Lina Benson

Assessment of female sex as a risk factor in atrial fibrillation in Sweden: nationwide retrospective cohort study.

Objective To determine whether women with atrial fibrillation have a higher risk of stroke than men. Design Nationwide retrospective cohort study. Setting Patients with a diagnosis of atrial fibrillation in the Swedish hospital discharge register between 1 July 2005 and 31 December 2008. Information about drug treatment taken from the Swedish drug register. Participants 100 802 patients with atrial fibrillation at any Swedish hospital or hospital affiliated outpatient clinic with a total follow-up of 139 504 years at risk (median 1.2 years). We excluded patients with warfarin at baseline, mitral stenosis, previous valvular surgery, or who died within 14 days from baseline. Main outcome measure Incidence of ischaemic stroke. Results Ischaemic strokes were more common in women than in men (6.2% v 4.2% per year, P<0.0001). The univariable hazard ratio for women compared with men was 1.47 (95% confidence 1.40 to 1.54), indicating a 47% higher incidence of ischaemic stroke in women than in men. Stratification according to the CHADS2 scheme showed increased stroke rates for women in all strata. After multivariable adjustment for 35 cofactors for stroke, an increased risk of stroke in women remained (1.18, 1.12 to 1.24). Among patients with “lone atrial fibrillation” (age <65 years and no vascular disease), the annual stroke rate tended to be higher in women than in men, although this difference was not significant (0.7% v 0.5%, P=0.09). When low risk patients with CHADS2 scores of 0-1 were stratified according to their CHA2DS2-VASc scores, women did not have higher stroke incidence than men at CHA2DS2-VASc scores of 2 or less. Conclusion Women with atrial fibrillation have a moderately increased risk of stroke compared with men, and thus, female sex should be considered when making decisions about anticoagulation treatment. However, women younger than 65 years and without other risk factors have a low risk for stroke, and do not need anticoagulant treatment.

Association Between Use of Renin-Angiotensin System Antagonists and Mortality in Patients With Heart Failure and Preserved Ejection Fraction

CONTEXT Heart failure with preserved ejection fraction (HFPEF) may be as common and as lethal as heart failure with reduced ejection fraction (HFREF). Three randomized trials of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ie, renin-angiotensin system [RAS] antagonists) did not reach primary end points but may have had selection bias or been underpowered. OBJECTIVE To test the hypothesis that use of RAS antagonists is associated with reduced all-cause mortality in an unselected population with HFPEF. DESIGN, SETTING, AND PATIENTS Prospective study using the Swedish Heart Failure Registry of 41,791 unique patients registered from 64 hospitals and 84 outpatient clinics between 2000 and 2011. Of these, 16,216 patients with HFPEF (ejection fraction ≥40%; mean [SD] age, 75 [11] years; 46% women) were either treated (n = 12,543) or not treated (n = 3673) with RAS antagonists. Propensity scores for RAS antagonist use were derived from 43 variables. The association between use of RAS antagonists and all-cause mortality was assessed in a cohort matched 1:1 based on age and propensity score and in the overall cohort with adjustment for propensity score as a continuous covariate. To assess consistency, separate age and propensity score-matched analyses were performed according to RAS antagonist dose in patients with HFPEF and in 20,111 patients with HFREF (ejection fraction <40%) in the same registry. MAIN OUTCOME MEASURE All-cause mortality. RESULTS In the matched HFPEF cohort, 1-year survival was 77% (95% CI, 75%-78%) for treated patients vs 72% (95% CI, 70%-73%) for untreated patients, with a hazard ratio (HR) of 0.91 (95% CI, 0.85-0.98; P = .008). In the overall HFPEF cohort, crude 1-year survival was 86% (95% CI, 86%-87%) for treated patients vs 69% (95% CI, 68%-71%) for untreated patients, with a propensity score-adjusted HR of 0.90 (95% CI, 0.85-0.96; P = .001). In the HFPEF dose analysis, the HR was 0.85 (95% CI, 0.78-0.83) for 50% or greater of target dose vs no treatment (P < .001) and 0.94 (95% CI, 0.87-1.02) for less than 50% of target dose vs no treatment (P = .14). In the age and propensity score-matched HFREF analysis, the HR was 0.80 (95% CI, 0.74-0.86; P < .001). CONCLUSION Among patients with heart failure and preserved ejection fraction, the use of RAS antagonists was associated with lower all-cause mortality.

