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BackgroundInhaled corticosteroids (ICS) are commonly used to treat COPD and are associated with increased risk of pneumonia. The aim of this study was to assess if accumulated use of ICS is associated with a dose-dependent risk of a positive airway culture with Pseudomonas aeruginosa in patients with COPD.MethodsWe conducted a multiregional epidemiological cohort study including Danish COPD patients followed in outpatient clinics during 2010–2017. ICS use was categorised based on accumulated prescriptions redeemed 365 days prior to cohort entry. Cox proportional hazard regression model was used to estimate the risk of acquiring P. aeruginosa. Propensity score matched models were used as sensitivity analyses.ResultsA total of 21 408 patients were included in the study, of which 763 (3.6%) acquired P. aeruginosa during follow-up. ICS use was associated with a dose-dependent risk of P. aeruginosa (low ICS dose: HR 1.38, 95% CI 1.03 to 1.84, p=0.03; moderate ICS dose: HR 2.16, 95% CI 1.63 to 2.85, pConclusionUse of ICS in patients with COPD followed in Danish outpatient clinics was associated with a substantially increased and dose-dependent risk of acquiring P. aeruginosa. Caution should be taken when administering high doses of ICS in severely ill patients with COPD. These results should be confirmed in comparable cohorts and other settings.

Background We aimed to analyse initiation of and persistence with P2Y12 inhibitors after first-time myocardial infarction (MI). Methods and results Using Danish nationwide registries, we identified patients ≥30 years with first-time MI during 1 January 2005–30 June 2016 and subsequent prescriptions of P2Y12 inhibitors. Independent factors related to initiation of and persistence with P2Y12 inhibitors were analysed by multivariable logistic regression and a Cox proportional hazards model. Patients were stratified by revascularization strategy: percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or medical therapy alone (MTA). Overall, 79 597 MI patients were included with 39 172 undergoing PCI, 2619 CABG, and 16 640 MTA, showing initiation of P2Y12 inhibitors of 93.4%, 49.0%, and 51.5%, respectively. Congestive heart failure, cerebrovascular disease, cardiac dysrhythmias, renal failure, previous bleeding, and oral anticoagulants were associated with less initiation of P2Y12 inhibitors. Female sex was associated with less initiation of P2Y12 inhibitors following MTA. MTA, coronary angiography, cerebrovascular disease, diabetes with complications, previous bleeding, antidiabetics, and ticagrelor as P2Y12 inhibitor were associated with non-persistence, whereas female sex, advanced age, and concomitant pharmacotherapy with angiotensin-converting enzyme inhibitors, beta-blockers, statins, oral anticoagulants, and aspirin were associated with high persistence. Conclusion Initiation of P2Y12 inhibitors in PCI-treated MI patients was high in contrast to those treated with CABG or MTA and patients with certain comorbidities. Further studies on the benefit–risk ratio of P2Y12 inhibitors in CABG-treated or MTA-treated patients and patients with comorbidities after first-time MI are warranted, as is focus on persistence among patients receiving MTA, patients with comorbidities, and users of ticagrelor.

Clinical decision-making in patients with ST-segment elevation myocardial infarction (STEMI) presenting beyond 12 h of symptom onset (late presenters) is challenging. However, the electrocardiogram (ECG) may provide helpful information. We investigated the association between three ECG-scores and myocardial salvage and infarct size in late presenters treated with primary percutaneous coronary intervention (primary PCI).Sixty-six patients with STEMI and ongoing symptoms presenting 12-72 h after symptom onset were included. Cardiac magnetic resonance was performed at day 1 (interquartile range [IQR], 1-1) and at follow-up at day 93 (IQR, 90-98). The pre-PCI ECG was analyzed for the presence of pathological QW (early QW) as well as Anderson-Wilkins acuteness score (AW-score), the classic Sclarovsky-Birnbaum Ischemia Grading System (classic SB-IG-score) and a modified SB-IG-score including any T-wave morphologies.Early QW was associated with a larger myocardium at risk (39 ± 12 versus 33 ± 12; p = 0.030) and final infarct size (20 ± 11 versus 14 ± 9; p = 0.021) as well as a numerical lower final myocardial salvage (0.52 ± 0.19 versus 0.61 ± 0.23; p = 0.09). The association with final infarct size disappeared after adjusting for myocardium at risk. An AW-score 3 showed a trend towards a larger final infarct size (18 ± 11 versus 11 ± 11; p = 0.08) and was not associated with salvage index (0.55 ± 0.20 versus 0.65 ± 0.30; p = 0.23). The classic and modified SB-IG-score were not associated with final infarct size (modified SB-IG-score, 17 ± 10 versus 21 ± 13; p = 0.28) or final myocardial salvage (0.53 ± 0.20 versus 0.53 ± 0.26; p = 0.96).Of three well-established ECG-scores only early QW and AW-score 3 showed association with myocardium at risk and infarct size to some extent, but the association with myocardial salvage was weak. Hence, neither of the three investigated ECG-scores are sufficient to guide clinical decision-making in patients with STEMI and ongoing symptoms presenting beyond 12 h of symptom onset.

Background: Patients with severe aortic stenosis frequently have coexisting coronary artery disease. Invasive hyperemic and nonhyperemic pressure indices are used to assess coronary artery disease severity but have not been evaluated in the context of severe aortic stenosis. Methods: We compared lesion reclassification rates of fractional flow reserve (FFR) and resting full-cycle ratio (RFR) measured before and 6 months after transcatheter aortic valve implantation using the conventional clinical cutoffs of ≤0.80 for FFR and ≤0.89 for RFR. This was a substudy of the ongoing NOTION-3 trial (Third Nordic Aortic Valve Intervention). Two-dimensional quantitative coronary analysis was used to assess changes in angiographic lesion severity. Results: Forty patients were included contributing 50 lesions in which FFR was measured. In 32 patients (36 lesions), RFR was also measured. There was no significant change in diameter stenosis from baseline to follow-up, 49.8% (42.9%–57.1%) versus 52.3% (43.2%–57.8%), P =0.50. RFR improved significantly from 0.88 (0.83%–0.93) at baseline to 0.92 (0.83–0.95) at follow-up, P =0.003, whereas FFR remained unchanged, 0.84 (0.81–0.89) versus 0.86 (0.78–0.90), P =0.72. At baseline, 11 out of 50 (22%) lesions were FFR-positive, whereas 15 out of 50 (30%) were positive at follow-up, P =0.219. Corresponding numbers for RFR were 23 out of 36 (64%) at baseline and 12 out of 36 (33%) at follow-up, P =0.003. Conclusions: In patients with severe aortic stenosis, physiological assessment of coronary lesions with FFR before transcatheter aortic valve implantation leads to lower reclassification rate at 6-month follow-up, compared with RFR.

