Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study.

OBJECTIVE: The magnitude of the cardiovascular risk from psoriasis and psoriatic arthritis is debated. We therefore investigated the psoriasis-related risk of adverse cardiovascular events and mortality. DESIGN, SETTING AND SUBJECTS: We conducted a cohort study of the entire Danish population aged ≥18 years followed from 1997 to 2006 by individual-level linkage of nationwide registers. Psoriasis was defined by prescription claims and classified as severe if patients received hospital-based treatment. Time-dependent Poisson regression models were applied to assess cardiovascular risk in patients with psoriasis and psoriatic arthritis. MAIN OUTCOME MEASURES: All-cause mortality, cardiovascular mortality and hospitalizations for myocardial infarction (MI), stroke and coronary revascularization were recorded. RESULTS: A total of 34 371 patients with mild psoriasis and 2621 with severe psoriasis, including 607 with psoriatic arthritis, were identified and compared with 4 003 265 controls. The event rates and rate ratios (RRs) of all-cause mortality, cardiovascular death, MI, coronary revascularization, stroke and a composite of MI, stroke and cardiovascular death were increased in patients with psoriasis. The rate ratio increased with disease severity and decreased with age of onset. The overall RRs for the composite endpoint were 1.20 (95% confidence interval [CI] 1.14-1.25) and 1.58 (95% CI 1.36-1.82) for mild and severe psoriasis, respectively. The corresponding RRs for cardiovascular death were 1.14 (95% CI 1.06-1.22) and 1.57 (95% CI1.27-1.94). The risk was similar in patients with severe skin affection alone and those with psoriatic arthritis. CONCLUSIONS: Psoriasis is associated with increased risk of adverse cardiovascular events and all-cause mortality. Young age, severe skin affection and/or psoriatic arthritis carry the most risk. Patients with psoriasis may be candidates for early cardiovascular risk factor modification.

Metformin treatment is associated with a low risk of mortality in diabetic patients with heart failure: a retrospective nationwide cohort study.

AIMS/HYPOTHESIS: The safety of metformin in heart failure has been questioned because of a perceived risk of life-threatening lactic acidosis, though recent studies have not supported this concern. We investigated the risk of all-cause mortality associated with individual glucose-lowering treatment regimens used in current clinical practice in Denmark. METHODS: All patients aged ≥ 30 years hospitalised for the first time for heart failure in 1997-2006 were identified and followed until the end of 2006. Patients who received treatment with metformin, a sulfonylurea and/or insulin were included and assigned to mono-, bi- or triple therapy groups. Multivariable Cox proportional hazard regression models were used to assess the risk of all-cause mortality. RESULTS: A total of 10,920 patients were included. The median observational time was 844 days (interquartile range 365-1,395 days). In total, 6,187 (57%) patients died. With sulfonylurea monotherapy used as the reference, adjusted hazard ratios for all-cause mortality associated with the different treatment groups were as follows: metformin 0.85 (95% CI 0.75-0.98, p = 0.02), metformin + sulfonylurea 0.89 (95% CI 0.82-0.96, p = 0.003), metformin + insulin 0.96 (95% CI 0.82-1.13, p = 0.6), metformin + insulin + sulfonylurea 0.94 (95% CI 0.77-1.15, p = 0.5), sulfonylurea + insulin 0.97 (95% CI 0.86-1.08, p = 0.5) and insulin 1.14 (95% CI 1.06-1.20, p = 0.0001). CONCLUSIONS/INTERPRETATION: Treatment with metformin is associated with a low risk of mortality in diabetic patients with heart failure compared with treatment with a sulfonylurea or insulin.

Clinical consequences of hospital variation in use of oral anticoagulant therapy after first-time admission for atrial fibrillation.

