Søren Paaske Johnsen

System delay and mortality among patients with STEMI treated with primary percutaneous coronary intervention

CONTEXT Timely reperfusion therapy is recommended for patients with ST-segment elevation myocardial infarction (STEMI), and door-to-balloon delay has been proposed as a performance measure in triaging patients for primary percutaneous coronary intervention (PCI). However, focusing on the time from first contact with the health care system to the initiation of reperfusion therapy (system delay) may be more relevant, because it constitutes the total time to reperfusion modifiable by the health care system. No previous studies have focused on the association between system delay and outcome in patients with STEMI treated with primary PCI. OBJECTIVE To evaluate the associations between system, treatment, patient, and door-to-balloon delays and mortality in patients with STEMI. DESIGN, SETTING, AND PATIENTS Historical follow-up study based on population-based Danish medical registries of patients with STEMI transported by the emergency medical service and treated with primary PCI from January 1, 2002, to December 31, 2008, at 3 high-volume PCI centers in Western Denmark. Patients (N = 6209) underwent primary PCI within 12 hours of symptom onset. The median follow-up time was 3.4 (interquartile range, 1.8-5.2) years. MAIN OUTCOME MEASURES Crude and adjusted hazard ratios of mortality obtained by Cox proportional regression analysis. RESULTS A system delay of 0 through 60 minutes (n = 347) corresponded to a long-term mortality rate of 15.4% (n = 43); a delay of 61 through 120 minutes (n = 2643) to a rate of 23.3% (n = 380); a delay of 121 through 180 minutes (n = 2092) to a rate of 28.1% (n = 378); and a delay of 181 through 360 minutes (n = 1127) to a rate of 30.8% (n = 275) (P < .001). In multivariable analysis adjusted for other predictors of mortality, system delay was independently associated with mortality (adjusted hazard ratio, 1.10 [95% confidence interval, 1.04-1.16] per 1-hour delay), as was its components, prehospital system delay and door-to-balloon delay. CONCLUSION System delay was associated with mortality in patients with STEMI treated with primary PCI.

Efficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents in routine clinical care (SORT OUT III): a randomised controlled superiority trial.

BACKGROUND In low-risk patients, the zotarolimus-eluting stent has been shown to reduce rates of restenosis without increasing the risk of stent thrombosis. We compared the efficacy and safety of the zotarolimus-eluting stent versus the sirolimus-eluting stent in patients with coronary artery disease who were receiving routine clinical care with no direct follow-up. METHODS We did a single-blind, all-comer superiority trial in adult patients with chronic stable coronary artery disease or acute coronary syndromes, and at least one target lesion. Patients were treated at one of five percutaneous coronary intervention centres between January, 2006, and August, 2007. Computer-generated block randomisation and a telephone allocation service were used to randomly assign patients to receive the zotarolimus-eluting or the sirolimus-eluting stent. Data for follow-up were obtained from national Danish administrative and health-care registries. The primary endpoint was a composite of major adverse cardiac events within 9 months: cardiac death, myocardial infarction, and target vessel revascularisation. Intention-to-treat analyses were done at 9-month and 18-month follow-up. This trial is registered with ClinicalTrials.gov, number NCT00660478. FINDINGS 1162 patients (1619 lesions) were assigned to receive the zotarolimus-eluting stent, and 1170 patients (1611 lesions) to receive the sirolimus-eluting stent. 67 patients (72 lesions) had stent failure, and six patients were lost to follow-up. All randomly assigned patients were included in analyses at 9-month follow-up; 2200 patients (94%) had completed 18-month follow-up by the time of our assessment. At 9 months, the primary endpoint had occurred in a higher proportion of patients treated with the zotarolimus-eluting stent than in those treated with the sirolimus-eluting stent (72 [6%] vs 34 [3%]; HR 2.15, 95% CI 1.43-3.23; p=0.0002). At 18-month follow-up, this difference was sustained (113 [10%] vs 53 [5%]; 2.19, 1.58-3.04; p<0.0001). For patients receiving the zotarolimus-eluting stent and those receiving the sirolimus-eluting stent, all cause-mortality was similar at 9-month follow-up (25 [2%] vs 18 [2%]; 1.40, 0.76-2.56; p=0.28), but was significantly different at 18-month follow-up (51 [4%] vs 32 [3%]; 1.61, 1.03-2.50; p=0.035). INTERPRETATION The sirolimus-eluting stent is superior to the zotarolimus-eluting stent for patients receiving routine clinical care. FUNDING Cordis and Medtronic.