Aims The aim of this study was to examine contemporary data on the 1-year prognosis of patients surviving acute coronary syndrome (ACS) and concomitant first-time detected atrial fibrillation (AF). Methods and results Using Danish nationwide registries, we identified all patients surviving a first-time admission with ACS from 2000 to 2018 and grouped them into (i) those without AF prior to or during ACS; (ii) those with a history of AF; and (iii) those with first-time detected AF during admission with ACS. With 1 year of follow-up, rates of ischaemic stroke, death, and bleeding were compared between study groups using multivariable adjusted Cox proportional hazards analysis. We included 161 266 ACS survivors: 135 878 (84.2%) without AF, 18 961 (11.8%) with history of AF, and 6427 (4.0%) with first-time detected AF at admission with ACS. Compared to those without AF, the adjusted 1-year rates of outcomes were as follows: ischaemic stroke [hazard ratio (HR) 1.38 (95% CI 1.22–1.56) for patients with history of AF and HR 1.67 (95% CI 1.38–2.01) for patients with first-time detected AF]; mortality [HR 1.25 (95% CI 1.21–1.31) for patients with history of AF and HR 1.52 (95% CI 1.43–1.62) for patients with first-time detected AF]; and bleeding [HR 1.22 (95% CI 1.14–1.30) for patients with history of AF and HR 1.28 (95% CI 1.15–1.43) for patients with first-time detected AF]. Conclusion In patients with ACS, first-time detected AF appeared to be at least as strongly associated with the 1-year rates of ischaemic stroke, mortality, and bleeding as compared with patients with a history of AF.

BACKGROUND: To compare effectiveness and safety of clopidogrel, prasugrel, and ticagrelor among all-comers with ST-segment elevation myocardial infarction (STEMI) and extend the knowledge from randomized clinical trials.METHODS: All consecutive patients with STEMI admitted to Copenhagen University Hospital, Rigshospitalet, from 2009 to 2016 were identified via the Eastern Danish Heart Registry. By individual linkage to Danish nationwide registries, claimed drugs and end points were obtained. Patients alive a week post-discharge were included, stratified according to clopidogrel, prasugrel, or ticagrelor treatment, and followed for a year. The effectiveness end point (a composite of all-cause mortality, recurrent myocardial infarction, and ischemic stroke) and safety end point (a composite of bleedings leading to hospitalization) were assessed by multivariate Cox proportional-hazards models.RESULTS: In total, 5123 patients were included (clopidogrel [1245], prasugrel [1902], ticagrelor [1976]) with ≥95% treatment persistency. Concomitant use of aspirin was ≥95%. Females accounted for 24% and elderly for 17%. Compared with clopidogrel, the effectiveness end point occurred less often for ticagrelor (HR 0.50, 95% CI 0.35-0.70) and prasugrel (HR 0.48, 95% CI 0.33-0.68) without differences in bleedings leading to hospitalization. No differences in comparative effectiveness or safety were found between prasugrel and ticagrelor. Sensitivity analyses with time-dependent drug exposure and the period 2011-2015 showed similar results.CONCLUSIONS: Among all-comers with STEMI, ticagrelor and prasugrel were associated with reduced incidence of the composite end point of all-cause mortality, recurrent myocardial infarction, and ischemic stroke without an increase in bleedings leading to hospitalization compared with clopidogrel. No differences were found between prasugrel and ticagrelor.

Background Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs). Methods PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065. Findings Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17 women, 745 [83 men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2 951.0-15.6) of 898 patients, with 66 (8.0 95.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9[SD 15.9]). Highly lipidic lesions (851 [24 of 3500 lesions, present in 520 [59 of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2.27, 95.25-4.13) and nonculprit lesion-specific MACEs (7.83, 4.12-14.89). Large plaque burden (787 [22 of 3629 lesions, present in 530 [59 of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7.095.0-10.0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13.295.4-17.6). Interpretation Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes. Copyright (C) 2021 Elsevier Ltd. All rights reserved. BackgroundNear-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs).MethodsPROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065.FindingsBetween June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55–70] years). Median follow-up was 3·7 (IQR 3·0–4·4) years. Adverse events within 4 years occurred in 112 (13·2%, 95% CI 11·0–15·6) of 898 patients, with 66 (8·0%, 95% CI 6·2–10·0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46·9% [SD 15·9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2·27, 95% CI 1·25–4·13) and non-culprit lesion-specific MACEs (7·83, 4·12–14·89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7·0% (95% CI 4·0–10·0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13·2% (95% CI 9·4–17·6).InterpretationCombined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes.FundingAbbott Vascular, Infraredx, and The Medicines Company.

BACKGROUND: New-onset atrial fibrillation (NEW-AF) following ST-segment elevation myocardial infarction (STEMI) is a common complication, but the true prognostic impact of NEW-AF is unknown. Additionally, the optimal treatment of NEW-AF among patients with STEMI is warranted.METHODS: A large cohort of consecutive patients with STEMI treated with percutaneous coronary intervention were identified using the Eastern Danish Heart Registry from 1999-2016. Medication and end points were retrieved from Danish nationwide registries. NEW-AF was defined as a diagnosis of AF within 30 days following STEMI. Patients without a history of AF and alive after 30 days after discharge were included. Incidence rates were calculated and multivariate analyses performed to determine the association between NEW-AF and long-term mortality, incidence of ischemic stroke, re-MI, and bleeding leading to hospitalization, and the comparative effectiveness of OAC therapy on these outcomes.RESULTS: Of 7944 patients with STEMI, 296 (3.7%) developed NEW-AF. NEW-AF was associated with increased long-term mortality (adjusted HR 1.48, 95% CI 1.20-1.82, PCONCLUSIONS: NEW-AF following STEMI is associated with increased long-term mortality. Treatment with OAC therapy in NEW-AF patients is associated with reduced long-term mortality.

Background Urgent recognition and treatment are needed in patients with acute coronary syndrome (ACS), however this may be difficult during the Coronavirus disease 2019 (COVID-19) pandemic with a national lock-down. We aimed to examine the incidence of ACS after national lock-down. Methods The Danish government announced national lock-down on March 11, 2020 and first phase of reopening was announced on April 6. Using Danish nationwide registries, we identified first-time ACS admissions in (1) January 1 to May 7, 2017-2019, and (2) January 1, 2020 to May 6, 2020. Incidence rates of ACS admissions per week for the 2017 to 2019 period and the 2020 period were computed and incidence rate ratios (IRR) were computed using Poisson regression analysis. Results The number of ACS admissions were 8,204 (34.6% female, median age 68.3 years) and 2,577 (34.0% female, median age 68.5 years) for the 2017 to 2019- and 2020 period, respectively. No significant differences in IRRs were identified for weeks 1 to 9 (January 1 to March 4) for 2020 compared with week 1 to 9 for 2017 to 2019. In 2020, significant lower IRRs were identified for week 10 (March 5 to 11) IRR = 0.71 (95% confidence intervals [CI]: 0.58 to 0.87), week 11 (12 to 18 March) IRR = 0.68 (0.56 to 0.84), and week 14 (April 2 to April 8) IRR = 0.79 (0.65 to 0.97). No significant differences in IRRs were identified for week 15 to 18 (April 9 to May 6). In subgroup analysis, we identified that the main result was driven by male patients, and patients ≥60 years. Conclusions During the COVID-19 pandemic with an established national lock-down we identified a significant decline around 30% in the incidence of ACS admissions. Along with the reopening of society, ACS admissions were stabilized at levels equal to previous years.

