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2.
Lancet Respir Med ; 2022 Oct 10.
Статья в английский | MEDLINE | ID: covidwho-2062045

Реферат

BACKGROUND: The large number of patients worldwide infected with the SARS-CoV-2 virus has overwhelmed health-care systems globally. The Anti-Coronavirus Therapies (ACT) outpatient trial aimed to evaluate anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin for prevention of disease progression in community patients with COVID-19. METHODS: The ACT outpatient, open-label, 2 × 2 factorial, randomised, controlled trial, was done at 48 clinical sites in 11 countries. Patients in the community aged 30 years and older with symptomatic, laboratory confirmed COVID-19 who were within 7 days of diagnosis and at high risk of disease progression were randomly assigned (1:1) to receive colchicine 0·6 mg twice daily for 3 days and then 0·6 mg once daily for 25 days versus usual care, and in a second (1:1) randomisation to receive aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome was assessed at 45 days in the intention-to-treat population; for the colchicine randomisation it was hospitalisation or death, and for the aspirin randomisation it was major thrombosis, hospitalisation, or death. The ACT outpatient trial is registered at ClinicalTrials.gov, NCT04324463 and is ongoing. FINDINGS: Between Aug 27, 2020, and Feb 10, 2022, 3917 patients were randomly assigned to colchicine or control and to aspirin or control; after excluding 36 patients due to administrative reasons 3881 individuals were included in the analysis (n=1939 colchicine vs n=1942 control; n=1945 aspirin vs 1936 control). Follow-up was more than 99% complete. Overall event rates were 5 (0·1%) of 3881 for major thrombosis, 123 (3·2%) of 3881 for hospitalisation, and 23 (0·6%) of 3881 for death; 66 (3·4%) of 1939 patients allocated to colchicine and 65 (3·3%) of 1942 patients allocated to control experienced hospitalisation or death (hazard ratio [HR] 1·02, 95% CI 0·72-1·43, p=0·93); and 59 (3·0%) of 1945 of patients allocated to aspirin and 73 (3·8%) of 1936 patients allocated to control experienced major thrombosis, hospitalisation, or death (HR 0·80, 95% CI 0·57-1·13, p=0·21). Results for the primary outcome were consistent in all prespecified subgroups, including according to baseline vaccination status, timing of randomisation in relation to onset of symptoms (post-hoc analysis), and timing of enrolment according to the phase of the pandemic (post-hoc analysis). There were more serious adverse events with colchicine than with control (34 patients [1·8%] of 1939 vs 27 [1·4%] of 1942) but none in either group that led to discontinuation of study interventions. There was no increase in serious adverse events with aspirin versus control (31 [1·6%] vs 31 [1·6%]) and none that led to discontinuation of study interventions. INTERPRETATION: The results provide no support for the use of colchicine or aspirin to prevent disease progression or death in outpatients with COVID-19. FUNDING: Canadian Institutes for Health Research, Bayer, Population Health Research Institute, Hamilton Health Sciences Research Institute, and Thistledown Foundation. TRANSLATIONS: For the Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

3.
Lancet Respir Med ; 2022 Oct 10.
Статья в английский | MEDLINE | ID: covidwho-2062044

Реферат

BACKGROUND: COVID-19 disease is accompanied by a dysregulated immune response and hypercoagulability. The Anti-Coronavirus Therapies (ACT) inpatient trial aimed to evaluate anti-inflammatory therapy with colchicine and antithrombotic therapy with the combination of rivaroxaban and aspirin for prevention of disease progression in patients hospitalised with COVID-19. METHODS: The ACT inpatient, open-label, 2 × 2 factorial, randomised, controlled trial was done at 62 clinical centres in 11 countries. Patients aged at least 18 years with symptomatic, laboratory confirmed COVID-19 who were within 72 h of hospitalisation or worsening clinically if already hospitalised were randomly assigned (1:1) to receive colchicine 1·2 mg followed by 0·6 mg 2 h later and then 0·6 mg twice daily for 28 days versus usual care; and in a second (1:1) randomisation, to the combination of rivaroxaban 2·5 mg twice daily plus aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome, assessed at 45 days in the intention-to-treat population, for the colchicine randomisation was the composite of the need for high-flow oxygen, mechanical ventilation, or death; and for the rivaroxaban plus aspirin randomisation was the composite of major thrombosis (myocardial infarction, stroke, acute limb ischaemia, or pulmonary embolism), the need for high-flow oxygen, mechanical ventilation, or death. The trial is registered at www. CLINICALTRIALS: gov, NCT04324463 and is ongoing. FINDINGS: Between Oct 2, 2020, and Feb 10, 2022, at 62 sites in 11 countries, 2749 patients were randomly assigned to colchicine or control and the combination of rivaroxaban and aspirin or to the control. 2611 patients were included in the analysis of colchicine (n=1304) versus control (n=1307); 2119 patients were included in the analysis of rivaroxaban and aspirin (n=1063) versus control (n=1056). Follow-up was more than 98% complete. Overall, 368 (28·2%) of 1304 patients allocated to colchicine and 356 (27·2%) of 1307 allocated to control had a primary outcome (hazard ratio [HR] 1·04, 95% CI 0·90-1·21, p=0·58); and 281 (26·4%) of 1063 patients allocated to the combination of rivaroxaban and aspirin and 300 (28·4%) of 1056 allocated to control had a primary outcome (HR 0·92, 95% CI 0·78-1·09, p=0·32). Results were consistent in subgroups defined by vaccination status, disease severity at baseline, and timing of randomisation in relation to onset of symptoms. There was no increase in the number of patients who had at least one serious adverse event for colchicine versus control groups (87 [6·7%] of 1304 vs 90 [6·9%] of 1307) or with rivaroxaban and aspirin versus control groups (85 [8·0%] vs 91 [8·6%]). Among patients assigned to colchicine, 8 (0·61%) had adverse events that led to discontinuation of study drug, mostly gastrointestinal in nature. 17 (1·6%) patients assigned to the combination of rivaroxaban and aspirin had bleeding compared with seven (0·66%) of those allocated to control (p=0·042); the number of serious bleeding events was two (0·19%) versus six (0·57%), respectively (p=0·18). No patients assigned to rivaroxaban and aspirin had serious adverse events that led to discontinuation of study drug. INTERPRETATION: Among patients hospitalised with COVID-19, neither colchicine nor the combination of rivaroxaban and aspirin prevent disease progression or death. FUNDING: Canadian Institutes for Health Research, Bayer, Population Health Research Institute, Hamilton Health Sciences Research Institute, Thistledown Foundation. TRANSLATIONS: For the Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

