You are here

Article Text

Article menu

Download PDFPDF

Original EBM Research
Impact of oral anticoagulants on 30-day readmission: a study from a single academic centre
  1. Mukul Bhattarai1,
  2. Tamer Hudali1,
  3. Robert Robinson1,
  4. Mohammad Al-Akchar1,
  5. Carrie Vogler2,
  6. Youssef Chami3
  1. 1 Division of General Internal Medicine, Department of Internal Medicine, School of Medicine, Southern Illinois University, Springfield, Illinois, USA
  2. 2 Department of Pharmacy Practice, Southern Illinois University Edwardsville School of Pharmacy, Edwardsville, Illinois, USA
  3. 3 Division of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Southern Illinois University, Springfield, Illinois, USA
  1. Correspondence to Dr Mukul Bhattarai, Department of Internal Medicine, School of Medicine, Southern Illinois University, Springfield, IL 62794-9636, USA; drmukulbhattarai{at}gmail.com

https://doi.org/10.1136/bmjebm-2018-111026

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Introduction

    Medical and therapeutic advances in inpatient care have improved patient outcomes, but at high financial cost to society. Considerable healthcare expenditure has been wasted by potentially preventable hospital readmissions within 30 days of discharge.1 Many studies have investigated risk factors for hospital readmission such as age, ethnicity, no regular clinical practitioner, major surgical treatment, multiple medical comorbidities, duration of hospital stay, previous admissions, lack of communication to outpatient providers, early discharge from the hospital and polypharmacy.2–5 Other factors such as patient behaviour, baseline activity level, socio-economic background and quality of life also play substantial roles in influencing the readmissions.6 7 These risk factors combine to produce an environment where 90% of hospital readmissions are unplanned and potentially avoidable.1

    Effective risk prediction models for hospital readmission are available, but these models fail to identify modifiable risks for hospital readmission.8–10 While searching for modifiable risk factors for readmission, researchers have focused on specific diagnoses11 and high-risk medications such as anticoagulants.12

    The use of oral anticoagulation medication is common and carries the risk of major bleeding and hospital readmission.12 13 Deitelzweig and colleagues13 have analysed the data obtained from the IMS Health National Disease and Therapeutic Index. They demonstrated that direct oral anticoagulants use has grown to 4.21 million (95% CI, 3.63 to 4.79; 38.2% of total) treatment visits in 2014. Oral anticoagulants are commonly used for the treatment of venous thromboembolism (VTE) including deep vein thrombosis, pulmonary embolism and long-term stroke prevention and systemic thrombosis in nonvalvular atrial fibrillation.14 The standard of care was the use of vitamin K antagonists (VKA) or low-molecular-weight heparin (LMWH), and now there are non-VKA agents known as direct oral anticoagulants (DOACs) as options for anticoagulation. These include factor Xa inhibitors (apixaban, rivaroxaban and edoxaban) and direct thrombin inhibitors (dabigatran). These DOACs are Food and Drug Administration (FDA) approved for the use in VTE and nonvalvular atrial fibrillation. Post marketing studies have shown variable results regarding the efficacy and safety of DOACs.15

    More clinicians are prescribing direct oral anticoagulants due to their competitive and favourable outcomes with advantages of no drug monitoring, less drug–drug interactions and no dietary restrictions compared with warfarin. The development of reversal agents will further improve the comfort for both providers and patients to use these newer drugs.14 16 Advancing age proportionally increases the occurrence of atrial fibrillation and stroke. Therefore, it is anticipated that patients taking oral anticoagulants will increase in number significantly. Despite their established efficacy, oral anticoagulants have also been implicated in complications including major gastroenterological and/or intracranial bleeding, with associated need for hospitalisation and readmission.12 Weeda et al compared the outcomes (including readmission) for about 8800 patients admitted to the hospital for pulmonary embolism treated with rivaroxaban and warfarin (bridged with heparin).17 The study showed no significant difference in the readmission rates for VTE (rivaroxaban: 1.5% vs warfarin: 1.7%) or major bleeding (rivaroxaban: 0.3% vs warfarin: 0.2%).17 The risk of 30-day readmission for patients on oral anticoagulation, the associated morbidity and mortality and cost with these readmissions is not fully studied.