Patients with severe chronic obstructive pulmonary disease (COPD) experience frequent acute exacerbations and require repeated courses of corticosteroid therapy, which may lead to adverse effects. Methotrexate (MTX) has anti-inflammatory properties. The objective of this study was to describe the risk of COPD exacerbation in patients exposed to MTX. In this nationwide cohort study of 58,580 COPD outpatients, we compared the risk of hospitalization-requiring COPD exacerbation or death within 180 days in MTX vs. non-MTX users in a propensity-score matched study population as well as an unmatched cohort, in which we adjusted for confounders. The use of MTX was associated with a reduction in risk of COPD exacerbation in the propensity-score matched population at 180 days follow-up (HR 0.66, CI 0.66–0.66, p &lt, 0.001). Similar results were shown in our sensitivity analyses at 180-day follow-up on unmatched population and 365-day follow-up on matched and unmatched population (HR 0.76 CI 0.59–0.99, HR 0.81 CI 0.81–0.82 and HR 0.92 CI 0.76–1.11, respectively). MTX was associated with a lower risk of COPD exacerbation within the first six months after study entry. The finding seems biologically plausible and could potentially be a part of the management of COPD patients with many exacerbations.

Introduction: Depressive symptoms appear frequently in COPD patients and are associated with reduced disease control and increased mortality. Both smoking and COPD increase the risk of depressive symptoms. Whether smoking cessation among COPD patients affects the occurrence of depressive symptoms is unknown. We hypothesized that smoking cessation in patients with COPD leads to reduced use of antidepressants and fewer admissions to psychiatric hospitals with depression, anxiety or bipolar disorder. Methods: We conducted a nationwide cohort study, in patients from The Danish Register for COPD (DrCOPD) with spirometry verified COPD, age ≥40 years, a history of smoking and absence of cancer. Consistent smokers were matched 1:1 with ex-smokers using a propensity score model. Prescription fillings of antidepressants and risk of psychiatric hospitals admissions were assessed by Cox proportional hazard models. Results: We included 21,184 patients. A total of n=2,011 consistent smokers collected antidepressant prescriptions compared with 1,821 ex-smokers. Consistent smoking was associated with increased risk of filling prescription on antidepressants (HR 1.4, 95% CI 1.3-1.5, p Conclusion: Consistent smoking among COPD patients was associated with increased use of antidepressants and admissions to psychiatric hospitals with either depression, anxiety or bipolar disorder, compared to smoking cessation.

Background: Roflumilast is given as an add on to inhalation medication in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis. However, sparse and diverging data exist regarding the effect of roflumilast to reduce exacerbations. Objectives: To determine the effects of roflumilast on risk of hospital admittance with either i) COPD exacerbation (AECOPD) or ii) pneumonia and all-cause mortality in outpatients with COPD in a 2-year follow-up period. Methods: Observational cohort study of 45,386 outpatients in Denmark. Patients with COPD using roflumilast (case group) were compared to a propensity score matched control group of patients with COPD, who did not use roflumilast. Results: Case group had an increased 2-year risk of admission with AECOPD-Hosp (HR 1.6, 95% CI 1.5 to 1.8) and hospitalisation-requiring pneumonia (HR 1.5, 95% CI 1.3 to 1.8) compared to controls. When adding an active comparator (theophylline) in the matching algorithm, the signal was largely unchanged. All-cause mortality was comparable between the groups. Conclusion: Roflumilast use was associated with increased AECOPD and pneumonia. Results were robust to adjustments, analysis in the full cohort and also when using an active comparator. Since data regarding risk of exacerbations in roflumilast users are sparse, these data are concerning, but could however be due to bias by indication.

OBJECTIVES To ascertain the effect of age on outcomes after culprit-only and complete revascularization after Primary PCI (PPCI) for ST-elevation myocardial infarction (STEMI). BACKGROUND The numbers of older patients being treated with PPCI are increasing. The optimal management of nonculprit stenoses in such patients is unclear. METHODS We conducted an analysis of patients aged ≥75 years randomized in the DANAMI-3-PRIMULTI study to either culprit-only or complete FFR-guided revascularization. The primary endpoint was a composite of all-cause mortality, nonfatal reinfarction, and ischaemia-driven revascularization of lesions in noninfarct-related arteries after a median of 27 months of follow-up. RESULTS One hundred and ten of six hundred and twenty seven patients in the DANAMI-3-PRIMULTI trial were aged ≥75 years. These patients were more likely female (p

Introduction Depressive symptoms appear more often among patients with COPD and are associated with reduced disease control and increased mortality. Both smoking and COPD increase the risk of depressive symptoms. Whether smoking cessation among COPD patients affects the occurrence of depressive symptoms is unknown. We hypothesised that smoking cessation in patients with COPD leads to reduced use of antidepressants and fewer admissions to psychiatric hospitals with depression, anxiety or bipolar disorder. Methods We conducted a nationwide retrospective case–control study, in patients from The Danish Register for COPD with spirometry-verified COPD, age ≥40 years, a history of smoking and absence of cancer. Consistent smokers were matched 1:1 with ex-smokers using a propensity score model. Prescription fillings of antidepressants and risk of admissions to psychiatric hospitals with either depression, anxiety or bipolar disorder both descriptively was assessed by Cox proportional hazard models. Results We included 21 184 patients. A total of 2011 consistent smokers collected antidepressant prescriptions compared with 1821 ex-smokers. Consistent smoking was associated with increased risk of filling prescription on antidepressants (HR 1.4, 95% CI 1.3–1.5, p, COPD patients who stop smoking have a lower risk of needing antidepressants and a lower risk of depression-related hospitalisations than their still-smoking peers https://bit.ly/2RKmy9v

ObjectiveThe Third Danish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction – Ischaemic Postconditioning (DANAMI-3-iPOST) did not show improved clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with ischaemic postconditioning. However, the use of thrombectomy was frequent and thrombectomy may in itself diminish the effect of ischaemic postconditioning. We evaluated the effect of ischaemic postconditioning in patients included in DANAMI-3-iPOST stratified by the use of thrombectomy.MethodsPatients with STEMI were randomised to conventional primary percutaneous coronary intervention (PCI) or ischaemic postconditioning plus primary PCI. The primary endpoint was a combination of all-cause mortality and hospitalisation for heart failure.ResultsFrom March 2011 until February 2014, 1234 patients were included with a median follow-up period of 35 (interquartile range 28 to 42) months. There was a significant interaction between ischaemic postconditioning and thrombectomy on the primary endpoint (p=0.004). In patients not treated with thrombectomy (n=520), the primary endpoint occurred in 33 patients (10%) who underwent ischaemic postconditioning (n=326) and in 35 patients (18%) who underwent conventional treatment (n=194) (adjusted hazard ratio (HR) 0.55 (95%confidence interval (CI) 0.34 to 0.89), p=0.016). In patients treated with thrombectomy (n=714), there was no significant difference between patients treated with ischaemic postconditioning (n=291) and conventional PCI (n=423) on the primary endpoint (adjusted HR 1.18 (95% CI 0.62 to 2.28), p=0.62).ConclusionsIn this post-hoc study of DANAMI-3-iPOST, ischaemic postconditioning, in addition to primary PCI, was associated with reduced risk of all-cause mortality and hospitalisation for heart failure in patients with STEMI not treated with thrombectomy.Trial registration numberNCT01435408.

