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1.
Lancet ; 2022 Nov 04.
Article in English | MEDLINE | ID: covidwho-2096175

ABSTRACT

BACKGROUND: For patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric carboxymaltose administration improves quality of life and exercise capacity in the short-term and reduces hospital admissions for heart failure up to 1 year. We aimed to evaluate the longer-term effects of intravenous ferric derisomaltose on cardiovascular events in patients with heart failure. METHODS: IRONMAN was a prospective, randomised, open-label, blinded-endpoint trial done at 70 hospitals in the UK. Patients aged 18 years or older with heart failure (left ventricular ejection fraction ≤45%) and transferrin saturation less than 20% or serum ferritin less than 100 µg/L were eligible. Participants were randomly assigned (1:1) using a web-based system to intravenous ferric derisomaltose or usual care, stratified by recruitment context and trial site. The trial was open label, with masked adjudication of the outcomes. Intravenous ferric derisomaltose dose was determined by patient bodyweight and haemoglobin concentration. The primary outcome was recurrent hospital admissions for heart failure and cardiovascular death, assessed in all validly randomly assigned patients. Safety was assessed in all patients assigned to ferric derisomaltose who received at least one infusion and all patients assigned to usual care. A COVID-19 sensitivity analysis censoring follow-up on Sept 30, 2020, was prespecified. IRONMAN is registered with ClinicalTrials.gov, NCT02642562. FINDINGS: Between Aug 25, 2016, and Oct 15, 2021, 1869 patients were screened for eligibility, of whom 1137 were randomly assigned to receive intravenous ferric derisomaltose (n=569) or usual care (n=568). Median follow-up was 2·7 years (IQR 1·8-3·6). 336 primary endpoints (22·4 per 100 patient-years) occurred in the ferric derisomaltose group and 411 (27·5 per 100 patient-years) occurred in the usual care group (rate ratio [RR] 0·82 [95% CI 0·66 to 1·02]; p=0·070). In the COVID-19 analysis, 210 primary endpoints (22·3 per 100 patient-years) occurred in the ferric derisomaltose group compared with 280 (29·3 per 100 patient-years) in the usual care group (RR 0·76 [95% CI 0·58 to 1·00]; p=0·047). No between-group differences in deaths or hospitalisations due to infections were observed. Fewer patients in the ferric derisomaltose group had cardiac serious adverse events (200 [36%]) than in the usual care group (243 [43%]; difference -7·00% [95% CI -12·69 to -1·32]; p=0·016). INTERPRETATION: For a broad range of patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric derisomaltose administration was associated with a lower risk of hospital admissions for heart failure and cardiovascular death, further supporting the benefit of iron repletion in this population. FUNDING: British Heart Foundation and Pharmacosmos.

2.
Eur Heart J ; 43(27): 2619-2621, 2022 07 14.
Article in English | MEDLINE | ID: covidwho-1831116
3.
Pharmacol Res ; 176: 106053, 2022 02.
Article in English | MEDLINE | ID: covidwho-1586872

ABSTRACT

BACKGROUND: Administration of glucocorticoids might reduce mortality in patients with severe COVID-19 but have adverse cardiometabolic effects. OBJECTIVES: to investigate the effect of systemic administration of glucocorticoids on cardiovascular complications and all-cause mortality in patients hospitalised with respiratory viral infections, including COVID-19, SARS, MERS and influenza. METHODS: We identified randomised trials published prior to July 28th, 2021. The Mantel-Haenszel random effects method and the Hartung and Knapp adjustment were used to obtain pooled estimates of treatment effect with 95% confidence intervals. RESULTS: No randomised trials of glucocorticoids for SARS, MERS or influenza reported relevant outcomes. We included eleven COVID-19 randomised trials (8109 patients). Overall, compared to placebo or standard care, glucocorticoids were not associated with a reduction of in-hospital mortality (p = 0.09). In a pre-specified sub-analysis, in-hospital mortality was reduced by 19% when follow-up was restricted to 14 days from randomisation (5/11 trials, 1329 patients, p = 0.02). With longer follow-up (9/11 trials, 7874 patients), administration of glucocorticoids was associated with a trend to benefit for those requiring mechanical ventilation (RR 0.86; 95% CI 0.57-1.27) but possible harm for those not receiving oxygen at randomisation (RR 1.27; 95% CI 1.00 - 1.61), an effect that was significantly different amongst subgroups (p = 0.0359). Glucocorticoids reduced the risk of worsening renal function by 37% (4/11 trials); reported rate of other cardiovascular complications was low. CONCLUSIONS: Administration of systemic glucocorticoids to patients hospitalised with COVID-19 does not lower mortality overall but may reduce it in those requiring respiratory support and increase it in those who do not.


