| Literature DB >> 34150404 |
Nicolina Scibelli1, Andrew Mangano1, Kathleen Raynor2, Sarah Wilson3, Pratishtha Singh1.
Abstract
Introduction Direct-acting oral anticoagulants (DOACs) are approved for stroke prevention in non-valvular atrial fibrillation and treatment of venous thromboembolism. Most recent guidelines recommend DOACs over warfarin for most diagnoses given their predictable pharmacodynamics, lack of required monitoring, and safety profile. Specific outcomes such as shock, acute renal failure, and blood transfusion requirement while on oral anticoagulation compared to no anticoagulation remain unknown in patients with upper gastrointestinal (GI) bleeds. Methods This retrospective study used the HCA Healthcare Enterprise Data Warehouse (EDW) to analyze 13,440 patients aged >18 years that were admitted with an upper GI bleed from January 2017 to December 2019. The patients were categorized based on oral anticoagulant (i.e. rivaroxaban, apixaban, dabigatran and warfarin). The control group was patients admitted with an upper GI bleed not on oral anticoagulation. We evaluated the severity of upper GI bleeds while on oral anticoagulation based on the outcomes: mortality rate, length of stay, acute renal failure, shock, and need for packed red blood cell transfusions (pRBC). Comorbid conditions assessed were coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), heart failure (HF), atrial fibrillation (AF), venous thromboembolism (VTE), peripheral vascular disease (PVD), tobacco abuse, alcohol abuse, and chronic kidney disease (CKD). Home use of proton pump inhibitors (PPI), aspirin, and P2Y12 inhibitors were also evaluated. Results Patients on a DOAC without home PPI have a mortality odds ratio of 3.066 with a confidence interval (CI) greater than 95% (1.48-6.26, p<0.05) compared to patients on a DOAC and home PPI. Patients on warfarin and no home PPI have a mortality odds ratio of 5.55 (95% CI (1.02-30.35), p<0.05) compared to those on warfarin with home PPI use. In the no anticoagulation group, those not on PPI have an odds ratio of 3.28 (95% CI (2.54-4.24), p<0.05) of death compared to home PPI use. There was no statistical difference in mortality between each DOAC and warfarin. There was no difference in the presence of acute renal failure or shock when comparing each DOAC, warfarin, and no medication. For patients presenting with GI bleed, 0.8414 units of pRBC were transfused. Patients not on oral anticoagulation were found to have statistically significant decrease in pRBC transfusion if they did not report alcohol use, CKD, HF, AF, VTE, PVD. Patients on DOACs and alcohol use have an average pRBC transfusion count that is 0.922 units more than those without reported alcohol use (p=0.006). In the warfarin group, there was no statistical significance noted when comparing pRBC transfusions and also when comparing to baseline comorbidities. Conclusion The retrospective study leads us to conclude that overall, patients taking the DOACs or warfarin had no statistically significant increase in RBC transfusions, length of stay, shock, acute renal failure, or mortality rate compared to patients who were not on oral anticoagulation. Home PPI use was shown to lower odds of mortality in patients on anticoagulation who presented with upper GI bleeding. PPI use had no effect on the need for transfusion or length of stay in patients on anticoagulation. These results can help predict which patients are likely to have higher mortality based on the use of home PPIs.Entities:
Keywords: apixaban; dabigatran; direct-acting oral anticoagulants; ppi; proton-pump inhibitor; rivaroxaban; ugib; upper gastrointestinal bleed; warfarin
Year: 2021 PMID: 34150404 PMCID: PMC8208175 DOI: 10.7759/cureus.15061
Source DB: PubMed Journal: Cureus ISSN: 2168-8184
Study demographics.
Demographic and clinical characteristics, including age, sex, race, and ethnicity, as well as preexisting comorbid conditions, of all patients admitted for gastrointestinal bleeding.
AC: anticoagulation; SD: standard deviation: PPI: proton pump inhibitor: HTN: hypertension: CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease; VTE: venous thromboembolism; DVT: deep venous thrombosis; PE: pulmonary embolus; PVD: peripheral vascular disease; CKD: chronic kidney disease.