Roflumilast is given as an add-on to inhalation medication in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis. Animal experiments have documented deleterious effects of roflumilast in bacterial infections, but trials have not reported the risk of bacterial infections in patients. The objective of this study is to determine, among outpatients with severe COPD in a two-year follow-up period, the risk of hospitalization-requiring pneumonia, severe acute exacerbation in COPD (AECOPD-hosp), and death. Patients with COPD using roflumilast (roflumilast users) were compared to a propensity score-matched COPD control group not using roflumilast (non-roflumilast users). Roflumilast users had an increased 2-year risk of hospitalization-requiring pneumonia (HR 1.5, 95% CI 1.3 to 1.8, p-value &lt, 0.0001) compared to controls, and of AECOPD-Hosp (hazard ratio(HR) 1.6, 95%, confidence interval (CI) 1.5 to 1.8, p-value &lt, 0.0001) and. When adding an active comparator (theophylline) as a matching variable, the signal was largely unchanged. In conclusion, roflumilast was associated with an increased number of hospitalizations for pneumonia and for AECOPD. Since trials have not reported risks of bacterial complications and data regarding severe exacerbations in roflumilast users are sparse and diverging, these data are concerning. Trials focused on the risk of pneumonia, AECOPD, and other bacterial infections in roflumilast users are needed urgently.

Aims The aim of this study was to describe the use of antithrombotic therapy following a bleeding event among patients with myocardial infarction (MI), and the associated risk of major adverse cardiac events (MACE). Methods and results Using Danish nationwide registries, patients hospitalized with a bleeding event within 1 year after MI were identified. Antithrombotic treatment with aspirin, clopidogrel, and/or vitamin K antagonists (VKA) was determined at the bleeding and at Day 90 and 180 post-bleed. Based on guidelines, patients were stratified into four groups: expected, reduced, discontinued, or intensified treatment. Risk of MACE (ischaemic stroke, MI, or death) within the first year was assessed by Cox proportional hazard models. A total of 3324 patients with a bleeding after MI were included. At Day 90 post-bleed, 1052 (31.7%) received expected antithrombotic treatment, 1301 (39.2%) reduced, 164 (4.9%) intensified, and 807 (24.3%) no treatment. Major adverse cardiac events occurred in 637 (19.2%) patients. With dual antiplatelet therapy as reference, adjusted hazard ratios for MACE were: aspirin 1.81 (1.06–3.09), clopidogrel 1.08 (0.64–1.82), VKA 1.08 (0.47–2.48), VKA + aspirin 1.97 (0.95–4.07), VKA + clopidogrel 0.26 (0.03–1.91), triple 1.73 (0.50–5.95), and no treatment 1.93 (1.11–3.36). Conclusion The majority of MI patients reduced or discontinued their antithrombotic therapy post-bleed. Patients in monotherapy with aspirin or no treatment post-bleed had a higher risk of MACE Further studies of optimal antithrombotic treatments after a bleed are needed.

Background The new generation thinner-strut silicon carbide (SiC) coated cobalt chromium (CoCr) bare-metal stents (BMS) are designed to accelerate rapid endothelialisation and reduce thrombogenicity when implanted in coronary arteries. However, smaller studies suggest higher rates of symptomatic restenosis in patients receiving the newer generation BMS. We investigated the efficacy of a newer generation ultrathin strut silicon-carbide coated cobalt-chromium (CoCr) BMS (SCC-BMS) as compared to an older thin-strut uncoated CoCr BMS (UC-BMS) in patients presenting with coronary artery disease requiring stenting of large vessels (≥3.0 mm). Methods All patients randomized to SCC- (n = 761) or UC-BMS (n = 765) in the two BASKET-PROVE trials were included. Design, patients, interventions and follow-up were similar between trials except differing regimens of dual antiplatelet therapy. The primary endpoint was clinically driven target-vessel revascularization within 24 months. Safety endpoints of cardiac death, non-fatal myocardial infarction (MI), and definite/probable stent thrombosis (ST) were also assessed. We used inverse probability weighted proportional hazards Cox regressions adjusting for known confounders. Results Demographics, clinical presentation, and risk factors were comparable between the groups, but patients receiving SCC-BMS underwent less complex procedures. The risk for clinically driven TVR was increased om the SCC-BMS group compared to the UC-BMS group (cumulative incidence, 10.6% vs. 8.4%; adjusted relative hazard [HR], 1.49 [95% CI, 1.05–2.10]). No differences in safety endpoints were detected, cardiac death (1.6% vs. 2.8%; HR, 0.62 [CI, 0.30–1.27]), non-fatal MI (3.2% vs. 2.5%; HR, 1.56 [CI, 0.83–2.91]), and definite/probable ST (0.8% vs. 1.1%; HR, 1.17 [CI, 0.39–3.50]). Differences in strut thickness between the two stents did not explain the association between stent type and clinically driven TVR. Conclusions In patients requiring stenting of large coronary arteries, use of the newer generation SCC-BMS was associated with a higher risk of clinically driven repeat revascularization compared to the UC-BMS with no signs of an offsetting safety benefit.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden. The ERIC-PPCI trial was funded by a British Heart Foundation clinical study grant (grant number CS/14/3/31002) and a University College London Hospitals/University College London Biomedical Research Centre clinical research grant. The CONDI-2 trial was funded by Danish Innovation Foundation grants (grant numbers 11-108354 and 11-115818), Novo Nordisk Foundation (grant number NNF13OC0007447), and TrygFonden (grant number 109624). DJH was supported by the British Heart Foundation (grant number FS/10/039/28270), the National Institute for Health Research (NIHR) Biomedical Research Centre at University College London Hospitals, the Duke-National University Singapore Medical School, the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist-Senior Investigator scheme (grant number NMRC/CSA-SI/0011/2017) and its Collaborative Centre Grant scheme (grant number NMRC/CGAug16C006), and the Singapore Ministry of Education Academic Research Fund Tier 2 (grant number MOE2016-T2-2-021). HEB was supported by the Novo Nordisk Foundation (grant numbers NNF14OC0013337, NNF15OC0016674). RKK is supported by the Oxford NIHR Biomedical Centre. The research was also supported by the NIHR infrastructure at Leeds. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health. This article is based on the work of COST Action EU-CARDIOPROTECTION (CA16225) and supported by COST (European Cooperation in Science and Technology). We thank all study personnel for their invaluable assistance. Sí

Background: The impact of P. aeruginosa on long-term prognosis in COPD remains unknown. Objective: To determine whether P. aeruginosa is associated with increased risk of exacerbation or death in patients with COPD. Methods: Observational cohort study on 22.053 COPD outpatients (Fig.1). Time-dependent Cox proportional hazard regression model was used to estimate a) hospitalisation for exacerbation or all-cause mortality and b) all-cause mortality after 2 years. Results:P. aeruginosa was found in 4.1% of the patients. Hospital admissions (80% and 48%,p Conclusions:P. aeruginosa is associated with substantially worsened long-term prognosis in COPD. A randomized controlled trial is needed to conclude whether targeted antibiotic interventions can improve the prognosis in this highly vulnerable group of patients.