OBJECTIVE: To analyse how hospital factors influence the use of oral anticoagulants (OAC) in atrial fibrillation (AF) patients and address the clinical consequences of hospital variation in OAC use. DESIGN AND SUBJECTS: By linkage of nationwide Danish administrative registers we conducted an observational study including all patients with a first-time hospitalization for AF between 1995 and 2004 as well as prescription claims for OAC. Multivariable logistic regression analysis was used to evaluate hospital factors associated with prescription of OAC therapy. Cox proportional-hazard models were used to estimate the risk of re-hospitalization for thromboembolism and haemorrhagic stroke with respect to discharge from a low, intermediate, or high OAC use hospital. RESULTS: Overall 40,133 (37%) out of 108,504 patients received OAC; ranging from 17% to 50% between the hospitals with the lowest and highest OAC use, respectively. Cardiology departments had the highest use of OAC, but neither tertiary university hospitals nor high volume hospitals had higher OAC use than local community hospitals and low volume hospitals. Risk of a thromboembolic event was significantly increased amongst patients from hospitals with a low OAC use (hazard ratio 1.16, confidence interval 1.10-1.22). Notably, higher OAC use was not associated with a higher risk of haemorrhagic stroke. CONCLUSION: In Denmark between 1995 and 2004, there was a major hospital variation in AF patients receiving OAC, and consequently, more thromboembolic events were observed amongst patients from low OAC use hospitals. Our study emphasizes the need for a continued vigilance on implementation of international AF management guidelines.

Initiation and persistence with clopidogrel treatment after acute myocardial infarction: a nationwide study.

AIMS: To identify possible underuse by analysing initiation and persistence with clopidogrel treatment in an unselected population of patients admitted with myocardial infarction (MI) with or without subsequent percutaneous coronary intervention (PCI). METHODS: Patients admitted with first-time MI from 2000 to 2005 and subsequent prescription claims of clopidogrel were identified by individual-level linkage of nationwide administrative registries in Denmark. Independent factors affecting initiation and persistence with treatment were analysed by multivariable logistic regression models and Cox proportional hazard models. RESULTS: A total of 46,190 MI patients were included in the study, of whom 14,939 were treated with PCI. From 2000 to 2005 initiation of clopidogrel increased from 80.4 to 93.7% among MI patients with PCI and from 2.8 to 39.3% among MI patients without PCI. MI patients with concomitant heart failure received less treatment [odds ratio (OR) 0.49, confidence interval (CI) 0.43, 0.56 among patients with PCI and OR 0.90, CI 0.81, 0.99 among patients without PCI in 2002-2003, and OR 0.89, CI 0.80, 1.00 in 2004-2005, respectively]. Of MI patients with PCI, 77.5% completed 9 months' clopidogrel treatment in 2004-2005, the corresponding figures for MI patients without PCI being 53.9%. CONCLUSIONS: Initiation and persistence with clopidogrel treatment is high in MI patients with PCI. However, we found substantial underuse among MI patients without PCI and in MI patients with heart failure.

Glyburide increases risk in patients with diabetes mellitus after emergent percutaneous intervention for myocardial infarction--a nationwide study.

BACKGROUND: Sulfonylureas have been linked to an increased cardiovascular risk by inhibition of myocardial preconditioning. Whether individual sulfonylureas affect outcomes in diabetic patients after emergent percutaneous coronary intervention for myocardial infarction is unknown. METHODS: All Danish patients receiving glucose-lowering drugs admitted with myocardial infarction between 1997 and 2006 who underwent emergent percutaneous coronary intervention were identified from national registers. Multivariable Cox proportional hazards models were used to analyze the risk of cardiovascular mortality and morbidity associated with sulfonylureas. RESULTS: A total of 926 patients were included and 163 (17.6%) patients died during the first year of which 155 (16.7%) were cardiovascular deaths. The most common treatment was sulfonylureas which were received by 271 (29.3%) patients, and 129 (13.9%) received metformin. Cox proportional hazard regression analyses adjusted for age, sex, calendar year, comorbidity and concomitant pharmacotherapy showed an increased risk of cardiovascular mortality (hazard ratio [HR] 2.91, 95% confidence interval [CI] 1.26-6.72 ; p=0.012), cardiovascular mortality and nonfatal myocardial infarction (HR 2.69 , 95% CI 1.21-6.00; p=0.016), and all-cause mortality (HR 2.46, 95% CI 1.11-5.47; p=0.027), respectively, with glyburide compared to metformin. CONCLUSIONS: Glyburide is associated with increased cardiovascular mortality and morbidity in patients with diabetes mellitus undergoing emergent percutaneous coronary intervention after myocardial infarction. Early reperfusion therapy is the mainstay in modern treatment of myocardial infarction and the time may have come to discard glyburide in favour of sulfonylureas that do not appear to confer increased cardiovascular risk.

Initiation and persistence to statin treatment in patients with diabetes receiving glucose-lowering medications 1997- 2006.

