Use of quinine and mortality-risk in patients with heart failure--a Danish nationwide observational study.

PURPOSE: Leg cramps are common in patients with heart failure. Quinine is frequently prescribed in low doses to these patients, but safety of this practice is unknown. We studied the outcomes associated with use of quinine in a nationwide cohort of patients with heart failure. METHODS: Through individual-level-linkage of Danish national registries, we identified patients discharged from first-time hospitalization for heart failure in 1997-2010. We estimated the risk of mortality associated with quinine treatment by time-dependent Poisson regression models. RESULTS: A total of 135 529 patients were included, with 14 510 patients (11%) using quinine at some point. During a median time of follow-up of 989 days (interquartile range 350-2004) 88 878 patients (66%) died. Patients receiving quinine had slightly increased mortality risk, adjusted incidence rate ratio (IRR) 1.04 (95% confidence interval [CI] 1.01 to 1.07). The risks differed according to concomitant ß-blocker treatment. For patients treated with both quinine and ß-blockers IRR was 1.15 (95% CI 1.09 to 1.21) vs. 0.99 (95% CI 0.96 to 1.03) for patients treated with quinine but not ß-blockers. The risks were highest shortly after initiation of therapy: for the first 14 days of treatment IRR was 2.12 (95% CI 1.54 to 2.93) for patients in treatment with ß-blockers and 1.17 (95% CI 0.86 to 1.59) for patients not treated with ß-blockers. CONCLUSIONS: Use of quinine was common and associated with increased mortality in heart failure, especially if administered together with ß-blockers and shortly after treatment initiation. Mechanisms underlying the findings remain to be established.

Nationwide trends in development of heart failure and mortality after first-time myocardial infarction 1997-2010: A Danish cohort study.

AIMS: Pharmacological and revascularization strategies following myocardial infarction (MI) have changed substantially during the last two decades. We investigated the temporal trends in heart failure (HF) incidence and mortality during the first 90 days following first-time MI between 1997 and 2010 in Denmark. METHODS AND RESULTS: Through administrative nationwide registers we identified 89,389 patients without prior HF hospitalized with first MI. The number of patients treated with percutaneous coronary intervention (PCI) days 0-1 after index MI increased from 2.5% in 1997-98 to 38.2% in 2009-10. Treatment with clopidogrel increased from 0.02% in 1997-98 to 68.1% in 2009-10 and statins from 8.1% in 1997-98 to 78.3% in 2009-10. The incidence of HF (defined as HF diagnosis or incident use of loop diuretics) decreased from 23.6% in 1997-98 to 19.6% in 2009-10 (p<0.001). Adjusted for age, sex, and comorbidity, hazard ratio was 0.77 (95% confidence interval [CI] 0.74-0.79) for developing HF in 2009-10, compared with 1997-98. Adjusted for coronary interventions, and pharmacotherapy HR increased to 0.82 (95% confidence interval (CI) 0.79-0.85) compared with 1997-98. The 90-day mortality decreased from 19.6% in 1997-98 to 11.7% in 2009-10 (p<0.001). Adjusted for age, sex, and comorbidity HR was 0.59 (CI 0.55-0.64) in 2009-10 compared with 1997-98; upon additional adjustment for coronary interventions and pharmacotherapy the estimate was 0.75 (95% CI 0.69-0.81). CONCLUSION: We found a temporal decrease in HF incidence and mortality during the first 90 days after MI in 1997-2010. This could partly be explained by changes in interventional and pharmacological treatment strategies.

Temporal trends in stroke admissions in Denmark 1997-2009.