Preadmission Use of Statins and Outcomes After Hospitalization With Pneumonia: Population-Based Cohort Study of 29 900 Patients

BACKGROUND While some experimental and clinical research suggests that statins improve outcomes after severe infections, the evidence for pneumonia is conflicting. We examined whether preadmission statin use decreased risk of death, bacteremia, and pulmonary complications after pneumonia. METHODS We conducted a population-based cohort study of 29,900 adults hospitalized with pneumonia for the first time between January 1, 1997, and December 31, 2004 in northern Denmark. Data on statin and other medication use, comorbidities, socioeconomic markers, laboratory findings, bacteremia, pulmonary complications, and death were obtained from medical databases. We used regression analyses to compute adjusted mortality rate ratios within 90 days and relative risks of bacteremia and pulmonary complications after hospitalization in both statin users and nonusers. RESULTS Of patients with pneumonia, 1371 (4.6%) were current statin users. Mortality among statin users was lower than among nonusers: 10.3% vs 15.7% after 30 days and 16.8% vs 22.4% after 90 days, corresponding to adjusted 30- and 90-day mortality rate ratios of 0.69 (95% confidence interval, 0.58-0.82) and 0.75 (0.65-0.86). Decreased mortality associated with statin use remained robust in various subanalyses and in a supplementary analysis using propensity score matching. In contrast, former use of statins and current use of other prophylactic cardiovascular drugs were not associated with decreased mortality from pneumonia. In statin users, adjusted relative risk for bacteremia was 1.07 (95% confidence interval, 0.69-1.67) and for pulmonary complications was 0.69 (0.42-1.14). CONCLUSION The use of statins is associated with decreased mortality after hospitalization with pneumonia.

Statin use and mortality within 180 days after bacteremia: a population-based cohort study.

Objective:To examine the association between preadmission statin use and mortality among patients with bacteremia in a population-based setting. Design:Observational study based on prospective registration of bacteremia episodes and mortality over a 6-yr period. Setting:North Jutland County, Denmark (population, 500,000). Patients:A total of 5,353 adult patients hospitalized with bacteremia from 1997 to 2002. Individuals treated with statins (n = 176) were identified by record-linkage with the County Prescription Database. Interventions:None. Measurements and Main Results:We compared mortality rates 0–30 and 31–180 days after bacteremia in patients with and without preadmission statin use, adjusted for gender, age group, level of comorbidity, alcohol-related conditions, use of immunosuppressive drugs and systemic antibiotics, and focus on infection. The 30-day mortality in statin users vs. nonusers was similar (20.0% vs. 21.6%, adjusted mortality rate ratio 0.93, 95% confidence interval 0.66–1.30). Among survivors after 30 days, however, statin therapy was associated with a substantially decreased mortality up until 180 days after the bacteremia (8.4% vs. 17.5%, adjusted mortality rate ratio 0.44, 95% confidence interval 0.24–0.80). This tendency toward similar short-term and decreased longer term mortality associated with statin use was observed consistently in both community-acquired and nosocomial bacteremia episodes and when analyses were restricted to patients with previous cardiovascular discharge diagnoses or diabetes. Conclusions:This study provides evidence against the hypothesis that statin use has an effect on short-term mortality after bacteremia. Statin use was, however, associated with a substantially decreased mortality between 31 and 180 days after bacteremia.

Arterial cardiovascular events, statins, low-dose aspirin and subsequent risk of venous thromboembolism: a population-based case-control study.

Summary.  Background: Atherosclerotic disease has been associated with the risk of venous thromboembolism, but the available data are conflicting. There are similar confusions regarding the association of the use of aspirin and statins with venous thromboembolism. Objectives: To determine whether arterial cardiovascular events, use of statins and low‐dose aspirin were associated with the risk of venous thromboembolism. Patients and methods: In this population‐based case–control study, we identified 5824 patients with venous thromboembolism and 58 240 population controls with a complete hospital and prescription history. We used logistic regression to estimate the relative risk of venous thromboembolism, adjusted for potentially confounding factors. Results: Patients with a history of arterial cardiovascular events had a clearly increased relative risk. An event within 3 months before the index date conferred large increases in risk [relative risk 4.22 (95% confidence interval (CI), 2.33–7.64) after myocardial infarction, 4.41 (95% CI, 2.92–6.65) after stroke]. Myocardial infarction more than 3 months before the index date was not significantly associated with risk, although there was a relative risk of 1.29 (95% CI, 1.05–1.57) for myocardial infarction more than 60 months previously. A history of stroke was associated with small increases in risk after 3 months. Current use of statins was associated with a reduced risk of venous thromboembolism [relative risk = 0.74 (95% CI, 0.63–0.85)]. Aspirin use was not associated with risk. Conclusions: Patients with cardiovascular events are at a short‐term increased risk of venous thromboembolism. Statins might prevent venous thromboembolism but aspirin does not. However, as the study is non‐randomized residual confounding cannot be excluded.

