Michael Dall

Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study

Abstract Objectives To assess the risk of serious upper gastrointestinal bleeding associated with the newer antithrombotic agents used alone or in combination with other antithrombotic drugs; to describe the trends in use of antithrombotic drugs in the background population. Design Population based case-control study. Setting Funen County, Denmark (population 470 000). Subjects 1443 cases of serious upper gastrointestinal bleeding identified during 2000-4; 57 720 age and sex matched controls. Main outcome measure Exposure to low dose aspirin, clopidogrel, dipyridamole, vitamin K antagonists, and combined antithrombotic treatment. Results Adjusted odds ratios associating drug use with upper gastrointestinal bleeding were 1.8 (95% confidence interval 1.5 to 2.1) for low dose aspirin, 1.1 (0.6 to 2.1) for clopidogrel, 1.9 (1.3 to 2.8) for dipyridamole, and 1.8 (1.3 to 2.4) for vitamin K antagonists. Corresponding figures for combined use were 7.4 (3.5 to 15) for clopidogrel and aspirin, 5.3 (2.9 to 9.5) for vitamin K antagonists and aspirin, and 2.3 (1.7 to 3.3) for dipyridamole and aspirin. Other combinations were used too infrequently to allow estimation. The number of treatment years needed to produce one excess case varied from 124 for the clopidogrel-aspirin combination to 8800 for clopidogrel alone. During the study period, exposure to combined antithrombotic regimens increased by 425% in the background population. Conclusion Antithrombotic treatment is becoming increasingly aggressive. Combined antithrombotic treatment confers particular risk and is associated with high incidence of gastrointestinal bleeding.

An Association Between Selective Serotonin Reuptake Inhibitor Use and Serious Upper Gastrointestinal Bleeding

BACKGROUND & AIMS In vitro studies have shown that selective serotonin reuptake inhibitors (SSRIs) inhibit platelet aggregation. It is controversial whether use of SSRIs is a cause of clinically important bleeding; results from observational studies have been equivocal. METHODS A population-based case-control study was conducted in Denmark. The 3652 cases all had a first discharge diagnosis of serious upper gastrointestinal bleeding (UGB) from 1995 to 2006. Controls (n = 36,502), matched for age and sex, were selected by risk-set sampling. Data on drug exposure and medical history were retrieved from a prescription database and the countys patient register. Confounders were controlled for by conditional logistic regression and the case-crossover design. RESULTS The adjusted odds ratio (OR) of UGB among current, recent, and past users of SSRIs was 1.67 (95% confidence interval [CI], 1.46-1.92), 1.88 (95% CI, 1.42-2.5), and 1.22 (95% CI, 1.07-1.39). The adjusted OR for concurrent use of SSRI and nonsteroidal anti-inflammatory drugs (NSAIDs) was 8.0 (95% CI, 4.8-13). The adjusted OR for the concurrent use of NSAID, aspirin, and SSRI was 28 (95% CI, 7.6-103). Of the UGB cases, 377 were current users of SSRI; the adjusted OR for UGB in the case crossover analysis was 2.8 (95% CI, 2.2-3.6). The adjusted OR among users of proton pump inhibitors was 0.96 (95% CI, 0.50-1.82). CONCLUSIONS Use of SSRI was associated with UGB, consistent with its antiplatelet effects. SSRIs should be prescribed with caution for patients at high risk for UGB.

There is an association between selective serotonin reuptake inhibitor use and uncomplicated peptic ulcers: a population-based case-control study.

Aliment Pharmacol Ther 2010; 32: 1383–1391

Helicobacter pylori and risk of upper gastrointestinal bleeding among users of selective serotonin reuptake inhibitors

Abstract Background. A number of studies have reported a possible association between use of selective serotonin reuptake inhibitors (SSRIs) and serious upper gastrointestinal bleeding (UGB). We conducted this case–control study to assess if Helicobacter pylori (H. pylori) potentiates the risk of serious UGB in SSRI users. Material and methods. A population-based case–control study was conducted in the county of Funen, Denmark. Cases were 53 SSRI users with serious UGB whose H. pylori status on their bleeding date could be established. Controls (n = 723) were selected among subjects who participated in a population H. pylori screening study, and who were users of SSRIs. Data on drug exposure and medical history were retrieved from a prescription database and the countys patient register. Confounders were controlled for by unconditional logistic regression. Results. H. pylori infection increased the risk of serious UGB in patients using SSRI with an adjusted odds ratio (OR) of 2.73 (95% confidence interval (CI), 1.17–6.36). The adjusted OR for serious UGB among users of non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) were 3.91 (95% CI, 2.03–7.52) and 3.00 (95% CI, 0.94–9.54), respectively. Conclusion. H. pylori infection increases the risk of SSRI-related serious UGB.

