Higher Risk Of Gastrointestinal Bleeding Research Articles

Effectiveness and Safety of Dabigatran and Warfarin in Real‐World US Patients With Non‐Valvular Atrial Fibrillation: A Retrospective Cohort Study

BackgroundThe recent availability of dabigatran, a novel oral anticoagulant, provided a new treatment option for stroke prevention in atrial fibrillation beyond warfarin, the main therapy for years. Little is known about their real‐world comparative effectiveness and safety, even less among patient demographic and clinical subgroups.Methods and ResultsUsing a cohort of non‐valvular AF patients initiating anticoagulation from October 2010 to December 2012 drawn from a large US database of commercial and Medicare supplement claims, we applied propensity score weights to Cox proportional hazards regression to assess the comparative effectiveness and safety of dabigatran versus warfarin. Analyses were repeated among clinical and demographic subgroups using stratum‐specific propensity scores as an exploratory analysis. Of the 64 935 patients initiating anticoagulation, 32.5% used dabigatran. Compared with warfarin, dabigatran was associated with a lower risk of ischemic stroke or systemic embolism (composite adjusted Hazard Ratio [aHR], 95% CI: 0.86, 95% CI: 0.79 to 0.93), hemorrhagic stroke (aHR: 0.51, 0.40 to 0.65), and acute myocardial infarction (aHR: 0.88, 95% CI: 0.77 to 0.99), and no relation was seen between dabigatran and the composite harm outcome (aHR: 0.94, 95% CI: 0.87 to 1.01). However, dabigatran was associated with a higher risk of gastrointestinal bleeding (aHR: 1.11, 95% CI: 1.02 to 1.22). Estimates of effectiveness and safety appeared to be mostly similar across subgroups.ConclusionsDabigatran could be a safe and potentially more effective alternative to warfarin in patients with atrial fibrillation managed in routine practice settings.

Mo1902 Patients With GAVE Are at a Higher Risk of Gastrointestinal Bleeding in the Absence of Cirrhosis

Mo1902 Patients With GAVE Are at a Higher Risk of Gastrointestinal Bleeding in the Absence of Cirrhosis

Impact of new oral anticoagulants on gastrointestinal bleeding in atrial fibrillation: A meta-analysis of interventional trials

BackgroundNew oral anticoagulants represent an alternative to standard therapy with vitamin K antagonists but data regarding gastrointestinal bleeding are still unclear. AimsTo investigate if new oral anticoagulants are associated with an enhanced risk of gastrointestinal bleeding vs warfarin in patients with atrial fibrillation. MethodsMeta-analysis of phase three randomized controlled trials to compare the incidence of gastrointestinal bleeding in atrial fibrillation patients treated with new oral anticoagulants (apixaban, dabigatran, edoxaban and rivaroxaban) vs warfarin. ResultsFour studies including 71,302 patients were selected. Compared with warfarin, new oral anticoagulants significantly increased gastrointestinal bleeding (RR: 1.23; 95% CI 1.03–1.46; p=0.01). Rivaroxaban (RR: 1.46; 95% CI 1.2–1.8; p<0.001) and high dosages of edoxaban (RR: 1.22; 95% CI 1.01–1.47; p=0.038) and dabigatran (RR: 1.50; 95% CI 1.20–1.88; p<0.001) significantly increased gastrointestinal bleeding while a null effect was detected with apixaban. ConclusionsThis meta-analysis suggests that rivaroxaban and high dosages of dabigatran and edoxaban should be avoided in patients at high risk of gastrointestinal bleeding.

Characteristics of gastrointestinal bleeding after placement of continuous-flow left ventricular assist device: a case series.

Medical management of patients with continuous-flow left ventricular assist devices (LVADs) remains challenging for the gastroenterologist given their high risk of gastrointestinal bleeding (GIB) and need for continuous anticoagulation. Our aim was to better characterize LVAD patients who presented with a GIB at our facility and delineate the prevalence, presentation, time to diagnosis, management, and therapeutic endoscopic interventions, including small bowel tools that may offer additional benefit. We retrospectively reviewed adult patients (>18 years) who underwent LVAD implantation at our tertiary care facility between October 2011 and October 2013. Electronic medical records were reviewed for presenting symptoms, average days to initial and repeat GIB, hospital course, and techniques that led to diagnosis and hemostasis. Eighteen patients underwent LVAD implantation, of which 61 % presented with a GIB for a total of 20 presentations (1.8 per patient). Mean time to initial GIB was 154 days. Patients required an average of 1.8 endoscopic procedures per admission. Esophagogastroduodenoscopy (EGD) and push enteroscopy (PE) were more likely to lead to a diagnosis, and EGD was the most commonly used diagnostic tool at initial presentation. Sixty percent of patients who initially received EGD presented with a recurrent GIB and required PE, which was diagnostic and therapeutic for small bowel angiodysplasias in 80 % of cases. We found a higher GIB rate compared with prior studies. Bleeding events were associated with multiple procedures and interventions. We recommend an algorithmic approach to LVAD patients who bleed. Our experience suggests that PE is warranted at initial presentation in order to achieve hemostasis, prevent recurrent GIB, and decrease subsequent readmission rates.

