IMPORTANCE It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2.OBJECTIVE To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTSTo examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020.EXPOSURES ACEI/ARB use was defined as prescription fillings 6 months prior to the index date. MAIN OUTCOMES AND MEASURESIn the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis. RESULTSIn the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age-and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]). CONCLUSIONS AND RELEVANCEPrior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.

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Background: The Danish government ordered a public lockdown on March 12, 2020, because of the coronavirus disease 2019 (COVID-19) pandemic. We investigated the immediate consequences of such a lockdown for patients with heart failure (HF). Methods: Using the Danish nationwide administrative databases, we investigated the incidence of new-onset HF and hospitalizations for worsening HF before and after the lockdown (January 1 to March 11 versus March 12 to March 31) in 2020 versus 2019. We also investigated the mortality for all patients with HF and in COVID-19–infected patients with HF. Results: Rates of new-onset HF between January 1 and March 11 were comparable for 2020 and 2019 (1.83 versus 1.78 per 10 000 person-years; P =0.19), while hospitalizations for worsening HF were slightly higher in 2020 versus 2019 (1.04 versus 0.93 per 1000 person-years; P =0.02). In the lockdown period, rates of new-onset HF diagnoses (1.26 versus 2.25 per 1000 person-years) and of hospitalizations for worsening HF (0.63 versus 0.99 per 1000 person-years) were significantly lower in 2020 versus 2019 ( P for both, <0.0001). Mortality was similar before and after the national lockdown for the population with HF. We observed 90 HF patients with diagnosed COVID-19 infection, of whom 37% (95% CI, 23%–50%) died within 15 days. Conclusions: The number of patients hospitalized with worsening HF or diagnosed with new-onset HF was markedly reduced after lockdown but has not yet impacted mortality in HF patients at a population-based level. However, these data raise concerns for a potential undertreatment of HF currently that may impact prognosis in the longer term.

Aim To determine the incidence, patient characteristics, and related events associated with new-onset atrial fibrillation (AF) during a national COVID-19 lockdown. Methods and results Using nationwide Danish registries, we included all patients, aged 18–90 years, receiving a new-onset AF diagnosis during the first 3 months of 2019 and 2020. The main comparison was between patients diagnosed during lockdown (12 March 12–1 April 2020) and patients diagnosed in the corresponding period 1 year previously. We found a lower incidence of new-onset AF during the 3 weeks of lockdown compared with the corresponding weeks in 2019 [incidence rate ratios with 95% confidence intervals (CIs) for the 3 weeks: 0.66 (0.56–0.78), 0.53 (0.45–0.64), and 0.41 (0.34–0.50)]. There was a 47% drop in total numbers (562 vs. 1053). Patients diagnosed during lockdown were younger and with a lower CHA2DS2-VASc score, while history of cancer, heart failure, and vascular disease were more prevalent. During lockdown, 30 (5.3%) patients with new-onset AF suffered an ischaemic stroke and 15 (2.7%) died, compared with 45 (4.3%) and 14 (1.3%) patients during the corresponding 2019 period, respectively. The adjusted odds ratio of a related event (ischaemic stroke or all-cause death) during lock-down compared with the corresponding weeks was 1.41 (95% CI 0.93–2.12). Conclusions Following a national lockdown in Denmark, a 47% drop in registered new-onset AF cases was observed. In the event of prolonged or subsequent lockdowns, the risk of undiagnosed AF patients developing complications could potentially translate into poorer outcomes in patients with AF during the COVID-19 pandemic.

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 May 16, 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 4,842 Covid-19 patients, 2,281 (47.1%) were men. Median age was 57 [25%-75% 43-73] for men versus 52 [38-71] for women (P&lt;0.001); however, octogenarians had equal sex distribution. Alcohol diagnosis, diabetes, hypertension, sleep apnea, prior MI and IHD (all P&lt;0.001) as well as AF, stroke and HF (all P=0.01) were more often seen in men, and so was CKD (P=0.03). Obesity diagnosis (P&lt;0.001) were more often seen in women. Other comorbidity differences were insignificant (P&gt;0.05). The fully adjusted average risk ratio was 1.63 [95% CI 1.44-1.84]. Conclusions Men with Covid-19 infection have &gt;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.