The Association between Use of Serotonergic Antidepressants and Perioperative Bleeding during Total Hip Arthroplasty – A Cohort Study

In vitro studies have shown that selective serotonin reuptake inhibitors inhibit platelet aggregation. It is well documented that SSRIs cause serious gastrointestinal bleeding, but studies on other bleeding manifestations have been equivocal. Our objective was to determine a possible association between use of serotonergic antidepressants (SA) and perioperative bleeding during hip replacements. We conducted a retrospective study between 1 January 2007 and 30 June 2012 among patients that underwent a primary unilateral uncemented total hip arthroplasty (THA). Information was collected on the observed blood loss and the need for blood transfusions among this group. We compared the blood loss between users of SA, users of non‐serotonergic antidepressants (NSA) and non‐users, while adjusting for potential confounders using multivariate linear regression. We indentified 1318 patients that underwent a THA in the study period. The average volume of surgical bleeding was 350 ml. The adjusted incremental blood loss associated with use of SA and NSA was 93, 95% confidence interval (38–147) ml and −50 (−125 to 25) ml compared with non‐use. Only 48 subjects (3.6%) had transfusions. Use of SA was associated with an increased blood loss compared with non‐users. The hypothesis that SA impairs haemostasis is supported by these results.

Re-prescribing of causative drugs in persons discharged after serious drug-induced upper gastrointestinal bleeding

Several drug classes are known to be associated with serious upper gastrointestinal bleeding (UGIB), among others NSAID, low‐dose acetylsalicylic acid (ASA), vitamin K antagonists (VKA), clopidogrel and selective serotonin reuptake inhibitors (SSRIs). There are few data on how and to what extent these drugs are reintroduced in patients who have been discharged after a bleeding episode related to any of them.

Significant association between the use of different proton pump inhibitors and microscopic colitis: A nationwide Danish case-control study

Microscopic colitis causes chronic watery diarrhoea and has previously been associated with the use of proton pump inhibitors.

Sa1879 A Model to Assess the Risk for ASA/NSAID-Related Ulcer Bleeding for the Individual Patient Based on the Number of Risk Factors

Background and goals: Recently we observed patients with chronic liver diseases (CLD) (n= 16) and chronic reflux symptoms (CRS) (n=38) that developed gastric polyps (GPs) while undergoing repeated esophagogastroduodenoscopy (EGD). The indications for repeated EGD were: persistent reflux symptoms (CRS patients) and monitoring of esophageal varices development (CLD patients). Herewith we identify risk factors for GP development and estimate the gastric polyp development time (GPDT). Methods: Data was retrospectively analyzed. GPDT was defined as days, since the first gastroscopy until polyp discovery. The presence of portal hypertension (PHT) in CLD patients was determined by the presence of esophageal varices with or without gastric varices. Results: CLD patients developed more hyperplastic gastric polyps (HGPs) than CRS patients (p= 0.021). CLD patients with PHT developed HGPs at a younger age (p=0.023) and had a tendency for a shorter GPDT than CLD patients without PHT: mean GPDT was 1184 ±787 days (for CLD patients with PHT) vs.2634 ±2345 days (for CLD patients without PHT). In order to further study the effect of PHT on the GPDT, Kaplan-Meier curves, indicating the individual GPDT, for all patients with HGPs, from the CRS and CLD groups, were constructed. A trend for shorter GPDT for CLD patients with PHT was demonstrated (Figure 1). In the CLD patients (irrespective to the presence PHT), a positive correlation between the GPDT and age was found; the older the patient, the longer the GPDT (p=0.014). In patients with CLD, Ki-67 labeling index values of HGPs were independent to the presence PHT, the patients gender, to infection with Helicobacter Pylori and to PPI exposure. However, a negative correlation between the patients age and the Ki-67 values was found; the younger the patient, the higher the Ki-67 value (p= 0.042).The histopathology features that were previously reported to be specific for GP tissue in patients with PHT were not detected more often in the CLD patients with HGPs, irrespective to the presence or absence of PHT. Conclusions: Compared to CRS patients, CLD patients with PHT, appear to develop HGPs at a greater number, at a younger age and in a shorter GPDT.