Risk for Myocardial Infarction Following 5-Fluorouracil Treatment in Patients With Gastrointestinal Cancer: A Nationwide Registry-Based Study.

Background: Myocardial infarction is a cardiac adverse event associated with 5-fluorouracil (5-FU). There are limited data on the incidence, risk, and prognosis of 5-FU-associated myocardial infarction. Objectives: The aim of this study was to examine the risk for myocardial infarction in patients with gastrointestinal (GI) cancer treated with 5-FU compared with age- and sex-matched population control subjects without cancer (1:2 ratio). Methods: Patients with GI cancer treated with 5-FU between 2004 and 2016 were identified within the Danish National Patient Registry. Prevalent ischemic heart disease in both groups was excluded. Cumulative incidences were calculated, and multivariable regression and competing risk analyses were performed. Results: A total of 30,870 patients were included in the final analysis, of whom 10,290 had GI cancer and were treated with 5-FU and 20,580 were population control subjects without cancer. Differences in comorbid conditions and select antianginal medications were nonsignificant (P > 0.05 for all). The 6-month cumulative incidence of myocardial infarction was significantly higher for 5-FU patients at 0.7% (95% CI: 0.5%-0.9%) versus 0.3% (95% CI: 0.3%-0.4%) in population control subjects, with a competing risk for death of 12.1% versus 0.6%. The 1-year cumulative incidence of myocardial infarction for 5-FU patients was 0.9% (95% CI: 0.7%-1.0%) versus 0.6% (95% CI: 0.5%-0.7%) among population control subjects, with a competing risk for death of 26.5% versus 1.4%. When accounting for competing risks, the corresponding subdistribution hazard ratios suggested an increased risk for myocardial infarction in 5-FU patients, compared with control subjects, at both 6 months (hazard ratio: 2.10; 95% CI: 1.50-2.95; P < 0.001) and 12 months (hazard ratio: 1.39; 95% CI: 1.05-1.84; P = 0.022). Conclusions: Despite a statistically significantly higher 6- and 12-month risk for myocardial infarction among 5-FU patients compared with population control subjects, the absolute risk for myocardial infarction was low, and the clinical significance of these differences appears to be limited in the context of the significant competing risk for death in this population

Adverse cardiac events in out-patients initiating clozapine treatment: a nationwide register-based study

Using national Danish registers, we estimated rates of clozapine-associated cardiac adverse events. Rates of undiagnosed myocarditis were estimated by exploring causes of death after clozapine initiation.Through nationwide health registers, we identified all out-patients initiating antipsychotic treatment (January 1, 1996-January 1, 2015). Rates of clozapine-associated myocarditis and pericarditis within 2\ua0months from clozapine initiation and rates of cardiomyopathy within 1-2\ua0years from clozapine initiation were compared to rates for other antipsychotics. Mortality within 2\ua0months from clozapine initiation was extracted.Three thousand two hundred and sixty-two patients of a total 7932 patients initiated clozapine as out-patients (41.12%). One patient (0.03%) developed myocarditis, and no patients developed pericarditis within 2\ua0months from clozapine initiation. Two (0.06%) and four patients (0.12%) developed cardiomyopathy within 1 and 2\ua0years respectively. Rates were similar for other antipsychotics. Twenty-six patients died within 2\ua0months from clozapine initiation. Pneumonia (23.08%) and stroke (11.54%) were the main causes of death. We estimated the maximum rate of clozapine-associated fatal myocarditis to 0.28%.Cardiac adverse effects in Danish out-patients initiating clozapine treatment are extremely rare and these rates appear to be comparable to those observed for other antipsychotic drugs

One-year incidence of depression, anxiety, or stress disorders following a first-time heart failure diagnosis: A Danish nationwide registry-based study

