Major Gastrointestinal Bleeding Events Research Articles

Protective effect of proton pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: a systematic review and meta-analysis

Abstract Background The concurrent use of proton pump inhibitor (PPI) in oral anticoagulant (OAC) treated patients may be associated with a lower risk of gastrointestinal bleeding (GIB), but evidence is still conflicting according to individual OACs. Purpose We conducted a meta-analysis to estimate the risk of GIB in patients with OAC and PPI co-therapy. Methods A systematic search of PubMed, EMBASE, and Cochrane was performed for studies reporting GIB risk in OAC and PPI co-therapy. Primary outcomes were total GIB and major GIB events. We calculated pooled estimates of GIB risk by a random-effect meta-analysis and reported as odds ratios (OR) and 95% CI. Stratified analyses according to the origin of GIB, ethnic groups, individual OACs, and the presence of underlying GIB risk factors were performed. Results A total of 10 studies (1 randomized controlled study and 9 observational studies) and 1,970,931 patients who received OAC were included. OAC and PPI co-therapy were associated with a lower risk of total GIB, and major GIB; OR (95% CI) was 0.67 (0.62–0.74) for total GIB and 0.68 (0.63–0.75) for major GIB, respectively. Among total GIB, only the risk of upper GIB was lower with OAC and PPI co-therapy (OR 0.67, 95% CI 0.64–0.70). No difference in the lower risk of primary GIB outcomes of PPI co-therapy was observed between Asians and non-Asians (p-for-difference, total GIB=0.695, major GIB=0.748, respectively) and among individual OACs except for edoxaban. The protective effect of PPI on total GIB was more significant in high-risk patients, defined as those with concurrent medication of antiplatelets or non-steroidal anti-inflammatory drugs (OR 0.62, 95% CI 0.52–0.73) and presence of high bleeding risk factors such as previous GIB history, HAS-BLED score ≥3, or underlying gastrointestinal diseases. (OR 0.65, 95% CI 0.61–0.70). Conclusion In patients who receive OAC, the use of PPI co-therapy was associated with a lower risk of total GIB and major GIB irrespective of ethnic group and OAC type except for edoxaban. PPI co-therapy can be considered particularly in patients on concomitant NSAID and antiplatelet use or patients with high GIB risk factors. Funding Acknowledgement Type of funding sources: None.

Protective effect of proton-pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: A systematic review and meta-analysis.

The evidence of a protective effect of proton-pump inhibitor (PPI) in oral anticoagulant (OAC)-treated patients against gastrointestinal bleeding (GIB) is still lacking. We conducted a meta-analysis to estimate the risk of GIB in patients with OAC and PPI cotherapy. A systematic search of PubMed, EMBASE, Cochrane and Scopus databases was performed for studies reporting GIB risk in OAC and PPI cotherapy. Primary outcomes were total GIB and major GIB events. Pooled estimates of GIB risk were calculated by a random-effect meta-analysis and reported as odds ratios and 95% confidence interval. A total of 10 studies and 1 970 931 patients were included. OAC and PPI cotherapy were associated with a lower odds of total and major GIB; odds ratio (95% confidence interval) was 0.67 (0.62-0.74) for total and 0.68 (0.63-0.75) for major GIB, respectively. No differences in the GIB of PPI cotherapy were observed between Asians and non-Asians (P-for-difference, total GIB = .70, major GIB = .75, respectively). For all kinds of OAC except for edoxaban, PPI cotreatment was related to lower odds of GIB by 24-44%. The protective effect of PPI on total GIB was more significant in concurrent antiplatelets or nonsteroidal anti-inflammatory drug users and those with high bleeding risks: patients with previous GIB history, HAS-BLED ≥3 or underlying gastrointestinal diseases. In patients who receive OAC, PPI cotherapy is associated with a lower total and major GIB irrespective of ethnic group and OAC type, except for edoxaban. PPI cotherapy can be considered particularly in patients with high risk of GIB.

Trends and Outcomes of Oral Anticoagulation With Direct Current Cardioversion for Atrial Fibrillation/Flutter at an Academic Medical Center.