| Apixaban (N=491) | Rivaroxaban (N=188) | Dabigatran (N=35) | Warfarin (N=225) | No oral AC (N=12501) | Statistical analysis | p-value | |
| Average age (years) (mean ± SD) | 70.96±13.22 | 69.40±13.74 | 74.49±8.42 | 68.38±13.59 | 58.50±18.07 | ANOVA | <0.0001 |
| Sex: male | 263 (53.56%) | 103 (54.79%) | 17 (48.57%) | 140 (62.22%) | 5980 (47.84%) | Chi-square | <0.0001 |
| Sex: female | 228 (46.44%) | 85 (45.21%) | 18 (51.43%) | 85 (37.78%) | 6521 (52.16%) | ||
| Race (N): Caucasian | 384 (78.21%) | 152 (80.85%) | 30 (85.71%) | 184 (81.78%) | 8523 (68.18%) | Fisher's Exact | <0.0001 |
| Race (N): African American | 98 (19.96%) | 27 (14.36%) | 3 (8.57%) | 33 (14.67%) | 3217 (25.73%) | ||
| Race (N): other | 9 (1.83%) | 9 (4.79%) | 2 (5.71%) | 8 (3.56%) | 761 (6.09%) | ||
| Confounding variables | |||||||
| Home aspirin use | 171 (34.83%) | 54 (28.72%) | 14 (40%) | 77 (34.22%) | 1591 (12.73%) | Chi square | <0.0001 |
| Home P2Y12 inhibitor | 71 (14.46%) | 19 (10.11%) | 4 (11.43%) | 18 (8%) | 595 (4.76%) | Fisher's Exact | <0.0001 |
| Home PPI use | 307 (62.53%) | 115 (61.17%) | 21 (60%) | 146 (64.89%) | 4859 (38.87%) | Chi square | <0.0001 |
| Past medical history (N) | |||||||
| HTN | 187 (38.09%) | 86 (45.74%) | 11 (31.43%) | 87 (38.67%) | 4701 (37.6%) | Chi square | <0.0001 |
| CAD | 175 (35.64%) | 58 (30.85%) | 16 (45.71%) | 74 (32.89%) | 1612 (12.89%) | Chi square | <0.0001 |
| COPD | 3 (.61%) | 2 (1.06%) | 0 (0%) | 1 (.44%) | 111 (0.89%) | Fisher's Exact | 0.9685 |
| Heart failure | 102 (20.77%) | 39 (20.74%) | 7 (20%) | 53 (23.56%) | 744 (5.95%) | Fisher's Exact | <0.0001 |
| Atrial fibrillation | 294 (59.88%) | 107 (56.91%) | 25 (71.43%) | 115 (51.11%) | 786 (6.29%) | Fisher's Exact | <0.0001 |
| History of VTE (chronic DVT + chronic PE) | 72 (14.66%) | 19 (10.11%) | 0 (0%) | 31 (13.78%) | 149 (1.19%) | Fisher's Exact | <0.0001 |
| PVD | 25 (5.09%) | 12 (6.38%) | 0 (0%) | 13 (5.78%) | 221 (1.77%) | Fisher's Exact | <0.0001 |
| CKD | 130 (26.48%) | 40 (21.28%) | 14 (40%) | 54 (24%) | 1083 (8.66%) | Fisher's Exact | <0.0001 |
| Diabetes mellitus | 127 (25.97%) | 40 (21.28%) | 7 (20%) | 52 (23.11%) | 1083(8.66%) | Fisher’s Exact | <0.0001 |
| Smoking: former | 190 (38.7%) | 63 (33.51%) | 18 (51.43%) | 75 (33.33%) | 2431 (19.45%) | Chi Square | <0.0001 |
| Smoking: current | 65 (13.24%) | 26 (13.83%) | 5 (14.29%) | 37 (16.44%) | 2798 (22.38%) | Chi Square | <0.0001 |
| Alcohol abuse | 25 (5.09%) | 11 (5.85%) | 3 (8.57%) | 17 (7.56%) | 924 (7.39%) | Fisher's Exact | 0.4598 |
Mortality, acute renal failure and shock in patients on DOACs vs. warfarin vs. no medications.
Number of patients in each group and percentage mortality, acute renal failure and shock associated with each group.
DOACs: direct-acting oral anticoagulants.
| Category | Mortality, N (%) | Acute renal failure, N (%) | Shock, N (%) |
| DOACs | 34 (4.76%) | 226 (31.65%) | 31 (4.3%) |
| Apixaban | 23 (4.68%) | 164 (33.40%) | 24 (4.89%) |
| Rivaroxaban | 11 (5.85%) | 50 (26.60%) | 5 (2.66%) |
| Dabigatran | 0 (0%) | 12 (34.29%) | 2 (5.71%) |
| Warfarin | 7 (3.11%) | 66 (29.33%) | 7 (3.1%) |
| No oral anticoagulation | 396 (3.17%) | 1777 (14.21%) | 256 (2.0%) |
Figure 1Odds ratio of mortality when comparing different DOACs, warfarin, and no AC.
Forest plot comparing the mortality of our different DOACs, warfarin and, no AC. The comparisons are shown as an odds ratio. The middle marker represents the odds ratio, the lower value marker representing the lower limit of the 95% CI (confidence interval), and the higher value marker representing the upper limit of the 95% CI. The comparisons in red were found to be statistically significant.
AC: anticoagulation.