Subject(s)
COVID-19/drug therapy , Cardiovascular Diseases/etiology , Coronavirus Infections/drug therapy , Glucocorticoids/therapeutic use , Influenza, Human/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , COVID-19/mortality , Cardiovascular Diseases/mortality , Coronavirus Infections/mortality , Hospitalization , Humans , Influenza, Human/mortality , Randomized Controlled Trials as Topic , SARS-CoV-2/drug effects
4.
J Thromb Haemost ; 19(10): 2533-2538, 2021 10.
Article in English | MEDLINE | ID: covidwho-1304122

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a common, life-threatening complication of COVID-19 infection. COVID-19 risk-prediction models include a history of VTE. However, it is unclear whether remote history (>9 years previously) of VTE also confers increased risk of COVID-19. OBJECTIVES: To investigate possible association between VTE and COVID-19 severity, independent of other risk factors. METHODS: Cohort study of UK Biobank participants recruited between 2006 and 2010. Baseline data, including history of VTE, were linked to COVID-19 test results, COVID-19-related hospital admissions, and COVID-19 deaths. The risk of COVID-19 hospitalization or death was compared for participants with a remote history VTE versus without. Poisson regression models were run univariately then adjusted stepwise for sociodemographic, lifestyle, and comorbid covariates. RESULTS: After adjustment for sociodemographic and lifestyle confounders and comorbid conditions, remote history of VTE was associated with nonfatal community (RR 1.61, 95% CI 1.02-2.54, p = .039), nonfatal hospitalized (RR 1.52, 95% CI 1.06-2.17, p = .024) and severe (hospitalized or fatal) (RR 1.40, 95% CI 1.04-1.89, p = .025) COVID-19. Associations with remote history of VTE were stronger among men (severe COVID-19: RR 1.68, 95% CI 1.14-2.42, p = .009) than for women (severe COVID-19: RR 1.07, 95% CI 0.66-1.74, p = .786). CONCLUSION: Our findings support inclusion of remote history of VTE in COVID-19 risk-prediction scores, and consideration of sex-specific risk scores.


Subject(s)
COVID-19 , Venous Thromboembolism , Venous Thrombosis , Aged , Biological Specimen Banks , Cohort Studies , Female , Humans , Male , Risk Factors , SARS-CoV-2 , United Kingdom/epidemiology , Venous Thromboembolism/diagnosis , Venous Thromboembolism/epidemiology
5.
Eur Heart J Qual Care Clin Outcomes ; 7(4): 378-387, 2021 07 21.
Article in English | MEDLINE | ID: covidwho-1246705

