapy is safe, feasible, and associated with low rates of hospitalization and death. Early treatment should be considered for high-risk patients as an emergency measure while we await randomized trials and guidelines for ambulatory management.


Subject(s)
Ambulatory Care/methods , COVID-19 Drug Treatment , Hydroxychloroquine/therapeutic use , Leprostatic Agents/therapeutic use , Telemedicine/methods , Adolescent , Adult , Aged , Aged, 80 and over , Antirheumatic Agents/therapeutic use , COVID-19/epidemiology , Child , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Treatment Outcome , Young Adult
20.
Rev Cardiovasc Med ; 21(1): 123-127, 2020 Mar 30.
Article in English | MEDLINE | ID: mdl-32259911

ABSTRACT

Infective endocarditis (IE) is a life threatening disease requiring lengthy hospitalizations, complex multidisciplinary management and high health care costs. In this study, we analyzed the National Readmissions' Database (NRD) to identify infective endocarditis cases and the causative organisms, clinical determinants, length of stay, in-hospital mortality, and 30-day hospital readmission rates. The study cohort was derived from Healthcare Cost and Utilization Project's National Readmission Database between 2010-15. We queried the National Readmissions' Database using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic code for infective endocarditis (421.0) and identified a total of 187,438 index admissions. SAS 9.4 (SAS Institute Inc., Cary, NC) was utilized for statistical analyses. A total of 187,438 patients with a primary diagnosis of IE were identified over 6 years (2010-2015). Twenty-four percent (44,151 patients) were readmitted within 30 days. Most common etiologies for readmission included sepsis (14%), acute heart failure (8%), acute kidney injury (6%), intracardiac device infection (5.6%) and recurrence of IE (2.7%). Predictors of increased readmissions included female sex, staphylococcus aureus infection, diabetes, chronic lung disease, chronic liver disease, acute kidney injury, acute heart failure and anemia. In-hospital mortality for the readmission of IE was 13%, and average length of stay during the re-admission was 12 days. IE is associated with high rates of index admission mortality and for 30-day readmissions of which are associated with a substantial risk of death.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Cardiac Surgical Procedures , Endocarditis/therapy , Patient Readmission , Anti-Bacterial Agents/adverse effects , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/mortality , Comorbidity , Databases, Factual , Endocarditis/diagnosis , Endocarditis/microbiology , Endocarditis/mortality , Female , Hospital Mortality , Humans , Length of Stay , Male , Middle Aged , Risk Assessment , Risk Factors , Time Factors , United States
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