4.
Annu Rev Med ; 2022 Sep 21.
Статья в английский | MEDLINE | ID: covidwho-2038362

Реферат

Shortly after the emergence of coronavirus disease 2019 (COVID-19) in late 2019, clinicians rapidly recognized an apparent association between the disease and both arterial and venous thrombotic complications, which was confirmed in epidemiologic studies. Based on these data, hospitals empirically developed and implemented protocols with different strategies for anticoagulation of hospitalized COVID-19 patients. Subsequent randomized controlled trials (RCTs) clarified the role of anticoagulation in patients hospitalized with COVID-19 and recently discharged from the hospital. In this review, we discuss the epidemiology and pathophysiology of thrombosis in patients with COVID-19, observational comparative effectiveness analyses that provided hints of a benefit from anticoagulation, and finally the RCTs that established which patients with COVID-19 benefit from treatment-dose anticoagulation. These RCTs have demonstrated that hospitalized, noncritically ill patients with COVID-19 benefit from treatment-dose anticoagulation, but patients who are hospitalized and critically ill, discharged from the hospital, or not hospitalized do not benefit. Expected final online publication date for the Annual Review of Medicine, Volume 74 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

5.
Kidney360 ; 3(4): 728-733, 2022 04 28.
Статья в английский | MEDLINE | ID: covidwho-1955524

Реферат

The coronavirus disease 2019 pandemic has had an unprecedented effect on health and health care and posed challenges to the conduct of clinical trials.Targeted mitigating strategies, on the basis of early and continued data collection from site surveys, limited disruption to the ASCEND trials.Flexibly allowing hemoglobin assessment at local laboratories to inform randomized treatment dosing was key to limiting the discontinuation of treatment.


Тема - темы
COVID-19 , Clinical Trials as Topic , Pandemics , COVID-19/epidemiology , Data Collection , Humans
6.
J Thromb Haemost ; 20(10): 2226-2236, 2022 10.
Статья в английский | MEDLINE | ID: covidwho-1916260

Реферат

Despite the emergence of high quality randomized trial data with the use of antithrombotic agents to reduce the risk of thromboembolism, end-organ failure, and possibly mortality in patients with coronavirus disease 2019 (COVID-19), questions still remain as to optimal patient selection for these strategies, the use of antithrombotics in outpatient settings and in-hospital settings (including critical care units), thromboprophylaxis in special patient populations, and the management of acute thrombosis in hospitalized COVID-19 patients. In October 2021, the International Society on Thrombosis and Haemostasis (ISTH) formed a multidisciplinary and international panel of content experts, two patient representatives, and a methodologist to develop recommendations on treatment with anticoagulants and antiplatelet agents for COVID-19 patients. The ISTH Guideline panel discussed additional topics to be well suited to a non-Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for Good Practice Statements (GPS) to support good clinical care in the antithrombotic management of COVID-19 patients in various clinical settings. The GPS panel agreed on 17 GPS: 3 in the outpatient (pre-hospital) setting, 12 in the hospital setting both in non-critical care (ward) as well as intensive care unit settings, and 2 in the immediate post-hospital discharge setting based on limited evidence or expert opinion that supports net clinical benefit in enacting the statements provided. The antithrombotic therapies discussed in these GPS should be available in low- and middle-income countries.