BackgroundIncreasing reports suggest the safe use of direct oral anticoagulants (DOACs) in electrical cardioversion. The aim of this study was to assess the trends and 30-day outcomes associated with anticoagulation for cardioversion.MethodsPatients who underwent electrical cardioversion from January 2015 to October 2020 with a 30-day follow-up were included; and outcomes including stroke, transient ischemic attack, intracranial hemorrhage (ICH), and major gastrointestinal bleeding were recorded.ResultsOf the 515 patients, 351 (68%) were men and 164 (32%) were women, with a mean CHA2DS2VASc score of 2.6 ± 1.6. Outpatient apixaban use increased from 10% in 2015 to 46% in 2020 (P < 0.001) with a decline in the use of warfarin from 24% in 2015 to 10% in 2020 (P = 0.023). Apixaban use peri-procedurally for cardioversion increased from 32% in 2015 to 35% in 2020 (P = 0.317), while warfarin use decreased from 23% in 2015 to 14% in 2020 (P = 0.164). At discharge, apixaban prescriptions increased from 21% in 2015 to 61% in 2020 (P < 0.001), while warfarin prescriptions declined from 30% in 2015 to 13% in 2020 (P = 0.009). No ICH was recorded in the 30 days after cardioversion. Ischemic stroke occurred in four (0.7%) patients with one (0.29%) of the 338 patients on a DOAC, one (0.8%) of the 124 patients on warfarin and two (5.5%) of the 36 patients not receiving anticoagulation post cardioversion. There were seven (1%) major gastrointestinal bleeding events in patients on oral anticoagulation, of which four (3%) were on warfarin and three (0.8%) were on DOACs.ConclusionsOur study shows the increasing and safe use of DOACs for the purpose of cardioversion. The rates of 30-day ischemic stroke post cardioversion were low and only occurred in patients admitted in the intensive care unit.

Differences In Gastrointestinal Safety Profiles Among Novel Oral Anticoagulants: Evidence From A Network Meta-Analysis.

BackgroundThere is no consensus at present regarding the differences in the risk of GI bleeding across various NOAC regimens. Therefore, we performed a network meta-analysis to compare the risk of gastrointestinal bleeding after different NOAC regimens.MethodsPubMed, Cochrane, Web of Science, Clinicaltrial.gov and Clinicaltrialresults.org were searched for randomized controlled trials (RCTs) assessing gastrointestinal bleeding of all NOAC regimens from inception to January 2018. The primary endpoint was major gastrointestinal (MGI) bleeding. The meta-regression was performed to access the association between the MGI bleeding events and mortality. The network meta-analysis was carried out with the Bayesian random-effect model.ResultsA total of 25 RCTs, including 139,392 patients, were identified. Meta-regression analysis showed that MGI bleeding was correlated with fatal bleeding events (odds ratios [OR], 1.76; 95% confidence interval [CI], 1.13–2.77], P=0.015). The network meta-analysis results showed that compared to the conventional regimens, rivaroxaban was associated with increased risk of MGI bleeding (OR, 1.37; 95% credible interval [CrI], 1.00–1.85), but not the apixaban (OR, 0.77; 95% CrI, 0.53–1.07]), edoxaban (OR, 0.86; 95%CrI, 0.52–1.18) and dabigatran etexilate (OR, 1.22; 95% CrI, 0.82–1.69). Compared to rivaroxaban, apixaban (OR, 0.56; 95% CrI, 0.35–0.88) and edoxaban (OR, 0.62; 95% CrI, 0.35–0.96) showed a significantly lower risk of MGI bleeding. Apixaban had the highest probability of being the safest option with regard to the risk of MGI bleeding (89.1%), followed by edoxaban (77.4%), conventional therapy (51.4%), dabigatran etexilate (23.8%) and rivaroxaban (8.3%).ConclusionThe risk of GI bleeding significantly varies among different NOAC regimens, and evidence shows that apixaban and edoxaban had the most favorable MGI bleeding safety profile, while rivaroxaban and dabigatran etexilate were the least safe.

Safety assessment of niacin in the US Food and Drug Administration's mini-sentinel system.

The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) trial found higher incidence rates of adverse reactions, including bleeding, in patients receiving the combination of extended-release niacin and laropiprant versus placebo. It is not known whether these adverse events are attributable to laropiprant, not approved in the USA, or to extended-release niacin. We compared rates of major gastrointestinal bleeding and intracranial hemorrhage among initiators of extended-release niacin and initiators of fenofibrate. We used Mini-Sentinel (now Sentinel) to conduct an observational, new user cohort analysis. We included data from 5 Data Partners covering the period from January 1, 2007 to August 31, 2013. Individuals who initiated extended-release niacin were propensity score-matched to individuals who initiated fenofibrate. Within the matched cohorts, we used Cox proportional hazards models to compare rates of hospitalization for major gastrointestinal bleeding events and intracranial hemorrhage assessed using validated claims-based algorithms. A total of 234242 eligible extended-release niacin initiators were identified, of whom 210 389 (90%) were 1:1 propensity score-matched to eligible fenofibrate initiators. In propensity score-matched analyses, no differences were observed between exposure groups in rates of major gastrointestinal bleeding (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.82 to 1.18) or intracranial hemorrhage (HR, 1.21; 95% CI, 0.66 to 2.22). Results were similar in pre-specified sensitivity and subgroup analyses. We did not observe evidence for an association between extended-release niacin versus fenofibrate and rates of major gastrointestinal bleeding or intracranial hemorrhage.