Figure 2Odds ratio of mortality when comparing different DOACs, warfarin, and no AC with and without home PPI use.
Forest plot comparing the effect of PPI on mortality between our different DOACs, warfarin and No AC. The comparison was shown as an odds ratio. The middle marker represents the odds ratio, the lower value marker representing the lower limit of the 95% CI, and the higher value marker representing the upper limit of the 95% CI. The comparisons in red were found to be statistically significant.
DOAC: direct-acting oral anticoagulant; AC: anticoagulation; PPI: proton pump inhibitor.
Mean red blood cell units transfused and length of stay in patients on DOACs vs. warfarin vs. no AC.
Number of patients in each group and associated standard deviations for RBC transfusions (in units) and length of stay (in days).
SD: standard deviation; DOAC: direct-acting oral anticoagulation; AC: anticoagulation.
| Category | Mean red blood cell units (±SD) | Mean length of stay (±SD) |
| DOACs | 0.958 (±2.026) | 4.76 (±6.759) |
| Apixaban | 1.089 (±2.095) | 5.872 (±7.547) |
| Dabigatran | 0.8 (±1.694) | 3.571 (±4.481) |
| Rivaroxaban | 0.984 (±1.905) | 4.851 (±4.477) |
| Warfarin | 0.906 (±1.7) | 6.098 ( ±7.418) |
| No oral anticoagulation | 0.428 (±1.543) | 2.566 (±5.29) |
Number of units of RBC transfused and LOS (days) when comparing exposure or lack of exposure to confounding variables seen in ours groups (no AC vs. warfarin vs. DOAC).
The number of units of RBCs transfused and the LOS (in days) for each of our studied groups (no AC vs. warfarin vs. DOAC) when exposed vs not exposed to each of our confounding variables. Marked with an asterisk (*) are the statistically significant values (p<0.05).
RBC: red blood cell; LOS: length of stay; AC: anticoagulation; DOAC: direct-acting oral anticoagulation; PPI: proton pump inhibitor; HTN: hypertension; CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease; VTE: venous thromboembolism; DVT: deep venous thrombosis; PE: pulmonary embolus; PVD: peripheral vascular disease; CKD: chronic kidney disease.
| RBC transfusion | LOS | |||||
| Variables | No AC | Warfarin | DOAC | No AC | Warfarin | DOAC |
| No home PPI | -0.298* | -0.503 | -0.293 | -1.364* | -0.417 | -0.874 |
| Home PPI | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| No home aspirin | -0.057 | -0.418 | -0.089 | -0.633* | -0.268 | -0.921 |
| Home aspirin | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| No home H2 blocker | 0.066 | 0.049 | 0.349 | -0.326 | 2.109 | 0.237 |
| Home H2 blocker | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| No home P2Y12 | -0.105 | 0.487 | -0.291 | -0.226 | 2.653 | -0.830 |
| Home P2Y12 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| No history of H. pylori | 0.071 | 1.351 | -5.922* | 0.676 | -3.509 | -6.790 |
| History of H. pylori | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| No home NSAIDs | -0.137* | -0.212 | 0.178 | 0.225 | 0.619 | 0.058 |
| Home NSAIDs | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| No home alcohol use | -0.475* | 0.141 | -0.922* | -1.993* | 1.202 | -1.969 |
| Home alcohol use | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| Female | -0.070* | -0.234 | -0.222 | -0.167 | -1.336 | -0.263 |
| Male | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| No history of CKD | -0.549* | -0.134 | -0.307 | -2.777* | 0.046 | -2.730* |
| History of CKD | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| No history of CAD | -0.074 | 0.034 | 0.098 | -0.624* | -2.419 | 0.151 |
| History of CAD | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| No history of COPD | -0.046 | 1.269 | -0.444 | 0.758 | 8.649 | 0.534 |
| History of COPD | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| No history of heart failure | -0.196* | -0.353 | -0.183 | -0.526* | 0.423 | 0.337 |
| History of heart failure | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| No history of atrial fibrillation | -0.346* | -0.207 | -0.236 | -2.764* | -0.212 | -0.529 |
| History of atrial fibrillation | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| No history of VTE | -0.374* | -0.389 | -0.260 | -2.180* | -5.198 | -1.376 |
| History of VTE | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| No history of PVD | -0.303* | 0.006 | 0.092 | -1.741* | -3.473 | -1.388 |
| History of PVD | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |
| Former smoker | 0.117* | 0.246 | -0.003 | 0.362* | 0.913 | -0.541 |
| Current smoker | 0.083* | 0.443 | 0.045 | 0.451* | 0.844 | 0.855 |
| Unknown smoking history | -0.014 | -0.174 | 0.601 | -0.489* | 0.779 | 5.862* |
| Never smoker | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 | 0.000 |