Тема - темы
COVID-19 , Fibrinolytic Agents , Anticoagulants/therapeutic use , COVID-19/drug therapy , Fibrinolytic Agents/therapeutic use , Hemostasis , Humans , Platelet Aggregation Inhibitors/therapeutic use , Thrombosis/drug therapy , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control
7.
Lancet Haematol ; 9(8): e594-e604, 2022 Aug.
Статья в английский | MEDLINE | ID: covidwho-1915206

Реферат

BACKGROUND: COVID-19 is associated with inflammation and an increased risk of thromboembolic complications. Prophylactic doses of low-molecular-weight heparin have been used in hospitalised and non-critically ill patients with COVID-19. We aimed to evaluate the efficacy and safety of prophylactic low-molecular-weight heparin (enoxaparin) versus standard of care (no enoxaparin) in at-risk outpatients with COVID-19. METHODS: This open-label, multicentre, randomised, controlled, phase 3b trial (ETHIC) was done at 15 centres in six countries (Belgium, Brazil, India, South Africa, Spain, and the UK). We consecutively enrolled participants aged at least 30 years who had not received a COVID-19 vaccine and had symptomatic, confirmed COVID-19 in the outpatient setting plus at least one risk factor for severe disease. Within 9 days of symptom onset and by use of a web-based random block design (block size either 2 or 4), eligible participants were randomly assigned (1:1) to receive either subcutaneous enoxaparin for 21 days (40 mg once daily if they weighed <100 kg and 40 mg twice daily if they weighed ≥100 kg) or standard of care (without enoxaparin). The primary efficacy endpoint was the composite of all-cause hospitalisation and all-cause mortality at 21 days after randomisation and, in our main analysis, was analysed in the intention-to-treat population, which comprised all patients who were randomly assigned. Safety was also analysed in the intention-to-treat population for our main analysis. This trial is registered with ClinicalTrials.gov, NCT04492254, and is complete. FINDINGS: Following the advice of the Data and Safety Monitoring Board, this study was terminated early due to slow enrolment and a lower-than-expected event rate. Between Oct 27, 2020, and Nov 8, 2021, 230 patients with COVID-19 were assessed for eligibility, of whom 219 were enrolled and randomly assigned to receive standard of care (n=114) or enoxaparin (n=105). 96 (44%) patients were women, 122 (56%) were men, and one patient had missing sex data. 141 (65%) of 218 participants with data on race and ethnicity were White, 60 (28%) were Asian, and 16 (7%) were Black, mixed race, or Arab or Middle Eastern. Median follow-up in both groups was 21 days (IQR 21-21). There was no difference in the composite of all-cause mortality and hospitalisation at 21 days between the enoxaparin group (12 [11%] of 105 patients) and the standard-of-care group (12 [11%] of 114 patients; unadjusted hazard ratio 1·09 [95% CI 0·49-2·43]; log-rank p=0·83). At 21 days, two (2%) of 105 patients in the enoxaparin group (one minor bleed and one bleed of unknown severity) and one (1%) of 114 patients in the standard-of-care group (major abnormal uterine bleeding) had a bleeding event. 22 (21%) patients in the enoxaparin group and 13 (11%) patients in the standard-of-care group had adverse events. The most common adverse event in both groups was COVID-19-related pneumonia (six [6%] patients in the enoxaparin group and five [4%] patients in the standard-of-care group). One patient in the enoxaparin group died and their cause of death was unknown. INTERPRETATION: The ETHIC trial results suggest that prophylaxis with low-molecular-weight heparin had no benefit for at-risk outpatients with COVID-19. Although the trial was terminated early, our data, combined with data from similar studies, provide further insights to inform international guidelines and influence clinical practice. FUNDING: The Thrombosis Research Institute and Sanofi UK.

8.
J Clin Med ; 11(13)2022 Jun 27.
Статья в английский | MEDLINE | ID: covidwho-1911429

Реферат

Cardiovascular comorbidities and immune-response dysregulation are associated with COVID-19 severity. We aimed to explore the key immune cell profile and understand its association with disease progression in 156 patients with hypertension that were hospitalized due to COVID-19. The primary outcome was progression to severe disease. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and immune cell subsets associated with the primary outcome. Obesity; diabetes; oxygen saturation; lung involvement on computed tomography (CT) examination; the C-reactive protein concentration; total lymphocyte count; proportions of CD4+ and CD8+ T cells; CD4/CD8 ratio; CD8+ HLA-DR MFI; and CD8+ NKG2A MFI on admission were all associated with progression to severe COVID-19. This study demonstrated that increased CD8+ NKG2A MFI at hospital admission, in combination with some clinical variables, is associated with a high risk of COVID-19 progression in hypertensive patients. These findings reinforce the hypothesis of the functional exhaustion of T cells with the increased expression of NKG2A in patients with severe COVID-19, elucidating how severe acute respiratory syndrome coronavirus 2 infection may break down the innate antiviral immune response at an early stage of the disease, with future potential therapeutic implications.

9.
CJC Open ; 4(6): 568-576, 2022 Jun.
Статья в английский | MEDLINE | ID: covidwho-1866977

Реферат

Background: Effective treatments for COVID-19 are urgently needed, but conducting randomized trials during the pandemic has been challenging. Methods: The Anti-Coronavirus Therapy (ACT) trials are parallel factorial international trials that aimed to enroll 3500 outpatients and 2500 inpatients with symptomatic COVID-19. The outpatient trial is evaluating colchicine vs usual care, and aspirin vs usual care. The primary outcome for the colchicine randomization is hospitalization or death, and for the aspirin randomization, it is major thrombosis, hospitalization, or death. The inpatient trial is evaluating colchicine vs usual care, and the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily vs usual care. The primary outcome for the colchicine randomization is need for high-flow oxygen, need for mechanical ventilation, or death, and for the rivaroxaban plus aspirin randomization, it is major thrombotic events, need for high-flow oxygen, need for mechanical ventilation, or death. Results: At the completion of enrollment on February 10, 2022, the outpatient trial had enrolled 3917 patients, and the inpatient trial had enrolled 2611 patients. Challenges encountered included lack of preliminary data about the interventions under evaluation, uncertainties related to the expected event rates, delays in regulatory and ethics approvals, and in obtaining study interventions, as well as the changing pattern of the COVID-19 pandemic. Conclusions: The ACT trials will determine the efficacy of anti-inflammatory therapy with colchicine, and antithrombotic therapy with aspirin given alone or in combination with rivaroxaban, across the spectrum of mild, moderate, and severe COVID-19. Lessons learned from the conduct of these trials will inform planning of future trials.