Patient-related predictors of implant failure after primary total hip replacement in the initial, short- and long-terms: A NATIONWIDE DANISH FOLLOW-UP STUDY INCLUDING 36 984 PATIENTS

We examined the association between patient-related factors and the risk of initial, short- and long-term implant failure after primary total hip replacement. We used data from the Danish Hip Arthroplasty Registry between 1 January 1995 and 31 December 2002, which gave us a total of 36 984 patients. Separate analyses were carried out for three follow-up periods: 0 to 30 days, 31 days to six months (short term), and six months to 8.6 years after primary total hip replacement (long term). The outcome measure was defined as time to failure, which included re-operation with open surgery for any reason. Male gender and a high Charlson co-morbidity index score were strongly predictive for failure, irrespective of the period of follow-up. Age and diagnosis at primary total hip replacement were identified as time-dependent predictive factors of failure. During the first 30 days after primary total hip replacement, an age of 80 years or more and hip replacement undertaken as a sequela of trauma, for avascular necrosis or paediatric conditions, were associated with an increased risk of failure. However, during six months to 8.6 years after surgery, being less than 60 years old was associated with an increased risk of failure, whereas none of the diagnoses for primary total hip replacement appeared to be independent predictors.

Major genetic susceptibility for venous thromboembolism in men: A study of Danish twins

Background. Although several genetic determinants (mutations or polymorphisms) have been associated with increased risk of venous thromboembolism, the overall influence of genetic factors on this disease is unknown. Methods. We linked the Danish Twin Registry, which includes twins born 1870–1953, with the Danish National Registry of Patients, comprising all hospitalizations in Denmark since 1977. We then determined the risk of venous thromboembolism as determined from discharge diagnosis. Results. We identified 26,982 twins who were alive on 1 January 1977, and computed measures of familial and genetic association of venous thrombotic disorders. Individuals were classified according to zygosity and hospitalization with venous thromboembolism. Since 1977, 678 twins were hospitalized with an episode of venous thromboembolism. Of these, only 545 pairs (281 male pairs and 264 female pairs) were alive in 1977. For men, the concordance rates for mono- and dizygotic twin pairs, respectively, were 0.22 (95% confidence interval = 0.14 to 0.30) and 0.08 (0.04–0.12). The odds ratio (interpreted as the relative risk of venous thromboembolism for one twin, given venous thromboembolism in the partner twin) was 13.5 (7.3–24.8) among monozygotic twins and 3.8 (1.8–8.3) among dizygotic twins. The respective correlations for venous thromboembolism were 0.55 (0.38–0.70) and 0.26 (0.09–0.42). The proportion of the variance attributable to genetic effects on venous thromboembolism in males was 55% (39%–68%). The remaining variation could be attributed to men’s nonfamilial environments. In contrast, for women there was no intra–twin pair similarity for venous thromboembolism. Conclusions. We found differences in genetic susceptibility to venous thromboembolism between the sexes, with genetic factors playing a substantially stronger role in males than in females.

In-Hospital Medical Complications, Length of Stay, and Mortality Among Stroke Unit Patients