BACKGROUND: The Stroke burden is increasing in many populations where health institutions may experience more patients. We wanted to examine whether incidence rates and absolute number of hospitalized stroke patients remained stable in Denmark during a 13 years period where exposure to major stroke risk factors decreased, changes in stroke treatment was implemented, and the age of the population increased. METHODS: The Danish National Patient Register was used to identify all subjects 25 years of age or above admitted with a first time stroke in Denmark from 1997-2009. Incidence rates (IRs) and age-adjusted Poisson regression analyses were used to examine trends in age-, gender- and stroke subtype (ischaemic or unspecified). RESULTS: During the 13-year observation period there were 53.5 million person-years at risk (PY) and a total of 84,626 male and 84,705 female stroke patients were admitted to Danish hospitals. The IRs of hospitalized strokes per 1000 PY was 3.21 (95% confidence interval [CI] 3.16-3.27) in 1997, 3.85 (95% CI 3.79-3.91) in 2003 and 3.22 (95% CI 3.16-3.28) in 2009, respectively.Incidence rate ratios of hospitalized stroke events adjusted for age in the period 2007-2009 compared to 1997-2000 were 0.89 (95% CI 0.87- 0.91) for men and 0.92 (95% CI 0.90-0.94) for women.The incidence of hospitalized unspecified strokes decreased from 1997 to 2009 whereas there was a steep rise in incidence for hospitalization with specified ischemic stroke during this period. CONCLUSION: This study found a constant rate of stroke hospitalization in Denmark from 1997-2009. The overall rate of hospitalized strokes adjusted for age decreased during this period.

Statin treatment and risk of recurrent venous thromboembolism: a nationwide cohort study.

OBJECTIVES: Statins may decrease the risk of primary venous thromboembolism (VTE), that is, deep vein thrombosis (DVT) and pulmonary embolism (PE) but the effect of statins in preventing recurrent VTE is less clear. The aim of this study was therefore to investigate the association between statin therapy and risk of recurrent VTE. DESIGN: A prospective cohort study. SETTING: All hospitals in Denmark. PARTICIPANTS: All patients with a hospital diagnosis of VTE in Denmark during 1997-2009 associated with a warfarin or heparin prescription were identified. MAIN OUTCOME MEASURES: Adjusted HR of recurrent hospitalised VTE (ie, fatal or non-fatal DVT or PE) associated with use of statins. RESULTS: 44 330 patients with VTE were included in the study. Of these 3914 were receiving statin therapy at baseline. Patients receiving statins were older (68±11 compared to 62±18 years), had more comorbidity and used more medications. The incidence rate for recurrent VTE was 24.4 (95% CI 22.8 to 26.2) per 1000 person-years among statin users and 48.5 (95% CI 47.4 to 49.7) per 1000 person-years among non-statin users. Statin use was associated with a significantly lower risk of a recurrent VTE, adjusted HR 0.74 (95% CI 0.68 to 0.80), compared with no statin use. The association between statin use and risk of recurrent VTE was significantly affected by age. Among younger individuals (≤80 years), statin use was associated with lower risk of recurrent VTE, HR 0.70 (95% CI 0.65 to 0.76) whereas in older individuals (>80 years) statin use was significantly associated with higher risk of recurrent VTE, HR 1.28 (95% CI 1.02 to 1.60), p for interaction=<0.0001. CONCLUSIONS: Statin use was associated with a decreased risk of recurrent VTE.

Patient adherence to evidence-based pharmacotherapy in systolic heart failure and the transition of follow-up from specialized heart failure outpatient clinics to primary care.

AIMS: Undertreatment with evidence-based pharmacotherapy for heart failure (HF) is an important problem, and it has been suggested that specialized HF clinics (HFCs) can improve treatment initiation and correct dosing. The objective of this study was to examine long-term adherence to and dosages of evidence-based pharmacotherapy during and after participation in specialized HFCs. METHODS AND RESULTS: Initiation, dosages, and adherence were studied in patients with systolic HF attending HFCs in Denmark from 2002 to 2009. Information was obtained from an electronic patient file and research database used in the HFCs combined with prescription data from the Danish Registry of Medicinal Product Statistics. A total of 8792 patients were included in the study. The mean age was 68 years; with a mean LVEF of 30%, and 72% were males. Long-term adherence to treatment was high for the patients who initiated renin-angiotensin system (RAS) inhibitors and beta-blockers. Adherence after 1 year was 93% for RAS inhibitors, 92% for beta-blockers, and 86% for spironolactone. After 3 years, it was 90% for RAS inhibitors, 88% for beta-blockers, and 74% for spironolactone. For patients referred back to their general practitioner (GP), adherence 1 year after they left the HFC was 89% for RAS inhibitors, 89% for beta-blockers, and 72% for spironolactone. CONCLUSION: In specialized outpatient HFCs, long-term adherence to RAS inhibitors and beta-blockers is close to optimal. Importantly, adherence was maintained after patients were referred back to their GP for continued management. This is likely to provide long-term benefits for the patients.