Contexte: Il est urgent de mettre au point des traitements efficaces contre la COVID-19, mais il n'est pas facile de réaliser des essais à répartition aléatoire dans un contexte pandémique. Méthodologie: Les essais internationaux factoriels ACT (Anti-Coronavirus Therapy) avaient un objectif d'inscription de 3 500 patients externes et de 2 500 patients hospitalisés présentant une COVID-19 symptomatique. L'essai mené auprès de patients externes visait à évaluer la colchicine par rapport aux soins habituels, et l'aspirine par rapport aux soins habituels. Le paramètre d'évaluation principal au terme de la répartition aléatoire des patients était l'hospitalisation ou le décès dans le groupe traité par la colchicine, et la thrombose majeure, l'hospitalisation ou le décès dans le groupe traité par l'aspirine. L'essai mené auprès de patients hospitalisés visant à évaluer la colchicine par rapport aux soins habituels, et un traitement associant le rivaroxaban à 2,5 mg deux fois par jour et l'aspirine à 100 mg une fois par jour par rapport aux soins habituels. Le paramètre d'évaluation principal au terme de la répartition aléatoire des patients était le recours à l'oxygénothérapie à haut débit ou à la ventilation mécanique ou le décès dans le groupe traité par la colchicine, et la survenue de manifestations thrombotiques majeures, le recours à l'oxygénothérapie à haut débit ou à la ventilation mécanique ou le décès dans le groupe traité par l'association rivaroxaban-aspirine. Résultats: À la fin de la période d'inscription, le 10 février 2022, 3 917 patients externes et 2 611 patients hospitalisés formaient la population des essais. Certains aspects se sont révélés problématiques, notamment le manque de données préliminaires sur les interventions à évaluer, les incertitudes liées aux taux d'événements prévus, les retards touchant les approbations réglementaires et éthiques et les interventions de recherche, de même que l'évolution de la pandémie de COVID-19. Conclusions: Les essais ACT détermineront l'efficacité du traitement anti-inflammatoire par la colchicine et du traitement antithrombotique par l'aspirine, administrée seule ou en association avec le rivaroxaban, contre la COVID-19 légère, modérée ou sévère. Les leçons tirées de ces essais orienteront la planification d'essais ultérieurs.

10.
Lancet ; 399(10319): 50-59, 2022 01 01.
Статья в английский | MEDLINE | ID: covidwho-1815305

Реферат

BACKGROUND: Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. METHODS: In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684. FINDINGS: From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2-3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12-0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. INTERPRETATION: In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. FUNDING: Bayer.


Тема - темы
Aftercare , Blood Coagulation/drug effects , COVID-19/complications , Factor Xa Inhibitors/pharmacology , Factor Xa Inhibitors/therapeutic use , Rivaroxaban/pharmacology , Rivaroxaban/therapeutic use , Venous Thromboembolism/prevention & control , Adult , Aged , COVID-19/drug therapy , Female , Heparin/administration & dosage , Heparin/therapeutic use , Hospitalization , Humans , Male , Middle Aged , Patient Discharge , Treatment Outcome
11.
Am Heart J ; 249: 76-85, 2022 07.
Статья в английский | MEDLINE | ID: covidwho-1803370

Реферат

BACKGROUND: Screening for atrial fibrillation (AF) is attractive because AF independently raises the risk of ischemic stroke, this risk is largely reversible by long-term oral anticoagulant therapy (OAC), and many patients with AF remain undiagnosed and untreated. Recent trials of one-time brief screening for AF have not produced a significant increase in the proportion of patients diagnosed with AF. Trials of longer-term screening have demonstrated an increase in AF diagnoses, primarily paroxysmal AF. To date, however, no trials have demonstrated that screening for AF results in lower rates of stroke. Clinical practice guidelines conflict in their level of support for screening for AF. METHODS: The GUARD-AF individually randomized trial is designed to test whether screening for AF in individuals age 70 years or greater using a 2-week single-lead electrocardiographic patch monitor can identify patients with undiagnosed AF and lead to treatment with OAC, resulting in a reduced rate of stroke in the screened population. The trial's efficacy end point is hospitalization for stroke (either ischemic or hemorrhagic) and the trial's safety end point is hospitalization for a bleeding event. End points will be ascertained via Medicare claims or electronic health records at 2.5 years after study start. Enrollment is based in primary care practices and the OAC decision for screen-detected cases is left to the patient and their physician. The initial planned target sample size was 52,000, with 26,000 allocated to either screening or to usual care. RESULTS: Trial enrollment was severely hampered by the novel coronavirus disease 2019 (COVID-19) pandemic and stopped at a total enrollment of 11,931 participants. Of 5,965 randomized to the screening arm, 5,713 patients (96%) returned monitors with analyzable results. Incidence of screen-detected and clinically detected AF and associated stroke and bleeding outcomes will be ascertained. CONCLUSIONS: GUARD-AF is the largest AF screening randomized trial using a longer-term patch-based continuous electrocardiographic monitor. The results will contribute important information on the yield of patch-based AF screening, the "burden" of AF detected (percent time in AF, longest episode), and physicians' OAC decisions as a function of AF burden. GUARD-AF's stroke and bleed results will contribute to pooled trial analyses of AF screening, thereby informing future studies and guidelines.