To predict irreversible reduction in left ventricular ejection fraction (LVEF) during admission for ST-segment elevation myocardial infarction (STEMI) using cardiac magnetic resonance (CMR) in addition to classical clinical parameters. Irreversible reduction in LVEF is an important prognostic factor after STEMI which necessitates medical therapy and implantation of prophylactic implantable cardioverter defibrillator (ICD).A post-hoc analysis of DANAMI-3 trial program (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) which recruited 649 patients who had CMR performed during index hospitalization and after 3 months. Patients were divided into two groups according to CMR-LVEF at 3 months: Group 1 with LVEF≤35% and Group 2 with LVEF35%. Group 1 included 15 patients (2.3%) while Group 2 included 634 patients (97.7%). A multivariate analysis showed that: Killip class1 (OR 7.39; CI:1.47-36.21, P = 0.01), symptom onset-to-wire ≥6 h (OR 7.19; CI 1.07-50.91, P = 0.04), LVEF≤35% using index echocardiography (OR 7.11; CI: 1.27-47.43, P = 0.03), and infarct size ≥40% of LV on index CMR (OR 42.62; CI:7.83-328.29, P 0.001) independently correlated with a final LVEF≤35%. Clinical models consisted of these parameters could identify 7 out of 15 patients in Group 1 with 100% positive predictive value.Together with other clinical measurements, the assessment of infarct size using late Gadolinium enhancement by CMR during hospitalization is a strong predictor of irreversible reduction in CMR_LVEF ≤35. That could potentially, after validation with future research, aids the selection and treatment of high-risk patients after STEMI, including implantation of prophylactic ICD during index hospitalization.

BackgroundDrug-eluting stents (DES) have proven superior to bare-metal stents (BMS) in terms of safety and efficacy. However, inference to the female subgroup has been limited by low enrolment rates of women in clinical trials. The objective of this study was to investigate the safety and efficacy of DES versus BMS in women and men.MethodsIn a pooled analysis of two all-comers randomised trials (Basel Stent Kosten-Effektivitäts Trial–Prospective Validation Examination (BASKET-PROVE) and BASKET-PROVE II) (n=4605), we examined safety and efficacy of DES versus BMS according to sex. Patients were followed 2 years for a composite endpoint of cardiac death, non-fatal myocardial infarction (MI) and clinically driven target-vessel revascularisation not related to MI.ResultsAmong the 1076 women and 3529 men included in the analysis, 65.6% of the women and 67.2% of the men were randomised to receive DES. At baseline, men had more complex coronary artery disease than women. After 2 years, DES reduced rates of major adverse cardiac events (MACE) compared with BMS in both women (cumulative incidence, 6.1% vs 14.7%; adjusted HR 0.36 (95% CI 0.24 to 0.54)) and men (7.7 vs 12.1%, HR 0.62 (0.50 to 0.77)), although the reduction in MACE rates was more pronounced in women (adjusted p=0.02 for sex-stent interaction). Event rates were lower in DES for both safety and efficacy outcomes, with the largest effect seen for non-MI TVR, in both women (2.3 vs 9.2%, adjusted HR 0.24 (0.13 to 0.44)) and men (4.0 vs 7.8%, adjusted HR 0.48 (0.36 to 0.64)) (adjusted p=0.049 for sex-stent interaction).ConclusionsIn patients requiring stenting of large coronary arteries, DES were associated with improved safety in women and superior efficacy in both sexes as compared with BMS.

Rheumatologic disorders are characterised by inflammation and an increased risk of coronary artery disease (CAD). However, the association between rheumatologic disorders and long-term prognosis in CAD patients undergoing percutaneous coronary intervention (PCI) is unknown. Thus, we aimed to examine the association between rheumatologic disorders and long-term prognosis in CAD patients undergoing PCI.A post-hoc analysis was performed in 4605 patients (age: 63.3 ± 11.0 years; male: 76.6%) with ST-segment elevation myocardial infarction (STEMI; n = 1396), non-STEMI ( n = 1541), and stable CAD ( n = 1668) from the all-comer stent trials, the BAsel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination (BASKET-PROVE) I and II trials. We evaluated the association between rheumatologic disorders and 2-year major adverse cardiac events (MACEs; cardiac death, nonfatal myocardial infarction (MI), and target vessel revascularisation (TVR)) by Cox regression analysis. Patients with rheumatologic disorders ( n = 197) were older, more often female, had a higher prevalence of renal disease, multi-vessel coronary disease, and bifurcation lesions, and had longer total stent lengths. During the 2-year follow-up, the MACE rate was 8.6% in the total cohort. After adjustment for potential confounders, rheumatologic disorders were associated with MACEs in the total cohort (adjusted hazard ratio: 1.55; 95% confidence interval (CI): 1.04-2.31) driven by the STEMI subgroup (adjusted hazard ratio: 2.38; 95% CI: 1.26-4.51). In all patients, rheumatologic disorders were associated with all-cause death (adjusted hazard ratio: 2.05; 95% CI: 1.14-3.70), cardiac death (adjusted hazard ratio: 2.63; 95% CI: 1.27-5.43), and non-fatal MI (adjusted hazard ratio: 2.64; 95% CI: 1.36-5.13), but not with TVR (adjusted hazard ratio: 0.81; 95% CI: 0.41-1.58).The presence of rheumatologic disorders appears to be independently associated with worse outcome in CAD patients undergoing PCI. This calls for further studies and focus on this high-risk group of patients following PCI.