AIMS: Since 2001 guidelines recommend statin treatment in most patients with diabetes. We investigated secular changes in initiation and persistence to statin treatment during a 10-year period in a nationwide cohort of patients initiating glucose-lowering medication (GLM). METHODS: All Danish citizens 30 years and older who claimed prescriptions of GLM between 1997 and 2006 were identified from nationwide registers of drug dispensing from pharmacies and hospitalizations, and followed until 2006. Statin treatment was registered if a prescription was claimed during the period. By logistic regression we analyzed factors related to initiation and persistence to statin treatment. RESULTS: In total 128,106 patients were included. In 1997 only 7% of the patients receiving GLM claimed statins within the first year after GLM initiation. Despite increasing statin prescriptions the following years, only 62% were using statins at the end of follow up. The chance of ever receiving statins was lowest if not initiated within 180-days following the first purchase of GLM (OR 0.75, 95% CI 0.74-0.76). A previous myocardial infarction was associated with increased statin treatment (OR 4.51; 95% CI 4.31 - 4.71), while low income was associated with lower use of statins (OR 0.68; 95%CI 0.66-0.72). Between 75-85 % of the patients who initiated statins treatment were persistent to treatment by 2007. CONCLUSIONS: In spite of increasing use of statins in diabetes patients over time, many patients remain untreated. Early initiation of statin treatment in diabetic patients and focus on patients with low socioeconomic status is needed to give long-term benefits.

Risk of myocardial infarction and death associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) among healthy individuals: a nationwide cohort study.

Use of some nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased cardiovascular risk in several patient groups, but whether this excess risk exists in apparently healthy individuals has not been clarified. Using a historical cohort design, we estimated the risk of death and myocardial infarction associated with the use of NSAIDs. Participants in the study were selected from the Danish population and were defined as healthy according to a history of no hospital admissions and no concomitant selected pharmacotherapy. The source population consisted of 4,614,807 individuals, of whom 1,028,437 were included in the study after applying selection criteria. Compared to no NSAID use, hazard ratios (95% confidence limits) for death/myocardial infarction were 1.01 (0.96-1.07) for ibuprofen, 1.63 (1.52-1.76) for diclofenac, 0.97 (0.83-1.12) for naproxen, 2.13 (1.89-2.41) for rofecoxib, and 2.01 (1.78-2.27) for celecoxib. A dose-dependent increase in cardiovascular risk was seen for selective COX-2 inhibitors and diclofenac. Caution should be exercised in NSAID use in all individuals, and particularly high doses should be avoided if possible.

Temporal decline in the prognostic impact of a recurrent acute myocardial infarction 1985 to 2002.

OBJECTIVE: To investigate trends in case-fatality and prognostic impact from recurrent acute myocardial infarction (re-AMI) during 1985-2002. DESIGN: Retrospective cohort study using nationwide administrative data from Denmark. SETTINGS: National registries on hospital admissions and causes of death were linked to identify patients with first AMI, re-AMI and subsequent prognosis. PATIENTS: Patients > or =30 years old with a discharge diagnosis of AMI during 1985-2002 were tracked for first hospital admission for re-AMI 1 year after discharge. MAIN OUTCOME MEASURES: One-year case-fatality. RESULTS: 166 472 patients were identified with a first AMI; 14 123 developed re-AMI. One-year crude case-fatality from first AMI/re-AMI was 39% versus 43% in 1985-1989 and 25% versus 29% in 2000-2002, respectively. In 1985-89, 35 795 patients survived to discharge (71%); of these 2.5% experienced reinfarction within 30 days (early reinfarction) and an additional 9.0% reinfarction within days 31-365 (late re-AMI). Re-AMI carried a poor prognosis in 1985-1989 compared to no re-AMI with age- and sex-adjusted relative risk of 1-year case-fatality of 7.5 (95% CI: 6.9 to 8.5) from early re-AMI and 11.7 (95% CI: 11.0 to 12.4) from late re-AMI. In 2000-2002, 23 552 patients (86%) survived to discharge; 4.4% had early re-AMI and 6.6% late re-AMI. Adjusted relative risk of 1-year case-fatality had declined to 2.1 (95% CI: 1.9 to 2.5) from early re-AMI and 5.6 (95% CI: 5.1 to 6.2) from late re-AMI compared to patients without reinfarction. CONCLUSION: Prognosis after AMI has improved substantially during the latest two decades and extends to patients with re-AMI.

Temporal trends in the prescription of vitamin K antagonists in patients with atrial fibrillation.