Background and Purpose— The relationship between in-hospital stroke-related medical complications and clinical outcome remains unclear. We examined whether medical complications were associated with length of stay (LOS) and mortality among stroke unit patients. Methods— Using population-based Danish medical registries, we performed a follow-up study among all patients with acute stroke admitted to stroke units in 2 counties between 2003 and 2009 (n=13 721). Data regarding in-hospital medical complications, including pneumonia, urinary tract infection, pressure ulcer, falls, deep venous thrombosis, pulmonary embolism, and severe constipation together with LOS and mortality were prospectively registered. Results— Overall, 25.2% of patients (n=3453) experienced 1 or more medical complications during hospitalization. The most common complications were urinary tract infection (15.4%), pneumonia (9.0%), and constipation (6.8%). Median LOS was 13 days (25th and 75th quartiles, 5 and 33). All medical complications were associated with longer LOS. The adjusted relative LOS extension ranged from 1.80 (95% CI, 1.54–2.11) for pneumonia to 3.06 (95% CI, 2.67–3.52) for falls. Patients with 1 or more complications had an increased 1-year mortality rate (adjusted mortality rate ratio [MRR], 1.20; 95% CI, 1.04–1.39). The association was mainly because of pneumonia, which was associated with higher mortality both after 30 days (adjusted MRR, 1.59; 95% CI, 1.31–1.93) and 1 year (adjusted MRR, 1.76; 95% CI, 1.45–2.14). Conclusions— In-hospital medical complications were associated with longer LOS and some, in particular pneumonia, also with an increased mortality among patients with acute stroke.

Smoking and venous thromboembolism: a Danish follow‐up study

Summary.  Background: Large‐scale prospective studies are needed to assess whether smoking is associated with venous thromboembolism (VTE) (i.e. deep venous thrombosis and pulmonary embolism) independently of established risk factors. Objective: To investigate the association between smoking and the risk of VTE among middle‐aged men and women. Methods: From 1993 to 1997, 27 178 men and 29 875 women, aged 50–64 years and born in Denmark, were recruited into the Danish prospective study ‘Diet, Cancer and Health’. During follow‐up, VTE cases were identified in the Danish National Patient Registry. Medical records were reviewed and only verified VTE cases were included in the study. Baseline data on smoking and potential confounders were included in gender stratified Cox proportional hazard models to asses the association between smoking and the risk of VTE. The analyses were adjusted for alcohol intake, body mass index, physical activity, and in women also for use of hormone replacement therapy. Results: During follow‐up, 641 incident cases of VTE were verified. We found a positive association between current smoking and VTE, with a hazard ratio of 1.52 (95% CI, 1.15–2.00) for smoking women and 1.32 (95% CI, 1.00–1.74) for smoking men, and a positive dose‐response relationship. Former smokers had the same hazard as never smokers. Conclusions: Smoking was an independent risk factor for VTE among middle‐aged men and women. Former smokers have the same risk of VTE as never smokers, indicating acute effects of smoking, and underscoring the potential benefits of smoking cessation.

Risk factors for venous thromboembolism in patients undergoing total hip replacement and receiving routine thromboprophylaxis.

BACKGROUND Data on the risk factors for venous thromboembolism among patients undergoing total hip replacement and receiving pharmacological thromboprophylaxis are limited. The purpose of this study was to examine potential patient-related risk factors for venous thromboembolism following total hip replacement in a nationwide follow-up study. METHODS Using medical databases, we identified all patients who underwent primary total hip replacement and received pharmacological thromboprophylaxis in Denmark from 1995 to 2006. The outcome measure was hospitalization with venous thromboembolism within ninety days of surgery. We considered age, sex, indication for primary total hip replacement, calendar year of surgery, and comorbidity history as potential risk factors. RESULTS The overall rate of hospitalization for venous thromboembolism within ninety days following a primary total hip replacement was 1.02% (686 hospitalizations after 67,469 procedures) at a median of twenty-two days. The incidence of symptomatic deep venous thrombosis and of nonfatal pulmonary embolism was 0.7% (499 of 67,469) and 0.3% (205 of 67,469), respectively. The incidence of death due to venous thromboembolism or from all causes was 0.05% (thirty-eight patients) and 1.0% (678 patients), respectively. Patients with rheumatoid arthritis had a reduced relative risk for venous thromboembolism compared with patients with primary osteoarthritis (adjusted relative risk = 0.47; 95% confidence interval, 0.25 to 0.90). Patients with a high score on the Charlson comorbidity index had an increased relative risk for venous thromboembolism compared with patients with a low score (adjusted relative risk = 1.45; 95% confidence interval, 1.02 to 2.05). Patients with a history of cardiovascular disease (relative risk = 1.40; 95% confidence interval, 1.15 to 1.70) or prior venous thromboembolism (relative risk = 8.09; 95% confidence interval, 6.07 to 10.77) had an increased risk for venous thromboembolism compared with patients without that history. CONCLUSIONS The cumulative incidence of a venous thromboembolism within ninety days of surgery among patients with total hip replacement receiving pharmacological thromboprophylaxis was 1%. This information on the associated risk factors could be used to better anticipate the risk of venous thromboembolism for an individual patient.