Bleeding events in relation to treatment of ST-segment elevation myocardial infarction (STEMI) have previously been associated with mortality. In this study, we investigated the incidence and prognosis of, and variables associated with serious bleedings within 30 days after primary percutaneous coronary intervention in patients from The Third Danish Study of Optimal Acute Treatment of Patients with ST-Segment Elevation Myocardial Infarction (DANAMI-3) (n = 2,217). Hospital charts were read within 30 days postadmission to assess bleeding events using thrombolysis in myocardial infarction (TIMI) and Bleeding Academic Research Consortium criteria. TIMI minor/major bleeding (TMMB) occurred in 59 patients (2.7%). Variables associated with TMMB were female gender (hazard ratio [HR] 3.9, 95% confidence interval [CI] 2.2 to 6.7, p 3 hours (HR 1.9, 95% CI 1.1 to 3.3, p = 0.02), use of glycoprotein IIb/IIIa inhibitor (HR 2.1, 95% CI 1.2 to 3.7, p = 0.01), and increasing S-creatinine (HR 1.1, 95% CI 1.0 to 1.2, p = 0.001). Undergoing 2 in-hospital procedures were not associated with increased risk of TMMB. TMMB was strongly associated with 30-day mortality in multivariable analysis (HR 4.8, 95% CI 2.2 to 10.4, p

Most studies reporting bleedings in patients with ST-segment elevation myocardial infarction (STEMI) are reports from clinical trials, which may be unrepresentative of incidences in real-life. In this study, we investigated 1-year bleeding and mortality incidences in an unselected STEMI population, and compared participants with nonparticipants of a randomized all-comer clinical trial (The Third DANish Study of Optimal Acute Treatment of Patients with STEMI (DANAMI-3)). Hospital charts were read and bleedings classified according to thrombolysis in myocardial infarction (TIMI) and Bleeding Academic Research Consortium (BARC) criteria in 2,490 consecutive STEMI patients who underwent primary percutaneous coronary intervention in a single, large, and tertiary heart center. Thrombolysis in myocardial infarction minor and/or major bleeding (TMMB) occurred in 4.4% day 0 to 30 and 2.1% day 31 to 365. DANAMI-3 nonparticipants (n = 887) had significantly higher 30-day bleeding rates than DANAMI-3-participants (n = 1,603) (7.2% vs 2.9%, p 2 and anemia. Patients with cardiac arrest, Killip-class>2, and anemia accounted for 70.0% of 30-day TMMBs, and the majority of these patients were DANAMI-3 nonparticipants. TMMB day 0 to 30 was associated with increased 30-day mortality (hazard ratio 3.1, 95% confidence interval 1.9 to 5.2, p 2 were accountable for a high rate of TMMBs. Bleeding incidences from clinical trials cannot be translated to an unselected STEMI population.

OBJECTIVES: Knowledge of the association between time and causes of death after coronary artery bypass grafting is sparse. We examined short- and long-term mortality and cause of death in patients undergoing coronary artery bypass grafting.METHODS: With the use of Danish nationwide registries, we identified all patients undergoing isolated coronary artery bypass grafting from 1998 to 2014. Cause of death was classified as cardiovascular or noncardiovascular according to death certificates. Landmark analyses of the cumulative incidences of cardiovascular and noncardiovascular mortality after 1, 3, and 5 years after coronary artery bypass grafting were performed. Multivariable cause-specific Cox regression models were used to evaluate changes over time in the risk of all-cause, cardiovascular, and noncardiovascular mortality after 1 and 7 years after coronary artery bypass grafting, respectively.RESULTS: Among 37,495 included patients, 12,230 (32.6%) died during a median follow-up of 7.4 years. Causes of death were classified as cardiovascular in 6459 patients (52.8%) and noncardiovascular in 5771 patients (47.2%). Within the first year, the incidence of cardiovascular death was higher compared with noncardiovascular death (3.9% vs 1.1%, P < .001). The cumulative incidences of cardiovascular and noncardiovascular were deaths similar in the periods 1 to 3 years (2.3% vs 2.6%, P = .004), 3 to 5 years (3.1% vs 3.2%, P = .75), and 5 to 7 years postsurgery (3.7% vs 4.0%, P = .07). The crude rates and adjusted risks of short- and long-term all-cause and cardiovascular mortality decreased during the study period despite an increase in age and burden of comorbidities.CONCLUSIONS: In patients undergoing coronary artery bypass grafting, cardiovascular causes were responsible for the majority of deaths within the first year. Deaths due to noncardiovascular causes gained importance over time elapsed since coronary artery bypass grafting.

Aims The purpose of this study was to describe adherence with non-vitamin K antagonists (NOACs) and vitamin K antagonists (VKA) in patients with non-valvular atrial fibrillation (NVAF). Methods and results By linkage of Danish nationwide registers, we identified patients with NVAF who claimed a prescription of a NOAC (dabigatran, rivaroxaban, and apixaban), or a VKA. Adherence was evaluated according to Proportions of Days Covered, refill gaps, and switch in treatment. Adjusted analyses were calculated with logistic regression and Cox proportional hazard models. Between 2011 and 2014, 46 675 patients with NVAF claimed a prescription of anticoagulation (OAC): 57.3% used VKA, 29.8% dabigatran, 8.5% rivaroxaban, and 4.4% apixaban. During the first 180 days, PDC >80% was the highest among users of rivaroxaban. Compared with rivaroxaban, OR was 0.79 with apixaban (95% CI 0.69-0.92), 0.72 with dabigatran (95% CI 0.66-0.80), and 0.76 with VKAs (95% CI 0.69-0.83). HR for refill gaps between 7 and 89 days of length were (rivaroxaban as reference): apixaban 1.52(95% CI 1.36-1.69), dabigatran 1.72 (95% CI 1.60-1.85), and VKA 2.36(95% CI 2.20-2.52). Refill gaps of more than 89 days occurred in 11.5% of VKA recipients, with substantially lower rates for patients treated with NOAC. Switch between OACs was the highest in users of dabigatran (21.0%) and the lowest in users of apixaban (8.6%). Conclusion Among NVAF patients treated with OAC, 42.7% received a NOAC. PDC > 80%, and periods without refill gaps were the highest among users of rivaroxaban. Refill gaps occurred most often with VKA, switch was most common with dabigatran use.

Aims Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophylaxis in atrial fibrillation (AF). We investigated ‘real-world’ information on how these drugs are being adopted. Methods and results Using Danish nationwide administrative registers, we identified all oral anticoagulation-naive AF patients initiating oral anticoagulation from 22 August 2011 through 31 October 2013. Using logistic regression analysis, baseline characteristics and temporal utilization trends were compared between initiators of warfarin vs. one of the N OACs: dabigatran, rivaroxaban, or apixaban. We identified 18 611 oral anticoagulation-naive AF patients of which 9902 (53%) initiated warfarin treatment, 7128 (38%) dabigatran, 1303 (7%) rivaroxaban, and 278 (1%) apixaban. Overall, 40% of newly initiated patients were started on dabigatran within the first 4 months of when the drug came on market. By October, 2013, 40% were being started on warfarin and dabigatran, respectively, and another 20% were started on either rivaroxaban or apixaban. Rivaroxaban and apixaban users generally had a higher predicted risk of stroke and bleeding compared with warfarin and dabigatran users. Older age, female gender, and prior stroke were some of the factors associated with NOAC use vs. warfarin, whereas chronic kidney disease, myocardial infarction, and heart failure showed the opposite association. Conclusion Among oral anticoagulation-naive AF patients initiated on oral anticoagulation in Denmark, warfarin initiation has declined since the introduction of dabigatran in August 2011. Dabigatran is the most frequently used alternative option to warfarin; however, use of rivaroxaban and apixaban is increasing. Patients initiated with rivaroxaban or apixaban in general have a higher predicted stroke and bleeding risks compared with warfarin or dabigatran initiators. [10.1093/europace/euu223][1] [1]: /lookup/doi/10.1093/europace/euu223