OBJECTIVES: Anticoagulation therapy is recommended in patients with atrial fibrillation (AF) and risk factors for stroke. We studied the temporal trends in the prescription of vitamin K antagonists (VKA) in patients with a first hospital diagnosis of AF in Denmark, 1995-2002. DESIGN: The Danish National Hospital Registry was used to identify subjects with a first hospital diagnosis of AF and the Danish Register of Medical Products Statistics to determine the proportion of these patients who claimed a prescription of VKA within 3 months from discharge. RESULTS: Amongst 68 546 patients aged 50-99 years with a diagnosis of AF who survived 3 months following discharge, 24 991 (36%) patients claimed a prescription of VKA within 3 months. In both men and women a gradual increase in the use of VKA with time was observed, the relative increase being largest amongst the 80- to 99-year olds. In all age groups, the prescription of VKA was lower in women than in men, including patients with a prior or concurrent stroke. CONCLUSIONS: From 1995 to 2002 the proportion of AF patients receiving VKA therapy increased significantly but the use of VKA therapy amongst women was lagging behind that of men. Even in patients with AF and prior stroke, the use of VKA seems to be less than optimal.

Trends in incidence and case fatality rates of acute myocardial infarction in Denmark and Sweden.

OBJECTIVE: To compare the incidence and case fatality of acute myocardial infarction in Denmark and Sweden. DESIGN: A cohort study, linking the national registries of hospital admissions and causes of death in the two countries. PATIENTS: All admissions and deaths with acute myocardial infarction as primary or secondary diagnosis were extracted (Denmark, 1978 to 1998; Sweden, 1987 to 1999). MAIN OUTCOME MEASURES: The incidence was estimated using the first acute myocardial infarct for each patient. Case fatality was estimated in the first 28 days after acute myocardial infarction, including prehospital deaths. All rates were adjusted for age. RESULTS: The incidence of myocardial infarction and the case fatality declined significantly among all subgroups of patients. Case fatality was higher in Denmark early in the study period (1987-1990) than in Sweden. The odds ratios (OR) ranged from 1.28 to 1.50 in the four age groups. In 1994-1999, the prognosis of patients younger than 75 years did not differ. Patients aged 75-94 years still fared worse in Denmark (OR 1.21, 95% confidence interval 1.17 to 1.27). Women aged 30-54 years had a worse prognosis than men in both Denmark and Sweden (OR associated with male sex 0.85 and 0.90, respectively). In contrast, for patients older than 65 years, women had a better prognosis than men. This difference in the effect of sex with age was significant (p < 0.0001) and did not change over time. CONCLUSIONS: Case fatality after acute myocardial infarction was notably higher in Denmark than in Sweden in 1987-1991, but in the later periods the prognosis was comparable in the two countries.

Impact of age and sex on sudden cardiovascular death following myocardial infarction.

OBJECTIVE: To evaluate and compare the risk of sudden cardiovascular death (SCD) and non-SCD after myocardial infarction (MI) associated with age and sex. DESIGN: Cohort study of patients admitted with an enzyme verified acute MI and discharged alive. Patients were followed up for up to four years. PATIENTS: 5983 consecutive hospital survivors of acute MI were enrolled in the TRACE (trandolapril cardiac evaluation) registry from 1990-92. Four age groups were prespecified: < 56, 56-65, 66-75, and > or = 76 years. MAIN OUTCOME MEASURES: SCD was defined as cardiovascular death within one hour of onset of symptoms. RESULTS: There were 536 SCD and 725 non-SCD. SCD mortality was 4.8% in the youngest and 15.7% in the oldest age groups. Non-SCD mortality was 3.5% and 25%, respectively. The ratio of SCD to non-SCD mortality varied from 1.44 in the youngest (< 56 years) to 0.55 in the oldest patients (> or = 76 years). Age significantly increased both SCD and non-SCD risk (p < 0.0001), but the increase in non-SCD risk was 40% higher (p < 0.0001). Male sex was associated with increased risk of SCD independently of age (risk ratio 1.34, p < 0.005). However, the absolute three year probability of SCD among women older than 66 years exceeded 10%. CONCLUSIONS: Compared with non-SCD the risk of SCD is relatively highest in the younger age groups, but the absolute risk of SCD is much higher among the upper age groups than the younger. The risk of SCD was slightly lower in women but not enough to warrant a different treatment strategy.