Balancing stroke and bleeding risks in patients with atrial fibrillation and renal failure: the Swedish Atrial Fibrillation Cohort study

BACKGROUND Patients who have both atrial fibrillation (AF) and renal failure have an increased risk of thrombo-embolism. Renal failure is also a risk factor for bleeding, which makes decisions regarding thromboprophylaxis complicated. Our aim was to determine risks for ischaemic stroke and bleeding in patients with AF and renal failure in relation to anticoagulant strategies. METHODS AND RESULTS This is retrospective non-randomized study of Swedish health registers comprising 307 351 patients with AF, of whom 13 435 had a previous diagnosis of renal failure. Ischaemic stroke occurred more often in AF patients with renal failure (annual rate, 3.9% vs. no renal failure, 2.9%), but this was related to concomitant comorbidities [adjusted hazard ratio (HR) 1.02, 95% confidence interval (CI) 0.95-1.10]. Adding renal failure to the established stroke risk stratification schemes (CHADS2 and CHA2DS2-VASc) did not improve their predictive value. Renal failure was an independent risk factor for intracranial bleeding [adjusted HR: 1.27 (1.09-1.49)]. Most patients with renal failure benefited from warfarin treatment, despite their high bleeding risk. The incidence of the combined endpoint ischaemic or haemorrhagic stroke or death was lower among those who used warfarin than among those who did not use warfarin (adjusted HR: 0.76, CI 0.72-0.80). CONCLUSIONS Patients with both AF and renal failure will probably benefit most from having the same treatment as is recommended for other patients with AF, without setting a higher or lower threshold for treatment. Adding additional points for renal failure to the CHADS2 and CHA2DS2-VASc scores did not improve their predictive value.

Association Between Use of β-Blockers and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction

IMPORTANCE Heart failure with preserved ejection fraction (HFPEF) may be as common and may have similar mortality as heart failure with reduced ejection fraction (HFREF). β-Blockers reduce mortality in HFREF but are inadequately studied in HFPEF. OBJECTIVE To test the hypothesis that β-blockers are associated with reduced all-cause mortality in HFPEF. DESIGN Propensity score-matched cohort study using the Swedish Heart Failure Registry. Propensity scores for β-blocker use were derived from 52 baseline clinical and socioeconomic variables. SETTING Nationwide registry of 67 hospitals with inpatient and outpatient units and 95 outpatient primary care clinics in Sweden with patients entered into the registry between July 1, 2005, and December 30, 2012, and followed up until December 31, 2012. PARTICIPANTS From a consecutive sample of 41,976 patients, 19,083 patients with HFPEF (mean [SD] age, 76 [12] years; 46% women). Of these, 8244 were matched 2:1 based on age and propensity score for β-blocker use, yielding 5496 treated and 2748 untreated patients with HFPEF. Also we conducted a positive-control consistency analysis involving 22,893 patients with HFREF, of whom 6081 were matched yielding 4054 treated and 2027 untreated patients. EXPOSURES β-Blockers prescribed at discharge from the hospital or during an outpatient visit, analyzed 2 ways: without consideration of crossover and per-protocol analysis with censoring at crossover, if applicable. MAIN OUTCOMES AND MEASURES The prespecified primary outcome was all-cause mortality and the secondary outcome was combined all-cause mortality or heart failure hospitalization. RESULTS Median follow-up in HFPEF was 755 days, overall; 709 days in the matched cohort; no patients were lost to follow-up. In the matched HFPEF cohort, 1-year survival was 80% vs 79% for treated vs untreated patients, and 5-year survival was 45% vs 42%, with 2279 (41%) vs 1244 (45%) total deaths and 177 vs 191 deaths per 1000 patient-years (hazard ratio [HR], 0.93; 95% CI, 0.86-0.996; P = .04). β-Blockers were not associated with reduced combined mortality or heart failure hospitalizations: 3368 (61%) vs 1753 (64%) total for first events, with 371 vs 378 first events per 1000 patient-years (HR, 0.98; 95% CI, 0.92-1.04; P = .46). In the matched HFREF cohort, β-blockers were associated with reduced mortality (HR, 0.89; 95% CI, 0.82-0.97, P=.005) and also with reduced combined mortality or heart failure hospitalization (HR, 0.89; 95% CI, 0.84-0.95; P = .001). CONCLUSIONS AND RELEVANCE In patients with HFPEF, use of β-blockers was associated with lower all-cause mortality but not with combined all-cause mortality or heart failure hospitalization. β-Blockers in HFPEF should be examined in a large randomized clinical trial.