BACKGROUND: Dual anti-platelet treatment with clopidogrel and aspirin is indicated for most patients after myocardial infarction. We examined the risk/benefit relationship of dual anti-platelet treatment according to age in a nationwide cohort of 30,532 myocardial infarction patients without revascularization.METHODS: Patients admitted with first-time myocardial infarction in 2002-2010, not undergoing revascularization, were identified from nationwide Danish registers. Dual anti-platelet treatment use was assessed by claimed prescriptions. Stratified into age groups, risk of bleeding, all-cause mortality and a combined endpoint of cardiovascular death, recurrent myocardial infarction and ischaemic stroke was analysed by Cox proportional-hazard models and tested in a propensity-score matched population.RESULTS: A total of 21,302 users and 9230 non-users of dual anti-platelet treatment were included (mean age 67.02 (±13.8) years and 64.7% males). Use of dual anti-platelet treatment decreased with age: 80% (79 years). We found a reduced risk of cardiovascular death, recurrent myocardial infarction and ischaemic stroke in users 79 years (HR=0.92; 95% CI 0.84-1.01, NS). Risk of bleeding increased with dual anti-platelet treatment use in patients aged 79 years (HR=1.46; 95% CI 1.22-1.74). Similar tendencies in all four age groups were found in the propensity-matched population.CONCLUSION: Dual anti-platelet treatment use was less likely among elderly patients although similar effects regarding both risk and benefit were found in all age groups. Increased focus on initiating dual anti-platelet treatment in elderly, non-invasively treated myocardial infarction patients is warranted.

IntroductionA large group of patients with chronic obstructive pulmonary disease (COPD) are exposed to an overload of oral corticosteroids (OCS) due to repeated exacerbations. This is associated with potential serious adverse effects. Therefore, we evaluated the impact of a recommended reduction of OCS duration in 2014 on the risk of pneumonia hospitalisation and all-cause mortality in patients with acute exacerbation of COPD (AECOPD).MethodsThis was a nationwide observational cohort study that was based on linked administrative registry data between 1 January 2010 and 31 October 2017. 10 152 outpatients with COPD (median age 70 years) treated with either a short (≤250 mg) or long course (>250 mg) of OCS for AECOPD were included in the study. Cox proportional hazards regression models were used to derive an estimation of multivariable adjusted HRs (aHRs) for pneumonia hospitalisation or all-cause mortality combined and pneumonia hospitalisation and all-cause mortality, separately.ResultsThe long course of OCS treatment for AECOPD was associated with an increased 1-year risk of pneumonia hospitalisation or all-cause mortality (aHR 1.3, 95% CI 1.1 to 1.4; pConclusionThe change of recommendations from long courses to short courses of OCS for AECOPD in 2014 was strongly associated with a decrease in pneumonia admissions and all-cause mortality, in favour of short courses of OCS.

Chronic obstructive pulmonary disease (COPD) is associated with long-term all-cause death after percutaneous coronary intervention with bare-metal stents. Regarding other outcomes, previous studies have shown conflicting results and the impact of drug-eluting stent (DES) in this population is not well known. We analyzed 4,605 patients who underwent percutaneous coronary intervention with bare-metal stents (33.1%) or DES (66.9%) from the Basel Stent Kosten-Effektivitats Trial-Prospective Validation Examination trials I and II. COPD patients (n = 283, 6.1%), were older and had more frequently a smoking or cardiovascular event history. At 2-year follow-up, cumulative event rates for patients with versus without COPD were the following: major adverse cardiac events (MACE: composite of cardiac death, nonfatal myocardial infarction, and target vessel revascularization): 15.2% versus 8.1% (p0.001); all-cause death: 11.7% versus 2.4% (p0.001); cardiac death: 5.7% versus 1.2% (p0.001); myocardial infarction: 3.5% versus 1.9% (p = 0.045); definite/probable/possible stent thrombosis: 2.5% versus 0.9% (p = 0.01); and major bleeding: 4.2% versus 2.1% (p = 0.014). After adjusting for confounders including smoking status, COPD remained an independent predictor for MACE (hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.31 to 2.49), all-cause death (HR 3.62, 95% CI 2.41 to 5.45), cardiac death (HR 3.12, 95% CI 1.74 to 5.60), and stent thrombosis (HR 2.39, 95% CI 1.03 to 5.54). We did not find evidence of an interaction between COPD and DES implantation (p for interaction = 0.29) for MACE. In conclusion, COPD is associated with increased 2-year rates of all-cause death, cardiac death, and stent thrombosis after stent implantation. DES use appears to be beneficial also in patients with COPD.

Antithrombotic therapy is a cornerstone of treatment in patients with cardiovascular disease with bleeding being the most feared complication. This review describes the risk of bleeding related to different combinations of antithrombotic drugs used for cardiovascular disease: acute coronary syndrome (ACS), atrial fibrillation (AF), cerebrovascular (CVD) and peripheral arterial disease (PAD). Different risk assessment schemes and bleeding definitions are compared. The HAS-BLED risk score is recommended in patients with AF and in ACS patients with AF. In patients with ACS with or without a stent dual antiplatelet therapy with a P2Y12 receptor antagonist and acetylsalicylic acid (ASA) is recommended for 12 months, preferable with prasugrel or ticagrelor unless there is an additional indication of warfarin or increased risk of bleeding. In patients with AF, warfarin is recommended if the risk of stroke is moderate to high, but newer emerging antithrombotic drugs will be recommended along with/or preferred to warfarin in the nearby future. Patients with CVD (without cardiogenic causes) are recommended clopidogrel treatment for secondary prevention, where as patients with PAD are recommended ASA or clopidogrel. With future implementation of new antithrombotic treatment regimens as monotherapy and in combinations with antiplatelet therapy, increased focus on risk of thromboembolic events and bleeding and individual tailoring of antithrombotic therapy is warranted.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • General use of hormone replacement therapy (HRT) dropped drastically after 2002 when pivotal randomized trials showed increased risk of coronary artery disease and other complications with HRT. • HRT is not recommended for primary or secondary prevention of coronary heart disease and guidelines recommend discontinuation of HRT after myocardial infarction (MI). • It is unknown whether women actually discontinue HRT after MI. WHAT THIS STUDY ADDS • Women who use HRT when they experience their MI generally continue using HRT. • We found a remarkably low increase in discontinuation after 2002, in contrast to the general drop in use of HRT. AIM To characterize the pattern of use and discontinuation of postmenopausal hormone replacement therapy (HRT) in women with myocardial infarction (MI) before and after 2002, where the general use of HRT dropped drastically subsequent to the results of the Women's Health Initiative trial. METHODS All Danish women aged ≥40 years hospitalized with MI in the period 1997 to 2005 and their use of HRT were identified by individual-level-linkage of nationwide registers of hospitalization and drug dispensing from pharmacies. Characteristics associated with HRT use at time of MI and subsequent HRT discontinuation were analysed by multivariable logistic regression. RESULTS In the study period, 34 778 women were discharged after MI. Of these, 3979 (11.4%) received HRT at the time of MI and their most used categories of HRT were vaginal oestrogen and oral oestrogen alone (46.6% and 28.7%, respectively). The percentage of women who continued HRT during the first year after discharge was 85.0% in the period 2000–2002 and had decreased to 79.6% in the period 2003–2005. Vaginal oestrogen use was associated with overall discontinuation of HRT (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.10, 1.72), whereas use of oral oestrogen alone and use of oral cyclic combined oestrogen/progestogen were associated with change of HRT after MI (OR 2.33, 95% CI 1.10, 4.93 and OR 2.94, 95% CI 1.35, 6.39, respectively). CONCLUSION The majority of women experiencing an MI during ongoing HRT continued HRT after discharge and this pattern of HRT use did not change markedly after 2002.