    This study will investigate the impact of warfarin and DOACs on hospital readmissions within 30 days of discharge and their pattern of use at the time of discharge in a university-affiliated hospital in the Midwest of USA.

    Materials and methods

    All adult medical patients discharged from the Southern Illinois University-School of Medicine (SIU-SOM) Hospitalist service from Memorial Medical Center from 1 January 2015 to 1 January 2017 were studied retrospectively to determine if the use of oral anticoagulants increases the risk of readmission (avoidable and unavoidable) within 30 days of discharge from the hospital. Exclusion criteria were transfer to another acute care hospital, leaving the hospital against medical advice or death. All-cause readmissions within 30 days of hospital discharge was the study endpoint. This is the endpoint used by the Medicare Hospital Readmission Reduction Program.

    Memorial Medical Center, located in Springfield, Illinois, USA, is a 507-bed not-for-profit university-affiliated tertiary care centre. The board-certified or board-eligible SIU-SOM hospitalist faculty provides the internal medicine residency teaching service. The hospitalist service predominantly admits the patients with acute medical issues via the hospital emergency department (ED) or transferred from other regional hospitals and express care clinics. Elective hospital admissions are unusual for this service.

    The variables including age, gender, diagnosis-related group, International Classification of Disease (ICD) codes, ED visits in the last 6 months, rehospitalisation within 30 days, discharge medications and the other parameters in the HOSPITAL score (Haemoglobin level at discharge, Oncology discharge, Sodium level at discharge, Procedure during hospitalisation, Index admission, number of hospital Admissions, Length of stay) and LACE index (Length of stay, Acute or emergent admission, Charlson comorbidity index score, ED visits in previous 6 months) were extracted from the electronic health record. The data were de-identified for analysis. Missing laboratory variables (haemoglobin and sodium from the day of discharge) were imputed to be in the normal range.

    The study hospital does not have a separate oncology inpatient service. To explore the increased readmission risk in oncology patients found in other studies using the HOSPITAL score, we categorised patients with oncology-related diagnosis ICD codes to have been discharged from an oncology service. In the local practice setting, hospitalists typically admit patients with oncologic problems. As the single-centre study, the readmissions at other hospitals could not be investigated.

    Institutional review board (IRB) review for this study was obtained from the Springfield Committee for Research Involving Human Subjects. The IRB determined that our study did not meet the criteria for research involving human subjects according to 45 CFR 46.101 and 45 CFR 46.102.

    Statistical analysis

    The use of oral anticoagulants was investigated as predictors of any cause hospital readmission within 30 days.

    HOSPITAL score, LACE index and Charlson comorbidity score were calculated and compared for each admission. We used these models because they have been successfully used for readmission risk assessment in the literature.8 18

    The discharge medication list for each patient was reviewed to determine which anticoagulants and antiplatelet agents were prescribed at the time of discharge. Variables were created to indicate if the patient was taking warfarin, a DOAC (apixaban, dabigatran and rivaroxaban were on formulary), aspirin and P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor were on formulary).

    Pearson χ2 or Fisher’s exact test compared the qualitative variables, which were reported as frequency (%). Non-parametric Mann-Whitney U test analysed quantitative variables, which were reported as mean ±SD deviation. Variables from univariate analysis with a p value of 0.05 or less were evaluated using multivariate logistic regression with backwards likelihood ratio-based method. The SPSS V.22 was used for statistical analysis. Two-sided p values <0.05 were considered significant.

    Results

    During the 2-year study period, 1916 discharges were recorded for the SIU-SOM Hospitalist service. The analysis includes data for the 1781 discharges for 1410 individual patients who met inclusion criteria (figure 1). Of these discharges, 456 (27%) were readmitted to the same hospital within 30 days. The overall study population was 47% female, had an average age of 63 years and spent an average of 7.9 days in the hospital.

