The sodium-glucose cotransporter 2 inhibitor empagliflozin reduces the risk of cardiovascular death or heart failure hospitalization in patients with chronic heart failure, but whether empagliflozin ...also improves clinical outcomes when initiated in patients who are hospitalized for acute heart failure is unknown. In this double-blind trial (EMPULSE; NCT04157751 ), 530 patients with a primary diagnosis of acute de novo or decompensated chronic heart failure regardless of left ventricular ejection fraction were randomly assigned to receive empagliflozin 10 mg once daily or placebo. Patients were randomized in-hospital when clinically stable (median time from hospital admission to randomization, 3 days) and were treated for up to 90 days. The primary outcome of the trial was clinical benefit, defined as a hierarchical composite of death from any cause, number of heart failure events and time to first heart failure event, or a 5 point or greater difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days, as assessed using a win ratio. More patients treated with empagliflozin had clinical benefit compared with placebo (stratified win ratio, 1.36; 95% confidence interval, 1.09-1.68; P = 0.0054), meeting the primary endpoint. Clinical benefit was observed for both acute de novo and decompensated chronic heart failure and was observed regardless of ejection fraction or the presence or absence of diabetes. Empagliflozin was well tolerated; serious adverse events were reported in 32.3% and 43.6% of the empagliflozin- and placebo-treated patients, respectively. These findings indicate that initiation of empagliflozin in patients hospitalized for acute heart failure is well tolerated and results in significant clinical benefit in the 90 days after starting treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this randomized, placebo-controlled trial, investigators evaluated the effects of the sodium–glucose cotransporter 2 inhibitor dapagliflozin in patients with heart failure and a reduced ejection ...fraction with or without type 2 diabetes. The risk of worsening heart failure or cardiovascular death was lower among those who received dapagliflozin, regardless of the presence or absence of diabetes.
The prevalence of both atrial fibrillation (AF) and malignancies are increasing in the elderly, but incidences of new onset AF in different cancer subtypes are not well described.The objectives of ...this study were therefore to determine the incidence of AF in different cancer subtypes and to examine the association of cancer and future AF.
Using national databases, the Danish general population was followed from 2000 until 2012. Every individual aged > 18 years and with no history of cancer or AF prior to study start was included. Incidence rates of new onset AF were identified and incidence rate ratios (IRRs) of AF in cancer patients were calculated in an adjusted Poisson regression model.
A total of 4,324,545 individuals were included in the study. Cancer was diagnosed in 316,040 patients. The median age of the cancer population was 67.0 year and 51.5% were females. Incidences of AF were increased in all subtypes of cancer. For overall cancer, the incidence was 17.4 per 1000 person years (PY) vs 3.7 per 1000 PY in the general population and the difference increased with age. The covariate adjusted IRR for AF in overall cancer was 1.46 (95% confidence interval (CI) 1.44-1.48). The strength of the association declined with time from cancer diagnosis (IRR
= 3.41 (3.29-3.54), (IRR-
= 1.57 (CI 1.50-1.64) and (IRR
= 1.12 (CI 1.09-1.15).
In this nationwide cohort study we observed that all major cancer subtypes were associated with an increased incidence of AF. Further, cancer and AF might be independently associated.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In a randomized trial, 5661 patients with acute myocardial infarction and a reduced left ventricular ejection fraction, pulmonary congestion, or both were assigned to receive either ...sacubitril–valsartan or ramipril. At a median of 22 months, there was no significant difference between the two groups in the incidence of death from cardiovascular causes or incident heart failure.
Background:
Fingolimod may be associated with risk of developing cardiovascular disease (CVD). Studies including reference groups and long follow-up are scarce.
Objectives:
We hypothesized that ...patients treated with fingolimod would be at higher risk of developing CVD compared to patients treated with natalizumab.