Background— Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals. Methods and Results— With the use of individual-level linkage of nationwide administrative registers, we identified a cohort of individuals without hospitalizations 5 years before first prescription claim of NSAIDs and without claimed drug prescriptions for selected concomitant medication 2 years previously. The risk of cardiovascular death, a composite of coronary death or nonfatal myocardial infarction, and fatal or nonfatal stroke associated with the use of NSAIDs was estimated by case-crossover and Cox proportional hazard analyses. The entire Danish population age 10 years or more consisted of 4 614 807 individuals on January 1, 1997, of which 2 663 706 (57.8%) claimed at least 1 prescription for NSAIDs during 1997 to 2005. Of these; 1 028 437 individuals were included in the study after applying selection criteria regarding comorbidity and concomitant pharmacotherapy. Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk. There was a trend for increased risk of fatal or nonfatal stroke associated with ibuprofen treatment (odds ratio, 1.29; 95% confidence interval, 1.02 to 1.63), but naproxen was not associated with increased cardiovascular risk (odds ratio for cardiovascular death, 0.84; 95% confidence interval, 0.50 to 1.42). Conclusions— Individual NSAIDs have different degrees of cardiovascular safety, which must be considered when choosing appropriate treatment. In particular, rofecoxib and diclofenac were associated with increased cardiovascular mortality and morbidity and should be used with caution in most individuals, whereas our results suggest that naproxen has a safer cardiovascular risk-profile.

A large proportion of melanoma patients host a spontaneous T-cell response specifically against ML-IAP-derived peptides. In this study, we describe that some ML-IAP-specific cytotoxic T cells isolated from melanoma patients cross react with an epitope from the auto-antigen SS56. SS56 is a recently described target of autoantibody responses in Sjögren's syndrome (SS) as well as systemic lupus erythematosus (SLE). Here, we describe that SS56 is also an auto-antigen for T cells in SS and SLE. Hence, SS56-specific T cells could readily be detected in circulation and among the infiltrating cells of SLE skin lesions. SS56-specific T cells were able to lyse target cells presenting the peptide epitope on the surface. Notably, SS56-specific CD8 T cells isolated from an SS patient cross reacted with the ML-IAP epitope. This early evidence of a target for auto-reactive CTL in SS and SLE patients; it is to our knowledge previously unreported and underscores the important role of CD8 T cells in autoimmune disorders. Furthermore, the cross-reactivity against the auto-antigen SS56 and the tumor-antigen ML-IAP confirms the link between autoimmunity and anti-cancer cellular immune responses.

BACKGROUND: Randomized clinical trials have found that early invasive strategies reduce mortality, myocardial infarction (MI), and rehospitalization compared with a conservative invasive approach in acute coronary syndromes (ACSs), but the effectiveness of such strategies in real-world settings is unknown.OBJECTIVE: To investigate adverse cardiovascular outcomes of an early versus a conservative invasive strategy in a national cohort of patients with ACSs.DESIGN: Retrospective cohort study.SETTING: Administrative health care data on hospitalizations, procedures, and outcomes abstracted from the Danish national registries and covering all acute invasive procedures in patients presenting with an ACS.PATIENTS: 19 704 propensity score-matched patients hospitalized with a first ACS between 1 January 2005 and 31 December 2011.MEASUREMENTS: Risk for cardiac death or rehospitalization for MI within 60 days of hospitalization.RESULTS: Compared with a conservative approach, early invasive strategies were associated with a lower risk for cardiac death (cumulative incidence, 5.9% vs. 7.6%; adjusted hazard ratio [HR], 0.75 [95% CI, 0.66 to 0.84]; P < 0.001). Similar results were found for rehospitalization for MI (cumulative incidence, 3.4% vs. 5.0%; adjusted odds ratio, 0.67 [CI, 0.58 to 0.77]; P < 0.001) and all-cause death (cumulative incidence, 7.3% vs. 10.6%; adjusted HR, 0.65 [CI, 0.59 to 0.72]; P < 0.001).LIMITATION: Potential residual confounding due to lack of core clinical variables.CONCLUSION: In this real-world cohort of patients with a first hospitalization for an ACS, the use of an early invasive treatment strategy was associated with a lower risk for cardiac death and rehospitalization for MI compared with a conservative invasive approach.PRIMARY FUNDING SOURCE: Department of Cardiology, University Hospital Gentofte.

AIMS: To examine trends in the use of diagnostic coronary angiography according to distance from home to the nearest invasive heart centre following implementation of fast-track protocols and extensive pre-hospital triaging of acute coronary syndrome patients.METHODS AND RESULTS: We performed a register-based cohort study of all patients admitted to Danish hospitals with incident acute coronary syndrome in 2005-2011. Diagnostic coronary angiography within 60 days of admission was investigated according to distance tertiles (DTs) calculated as range from each patient's home to the nearest invasive heart centre (short DT: 65 km). Cox proportional hazards models were applied. Among the 52,409 patients included, diagnostic coronary angiography was increasingly used during 2005-2011 (short DT: 76% to 81%; medium DT: 74% to 81%; long DT: 69% to 78%; all p-values for trend CONCLUSIONS: This nationwide study found significant increases in diagnostic coronary angiography use over time in incident acute coronary syndrome patients with a relatively larger increase in patients residing farthest from an invasive heart centre. Additionally, selected quality of care measures improved in the entire cohort, suggesting a benefit of national clinical protocols.

Based on the detection of spontaneous immune responses in cancer patients with cancer of different origin, Bcl-X(L) was recently described as a highly interesting tumor antigen recognized by CD8 positive cytotoxic T lymphocytes. To further characterize Bcl-X(L) as a tumor antigen we isolated and expanded Bcl-X(L) specific T cells from the peripheral blood of a breast cancer patient hosting a strong Bcl-X(L) specific T cell response. We describe that HLA-A2 restricted Bcl-X(L) specific T cell clones very efficiently lyse peptide pulsed T2 cells. Furthermore, tumor cell lines of different origin, i.e., breast cancer, colon cancer, and melanoma, are efficiently lysed in an HLA-dependent manner. Finally, ex vivo-isolated leukemia cells, but not non-malignant B and T cells are killed by Bcl-X(L) specific T cells. Our data underline Bcl-X(L) as an universal tumor antigen widely applicable in specific anticancer immunotherapy.