Another meta-analysis by Sipahi et al. In contrast, the present study was based on real-world patients, where physicians have a more free choice of selecting an OAC fitting the patients' profile. However, if physicians fit dabigatran use for patients with a non-increased potential for adverse gastrointestinal events, this may lead to a possible underestimation of our results.
Another recently published observational study 25 from Denmark found similar results as to our results except for OAC-naive dabigatran , who had a HR, 0. Moreover, our results were based on diagnosis codes of all major and non-major gastrointestinal bleeding, whereas the other study only used diagnosis codes of major gastrointestinal bleeding.
We would assume that in clinical practice, many physicians would probably not start dabigatran treatment on patients with a history of gastrointestinal diseases especially dyspepsia or gastrointestinal bleeding given the association with this drug in the RE-LY trial. In our study, we selected patients with no history of gastrointestinal diseases or PPI use days before baseline to reduce selection bias and to answer the question whether this group of patients has a higher risk of gastrointestinal adverse events when treated with dabigatran compared with warfarin.
The difference in the inclusion and exclusion criteria between our study, the RE-LY trial, and other studies can also explain our finding that patients on dabigatran did not have a higher risk of gastrointestinal adverse effects.
The RE-LY trial and another observational study 3 reported higher rates of discontinuation for dabigatran mg and dabigatran mg compared with warfarin. In our study, OAC-experienced dabigatran patients were the ones to discontinue with treatment. We could not extract information about whether a physician stopped the dabigatran treatment or it was due to non-adherence for the OAC-experienced dabigatran Additionally, we could not point out an association between a gastrointestinal outcome and discontinuation with dabigatran.
However, it is still possible that discontinuation of dabigatran is due to gastrointestinal adverse effects, if the patient decided to stop treatment due to an adverse gastrointestinal event without consulting a physician.
In an everyday clinical setting, our results can offer an improved safety of dabigatran. Relative to OAC-naive warfarin: i patients initiating dabigatran mg showed a greater need for PPIs; ii patients initiating dabigatran mg had the same risk of admission due to upper dyspepsia-like diagnoses, gastrointestinal bleeding, and subsequently PPI use; iii patients with warfarin experience treated with dabigatran, independent of dose, had the same risk of admission due to upper dyspepsia-like diagnoses, gastrointestinal bleeding, and subsequent PPI use; iv only patients with warfarin experience treated with dabigatran mg had an increased risk of discontinuation of treatment.
Alternately, physicians could consider another OAC agent. However, the Danish registries are well validated. Owing to the financial reimbursement with prescriptions, we could maintain the persistence of drug use and then minimize the limitations. Moreover, we presumed that the majority of patients initiating OAC with subsequently adverse gastrointestinal events would contact a physician, who would prescribe a PPI. It was a limitation that we were not able to distinguish between if PPI was prescribed as prophylaxis or as treatment for gastrointestinal adverse effects.
The drug reimbursement regime in Denmark reduced the differences in drug costs between dabigatran and warfarin. Therefore, a selection bias due to the difference in drug cost would be minimal. By using major and non-major diagnosis codes of gastrointestinal bleeding, gastroesophageal reflux, gastritis, gastric, and duodenal ulcer, we entailed a high sensitivity, but it was a limitation that the outcomes only were based on diagnosis codes without clinical information.
Furthermore, the sensitivity of the outcomes had not been validated in previous studies. Our results could underestimate the association between dabigatran and the gastrointestinal outcomes, because we were unable to include patients with dyspepsia without diagnosis codes from an admission and because of confounding by indication.
To overcome this limitation, we looked into PPI use and discontinuation of treatment. We chose not to include dabigatran-experienced warfarin initiators in this study, since only 59 patients were identified in this group, and this would not qualify for adequate power.
Furthermore, warfarin-experienced warfarin patients were not included, because we wanted to compare patients initiated on dabigatran with patients initiated on warfarin. When a physician plans to initiate oral anticoagulation, this study design could help him to choose initiation of dabigatran or warfarin. Our study was not divided into time periods, and therefore, a part of the included patients could potentially switch OAC therapy during follow-up, leading to an underestimation of the true association.
Labile international normalized ratio, body mass index, and other potential confounders, which cannot be identified in the registries, could have influenced our results. We made an effort to minimize this by making a sensitivity analysis with adjustments of chronic kidney diseases and by using methods from previous parallel studies. Nonetheless, the results from this study were comparable with previous studies.
In conclusion, treatment with dabigatran was not associated with subsequent PPI use, upper dyspepsia-like diagnoses, or gastrointestinal bleeding requiring hospitalization compared with warfarin among patients with AF and no history of gastrointestinal diseases or PPI use days before dabigatran or warfarin treatment was started. However, patients dosed with dabigatran b. Discontinuation of dabigatran was more common among patients with a prior warfarin experience treated with dabigatran mg b.