Prevalence, correlates, and prognostic significance of QRS prolongation in heart failure with reduced and preserved ejection fraction

AIMS The independent clinical correlates and prognostic impact of QRS prolongation in heart failure (HF) with reduced and preserved ejection fraction (EF) are poorly understood. The rationale for cardiac resynchronization therapy (CRT) in preserved EF is unknown. The aim was to determine the prevalence of, correlates with, and prognostic impact of QRS prolongation in HF with reduced and preserved EF. METHODS AND RESULTS We studied 25,171 patients (age 74.6 ± 12.0 years, 39.9% women) in the Swedish Heart Failure Registry. We assessed QRS width and 40 other clinically relevant variables. Correlates with QRS width were assessed with multivariable logistic regression, and the association between QRS width and all-cause mortality with multivariable Cox regression. Pre-specified subgroup analyses by EF were performed. Thirty-one per cent had QRS ≥120 ms. Strong predictors of QRS ≥120 ms were higher age, male gender, dilated cardiomyopathy, longer duration of HF, and lower EF. One-year survival was 77% in QRS ≥120 vs. 82% in QRS <120 ms, and 5-year survival was 42 vs. 51%, respectively (P < 0.001). The adjusted hazard ratio for all-cause mortality was 1.11 (95% confidence interval 1.04-1.18, P = 0.001) for QRS ≥120 vs. <120 ms. There was no interaction between QRS width and EF. CONCLUSION QRS prolongation is associated with other markers of severity in HF but is also an independent risk factor for all-cause mortality. The risk associated with QRS prolongation may be similar regardless of EF. This provides a rationale for trials of CRT in HF with preserved EF.

Association of Candesartan vs Losartan With All-Cause Mortality in Patients With Heart Failure

CONTEXT Angiotensin II receptor blockers (ARBs) reduce combined mortality and hospitalization in patients with heart failure (HF) with reduced left ventricular ejection fraction. Different agents have different affinity for the AT(1) receptor and may have different clinical effects, but have not been tested against each other in HF. OBJECTIVE To assess the association of candesartan vs losartan with all-cause mortality in patients with HF. DESIGN, SETTING, AND PATIENTS An HF registry (the Swedish Heart Failure Registry) of 30,254 unique patients registered from 62 hospitals and 60 outpatient clinics between 2000 and 2009. A total of 5139 patients (mean [SD] age, 74 [11] years; 39% women) were treated with candesartan (n = 2639) or losartan (n = 2500). Survival as of December 14, 2009, by ARB agent was analyzed by Kaplan-Meier method and predictors of survival determined by univariate and multivariate proportional hazard regression models, with and without adjustment for propensity scores and interactions. Stratified analyses and quantification of residual confounding were also performed. MAIN OUTCOME MEASURES All-cause mortality at 1 and 5 years. RESULTS One-year survival was 90% (95% confidence interval [CI], 89%-91%) for patients receiving candesartan and 83% (95% CI, 81%-84%) for patients receiving losartan, and 5-year survival was 61% (95% CI, 54%-68%) and 44% (95% CI, 41%-48%), respectively (log-rank P < .001). In multivariate analysis with adjustment for propensity scores, the hazard ratio for mortality for losartan compared with candesartan was 1.43 (95% CI, 1.23-1.65; P < .001). The results persisted in stratified analyses. CONCLUSION In this registry of patients with HF, the use of candesartan compared with losartan was associated with a lower mortality risk.