Methods:
A nationwide 12-year cohort study linking individual-level data from the Danish Multiple Sclerosis Registry with health registries on 2095 adult patients with multiple sclerosis (MS) without any health records of CVD at follow-up start. Exposure to fingolimod and natalizumab was defined by the first treatment of at least 3 months. Cohort entry was from 2011 to 2018. We defined CVD as a composite measure, including hypertension, ischemic heart disease, atrial fibrillation, heart failure, and stroke. We used multivariable adjusted Cox regression.
Results:
There were 28.8 and 17.4 CVD events per 1000 person-years in fingolimod and natalizumab groups, respectively. Compared to natalizumab-treated patients, fingolimod-treated patients had a higher risk of CVD (hazard ratio (HR) = 1.57; 95% confidence interval (CI) = 1.18–2.08). Hypertension comprised 200 of 244 CVD events.
Conclusion:
We found an increased risk of CVD in patients with MS treated with fingolimod. This increased risk was mainly due to hypertension.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Abstract
Background and Objectives
Male sex has been associated with severe coronavirus disease 2019 (COVID-19) infection. We examined the association between male sex and severe COVID-19 infection ...and if an increased risk remains after adjustment for age and comorbidities.
Methods
Nationwide register-based follow-up study of COVID-19 patients in Denmark until 16 May 2020. Average risk ratio comparing 30-day composite outcome of all-cause death, severe COVID-19 diagnosis or intensive care unit (ICU) admission for men versus women standardized to the age and comorbidity distribution of all patients were derived from multivariable Cox regression. Included covariates were age, hypertension, diagnoses including obesity, alcohol, sleep apnea, diabetes, chronic obstructive pulmonary disease, previous myocardial infarction (MI), ischemic heart disease (IHD), heart failure (HF), atrial fibrillation (AF), stroke, peripheral artery disease, cancer, liver, rheumatic, and chronic kidney disease (CKD).
Results
Of 4842 COVID-19 patients, 2281 (47.1%) were men. Median age was 57 25%–75% 43–73 for men versus 52 38–71 for women (P < .001); however, octogenarians had equal sex distribution. Alcohol diagnosis, diabetes, hypertension, sleep apnea, prior MI and IHD (all P < .001) as well as AF, stroke, and HF (all P = .01) were more often seen in men, and so was CKD (P = .03). Obesity diagnosis (P < .001) were more often seen in women. Other comorbidity differences were insignificant (P > .05). The fully adjusted average risk ratio was 1.63 95% CI, 1.44–1.84.
Conclusions
Men with COVID-19 infection have >50% higher risk of all-cause death, severe COVID-19 infection, or ICU admission than women. The excess risk was not explained by age and comorbidities.
Men with COVID-19 infection have a more than 50% higher risk of a 30-day composite outcome of all-cause death, severe COVID-19 infection, or ICU admission than women. This excess risk was not explained by age or underlying comorbid conditions.
Abstract
Background
On 13 March 2020, the Danish authorities imposed extensive nationwide lockdown measures to prevent the spread of the coronavirus disease 2019 (COVID-19) and reallocated limited ...healthcare resources. We investigated mortality rates, overall and according to location, in patients with established cardiovascular disease before, during, and after these lockdown measures.
Methods and results
Using Danish nationwide registries, we identified a dynamic cohort comprising all Danish citizens with cardiovascular disease (i.e. a history of ischaemic heart disease, ischaemic stroke, heart failure, atrial fibrillation, or peripheral artery disease) alive on 2 January 2019 and 2020. The cohort was followed from 2 January 2019/2020 until death or 16/15 October 2019/2020. The cohort comprised 340 392 and 347 136 patients with cardiovascular disease in 2019 and 2020, respectively. The overall, in-hospital, and out-of-hospital mortality rate in 2020 before lockdown was significantly lower compared with the same period in 2019 adjusted incidence rate ratio (IRR) 0.91, 95% confidence interval (CI) CI 0.87–0.95; IRR 0.95, 95% CI 0.89–1.02; and IRR 0.87, 95% CI 0.83–0.93, respectively. The overall mortality rate during and after lockdown was not significantly different compared with the same period in 2019 (IRR 0.99, 95% CI 0.97–1.02). However, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during and after lockdown compared with the same period in 2019 (in-hospital, IRR 0.92, 95% CI 0.88–0.96; out-of-hospital, IRR 1.04, 95% CI1.01–1.08). These trends were consistent irrespective of sex and age.