Risk of Bleeding With Dabigatran in Atrial Fibrillation

ImportanceIt remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice.ObjectiveTo compare the risk of bleeding associated with dabigatran and warfarin using Medicare data.Design, Setting, and ParticipantsIn this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011.ExposuresDabigatran users (n = 1302) and warfarin users (n = 8102).Main Outcomes and MeasuresWe identified any bleeding events and categorized them as major and minor bleeding by anatomical site. Major bleeding events included intracranial hemorrhage, hemoperitoneum, and inpatient or emergency department stays for hematuria, gastrointestinal, or other hemorrhage. We used a propensity score weighting mechanism to balance patient characteristics between 2 groups and Cox proportional hazards regression models to evaluate the risk of bleeding. We further examined the risk of bleeding for 4 subgroups of high-risk patients: those 75 years or older, African Americans, those with chronic kidney disease, and those with more than 7 concomitant comorbidities.ResultsDabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of major bleeding among dabigatran users was especially high for African Americans and patients with chronic kidney disease.Conclusions and RelevanceDabigatran was associated with a higher incidence of major bleeding (regardless of the anatomical site), a higher risk of gastrointestinal bleeding, but a lower risk of intracranial hemorrhage. Thus, dabigatran should be prescribed with caution, especially among high-risk patients.

Bleeding Rates in Veterans Affairs Patients with Atrial Fibrillation Who Switch from Warfarin to Dabigatran

ObjectivesClinical trial data suggest that dabigatran and warfarin have similar rates of major bleeding but higher rates of gastrointestinal bleeding. These findings have not been evaluated outside of a clinical trial. We evaluated the relative risks of any, gastrointestinal, intracranial, and other bleeding for Veterans Affairs patients who switched to dabigatran after at least 6 months on warfarin, compared with patients who continued on warfarin. MethodsWe used national Veterans Affairs administrative encounter and pharmacy data from fiscal years 2010-2012 to identify 85,344 patients with atrial fibrillation who had been taking warfarin for at least 180 days before June 2011, of whom 1394 (1.7%) received dabigatran (150 mg) during the next 15 months. Dates of the first occurrence of each type of bleed and dates of death from June 2011 to September 2012 were determined. Baseline and time-dependent patient characteristics were identified, including comorbid conditions, stroke and bleeding risk scores, and time in therapeutic range for international normalized ratios. Marginal structural models were used to address selection bias in the longitudinal observational data. Weighted logistic regression models were fit using generalized estimating equations and reflected baseline and time-dependent covariates and weekly indicators of anticoagulant type (warfarin or dabigatran). ResultsCompared with patients who never used dabigatran, patients who used dabigatran at least once were younger, were more likely to be white, had lower international normalized ratio time in therapeutic range on warfarin, had lower stroke risk scores, and had similar bleeding risk scores. Overall, 10,734 patients experienced bleeding events, including 131 events after dabigatran use. The risk-adjusted rate of any bleeding was higher with dabigatran compared with warfarin, which was largely driven by a 54% higher risk of gastrointestinal bleeding with dabigatran. Rates of intracranial, other bleeding, and death were similar for dabigatran and warfarin. ConclusionsDabigatran may increase the likelihood of gastrointestinal bleeds.

Safety of deferasirox: a retrospective cohort study on the risks of gastrointestinal, liver and renal events.