Тема - темы
Atrial Fibrillation , COVID-19 , Stroke , Aged , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Electrocardiography , Hemorrhage/chemically induced , Humans , Medicare , Risk Factors , Stroke/epidemiology , Stroke/etiology , Stroke/prevention & control , United States
12.
Am Heart J ; 249: 86-97, 2022 07.
Статья в английский | MEDLINE | ID: covidwho-1777919

Реферат

BACKGROUND: We explored the effect of discontinuing versus continuing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on clinical outcomes in patients with COVID-19 according to baseline disease severity. METHODS: We randomized 659 patients with a confirmed diagnosis of COVID-19 and classified them as having mild or moderate COVID-19 disease severity at hospital presentation using blood oxygen saturation and lung imaging. The primary outcome was the mean ratio of number of days alive and out of the hospital at 30 days according to disease severity. RESULTS: At presentation, 376 patients (57.1%) had mild and 283 (42.9%) had moderate COVID-19. In patients with mild disease, there was no significant difference in the number of days alive and out of the hospital between ACEI/ARB discontinuation (mean 23.5 [SD 6.3] days) and continuation (mean 23.8 [SD 6.5] days), with a mean ratio of 0.98 (95% CI 0.92-1.04). However, in patients with moderate disease, there were fewer days alive and out of the hospital with ACEI/ARB discontinuation (mean 19.6 [SD 9.5] days) than continuation (mean 21.6 [SD 7.6] days), with a mean ratio of 0.90 (95% CI 0.81-1.00; P-interaction = .01). The impact of discontinuing versus continuing ACEIs/ARBs on days alive and out of hospital through 30 days differed according to baseline COVID-19 disease severity. CONCLUSIONS: Unlike patients with mild disease, patients with moderate disease who continued ACEIs/ARBs had more days alive and out of hospital through 30 days than those who discontinued ACEIs/ARBs. This suggests that ACEIs/ARBs should be continued for patients with moderate COVID-19 disease severity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04364893).


Тема - темы
COVID-19 , Hypertension , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Humans , SARS-CoV-2 , Severity of Illness Index
13.
Lancet Reg Health Am ; 11: 100243, 2022 Jul.
Статья в английский | MEDLINE | ID: covidwho-1768385

Реферат

Background: Previous Randomised controlled trials (RCT) evaluating chloroquine and hydroxychloroquine in non-hospitalised COVID-19 patients have found no significant difference in hospitalisation rates. However, low statistical power precluded definitive answers. Methods: We conducted a multicenter, double-blind, RCT in 56 Brazilian sites. Adults with suspected or confirmed COVID-19 presenting with mild or moderate symptoms with ≤ 07 days prior to enrollment and at least one risk factor for clinical deterioration were randomised (1:1) to receive hydroxychloroquine 400 mg twice a day (BID) in the first day, 400 mg once daily (OD) thereafter for a total of seven days, or matching placebo. The primary outcome was hospitalisation due to COVID-19 at 30 days, which was assessed by an adjudication committee masked to treatment allocation and following the intention-to-treat (ITT) principle. An additional analysis was performed only in participants with SARS-CoV-2 infection confirmed by molecular or serology testing (modified ITT [mITT] analysis). This trial was registered at ClinicalTrials.gov, NCT04466540. Findings: From May 12, 2020 to July 07, 2021, 1372 patients were randomly allocated to hydroxychloroquine or placebo. There was no significant difference in the risk of hospitalisation between hydroxychloroquine and placebo groups (44/689 [6·4%] and 57/683 [8·3%], RR 0·77 [95% CI 0·52-1·12], respectively, p=0·16), and similar results were found in the mITT analysis with 43/478 [9·0%] and 55/471 [11·7%] events, RR 0·77 [95% CI 0·53-1·12)], respectively, p=0·17. To further complement our data, we conducted a meta-analysis which suggested no significant benefit of hydroxychloroquine in reducing hospitalisation among patients with positive testing (69/1222 [5·6%], and 88/1186 [7·4%]; RR 0·77 [95% CI 0·57-1·04]). Interpretation: In outpatients with mild or moderate forms of COVID-19, the use of hydroxychloroquine did not reduce the risk of hospitalisation compared to the placebo control. Our findings do not support the routine use of hydroxychloroquine for treatment of COVID-19 in the outpatient setting. Funding: COALITION COVID-19 Brazil and EMS.