Our study did not support an association between dabigatran and subsequent PPI use, upper dyspepsia-like diagnoses, or gastrointestinal bleeding requiring hospitalization, or cessation of dabigatran. Supplementary material is available at Europace online. The sponsors had no influence on the study design, interpretation of results, or the decision to submit the manuscript for publication. Conflict of interest: G. Europace ; 17 : — Google Scholar. Fatal gastrointestinal hemorrhage after a single dose of dabigatran.
Clin Toxicol ; 50 : — 3. Adherence, persistence, and switching patterns of dabigatran etexilate. Am J Manage Care ; 19 : e — Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med ; : — Europace ; 12 : — Dabigatran use in Danish atrial fibrillation patients in a nationwide study. BMJ Open ; 3 : e J Am Coll Cardiol ; 61 : — New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis.
Gastroenterology ; : — Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet ; : — A comparison of results of the US food and drug administration's mini-sentinel program with randomized clinical trials: the case of gastrointestinal tract bleeding with dabigatran. The Danish National Patient Register.
Scand J Public Health ; 39 : 30 — 3. The Danish National Prescription Registry. Scand J Public Health ; 39 : 38 — Pedersen CB.
The Danish Civil Registration System. Scand J Public Health ; 39 : 22 — 5. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study.
BMJ ; : d — d Accuracy of a heart failure diagnosis in administrative registers. Eur J Heart Fail ; 10 : — Bleeding after initiation of multiple antithrombotic drugs, including triple therapy, in atrial fibrillation patients following myocardial infarction and coronary intervention: a nationwide cohort study. Circulation ; : — Survey of the use of warfarin and the newer anticoagulant dabigatran in patients with atrial fibrillation.
Patient Prefer Adherence ; 8 : — Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. Am J Gastroenterol ; : — Assessment of dabigatran utilization and prescribing patterns for atrial fibrillation in a physician group practice setting.
Am J Cardiol ; : — 4. Expert position paper on the use of proton pump inhibitors in patients with cardiovascular disease and antithrombotic therapy. Eur Heart J ; 34 : — Dabigatran etexilate for stroke prevention in patients with atrial fibrillation: resolving uncertainties in routine practice. Thromb Haemost ; : Boehringer Ingelheim. Advisory Committee Briefing Document. Products affected Information for consumers and caregivers Information for healthcare professionals Data summary What action is Medsafe taking?
How to report Further information. It helps stop blood clots forming after surgery. It is also used to stop blood clots and strokes in patients with an abnormal heart beat atrial fibrillation.
Pradaxa is known to be associated with the development of ulcers in the digestive tract. However, recent case reports have highlighted that Pradaxa can also cause the development of ulcers in the oesophagus food pipe. The risk of developing oesophageal ulcers can be minimised by always taking Pradaxa with food and a full glass of water. Talk with your healthcare provider about your risk for severe bleeding from the uterus if you are treated with blood thinner medicines, including PRADAXA.
Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is important to tell your healthcare provider about all medicines prescription and over-the-counter , vitamins, and supplements you take. Some important considerations you'll want to discuss with your doctor There are different treatment options for your condition.
Important safety and side effects information Because PRADAXA is available only by prescription, the decision to prescribe it is made by a healthcare professional after discussing a range of important considerations with the individual adult patient. You may have a higher risk of bleeding if you take PRADAXA and: are 75 years old or older have kidney problems have stomach or intestine bleeding that is recent or keeps coming back, or you have a stomach ulcer take other medicines that increase your risk of bleeding, including: aspirin or aspirin-containing products long-term chronic use of non-steroidal anti-inflammatory drugs NSAIDs warfarin sodium a medicine that contains heparin clopidogrel bisulfate prasugrel if you have kidney problems and take dronedarone or ketoconazole tablets Tell your healthcare provider if you take any of these medicines.
While you take PRADAXA: you may bruise more easily it may take longer for any bleeding to stop Call your healthcare provider or seek immediate medical care if you have any of the following signs or symptoms of bleeding: any unexpected, severe, or uncontrollable bleeding; or bleeding that lasts a long time unusual or unexpected bruising coughing up or vomiting blood; or vomit that looks like coffee grounds pink or brown urine; red or black stools looks like tar unexpected pain, swelling, or joint pain headaches, feeling dizzy or weak Take PRADAXA Capsules exactly as prescribed.
Your risk of developing a spinal or epidural blood clot is higher if: a thin tube called an epidural catheter is placed in your back to give you certain medicine you take NSAIDs or a medicine to prevent blood from clotting you have a history of difficult or repeated epidural or spinal punctures you have a history of problems with your spine or have had surgery on your spine.
Tell your healthcare provider or get medical help right away if you get any of the following symptoms of a serious allergic reaction to PRADAXA Capsules: chest pain or chest tightness swelling of your face or tongue trouble breathing or wheezing feeling dizzy or faint.
Most common side effects Common side effects of PRADAXA include: indigestion, upset stomach, or burning stomach pain Tell your healthcare provider if you have any side effect that bothers you or does not go away. With atrial fibrillation, part of the heart does not beat the way it should. This can lead to blood clots forming and increase your risk of a stroke.
0コメント