Conclusions
Among patients with established cardiovascular disease, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during lockdown compared with the same period in the preceding year, irrespective of age and sex.
Graphical Abstract
Abuse of anabolic androgenic steroids (AAS) is highly prevalent among male recreational athletes. The objective of this study was to investigate the impact of AAS abuse on reproductive hormone levels ...and symptoms suggestive of hypogonadism in current and former AAS abusers.
This study had a cross-sectional case-control design and involved 37 current AAS abusers, 33 former AAS abusers (mean (95%CI) elapsed duration since AAS cessation: 2.5 (1.7; 3.7) years) and 30 healthy control participants. All participants were aged 18-50 years and were involved in recreational strength training. Reproductive hormones (FSH, LH, testosterone, inhibin B and anti-Müllerian hormone (AMH)) were measured using morning blood samples. Symptoms of hypogonadism (depressive symptoms, fatigue, decreased libido and erectile dysfunction) were recorded systematically.
Former AAS abusers exhibited significantly lower median (25th -75th percentiles) total and free testosterone levels than control participants (total testosterone: 14.4 (11.9-17.7) nmol/l vs. 18.8 (16.6-22.0) nmol/l) (P < 0.01). Overall, 27.2% (13.3; 45.5) of former AAS abusers exhibited plasma total testosterone levels below the lower reference limit (12.1 nmol/l) whereas no control participants exhibited testosterone below this limit (P < 0.01). Gonadotropins were significantly suppressed, and inhibin B and AMH were significantly decreased in current AAS abusers compared with former AAS abusers and control participants (P < 0.01). The group of former AAS abusers had higher proportions of participants with depressive symptoms ((24.2%) (11.1; 42.2)), erectile dysfunction ((27.3%) (13.3; 45.6)) and decreased libido ((40.1%) (23.2; 57.0)) than the other two groups (trend analyses: P < 0.05).
Former AAS abusers exhibited significantly lower plasma testosterone levels and higher frequencies of symptoms suggestive of hypogonadism than healthy control participants years after AAS cessation. Current AAS abusers exhibited severely decreased AMH and inhibin B indicative of impaired spermatogenesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Aims
In the DAPA-HF trial, the SGLT2 inhibitor dapagliflozin reduced the risk of worsening heart failure (HF) and death in patients with HF and reduced ejection fraction. We examined whether ...this benefit was consistent in relation to background HF therapy.
Methods and results
In this post hoc analysis, we examined the effect of study treatment in the following yes/no subgroups: diuretic, digoxin, mineralocorticoid receptor antagonist (MRA), sacubitril/valsartan, ivabradine, implanted cardioverter-defibrillating (ICD) device, and cardiac resynchronization therapy. We also examined the effect of study drug according to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker dose, beta-blocker (BB) dose, and MRA (≥50% and <50% of target dose). We analysed the primary composite endpoint of cardiovascular death or a worsening HF event. Most randomized patients (n = 4744) were treated with a diuretic (84%), renin–angiotensin system (RAS) blocker (94%), and BB (96%); 52% of those taking a BB and 38% taking a RAS blocker were treated with ≥50% of the recommended dose. Overall, the dapagliflozin vs. placebo hazard ratio (HR) was 0.74 95% confidence interval (CI) 0.65–0.85 for the primary composite endpoint (P < 0.0001). The effect of dapagliflozin was consistent across all subgroups examined: the HR ranged from 0.57 to 0.86 for primary endpoint, with no significant randomized treatment-by-subgroup interaction. For example, the HR in patients taking a RAS blocker, BB, and MRA at baseline was 0.72 (95% CI 0.61–0.86) compared with 0.77 (95% CI 0.63–0.94) in those not on all three of these treatments (P-interaction 0.64).
Conclusion
The benefit of dapagliflozin was consistent regardless of background therapy for HF.
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