Major Gastrointestinal Bleeding Often Is Caused by Occult Malignancy in Patients Receiving Warfarin or Dabigatran toPrevent Stroke and Systemic Embolism From AtrialFibrillation.

Gastrointestinal (GI) bleeding in patients receiving anticoagulation agents can be causedbyoccult malignancies. We investigated the proportions and features of major GI bleeding (MGIB) events related to occult GI cancers in patients receiving anticoagulation therapy. We analyzed data from the Randomized Evaluation of Long Term Anticoagulant Therapy study (conducted between December 2005 and March 2009 in 951 clinical centers in 44 countries worldwide), which compared the abilities of dabigatran vs warfarin to prevent stroke and systemic embolism in 18,113 patients with atrial fibrillation. Two blinded gastroenterologists independently reviewed source documents of MGIB events (n= 595) that occurred during the study period. We collected data on MGIB events caused by previously unidentified GI malignancies, and compared characteristics of MGIB events in patients who received dabigatran vs warfarin (primary end point), and in patients with bleeding from cancer, vs patients bleeding from a nonmalignant or unidentified source. Of 546 unique MGIB events, 44 (8.1%) were found to be from GI cancers (34 of 398 MGIBevents in dabigatran users and 10 of 148 MGIB events in warfarin users; P= .60). Colorectal cancer accounted for 35 of 44 of all cancers identified. There were more colorectal cancer-associated MGIB events in the dabigatran group (30 of 34) than in the warfarin group (5 of 10) (P= .02), but more gastric cancer-associated MGIB events in the warfarin group (5 of 10) than in the dabigatran group (1 of 34) (P= .001). There were no differences in the short-term outcomes of cancer-related MGIB events in the dabigatran vs the warfarin group, but 75% of all cancer-related MGIB events required at least 1 bloodtransfusion and the mean hospital stay was 10.1 days. Compared with MGIB eventsfrom a nonmalignant or unidentified source, MGIB from cancer occurred sooner (343.0 vs 223.1 d; P= .003), but the bleeding was more likely to be chronic (for >7 d) (27.3% vs 63.6%; P < .001). In evaluating data from a study of the effects of anticoagulation therapy, we found approximately 1 of every 12 MGIB events to be related to an occult cancer. Approximately two thirds of cancer-related MGIB presents with chronic bleeding, and morbidity, and resource utilization ishigh.

Anticoagulant therapy with dabigatran in elderly patients ≥80 years of age with atrial fibrillation

Atrial fibrillation is a potent risk factor for stroke, and the administration of anticoagulant therapy is important for preventing thromboembolism. Dabigatran is the first new oral anticoagulant developed as an alternative to warfarin. However, serious major gastrointestinal bleeding events have been observed in elderly patients in post-market case reports. We therefore retrospectively investigated elderly cases of the use of anticoagulant therapy with dabigatran. Twenty-eight patients over 80 years of age were treated with anticoagulant therapy at our satellite hospital. Nine of the patients received dabigatran, and all others received warfarin. We evaluated the CHADS2 score, HAS-BLED score, renal function and incidence of adverse effects in nine patients treated with dabigatran. All of the nine patients received 220 mg/day of dabigatran, with no antiplatelet agents. Seven patients continued to receive dabigatran. One patient had an impaired renal function (Cr 1.55 mg/dl, Ccr 30 ml/min). However, the activated partial thromboplastin time (APTT) was not prolonged and neither major bleeding nor stroke were noted in seven patients. Although two patients were unable to continue dabigatran treatment due to APTT prolongation, no serious complications were observed during the administration of dabigatran. No serious adverse effects of dabigatran anticoagulant therapy were detected in our elderly patients. Although it is necessary to monitor the risk of bleeding, renal dysfunction, effects of drug combination and so on, some elderly patients with atrial fibrillation are good candidates for dabigatran treatment.

