Emil L. Fosbøl

Association of national initiatives to improve cardiac arrest management with rates of bystander intervention and patient survival after out-of-hospital cardiac arrest

IMPORTANCE Out-of-hospital cardiac arrest is a major health problem associated with poor outcomes. Early recognition and intervention are critical for patient survival. Bystander cardiopulmonary resuscitation (CPR) is one factor among many associated with improved survival. OBJECTIVE To examine temporal changes in bystander resuscitation attempts and survival during a 10-year period in which several national initiatives were taken to increase rates of bystander resuscitation and improve advanced care. DESIGN, SETTING, AND PARTICIPANTS Patients with out-of-hospital cardiac arrest for which resuscitation was attempted were identified between 2001 and 2010 in the nationwide Danish Cardiac Arrest Registry. Of 29,111 patients with cardiac arrest, we excluded those with presumed noncardiac cause of arrest (n = 7390) and those with cardiac arrests witnessed by emergency medical services personnel (n = 2253), leaving a study population of 19,468 patients. MAIN OUTCOMES AND MEASURES Temporal trends in bystander CPR, bystander defibrillation, 30-day survival, and 1-year survival. RESULTS The median age of patients was 72 years; 67.4% were men. Bystander CPR increased significantly during the study period, from 21.1% (95% CI, 18.8%-23.4%) in 2001 to 44.9% (95% CI, 42.6%-47.1%) in 2010 (P < .001), whereas use of defibrillation by bystanders remained low (1.1% [95% CI, 0.6%-1.9%] in 2001 to 2.2% [95% CI, 1.5%-2.9%] in 2010; P = .003). More patients achieved survival on hospital arrival (7.9% [95% CI, 6.4%-9.5%] in 2001 to 21.8% [95% CI, 19.8%-23.8%] in 2010; P < .001). Also, 30-day survival improved (3.5% [95% CI, 2.5%-4.5%] in 2001 to 10.8% [95% CI, 9.4%-12.2%] in 2010; P < .001), as did 1-year survival (2.9% [95% CI, 2.0%-3.9%] in 2001 to 10.2% [95% CI, 8.9%-11.6%] in 2010; P < .001). Despite a decrease in the incidence of out-of-hospital cardiac arrests during the study period (40.4 to 34.4 per 100,000 persons in 2001 and 2010, respectively; P = .002), the number of survivors per 100,000 persons increased significantly (P < .001). For the entire study period, bystander CPR was positively associated with 30-day survival, regardless of witnessed status (30-day survival for nonwitnessed cardiac arrest, 4.3% [95% CI, 3.4%-5.2%] with bystander CPR and 1.0% [95% CI, 0.8%-1.3%] without; odds ratio, 4.38 [95% CI, 3.17-6.06]). For witnessed arrest the corresponding values were 19.4% (95% CI, 18.1%-20.7%) vs 6.1% (95% CI, 5.4%-6.7%); odds ratio, 3.74 (95% CI, 3.26-4.28). CONCLUSIONS AND RELEVANCE In Denmark between 2001 and 2010, an increase in survival following out-of-hospital cardiac arrest was significantly associated with a concomitant increase in bystander CPR. Because of the co-occurrence of other related initiatives, a causal relationship remains uncertain.

‘Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study’

AIMS The impact of insulin secretagogues (ISs) on long-term major clinical outcomes in type 2 diabetes remains unclear. We examined mortality and cardiovascular risk associated with all available ISs compared with metformin in a nationwide study. METHODS AND RESULTS All Danish residents >20 years, initiating single-agent ISs or metformin between 1997 and 2006 were followed for up to 9 years (median 3.3 years) by individual-level linkage of nationwide registers. All-cause mortality, cardiovascular mortality, and the composite of myocardial infarction (MI), stroke, and cardiovascular mortality associated with individual ISs were investigated in patients with or without previous MI by multivariable Cox proportional-hazard analyses including propensity analyses. A total of 107 806 subjects were included, of whom 9607 had previous MI. Compared with metformin, glimepiride (hazard ratios and 95% confidence intervals): 1.32 (1.24-1.40), glibenclamide: 1.19 (1.11-1.28), glipizide: 1.27 (1.17-1.38), and tolbutamide: 1.28 (1.17-1.39) were associated with increased all-cause mortality in patients without previous MI. The corresponding results for patients with previous MI were as follows: glimepiride: 1.30 (1.11-1.44), glibenclamide: 1.47 (1.22-1.76), glipizide: 1.53 (1.23-1.89), and tolbutamide: 1.47 (1.17-1.84). Results for gliclazide [1.05 (0.94-1.16) and 0.90 (0.68-1.20)] and repaglinide and [0.97 (0.81-1.15) and 1.29 (0.86-1.94)] were not statistically different from metformin in both patients without and with previous MI, respectively. Results were similar for cardiovascular mortality and for the composite endpoint. CONCLUSION Monotherapy with the most used ISs, including glimepiride, glibenclamide, glipizide, and tolbutamide, seems to be associated with increased mortality and cardiovascular risk compared with metformin. Gliclazide and repaglinide appear to be associated with a lower risk than other ISs.