    Figure 1: Study Flow Diagram
    Figure 1: Study Flow Diagram

    The patients readmitted within 30 days of discharge were more frequently admitted to the hospital in the last year, evaluated in the ED in the last 6 months, had higher HOSPITAL scores, higher LACE index values, higher Charlson comorbidity index score, were taking aspirin and were taking warfarin for anticoagulation. The medical comorbidities of a history of myocardial infarction, congestive heart failure, cirrhosis, diabetes and renal disease were seen more frequently in the patients readmitted within 30 days of hospital discharge. These differences were statistically significant in the univariate analysis (table 1).

    View this table:
    Table 1

    Baseline characteristics of the study population by 30-day readmission status

    Multivariate analysis identified the number of hospital admissions within the last year, the number of ED visits in the last 6 months, the HOSPITAL score, the LACE index, a history of congestive heart failure, a history of renal disease and the use of warfarin therapy at discharge as significant predictors of hospital readmission (table 2).

    View this table:
    Table 2

    Multivariate logistic regression of potential risk factors for hospital readmission within 30 days of discharge

    Warfarin was the most common anticoagulant prescribed at the time of hospital discharge (273 discharges with warfarin vs 94 discharges with DOACs). Rivaroxaban (n=52) was the most commonly used DOAC. Warfarin therapy is more common in patients readmitted to the hospital within 30 days of discharge (20% vs 14%, p<0.001). This increased prevalence of warfarin was associated with an increased risk of hospital readmission (OR 1.36, p=0.045) in multivariate analysis. Therapy with any DOAC was not associated with an increased risk of hospital readmission in this population (4% vs 6%, p=0.219).

    Hospital readmissions were more common for patients taking oral anticoagulation with aspirin (8% readmitted vs 4% not readmitted, p=0.008 for warfarin +aspirin; 1% readmitted vs 3% not readmitted, p=0.047 for DOACs+aspirin). Combination of anticoagulants with P2Y12 inhibitors or dual antiplatelet therapy (DAPT) did not appear to be more prevalent in patients readmitted to the hospital (table 1). Multivariate analysis did not show the combination of an anticoagulant with aspirin to be a risk factor for hospital readmission (table 2).

    Discussion

    This analysis evaluated the impact of oral anticoagulant therapy on 30 day all-cause readmissions for 1781 patients. Patients taking warfarin at the time of discharge had a higher risk of hospital readmission within 30 days of discharge (OR 1.37, p=0.040). The use of DOACs was not associated with an increased risk of hospital readmission. Well-established risk factors such as the number of hospital readmissions in the past year (OR 1.26), the number of ED visits in the last 6 months (OR 1.21), and the HOSPITAL score (OR 1.47) were identified in this investigation and have magnitudes comparable to warfarin therapy. These results suggest warfarin-based anticoagulation may be an important target for interventions focused on reducing hospital readmissions.

    Hospital readmission is one of the leading problems facing the US healthcare system. The Centers for Medicare and Medicaid Services and other players are increasingly emphasising to reduce the readmission rates, improve quality of care and reduce cost.19 Agency for Healthcare Research and Quality finds that nearly one in five of all hospital patients covered by Medicare are readmitted within 30 days, costing $15 billion a year.20 The Hospital Value-based Purchasing Program started in 2013 making value-based incentive payments to acute care hospitals.21 Short-term acute-care hospitals are reimbursed under the inpatient prospective payment system (IPPS).19 IPPS payments are reduced for the hospitals with excess readmissions. However, the causes of readmissions are multifactorial, and less often related to the condition that led to the index hospitalisation.