Long-term Use of Aspirin and Nonsteroidal Anti-inflammatory Drugs and Risk of Colorectal Cancer

Randomized trials of short-term aspirin use for prevention of recurrent colorectal adenoma have provided compelling evidence of a causal relationship between aspirin and colorectal neoplasia. However, data on long-term risk of colorectal cancer according to dose, timing, or duration of therapy with aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) remain limited. To examine the influence of aspirin and NSAIDs in prevention of colorectal cancer. Prospective cohort study of 82 911 women enrolled in the Nurses' Health Study providing data on medication use biennially since 1980 and followed up through June 1, 2000. Incident colorectal cancer. Over a 20-year period, we documented 962 cases of colorectal cancer. Among women who regularly used aspirin (> or =2 standard [325-mg] tablets per week), the multivariate relative risk (RR) for colorectal cancer was 0.77 (95% confidence interval [CI], 0.67-0.88) compared with nonregular users. However, significant risk reduction was not observed until more than 10 years of use (P< or =.001 for trend). The benefit appeared related to dose: compared with women who reported no use, the multivariate RRs for cancer were 1.10 (95% CI, 0.92-1.31) for women who used 0.5 to 1.5 standard aspirin tablets per week, 0.89 (95% CI, 0.73-1.10) for 2 to 5 aspirin per week, 0.78 (95% CI, 0.62-0.97) for 6 to 14 aspirin per week, and 0.68 (95% CI, 0.49-0.95) for more than 14 aspirin per week (P<.001 for trend). Notably, women who used more than 14 aspirin per week for longer than 10 years in the past had a multivariate RR for cancer of 0.47 (95% CI, 0.31-0.71). A similar dose-response relationship was found for nonaspirin NSAIDs (P = .007 for trend). The incidence of reported major gastrointestinal bleeding events per 1000 person-years also appeared to be dose-related: 0.77 among women who denied any aspirin use; 1.07 for 0.5 to 1.5 standard aspirin tablets per week; 1.07 for 2 to 5 aspirin per week; 1.40 for 6 to 14 aspirin per week; and 1.57 for more than 14 aspirin per week. Regular, long-term aspirin use reduces risk of colorectal cancer. Nonaspirin NSAIDs appear to have a similar effect. However, a significant benefit of aspirin is not apparent until more than a decade of use, with maximal risk reduction at doses greater than 14 tablets per week. These results suggest that optimal chemoprevention for colorectal cancer requires long-term use of aspirin doses substantially higher than those recommended for prevention of cardiovascular disease, but the dose-related risk of gastrointestinal bleeding must also be considered.

Cardiovascular News

Cardiovascular News

Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. Preventive Services Task Force.

The use of aspirin to prevent cardiovascular disease events in patients without a history of cardiovascular disease is controversial. To examine the benefits and harms of aspirin chemoprevention. MEDLINE (1966 to May 2001). 1) Randomized trials at least 1 year in duration that examined aspirin chemoprevention in patients without previously known cardiovascular disease and 2) systematic reviews, recent trials, and observational studies that examined rates of hemorrhagic strokes and gastrointestinal bleeding secondary to aspirin use. One reviewer read and extracted data from each included article and constructed evidence tables. A second reviewer checked the accuracy of the data extraction. Discrepancies were resolved by consensus. Meta-analysis was performed, and the quantitative results of the review were then used to model the consequences of treating patients with different levels of baseline risk for coronary heart disease. Five trials examined the effect of aspirin on cardiovascular events in patients with no previous cardiovascular disease. For patients similar to those enrolled in the trials, aspirin reduces the risk for the combined end point of nonfatal myocardial infarction and fatal coronary heart disease (summary odds ratio, 0.72 [95% CI, 0.60 to 0.87]). Aspirin increased the risk for hemorrhagic strokes (summary odds ratio, 1.4 [CI, 0.9 to 2.0]) and major gastrointestinal bleeding (summary odds ratio, 1.7 [CI, 1.4 to 2.1]). All-cause mortality (summary odds ratio, 0.93 [CI, 0.84 to 1.02]) was not significantly affected. For 1000 patients with a 5% risk for coronary heart disease events over 5 years, aspirin would prevent 6 to 20 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events. For patients with a risk of 1% over 5 years, aspirin would prevent 1 to 4 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events. The net benefit of aspirin increases with increasing cardiovascular risk. In the decision to use aspirin chemoprevention, the patient's cardiovascular risk and relative utility for the different clinical outcomes prevented or caused by aspirin use must be considered.