Deferasirox (DFX) is an effective and well-tolerated oral iron chelator elevating the adherence to iron chelating therapy among patients with iron overload. However, the US Food and Drug Administration issued a warning about the potential adverse events associated with DFX in 2010. To examine the risks of gastrointestinal (GI) bleeding, acute liver necrosis, and acute renal failure among DFX users compared with desferrioxamine (DFO) users in a real-world setting, first-time users of DFX or DFO between 2005 and 2008 in Taiwan's National Health Insurance database were observed in this population-based retrospective cohort study. The risks of different adverse events were individually analyzed by Cox proportional hazards models and adjusted by age, sex, concomitant medications, and prior medical conditions. Deferasirox users had the highest incidence rates of GI bleeding (2.03 per 10 000 patient-days), acute liver necrosis (0.26 per 10 000 patient-days) and acute renal failure (1.45 per 10 000 patient-days) compared with other iron chelator users. Compared with DFO users, DFX users were not associated with the risk of GI bleeding (adjusted HR 1.03, 95% CI 0.61-1.74, p = 0.90) and the risk of acute liver necrosis (adjusted HR 2.13, 95% CI 0.49-9.33, p = 0.32). The association between DFX use and acute renal failure was found to be statistically significant (HR 2.18, 95% CI 1.18-4.02, p = 0.01; adjusted HR 2.41, 95% CI 1.27-4.58, p = 0.01). In this study, we found statistically significant higher risk of acute renal failure and non-statistically significant higher risk of GI bleeding and acute liver necrosis associated with DFX use. More researches are warranted to evaluate the association between DFX use and potential adverse events.

Risk factors for acute gastrointestinal bleeding following myocardial infarction in veteran patients who are prescribed clopidogrel

Our aim was to identify risk factors for acute gastrointestinal (GI) bleeding in patients with myocardial infarction (MI) who were prescribed clopidogrel following hospital discharge. Data were collected retrospectively from patients treated in Veteran Affairs hospitals in Ohio, USA, from 2001 to 2008 with a primary diagnosis of MI (International Classification of Diseases, 9th Revision) and a prescription for clopidogrel filled within 48 h of discharge. Primary outcome was acute GI bleeding after discharge. Acute GI bleeding occurred in 107 of 3218 patients. Bleeding occurred in those who were elder (66.2 vs. 62.4 years, P = 0.0002), had lower glomerular filtration rate (74 vs. 81 mL/min, P = 0.024), had filled prescription for warfarin (15.9% vs. 6.9%, P = 0.0004), diagnosed as atrial fibrillation (20.6% vs. 11.1%, P = 0.003), chronic liver (5.6% vs. 2.2%, P = 0.018) or kidney disease (29.0% vs. 19.4%, P = 0.016). A risk model and GI bleed risk score were developed and showed that patients with age >65 years, use of warfarin, the presence of chronic liver or kidney disease were at increased risk for GI bleeding. Veterans patients of advanced age, using warfarin and with chronic liver and kidney disease may be at increased risk of GI bleeding when prescribed clopidogrel following MI. A scoring system may help to identify patients at high risk for GI bleeding.

Treatment with novel oral anticoagulants

To summarize data relevant to novel oral anticoagulants (nOACs), mainly apixaban, dabigatran and rivaroxaban, as alternatives to vitamin K antagonists (VKAs). RE-LY was the first contemporaneous study to compare a nOAC, dabigatran, with dose-adjusted warfarin, for prevention of stroke and systemic embolism in atrial fibrillation. Since then multiple studies have compared nOACs to warfarin for acute (RE-COVER, RECOVER-II, EINSTEIN-DVT and EINSTEIN-PE) and extended treatment of venous thromboembolism (VTE) (AMPLIFY-EXT, RE-MEDY and RE-SONATE). Additional studies have examined stroke prevention in atrial fibrillation (ARISTOTLE and ROCKET-AF). We do not examine, in depth, use of nOACs in coronary artery disease. nOACs are an acceptable alternative to VKAs in certain situations - these are at least as effective as warfarin for secondary prevention of VTE and for prevention of stroke and systemic embolism in patients with atrial fibrillation. These compare favorably with warfarin with respect to their rate of fatal and major bleeding. However, special attention should be given when using these drugs in certain patient populations, in particular in patients with renal insufficiency, those receiving additional antithrombotic therapy, those with questionable compliance, patients of child bearing potential and those with a high risk of gastrointestinal bleeding.