Association between demographic, organizational, clinical, and socio-economic characteristics and underutilization of cardiac resynchronization therapy : results from the Swedish Heart Failure Registry.

Cardiac resynchronization therapy (CRT) improves outcomes in heart failure (HF) but may be underutilized. The reasons are unknown.

Gender, underutilization of cardiac resynchronization therapy, and prognostic impact of QRS prolongation and left bundle branch block in heart failure

AIMS It has been suggested that cardiac resynchronization therapy (CRT) is less utilized, dyssynchrony occurs at narrower QRS, and CRT is more beneficial in women compared with men. We tested the hypotheses that (i) CRT is more underutilized and (ii) QRS prolongation and left bundle branch block (LBBB) are more harmful in women. METHODS AND RESULTS We studied 14 713 patients (28% women) with left ventricular ejection fraction (LVEF) <40% in the Swedish Heart Failure Registry. In women vs. men, CRT was present in 4 vs. 7% (P < 0.001) and was absent but with indication in 30 vs. 31% (P = 0.826). Next, among 13 782 patients (28% women) without CRT, 9% of women and 17% of men had non-specific intraventricular conduction delay (IVCD) and 27% of women and 24% of men had LBBB. One-year survival with narrow QRS was 85% in women and 88% in men, with IVCD 74 and 78%, and with LBBB 84 and 82%, respectively. Compared with narrow QRS, IVCD had a multivariable hazard ratio of 1.24 (95% CI 1.05-1.46, P = 0.011) in women and 1.30 (95% CI 1.19-1.42, P < 0.001) in men, and LBBB 1.03 (95% CI 0.91-1.16, P = 0.651) in women and 1.16 (95% CI 1.07-1.26, P < 0.001) in men, P for interaction between gender and QRS morphology, 0.241. CONCLUSIONS While the proportion with CRT was lower in women, CRT was equally underutilized in both genders. QRS prolongation with or without LBBB was not more harmful in women than in men. Efforts to improve CRT implementation should be directed equally towards women and men.

Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of ≥50%

Background—The pathophysiology of heart failure with preserved ejection fraction is poorly understood, but may involve a systemic proinflammatory state. Therefore, statins might improve outcomes in patients with heart failure with preserved ejection fraction defined as ≥50%. Methods and Results—Of 46 959 unique patients in the prospective Swedish Heart Failure Registry, 9140 patients had heart failure and ejection fraction ≥50% (age 77±11 years, 54.0% women), and of these, 3427 (37.5%) were treated with statins. Propensity scores for statin treatment were derived from 40 baseline variables. The association between statin use and primary (all-cause mortality) and secondary (separately, cardiovascular mortality, and combined all-cause mortality or cardiovascular hospitalization) end points was assessed with Cox regressions in a population matched 1:1 based on age and propensity score. In the matched population, 1-year survival was 85.1% for statin-treated versus 80.9% for untreated patients (hazard ratio, 0.80; 95% confidence interval, 0.72–0.89; P<0.001). Statins were also associated with reduced cardiovascular death (hazard ratio, 0.86; 95% confidence interval, 0.75–0.98; P=0.026) and composite all-cause mortality or cardiovascular hospitalization (hazard ratio, 0.89; 95% confidence interval, 0.82–0.96; P=0.003). Conclusions—In heart failure with ejection fraction ≥50%, the use of statins was associated with improved outcomes. The mechanisms should be evaluated and the effects tested in a randomized trial.