14.
Arq Bras Cardiol ; 118(2): 378-387, 2022 02.
Статья в английский, португальский | MEDLINE | ID: covidwho-1737608

Реферат

BACKGROUND: Despite the need for targeting specific therapeutic options for coronavirus disease 2019 (COVID-19), there has been no evidence of effectiveness of any specific treatment for the outpatient clinical setting. There are few randomized studies evaluating hydroxychloroquine (HCQ) in non-hospitalized patients. These studies indicate no benefit from the use of HCQ, but they assessed different primary outcomes and presented important biases for outcome evaluation. OBJECTIVE: To evaluate if HCQ may prevent hospitalization due to COVID-19 compared to a matching placebo. METHODS: The COVID-19 Outpatient Prevention Evaluation (COPE) study is a pragmatic, randomized, double-blind, placebo-controlled clinical trial evaluating the use of HCQ (800 mg on day 1 and 400 mg from day 2 to day 7) or matching placebo for the prevention of hospitalization due to COVID-19 in early non-hospitalized confirmed or suspected cases. Inclusion criteria are adults (≥ 18 years) seeking medical care with mild symptoms of COVID-19, with randomization ≤ 7 days after symptom onset, without indication of hospitalization at study screening, and with at least one risk factor for complication (> 65 years; hypertension; diabetes mellitus; asthma; chronic obstructive pulmonary disease or other chronic lung diseases; smoking; immunosuppression; or obesity). All hypothesis tests will be two-sided. A p-value < 0.05 will be considered statistically significant in all analyses. Clinicaltrials.gov: NCT04466540. RESULTS: Clinical outcomes will be centrally adjudicated by an independent clinical event committee blinded to the assigned treatment groups. The primary efficacy endpoint will be assessed following the intention-to-treat principle. CONCLUSION: This study has the potential to reliably answer the scientific question of HCQ use in outpatients with COVID-19. To our knowledge, this is the largest trial evaluating HCQ in non-hospitalized individuals with COVID-19.


FUNDAMENTO: Apesar da necessidade de opções terapêuticas específicas para a doença do coronavírus 2019 (covid-19), ainda não há evidências da eficácia de tratamentos específicos no contexto ambulatorial. Há poucos estudos randomizados que avaliam a hidroxicloroquina (HCQ) em pacientes não hospitalizados. Esses estudos não indicaram benefício com o uso da HCQ; no entanto, avaliaram desfechos primários diferentes e apresentaram vieses importantes na avaliação dos desfechos. OBJETIVO: Investigar se a HCQ possui o potencial de prevenir hospitalizações por covid-19 quando comparada ao placebo correspondente. MÉTODOS: O estudo COVID-19 Outpatient Prevention Evaluation (COPE) é um ensaio clínico randomizado, pragmático, duplo-cego, multicêntrico e controlado por placebo que avalia o uso da HCQ (800 mg no dia 1 e 400 mg do dia 2 ao dia 7) ou placebo correspondente na prevenção de hospitalizações por covid-19 em casos precoces confirmados ou suspeitos de pacientes não hospitalizados. Os critérios de inclusão são adultos (≥ 18 anos) que procuraram atendimento médico com sintomas leves de covid-19, com randomização ≤ 7 dias após o início dos sintomas, sem indicação de hospitalização na triagem do estudo e com pelo menos um fator de risco para complicações (> 65 anos, hipertensão, diabetes melito, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). Todos os testes de hipótese serão bilaterais. Um valor de p < 0,05 será considerado estatisticamente significativo em todas as análises. Clinicaltrials.gov: NCT04466540. RESULTADOS: Os desfechos clínicos serão avaliados centralmente por um comitê de eventos clínicos independente cegado para a alocação dos grupos de tratamento. O desfecho primário de eficácia será avaliado de acordo com o princípio da intenção de tratar. CONCLUSÃO: Este estudo apresenta o potencial de responder de forma confiável a questão científica do uso da HCQ em pacientes ambulatoriais com covid-19. Do nosso conhecimento, este é o maior estudo avaliando o uso de HCQ em indivíduos com covid-19 não hospitalizados.


Тема - темы
COVID-19 , Hydroxychloroquine , Adult , COVID-19/drug therapy , Humans , Hydroxychloroquine/adverse effects , Hydroxychloroquine/therapeutic use , Outpatients , SARS-CoV-2 , Treatment Outcome
15.
Arquivos brasileiros de cardiologia ; 118(2):378-387, 2022.
Статья в португальский | EuropePMC | ID: covidwho-1710542