    The bleeding-related hospital readmissions among hospitalised nonvalvular atrial fibrillation patients, and the effectiveness and risk of bleeding in regards to DOACs versus warfarin in treatment of VTE have been studied.12 22–24 In a study on rivaroxaban conducted by Ageno et al(2016), rivaroxaban showed lower rates of recurrent thromboembolism and major bleeding as compared to warfarin (recurrent VTE 1.4% vs 2.1% and major bleeding 0.8% vs. 2.3%).22 A meta-analysis comparing the different options of anticoagulation treatment for VTE showed that DOACs had less frequent major bleeding events as compared to warfarin (1.08% vs. 1.73% for VKAs, RR 0.63, 95% CI 0.51 to 0.77) and are as effective in preventing recurrent VTE (RR 0.89, 95% CI 0.75 to 1.05).23 The risk of bleeding was further studied in the meta-analysis comparing DOACs and VKA in various treatment indications.24 The study showed that DOACs as compared to VKA have significantly lower risk of overall major bleeding (RR 0.72, p<0.01), fatal bleeding (RR 0.53, p<0.01), intracranial bleeding (RR 0.43, p<0.01), clinically relevant nonmajor bleeding (RR 0.78, p<0.01) and total bleeding (RR 0.76, p<0.01).24 Another systematic analysis comparing rivaroxaban and warfarin found no difference in readmission rates.25 However, the study was limited to the patients with pulmonary embolism taking anticoagulants. The researchers still demonstrated that the length of stay and cost were significantly lower in the rivaroxaban group.

    Unlike the studies mentioned above, our study included and compared all FDA-approved oral anticoagulants to understand the impact on all-cause 30-day readmission without limiting the bleeding-related complications. Furthermore, we learnt the pattern of different types of anticoagulation use in a similar cohort of hospitalised patients. Warfarin was still the most commonly prescribed anticoagulant followed by rivaroxaban. In comparison to warfarin, rivaroxaban performed better in terms of 30-day all-cause readmissions. Overall the DOACs are better tolerated and is continually gaining popularity as compared to VKA.26 The study also reports the significant lower discontinuation rate of rivaroxaban as compared to VKA.23

    In fact, addressing anticoagulation can potentially reduce readmission and healthcare costs while simultaneously improving patient care. A multidisciplinary approach should include effective inpatient education, specialty care, literacy appropriate discharge instructions, coordination of care especially between the cardiologist and regular healthcare provider and close postdischarge follow-up. The addition of a pharmacist to counsel patients about different anticoagulation therapies and discuss treatment options with prescribers can provide additional guidance in drug therapy selection. Comprehensive medication management (CMM) performed by a pharmacist reduces the rate of readmission at 30 days post discharge and may have the largest impact among patients at highest risk of readmission.27 Patients who received a CMM visit had a significantly lower rate of 30-day readmissions (8.6% vs 12.8%, p<0.001). The 60-day readmission rate did not reach statistical significance (15.6% vs 17.6%; p=0.0528), but was still reduced. Furthermore, pharmacy team-led postdischarge intervention was significantly lower than the all-cause readmission rate.28

    The area that is unclear in a retrospective review is how patients are selected to receive warfarin therapy or a DOAC on therapy initiation. Our cohort would have included patients whether they were already established on an anticoagulant on admission or they were initiated during the hospitalisation and discharged on the medication. Likewise, patients readmitted in our study were more likely to have renal disease, which impacts the choice of anticoagulant since many of the DOACs were not studied or have limited data on patients with poor kidney function. There is a lack of evidence to know if DOACs will adequately anticoagulate patients who have distinct patient-specific factors when none or limited studies have been performed. Specific patient populations where more evidence is needed for the use of DOACs is patients with impaired kidney function, obese or underweight patients, elderly and patients with other comorbidities such as malignancy.29–31 When it is unclear if a DOAC is efficacious or safe, warfarin is being used frequently due to the ability to monitor drug levels and adjust doses. Drug–drug interactions can also impact both the efficacy and safety of medications. Although warfarin has many more known drug–drug interactions, DOACs also can interact with a select number of medications.