Continuous Flow Left Ventricular Assist Device Patients Are Not at Higher Risk of Gastrointestinal Bleeding with More Aggressive Anticoagulation

Purpose Continuous flow left ventricular assist devices (CF-LVADs) have become a cornerstone of heart failure therapy. The risk of gastrointestinal bleeding has been noted to be higher in these CF-LVAD patients than in previous generations of pulsatile flow LVADs. A more aggressive anticoagulation regimen could reduce the incidence of thromboembolic complications. Our aim was to evaluate the risk of gastrointestinal bleeding (GIB) before and after the initiation of an aggressive anticoagulation regimen. Methods and Materials 137 consecutive patients received a CF- LVAD with either a Heartmate II, Heartware or VentrAssist device. We undertook a retrospective review of our database of our single institution experience. We divided patients into two groups, one group was implanted prior to 3/15/2011 under a more conservative anticoagulation protocol and the second group was implanted after 3/15/2011 under a more aggressive anticoagulation protocol. Results The 6 month and 1 year mortality in our patients were 14.3% and 30.9% respectively. Gastrointestinal bleeding occurred in 25 patients with a total of 45 bleeding episodes for an overall rate of 0.53 bleeding episodes per patient year on support. When broken out into conservative and aggressive anticoagulation groups the bleeding rate was 0.51 and 0.63 per patient years on support, which was not statistically different. There were 9 patients (36%) with recurrent GIBs. In patients who suffered a GIB the average INR at the time of the bleeding episode was 2.1, and 57.8% of patients were on a full anticoagulation regimen at the time of their bleeding event. Conclusions CF-LVADs will continue to play a major role in the management of end stage heart failure. We have shown that a more aggressive management strategy for anticoagulation in an effort to reduce thromboembolic complications is safe and does not lead to a significant increase in GIB events in our population.

404 Identification of Risk Factors to Decrease the Incidence of Gastrointestinal Bleeding After Cardiac Surgery

404 Identification of Risk Factors to Decrease the Incidence of Gastrointestinal Bleeding After Cardiac Surgery

Proton-Pump Inhibitors Often Are Prescribed Inappropriately at U.S. Teaching Hospitals

Stress ulcer prophylaxis has demonstrated efficacy in critically ill patients who are at high risk for gastrointestinal bleeding (e.g., mechanical ventilation >48 hours, coagulopathy). Prophylaxis in general ward patients also has become common, despite the lack of evidence to support this practice. Researchers performed a retrospective review of administrative data for hospitalized adult …

Clopidogrel and proton pump inhibitors - where do we stand in 2012?

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events. Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines. Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19 (CYP2C19) and proton pump inhibitors (PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well. Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole, but not for pantoprazole. Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events, when under clopidogrel and PPI treatment at the same time. These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI (especially omeprazole) in the same year. In contrast, more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel. Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality, with high and moderate quality studies not reporting any association, rising concern about unmeasured confounders biasing the low quality studies. Thus, no definite evidence exists for an effect on mortality. Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding, combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.

Optimal Management of Antiplatelet Therapy and Proton Pump Inhibition Following Percutaneous Coronary Intervention

Dual antiplatelet therapy (aspirin and a P2Y(12) antagonist) is required after the insertion of a coronary artery stent. If the stent has been inserted in the context of an acute coronary syndrome (ACS), then clopidogrel or a high-potency P2Y(12) antagonist such as prasugrel or ticagrelor should be considered. Current indications for the use of prasugrel in this situation include ST elevation, diabetes, or previous stent thrombosis on clopidogrel therapy. If the stent has been inserted electively for stable ischemic heart disease, then the patient should normally receive clopidogrel. Next, it is important to consider the patient's bleeding risk. The CRUSADE score can be used to determine the likelihood of a subsequent gastrointestinal (GI) bleed. For patients treated with aspirin and clopidogrel who are at high risk of a GI bleed, the current evidence suggests that a proton pump inhibitor (PPI) is the most effective way to reduce this risk. There is evidence that omeprazole may attenuate the pharmacodynamic effect of clopidogrel and, therefore, it would be reasonable to use an alternative PPI that has less risk of negative pharmacokinetic and pharmacodynamic interaction, such as pantoprazole. If a patient is at moderate or low risk of bleeding, then a PPI should be avoided in combination with clopidogrel as the risk of negative interaction is greater than the risk of GI bleeding. There is no substantive evidence that PPIs attenuate the therapeutic effect of prasugrel or ticagrelor; therefore, patients at moderate or high risk of GI bleeding should be offered a PPI.

Risk Factors for Gastrointestinal Bleeding in Patients Treated with Radiation Therapy for Intrahepatic Cholangiocarcinoma

A previous study from our institution showed that patients treated with radiation therapy for intrahepatic cholangiocarcinoma had a high risk of gastrointestinal bleeding (GIB). Our goal was to identify clinical and dosimetric factors associated with GIB in these patients.