Duration of Treatment With Nonsteroidal Anti-Inflammatory Drugs and Impact on Risk of Death and Recurrent Myocardial Infarction in Patients With Prior Myocardial Infarction A Nationwide Cohort Study

Background— Despite the fact that nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated among patients with established cardiovascular disease, many receive NSAID treatment for a short period of time. However, little is known about the association between NSAID treatment duration and risk of cardiovascular disease. We therefore studied the duration of NSAID treatment and cardiovascular risk in a nationwide cohort of patients with prior myocardial infarction (MI). Methods and Results— Patients ≥30 years of age who were admitted with first-time MI during 1997 to 2006 and their subsequent NSAID use were identified by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. Risk of death and recurrent MI according to duration of NSAID treatment was analyzed by multivariable time-stratified Cox proportional-hazard models and by incidence rates per 1000 person-years. Of the 83 677 patients included, 42.3% received NSAIDs during follow-up. There were 35 257 deaths/recurrent MIs. Overall, NSAID treatment was significantly associated with an increased risk of death/recurrent MI (hazard ratio, 1.45; 95% confidence interval, 1.29 to 1.62) at the beginning of the treatment, and the risk persisted throughout the treatment course (hazard ratio, 1.55; 95% confidence interval, 1.46 to 1.64 after 90 days). Analyses of individual NSAIDs showed that the traditional NSAID diclofenac was associated with the highest risk (hazard ratio, 3.26; 95% confidence interval, 2.57 to 3.86 for death/MI at day 1 to 7 of treatment). Conclusions— Even short-term treatment with most NSAIDs was associated with increased risk of death and recurrent MI in patients with prior MI. Neither short- nor long-term treatment with NSAIDs is advised in this population, and any NSAID use should be limited from a cardiovascular safety point of view.

Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure.

BACKGROUND Accumulating evidence indicates increased cardiovascular risk associated with nonsteroidal anti-inflammatory drug (NSAID) use, in particular in patients with established cardiovascular disease. We studied the risk of death and hospitalization because of acute myocardial infarction and heart failure (HF) associated with use of NSAIDs in an unselected cohort of patients with HF. METHODS We identified 107,092 patients surviving their first hospitalization because of HF between January 1, 1995, and December 31, 2004, and their subsequent use of NSAIDs from individual-level linkage of nationwide registries of hospitalization and drug dispensing by pharmacies in Denmark. Data analysis was performed using Cox proportional hazard models adjusted for age, sex, calendar year, comorbidity, medical treatment, and severity of disease, and propensity-based risk-stratified models and case-crossover models. RESULTS A total of 36,354 patients (33.9%) claimed at least 1 prescription of an NSAID after discharge; 60,974 (56.9%) died, and 8970 (8.4%) and 39,984 (37.5%) were hospitalized with myocardial infarction or HF, respectively. The hazard ratio (95% confidence interval) for death was 1.70 (1.58-1.82), 1.75 (1.63-1.88), 1.31 (1.25-1.37), 2.08 (1.95-2.21), 1.22 (1.07-1.39), and 1.28 (1.21-1.35) for rofecoxib, celecoxib, ibuprofen, diclofenac, naproxen, and other NSAIDs, respectively. Furthermore, there was a dose-dependent increase in risk of death and increased risk of hospitalization because of myocardial infarction and HF. Propensity-based risk-stratified analysis and case-crossover models yielded similar results. CONCLUSIONS NSAIDs are frequently used in patients with HF and are associated with increased risk of death and cardiovascular morbidity. Inasmuch as even commonly used NSAIDs exerted increased risk, the balance between risk and benefit requires careful consideration when any NSAID is given to patients with HF.

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.