Association Between Use of Statins and Outcomes in Heart Failure With Reduced Ejection Fraction Prospective Propensity Score Matched Cohort Study of 21 864 Patients in the Swedish Heart Failure Registry

Background— In heart failure (HF) with reduced ejection fraction, randomized trials of statins did not demonstrate improved outcomes. However, randomized trials may not always be generalizable. The aim was to determine whether statins are associated with improved outcomes in an unselected nationwide population of patients with HF with reduced ejection fraction overall and in relation to ischemic heart disease (IHD). Methods and Results— In the Swedish Heart Failure Registry, 21 864 patients with HF with reduced ejection fraction (age ± SD, 72±12 years; 29% women), of whom 10 345 (47%) were treated with statins, were studied. Propensity scores for statin use were derived from 42 baseline variables. The associations between statin use and outcomes were assessed with Cox regressions in a population matched 1:1 based on propensity score and age and in the overall population with adjustment for propensity score and age. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular mortality; HF hospitalization; and combined all-cause mortality or cardiovascular hospitalization. Survival at 1 year in the matched population was 83% for statin-treated versus 79% for untreated patients (hazard ratio, 0.81; 95% confidence interval, 0.76–0.86; P <0.001). In the unmatched population, 1-year survival was 85% for statin-treated versus 79% for untreated patients, hazard ratio after adjustment for propensity score and age was 0.84 (95% confidence interval, 0.80–0.89; P <0.001). No examined baseline variables interacted with statin use except for IHD ( P =0.001), with a hazard ratio of 0.76 (95% confidence interval, 0.70–0.82, P <0.001) with IHD and 0.95 (95% confidence interval, 0.85–1.07; P =0.430 without IHD. Statin use was also associated with reduced risk for all 3 secondary outcomes. Conclusions— In an unselected nationwide population of patients with HF with reduced ejection fraction, statins were associated with improved outcomes, specifically in the presence of IHD. This contrasts with previous randomized controlled trials. Additional randomized controlled trials with more generalized inclusion or focused on IHD may be warranted.Background—In heart failure (HF) with reduced ejection fraction, randomized trials of statins did not demonstrate improved outcomes. However, randomized trials may not always be generalizable. The aim was to determine whether statins are associated with improved outcomes in an unselected nationwide population of patients with HF with reduced ejection fraction overall and in relation to ischemic heart disease (IHD). Methods and Results—In the Swedish Heart Failure Registry, 21 864 patients with HF with reduced ejection fraction (age ± SD, 72±12 years; 29% women), of whom 10 345 (47%) were treated with statins, were studied. Propensity scores for statin use were derived from 42 baseline variables. The associations between statin use and outcomes were assessed with Cox regressions in a population matched 1:1 based on propensity score and age and in the overall population with adjustment for propensity score and age. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular mortality; HF hospitalization; and combined all-cause mortality or cardiovascular hospitalization. Survival at 1 year in the matched population was 83% for statin-treated versus 79% for untreated patients (hazard ratio, 0.81; 95% confidence interval, 0.76–0.86; P<0.001). In the unmatched population, 1-year survival was 85% for statin-treated versus 79% for untreated patients, hazard ratio after adjustment for propensity score and age was 0.84 (95% confidence interval, 0.80–0.89; P<0.001). No examined baseline variables interacted with statin use except for IHD (P=0.001), with a hazard ratio of 0.76 (95% confidence interval, 0.70–0.82, P<0.001) with IHD and 0.95 (95% confidence interval, 0.85–1.07; P=0.430 without IHD. Statin use was also associated with reduced risk for all 3 secondary outcomes. Conclusions—In an unselected nationwide population of patients with HF with reduced ejection fraction, statins were associated with improved outcomes, specifically in the presence of IHD. This contrasts with previous randomized controlled trials. Additional randomized controlled trials with more generalized inclusion or focused on IHD may be warranted.