Pantoprazole for the prevention of gastrointestinal bleeding in high-risk patients with acute coronary syndromes

PurposeThe aim of this study is to evaluate the preventive effect of proton pump inhibitors on gastrointestinal (GI) bleeding in patients with acute coronary syndromes (ACS) who are at high risk for GI bleeding. Materials and MethodsWe enrolled 665 patients with ACS who had one or more of the following risk factors for GI bleeding: 75 years of age or older, history of peptic ulcer disease, history of GI bleeding, cardiogenic shock, and chronic renal dysfunction (serum creatinine, >2 mg/dL). Patients were randomly assigned to receive 40 mg of pantoprazole or placebo twice daily for 7 days, in addition to standard treatment of ACS. The primary end point was the occurrence of GI bleeding during hospitalization. ResultsDuring a median time of hospitalization of 12 days, 12 (3.6%) of 332 patients in the placebo group had an occurrence of GI bleeding, as compared with 4 (1.2%) of the 333 patients in the pantoprazole group (P = .046, Fisher exact test). The log-rank test showed a significant difference between the 2 groups in the time to the occurrence of GI bleeding (P = .015). Major GI bleeding occurred in 5 (1.5%) patients in the placebo group but only in 1 (0.3%) in the pantoprazole group (P = .12). Pneumonia developed in 22 (6.6%) patients in the placebo group and 24 (7.2%) in the pantoprazole group (χ2 = 0.077, P = .88). The 30-day mortality was 10.2% (34/332) in the placebo group and 10.5% (35/333) in the pantoprazole group. ConclusionsIn patients with ACS who are at high risk for GI hemorrhage, prophylactic treatment with pantoprazole could reduce the risk of GI bleeding with no significant effects on the incidence of hospital-acquired pneumonia and 30-day mortality.

4. Impact of CYP2C19 Polymorphism and Proton Pump Inhibitors on Clinical Outcomes during Dual Antiplatelet Therapy

Clopidogrel is a prodrug that has to be converted to an active metabolite. CYP2C19 genotype is a key factor impacting the response to clopidogrel and the drug interaction between proton pump inhibitors (PPIs) and clopidogrel. The prevalence of CYP2C19 loss-of-function alleles is much higher in East Asians including Japanese, than in people in Western countries. The American College of Cardiology Foundation (ACCF), American College of Gastroenterology (ACG) and American Heart Association (AHA) recommended in a 2010 conference that it is acceptable to use PPI with thienopyridines such as clopidogrel in patients at high risk of upper gastrointestinal bleeding. Several studies have indicated that concomitant use of clopidogrel and PPI is associated with reduced antiplatelet efficacy of clopidogrel, and increased adverse clinical outcomes after stent implantation in patients with acute coronary syndrome. However, several reports show that concomitant use of PPI and clopidogrel after stent implantation is not associated with an increased risk of cardiovascular events. We investigated whether CYP2C19 polymorphism or concomitant use of PPI and clopidogrel is associated with on-treatment platelet reactivity and clinical outcomes following stent implantation in patients with coronary artery disease. Our results indicated that the presence of CYP2C19 loss-of-function allele, but not the use of a PPI, was associated with an increased risk of cardiovascular outcomes. In conclusion, the use of a PPI should not be hesitated in patients with a high risk of gastrointestinal bleeding or ulcer.

High Incidence of Technical Errors Involving the EEA Circular Stapler: A Single Institution Experience

The use of stapling devices is now widespread in colorectal resections. However, the incidence and clinical consequence of technical error involving the circular stapler are still poorly characterized. We reviewed the operative reports and Web-based charts for all colon and rectal resections performed at our institution that used a circular stapler. Technical error was defined as any deviation from the normal technical performance of the circular stapler, including, but not limited to, surgeon misfiring, incomplete anastomosis (inadequate donuts or staple line defects), and primary device failure. The unpaired t- and chi-square tests were used for statistical analysis; p < 0.05. There were 349 colorectal resections performed and 67 (19%) featured a technical error. Thirty-two resections (9%) included an anastomotic error. The control group (n = 282) and the error group (n = 67) were comparable with regard to leaks, reoperation, suture line strictures, and hospital stay. The malfunction group had higher incidences of proximal diversions (34% versus 16%; p = 0.0003), ileus (24% versus 8%; p = 0.002), gastrointestinal bleeding (4% versus 0.4%; p = 0.023), and transfusion requirements (13% versus 4%; p = 0.004). Although proximal diversions in the error cohorts were also less likely to be planned (p < 0.001), reversal rates were similar in both groups (p = 0.28). The incidence of technical error involving the circular stapler is considerable. Technical error was found to be associated with a significantly higher risk of gastrointestinal bleeding, transfusions, and unplanned proximal diversions.