Location of Cardiac Arrest in a City Center Strategic Placement of Automated External Defibrillators in Public Locations

Background— Public-access defibrillation with automated external defibrillators (AEDs) is being implemented in many countries worldwide with considerable financial implications. The potential benefit and economic consequences of focused or unfocused AED deployment are unknown. Methods and Results— All cardiac arrests in public in Copenhagen, Denmark, from 1994 through 2005 were geographically located, as were 104 public AEDs placed by local initiatives. In accordance with European Resuscitation Council and American Heart Association (AHA) guidelines, areas with a high incidence of cardiac arrests were defined as those with 1 cardiac arrest every 2 or 5 years, respectively. There were 1274 cardiac arrests in public locations. According to the European Resuscitation Council or AHA guidelines, AEDs needed to be deployed in 1.2% and 10.6% of the city area, providing coverage for 19.5% (n=249) and 66.8% (n=851) of all cardiac arrests, respectively. The excessive cost of such AED deployments was estimated to be

Association of Bystander and First-Responder Intervention With Survival After Out-of-Hospital Cardiac Arrest in North Carolina, 2010-2013

33 100 or

Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study

41 000 per additional quality-adjusted life year, whereas unguided AED placement covering the entire city had an estimated cost of

Cause-Specific Cardiovascular Risk Associated With Nonsteroidal Antiinflammatory Drugs Among Healthy Individuals

108 700 per quality-adjusted life year. Areas with major train stations (1.8 arrests every 5 years per area), large public squares, and pedestrianized areas (0.6 arrests every 5 years per area) were main predictors of frequent cardiac arrests. Conclusion— To achieve wide AED coverage, AEDs need to be more widely distributed than recommended by the European Resuscitation Council guidelines but consistent with the American Heart Association guidelines. Strategic placement of AEDs is pivotal for public-access defibrillation, whereas with unguided initiatives, AEDs are likely to be placed inappropriately.

The pattern of use of non-steroidal anti-inflammatory drugs (NSAIDs) from 1997 to 2005: a nationwide study on 4.6 million people†‡

IMPORTANCE Out-of-hospital cardiac arrest is associated with low survival, but early cardiopulmonary resuscitation (CPR) and defibrillation can improve outcomes if more widely adopted. OBJECTIVE To examine temporal changes in bystander and first-responder resuscitation efforts before arrival of the emergency medical services (EMS) following statewide initiatives to improve bystander and first-responder efforts in North Carolina from 2010-2013 and to examine the association between bystander and first-responder resuscitation efforts and survival and neurological outcome. DESIGN, SETTINGS, AND PARTICIPANTS We studied 4961 patients with out-of-hospital cardiac arrest for whom resuscitation was attempted and who were identified through the Cardiac Arrest Registry to Enhance Survival (2010-2013). First responders were dispatched police officers, firefighters, rescue squad, or life-saving crew trained to perform basic life support until arrival of the EMS. EXPOSURES Statewide initiatives to improve bystander and first-responder interventions included training members of the general population in CPR and in use of automated external defibrillators (AEDs), training first responders in team-based CPR including AED use and high-performance CPR, and training dispatch centers in recognition of cardiac arrest. MAIN OUTCOMES AND MEASURES The proportion of bystander and first-responder resuscitation efforts, including the combination of efforts between bystanders and first responders, from 2010 through 2013 and the association between these resuscitation efforts and survival and neurological outcome. RESULTS The combination of bystander CPR and first-responder defibrillation increased from 14.1% (51 of 362; 95% CI, 10.9%-18.1%) in 2010 to 23.1% (104 of 451; 95% CI, 19.4%-27.2%) in 2013 (P < .01). Survival with favorable neurological outcome increased from 7.1% (82 of 1149; 95% CI, 5.8%-8.8%) in 2010 to 9.7% (129 of 1334; 95% CI, 8.2%-11.4%) in 2013 (P = .02) and was associated with bystander-initiated CPR. Adjusting for age and sex, bystander and first-responder interventions were associated with higher survival to hospital discharge. Survival following EMS-initiated CPR and defibrillation was 15.2% (30 of 198; 95% CI, 10.8%-20.9%) compared with 33.6% (38 of 113; 95% CI, 25.5%-42.9%) following bystander-initiated CPR and defibrillation (odds ratio [OR], 3.12; 95% CI, 1.78-5.46); 24.2% (83 of 343; 95% CI, 20.0%-29.0%) following bystander CPR and first-responder defibrillation (OR, 1.70; 95% CI, 1.06-2.71); and 25.2% (109 of 432; 95% CI, 21.4%-29.6%) following first-responder CPR and defibrillation (OR, 1.77; 95% CI, 1.13-2.77). CONCLUSIONS AND RELEVANCE Following a statewide educational intervention on rescusitation training, the proportion of patients receiving bystander-initiated CPR and defibrillation by first responders increased and was associated with greater likelihood of survival. Bystander-initiated CPR was associated with greater likelihood of survival with favorable neurological outcome.