Реферат

Resumo Fundamento Apesar da necessidade de opções terapêuticas específicas para a doença do coronavírus 2019 (covid-19), ainda não há evidências da eficácia de tratamentos específicos no contexto ambulatorial. Há poucos estudos randomizados que avaliam a hidroxicloroquina (HCQ) em pacientes não hospitalizados. Esses estudos não indicaram benefício com o uso da HCQ;no entanto, avaliaram desfechos primários diferentes e apresentaram vieses importantes na avaliação dos desfechos. Objetivo Investigar se a HCQ possui o potencial de prevenir hospitalizações por covid-19 quando comparada ao placebo correspondente. Métodos O estudo COVID-19 Outpatient Prevention Evaluation (COPE) é um ensaio clínico randomizado, pragmático, duplo-cego, multicêntrico e controlado por placebo que avalia o uso da HCQ (800 mg no dia 1 e 400 mg do dia 2 ao dia 7) ou placebo correspondente na prevenção de hospitalizações por covid-19 em casos precoces confirmados ou suspeitos de pacientes não hospitalizados. Os critérios de inclusão são adultos (≥ 18 anos) que procuraram atendimento médico com sintomas leves de covid-19, com randomização ≤ 7 dias após o início dos sintomas, sem indicação de hospitalização na triagem do estudo e com pelo menos um fator de risco para complicações (> 65 anos, hipertensão, diabetes melito, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). Todos os testes de hipótese serão bilaterais. Um valor de p < 0,05 será considerado estatisticamente significativo em todas as análises. Clinicaltrials.gov: NCT04466540. Resultados Os desfechos clínicos serão avaliados centralmente por um comitê de eventos clínicos independente cegado para a alocação dos grupos de tratamento. O desfecho primário de eficácia será avaliado de acordo com o princípio da intenção de tratar. Conclusão Este estudo apresenta o potencial de responder de forma confiável a questão científica do uso da HCQ em pacientes ambulatoriais com covid-19. Do nosso conhecimento, este é o maior estudo avaliando o uso de HCQ em indivíduos com covid-19 não hospitalizados.

16.
Am Heart J ; 247: 76-89, 2022 05.
Статья в английский | MEDLINE | ID: covidwho-1670114

Реферат

BACKGROUND: Renin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection coronavirus disease 2019 (COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes. METHODS: The RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]) and the intention-to-treat principle. RESULTS: Overall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5); P = .60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 [95% CI 1.06-2.62]; P = .027); RAASi discontinuation increased brain natriuretic peptide levels (% change from baseline: +16.7% vs -27.5%; P = .024) and the incidence of acute heart failure (33% vs 4.2%, P = .016). CONCLUSION: RAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased brain natriuretic peptide levels and may increase risk of acute heart failure; where possible, RAASi should be continued.


Тема - темы
COVID-19 , Heart Failure , Adult , Aged , Aldosterone , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/therapeutic use , Female , Heart Failure/drug therapy , Hospitals , Humans , Natriuretic Peptide, Brain , Renin-Angiotensin System
17.
JAMA ; 327(3): 227-236, 2022 01 18.
Статья в английский | MEDLINE | ID: covidwho-1669289

Реферат

Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.


Тема - темы
Anticoagulants/administration & dosage , COVID-19/drug therapy , Heparin/administration & dosage , Inpatients , Purinergic P2Y Receptor Antagonists/administration & dosage , Aged , Aged, 80 and over , Anticoagulants/adverse effects , COVID-19/blood , COVID-19/mortality , Clopidogrel/administration & dosage , Clopidogrel/adverse effects , Comorbidity , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Hemorrhage/chemically induced , Heparin/adverse effects , Hospital Mortality , Humans , Male , Medical Futility , Middle Aged , Outcome Assessment, Health Care , Oxygen Inhalation Therapy/statistics & numerical data , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Purinergic P2Y Receptor Antagonists/adverse effects , Receptors, Purinergic P2Y12 , Respiration, Artificial/statistics & numerical data , Thrombosis/epidemiology , Ticagrelor/administration & dosage , Ticagrelor/adverse effects , Time Factors , Treatment Outcome
18.
JAMA ; 327(4): 331-340, 2022 01 25.
Статья в английский | MEDLINE | ID: covidwho-1649976

Реферат

Importance: Vaccination against COVID-19 provides clear public health benefits, but vaccination also carries potential risks. The risks and outcomes of myocarditis after COVID-19 vaccination are unclear. Objective: To describe reports of myocarditis and the reporting rates after mRNA-based COVID-19 vaccination in the US. Design, Setting, and Participants: Descriptive study of reports of myocarditis to the Vaccine Adverse Event Reporting System (VAERS) that occurred after mRNA-based COVID-19 vaccine administration between December 2020 and August 2021 in 192 405 448 individuals older than 12 years of age in the US; data were processed by VAERS as of September 30, 2021. Exposures: Vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna). Main Outcomes and Measures: Reports of myocarditis to VAERS were adjudicated and summarized for all age groups. Crude reporting rates were calculated across age and sex strata. Expected rates of myocarditis by age and sex were calculated using 2017-2019 claims data. For persons younger than 30 years of age, medical record reviews and clinician interviews were conducted to describe clinical presentation, diagnostic test results, treatment, and early outcomes. Results: Among 192 405 448 persons receiving a total of 354 100 845 mRNA-based COVID-19 vaccines during the study period, there were 1991 reports of myocarditis to VAERS and 1626 of these reports met the case definition of myocarditis. Of those with myocarditis, the median age was 21 years (IQR, 16-31 years) and the median time to symptom onset was 2 days (IQR, 1-3 days). Males comprised 82% of the myocarditis cases for whom sex was reported. The crude reporting rates for cases of myocarditis within 7 days after COVID-19 vaccination exceeded the expected rates of myocarditis across multiple age and sex strata. The rates of myocarditis were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). There were 826 cases of myocarditis among those younger than 30 years of age who had detailed clinical information available; of these cases, 792 of 809 (98%) had elevated troponin levels, 569 of 794 (72%) had abnormal electrocardiogram results, and 223 of 312 (72%) had abnormal cardiac magnetic resonance imaging results. Approximately 96% of persons (784/813) were hospitalized and 87% (577/661) of these had resolution of presenting symptoms by hospital discharge. The most common treatment was nonsteroidal anti-inflammatory drugs (589/676; 87%). Conclusions and Relevance: Based on passive surveillance reporting in the US, the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata and was highest after the second vaccination dose in adolescent males and young men. This risk should be considered in the context of the benefits of COVID-19 vaccination.