Stress Ulcer Prophylaxis in the Intensive Care Unit

Stress-related mucosal disease (SRMD) is an acute, erosive gastritis representing conditions ranging from stress-related injury to stress ulcers (1, 2). Stress-related injury is superficial mucosal damage that presents primarily as erosions, whereas stress ulcers are deep, focal mucosal damage penetrating the submucosa with high risk for gastrointestinal bleeding (2, 3). Mucosal damage has been reported to occur during the first 24 hours of hospital admission in 75% to 100% of intensive care unit (ICU) patients (4, 5). Clinically important gastrointestinal bleeding can cause hemodynamic instability and increase the need for red blood cell transfusions (1). Significant bleeding may also increase the length of stay in the ICU and mortality (1). Initiation of acid suppression therapy (AST) for stress ulcer prophylaxis (SUP) in the ICU setting is well established, but the use of SUP in general medicine patients has not been deemed necessary since most experts consider the risk of clinically important bleeding outside of the ICU too low for continuation of SUP (3). The American Society of Health-System Pharmacists (ASHP) published the only available guidelines in 1999 for the use of SUP in medical, surgical, respiratory, and pediatric ICU patients. The guidelines do not recommend SUP in adult patients in non-ICU settings since most clinical trials discontinued prophylaxis without evidence of clinically important bleeding upon extubation or ICU discharge (5). Furthermore, it has been reported that the number needed to treat is >900 patients with low risk for clinically important bleeding to prevent a single episode of clinically significant gastrointestinal bleeding (6). Thus, continuation of SUP in the general medicine setting is not necessary unless patients have at least one independent risk factor increasing the risk of clinically important bleeding (6). Interestingly, case reports have noted that 56% to 75% of general medicine patients begin inappropriate AST in the hospital (7). As many as 55% of patients continue AST once discharged without an appropriate indication (7). A retrospective chart review of medical and surgical ICU patients reported that 80% of patients transferred from the ICU continued to receive AST (60% was inappropriate AST), and 24.4% of those patients were discharged from the hospital with AST and no appropriate indication (7, 8).

A comparison of aspirin and clopidogrel with or without proton pump inhibitors for the secondary prevention of cardiovascular events in patients at high risk for gastrointestinal bleeding

Objective: This study was conducted to compare the risk of recurrent hospitalization for major gastrointestinal (GI) complications (peptic ulcer, bleeding, and perforation) in patients at high GI risk who require ongoing antiplatelet therapy (aspirin [acetylsalicylic acid] or clopidogrel) with or without proton pump inhibitors (PPIs). Methods: This population-based, retrospective cohort study employed data from the Taiwanese National Health Insurance database (January 2001 through December 2006) for patients who had a history of hospitalization for GI complications before the initiation of antiplatelet therapy with aspirin or clopidogrel. Recurrent hospitalizations for major GI complications were analyzed using a Cox proportional hazards model, with adjustment for age, sex, ulcer-related medical history, ulcer-related risk factors, and use of ulcer-related medications during follow-up. The propensity score method was applied to adjust for selection bias. Results: The analysis included data from 14,627 patients (12,001 receiving aspirin, 2626 receiving clopidogrel). The incidence of recurrent hospitalization for major GI complications was 0.125 per person-year in aspirin users, 0.103 per person-year in users of aspirin plus a PPI, 0.128 per person-year in clopidogrel users, and 0.152 per person-year in users of clopidogrel plus a PPI. Among aspirin users, those taking PPIs had a significantly lower adjusted risk of hospitalization for major GI complications than did non-PPI users (hazard ratio [HR] = 0.76; 95% CI, 0.64–0.91). Use of a PPI was not associated with a significant risk reduction among clopidogrel users (HR = 1.08; 95% CI, 0.89–1.33). An adjusted survival curve for the risk of recurrent hospitalization for major GI complications indicated that the risk increased numerically faster in clopidogrel users compared with those using aspirin plus a PPI, although the mean drug cost per personyear was 5.08 times higher in clopidogrel users than in users of aspirin plus a PPI. Conclusions: In this analysis in patients at high GI risk who were receiving antiplatelet therapy for the secondary prevention of cardiovascular events, aspirin plus a PPI was associated with a reduced risk of recurrent hospitalization for major GI complications. This was not the case for clopidogrel plus a PPI.