ABSTRACT

AIMS: We hypothesized that a decline in admissions with heart failure during COVID-19 pandemic would lead to a reciprocal rise in mortality for patients with heart failure in the community. METHODS AND RESULTS: We used National Heart Failure Audit data to identify 36 974 adults who had a hospital admission with a primary diagnosis of heart failure between February and May in either 2018, 2019, or 2020. Hospital admissions for heart failure in 2018/19 averaged 160/day but were much lower in 2020, reaching a nadir of 64/day on 27 March 2020 [incidence rate ratio (IRR): 0.40, 95% confidence interval (CI): 0.38-0.42]. The proportion discharged on guideline-recommended pharmacotherapies was similar in 2018/19 compared to the same period in 2020. Between 1 February-2020 and 31 May 2020, there was a 29% decrease in hospital deaths related to heart failure (IRR: 0.71, 95% CI: 0.67-0.75; estimated decline of 448 deaths), a 31% increase in heart failure deaths at home (IRR: 1.31, 95% CI: 1.24-1.39; estimated excess 539), and a 28% increase in heart failure deaths in care homes and hospices (IRR: 1.28, 95% CI: 1.18-1.40; estimated excess 189). All-cause, inpatient death was similar in the COVID-19 and pre-COVID-19 periods [odds ratio (OR): 1.02, 95% CI: 0.94-1.10]. After hospital discharge, 30-day mortality was higher in 2020 compared to 2018/19 (OR: 1.57, 95% CI: 1.38-1.78). CONCLUSION: Compared with the rolling daily average in 2018/19, there was a substantial decline in admissions for heart failure but an increase in deaths from heart failure in the community. Despite similar rates of prescription of guideline-recommended therapy, mortality 30 days from discharge was higher during the COVID-19 pandemic period.


Subject(s)
COVID-19 , Communicable Disease Control , Heart Failure , Hospital Mortality/trends , Hospitalization/statistics & numerical data , Aged, 80 and over , COVID-19/epidemiology , COVID-19/prevention & control , Cause of Death , Clinical Audit/statistics & numerical data , Communicable Disease Control/methods , Communicable Disease Control/organization & administration , Electronic Health Records/statistics & numerical data , Female , Heart Failure/mortality , Heart Failure/therapy , Humans , Male , Mortality , Quality of Health Care , SARS-CoV-2 , Severity of Illness Index , State Medicine/standards , State Medicine/statistics & numerical data , United Kingdom/epidemiology
6.
J Am Coll Cardiol ; 76(20): 2368-2378, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-912306

ABSTRACT

The coronavirus disease-2019 (COVID-19) pandemic has profoundly changed clinical care and research, including the conduct of clinical trials, and the clinical research ecosystem will need to adapt to this transformed environment. The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory and the Academic Research Consortium, composed of academic investigators from the United States and Europe, patients, the U.S. Food and Drug Administration, the National Institutes of Health, and industry members. A series of meetings were convened to address the challenges caused by the COVID-19 pandemic, review options for maintaining or altering best practices, and establish key recommendations for the conduct and analysis of clinical trials for cardiovascular disease and heart failure. This paper summarizes the discussions and expert consensus recommendations.


Subject(s)
Clinical Trials as Topic , Coronavirus Infections , Pandemics , Pneumonia, Viral , COVID-19 , Endpoint Determination , Humans , Socioeconomic Factors , Statistics as Topic
7.
Eur Heart J ; 41(19): 1810-1817, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-629506

ABSTRACT

AIMS: The current pandemic coronavirus SARS-CoV-2 infects a wide age group but predominantly elderly individuals, especially men and those with cardiovascular disease. Recent reports suggest an association with use of renin-angiotensin-aldosterone system (RAAS) inhibitors. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses. Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors. METHODS AND RESULTS: We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort). Results were validated in 1123 men and 575 women (validation cohort).The median age was 69 years for men and 75 years for women. The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively). In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2. In the validation cohort, ACE inhibitor (estimate = -0.17, P = 0.002) and ARB use (estimate = -0.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations. CONCLUSION: In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Heart Failure/blood , Mineralocorticoid Receptor Antagonists/therapeutic use , Peptidyl-Dipeptidase A/blood , Renin-Angiotensin System/drug effects , Aged , Angiotensin-Converting Enzyme 2 , Betacoronavirus , COVID-19 , Coronavirus Infections , Europe , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral , SARS-CoV-2 , Sex Factors
8.
Eur Heart J ; 41(22): 2080-2082, 2020 06 07.
Article in English | MEDLINE | ID: covidwho-401208
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