Тема - темы
2019-nCoV Vaccine mRNA-1273/adverse effects , BNT162 Vaccine/adverse effects , Myocarditis/etiology , Adolescent , Adult , Age Distribution , COVID-19 Vaccines/adverse effects , Female , Humans , Immunization, Secondary/adverse effects , Male , Myocarditis/epidemiology , Risk Factors , Sex Distribution , United States/epidemiology , Young Adult
19.
N Engl J Med ; 385(25): 2325-2335, 2021 12 16.
Статья в английский | MEDLINE | ID: covidwho-1575626

Реферат

BACKGROUND: Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHIs) are as effective as erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels. METHODS: In this randomized, open-label, phase 3 trial, we assigned patients with CKD who were undergoing dialysis and who had a hemoglobin level of 8.0 to 11.5 g per deciliter to receive an oral HIF-PHI (daprodustat) or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). The two primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 (noninferiority margin, -0.75 g per deciliter) and the first occurrence of a major adverse cardiovascular event (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), with a noninferiority margin of 1.25. RESULTS: A total of 2964 patients underwent randomization. The mean (±SD) baseline hemoglobin level was 10.4±1.0 g per deciliter overall. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.28±0.02 g per deciliter in the daprodustat group and 0.10±0.02 g per deciliter in the ESA group (difference, 0.18 g per deciliter; 95% confidence interval [CI], 0.12 to 0.24), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 2.5 years, a major adverse cardiovascular event occurred in 374 of 1487 patients (25.2%) in the daprodustat group and in 394 of 1477 (26.7%) in the ESA group (hazard ratio, 0.93; 95% CI, 0.81 to 1.07), which also met the prespecified noninferiority margin for daprodustat. The percentages of patients with other adverse events were similar in the two groups. CONCLUSIONS: Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-D ClinicalTrials.gov number, NCT02879305.).


Тема - темы
Anemia/drug therapy , Barbiturates/therapeutic use , Darbepoetin alfa/therapeutic use , Epoetin Alfa/therapeutic use , Glycine/analogs & derivatives , Hematinics/therapeutic use , Renal Dialysis , Renal Insufficiency, Chronic/complications , Aged , Anemia/etiology , Barbiturates/adverse effects , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Darbepoetin alfa/adverse effects , Epoetin Alfa/adverse effects , Female , Glycine/adverse effects , Glycine/therapeutic use , Hematinics/adverse effects , Hemoglobins/analysis , Humans , Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & inhibitors , Intention to Treat Analysis , Male , Middle Aged , Myocardial Infarction/epidemiology , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/therapy , Stroke/epidemiology
20.
N Engl J Med ; 385(25): 2313-2324, 2021 12 16.
Статья в английский | MEDLINE | ID: covidwho-1575625

Реферат

BACKGROUND: Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. In patients with chronic kidney disease (CKD) who are not undergoing dialysis, the efficacy and safety of daprodustat, as compared with the conventional erythropoiesis-stimulating agent darbepoetin alfa, are unknown. METHODS: In this randomized, open-label, phase 3 trial with blinded adjudication of cardiovascular outcomes, we compared daprodustat with darbepoetin alfa for the treatment of anemia in patients with CKD who were not undergoing dialysis. The primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 and the first occurrence of a major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke). RESULTS: Overall, 3872 patients were randomly assigned to receive daprodustat or darbepoetin alfa. The mean (±SD) baseline hemoglobin levels were similar in the two groups. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.74±0.02 g per deciliter in the daprodustat group and 0.66±0.02 g per deciliter in the darbepoetin alfa group (difference, 0.08 g per deciliter; 95% confidence interval [CI], 0.03 to 0.13), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 1.9 years, a first MACE occurred in 378 of 1937 patients (19.5%) in the daprodustat group and in 371 of 1935 patients (19.2%) in the darbepoetin alfa group (hazard ratio, 1.03; 95% CI, 0.89 to 1.19), which met the prespecified noninferiority margin of 1.25. The percentages of patients with adverse events were similar in the two groups. CONCLUSIONS: Among patients with CKD and anemia who were not undergoing dialysis, daprodustat was noninferior to darbepoetin alfa with respect to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-ND ClinicalTrials.gov number, NCT02876835.).


Тема - темы
Anemia/drug therapy , Barbiturates/therapeutic use , Darbepoetin alfa/therapeutic use , Glycine/analogs & derivatives , Hematinics/therapeutic use , Renal Insufficiency, Chronic/complications , Aged , Anemia/etiology , Barbiturates/adverse effects , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Darbepoetin alfa/adverse effects , Female , Glycine/adverse effects , Glycine/therapeutic use , Hematinics/adverse effects , Hemoglobins/analysis , Humans , Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & inhibitors , Intention to Treat Analysis , Male , Middle Aged , Myocardial Infarction/epidemiology , Renal Insufficiency, Chronic/blood , Stroke/epidemiology
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