Study objective: To examine first-time depression, anxiety, stress disorders or psychotropic drug prescriptions within one year after incident heart failure (HF). Design: Nationwide Epidemiological registry study. Setting: National patient registries. Participants: Patients in Denmark with a first-time HF diagnosis during 2005–2015. Interventions: None. Main outcome measures: Incidences of depression, anxiety, stress disorders or first-time prescription of a psychotropic drug were determined. Results: A total of 94,712 HF patients and 473,560 matched controls were included (median age 74.0 [64.0–81.0] years, 60.8 % males). At one year after incident HF, 11.9 % met the primary composite endpoint (depression, anxiety, or stress disorders or prescription of related psychotropic drugs), with 8.6 % outpatients and 13.3 % in-patients, versus 2.4 % of the controls. Starting psychotropic medication accounted for most of the composite endpoint events, as 11.6 % of the HF patients started antidepressants, anxiolytics, hypnotics, or sedative drugs (2.4 % among controls), while 0.6 % received a registered diagnosis of depression, anxiety, or stress disorder (<0.1 % among controls). The relative risk of psychotropic drug prescriptions in HF patients versus controls (standardized to the age, sex, and selected comorbidity distributions of all included subjects) was 3.85 [95 % CI 3.73–3.98]. The corresponding relative risk for one of the psychiatric diagnoses was 12.90 [95 % CI 10.60–15.19]. Conclusion: A substantial part of patients with newly diagnose heart failure started treatment with psychotropic drugs whereas only a small fraction was registered with depression, anxiety, or stress disorders within one-year follow-up. The incidences were significantly higher than in the background population

Diabetic ketoacidosis in patients exposed to antipsychotics: a systematic literature review and analysis of Danish adverse drug event reports

RATIONALE: Patients exposed to second-generation antipsychotics (SGAs) have approximately 10 times increased risk of diabetic ketoacidosis (DKA) compared with the general population. However, as DKA is a rare complication of type 2 diabetes mellitus, and susceptible patients exposed to antipsychotics may rapidly develop DKA independently of treatment duration and weight gain, this is rather suggestive of type 1 diabetes mellitus (T1DM) or latent autoimmune diabetes in adults.OBJECTIVES: We performed a systematic review of current studies regarding antipsychotic-associated DKA with type 1 etiology and analyzed Danish adverse drug event (ADE) reports (previously unpublished cases).METHODS: PubMed, Embase, and the Cochrane Library were searched for all relevant studies, and the Danish Medicines Agency retrieved ADE reports using the Danish ADE database (up to date as of June 28, 2016). Diagnosis of antipsychotic-associated DKA with type 1 etiology was either considered confirmed or possible depending on authors' conclusions in the studies and/or clinical aspects. In addition, clinico-demographic risk factors were extracted.RESULTS: A total of 655 records and 11 ADE reports were identified, and after screening for eligibility, we included 21 case reports/series and two ADE reports (n = 24). No relevant clinical studies were included. Although fatal cases were identified, these were excluded because of diagnostic uncertainties (n = 15). DKA occurred in 15 males (62.5 %) and nine females (37.5 %), with a mean age ± standard deviation of 34.8 ± 12.4 years. Median time to DKA was 5 months (interquartile range: 1.4-11 months). Associated antipsychotics were olanzapine (n = 9, 36 %), aripiprazole (n = 6, 24 %), risperidone (n = 6, 24 %), clozapine (n = 3, 12 %), and quetiapine (n = 1, 4 %). Nine patients (37.5 %) were confirmedly diagnosed with T1DM following DKA resolution, whereas 15 patients (62.5 %) had possible T1DM. In 22 patients (91.7 %), ongoing insulin treatment was required for glycemic control.CONCLUSIONS: Increased awareness of the potential risk of antipsychotic-associated DKA and subsequent T1DM diagnosis, with insulin requirements for glycemic control, is warranted. The underlying mechanisms are poorly understood but most probably multifactorial. Certainly, further studies are warranted. Clinicians must utilize appropriate monitoring in susceptible patients and consider the possibility of continuing antipsychotic treatment with appropriate diabetic care.</p