    Our study also looked at the association of anticoagulation therapy with the use of DAPT and the risk of readmission. Despite a low subgroup sample size, our study showed no significant effect on hospital readmission when antiplatelet therapy is included with anticoagulation (with either DOACs or warfarin) using a multivariate analysis. Previous studies showed that anticoagulation on top of DAPT increases the risk of bleeding by twofold to fivefold as compared to the use of anticoagulation alone.32 A multicenter study compared the used of DAPT combined with rivaroxaban (low and high doses) compared to warfarin, showing that the risk of bleeding was significantly lower in the rivaroxaban groups.33 Our study showed overall no significant difference in the number of patients on antiplatelet therapy with DOACs or warfarin (table 1), except patients using warfarin and aspirin where we saw a lower number of patients in the readmitted group. This minimises the confounding effect of adding antiplatelet therapy to the risk of readmission in our patient population.

    Our study was limited in its scope as it was a retrospective, single-centre study. This study evaluated any-cause readmission, so it is unclear how many readmissions were directly related to the anticoagulant therapy. Further evaluation of readmissions for bleeding, thrombosis or stroke and the anticoagulant used would help better understand how the anticoagulation impacts readmission rates. It is also unclear if patients taking warfarin had therapeutic warfarin levels, which would impact their risk for both bleeding and thrombosis complications. Patient’s medication adherence to their anticoagulation therapy prior to admission was not assessed in this study. A larger sample size of patients on DOAC therapy will be more feasible with the increased use of DOAC therapy for future studies. More research needs to be done to determine what underlying causes besides taking an anticoagulant can increase the risk of hospital readmission.

    Conclusions

    Providing special care for patients on anticoagulation who are at a high risk of readmission can significantly improve the chances of avoiding rehospitalizations. Our data suggests that warfarin therapy is a risk factor for all-cause 30-day hospital readmission. DOAC therapy is not found to be associated with a higher risk of hospital readmission. However, there are several factors that play in account confounding with anticoagulation use. Identifying patients at risk of rehospitalisation can guide efficient resource utilisation and is a cost-effective measure that can save millions of healthcare dollars each year. Warfarin used for anticoagulation may be an important target for interventions to reduce hospital readmissions.

    Acknowledgments

    We would like to thank Adam Roloff, MLIS, Reference & Education Services Librarian, from Medical Library, SIU School of Medicine for language editing while finalising the manuscript.

    References

    1. 1.↵
      2. Jencks SF ,
      3. Williams MV ,
      4. Coleman EA
      . Rehospitalizations among patients in the Medicare fee-for-service program. N Engl J Med 2009;360:1418–28.doi:10.1056/NEJMsa0803563
      OpenUrlCrossRefPubMedWeb of Science
    2. 2.↵
      2. Auerbach AD ,
      3. Kripalani S ,
      4. Vasilevskis EE , et al
      . Preventability and causes of readmissions in a national cohort of general medicine patients. JAMA Intern Med 2016;176:484–93.doi:10.1001/jamainternmed.2015.7863
      OpenUrl
    3. 3.↵
      2. Hasan O ,
      3. Meltzer DO ,
      4. Shaykevich SA , et al
      . Hospital readmission in general medicine patients: a prediction model. J Gen Intern Med 2010;25:211–9.doi:10.1007/s11606-009-1196-1
      OpenUrlCrossRefPubMed
    4. 4.↵
      2. Picker D ,
      3. Heard K ,
      4. Bailey TC , et al
      . The number of discharge medications predicts thirty-day hospital readmission: a cohort study. BMC Health Serv Res 2015;15:282.doi:10.1186/s12913-015-0950-9
      OpenUrl
    5. 5.↵
      2. Silverstein MD ,
      3. Qin H ,
      4. Mercer SQ , et al
      . Risk factors for 30-day hospital readmission in patients ≥65 years of age. Proc 2008;21:363–72.doi:10.1080/08998280.2008.11928429
      OpenUrl
    6. 6.↵
      2. Nagasako EM ,
      3. Reidhead M ,
      4. Waterman B , et al
      . Adding socioeconomic data to hospital readmissions calculations may produce more useful results. Health Aff 2014;33:786–91.doi:10.1377/hlthaff.2013.1148
      OpenUrlAbstract/FREE Full Text
    7. 7.↵
      2. Padhukasahasram B ,
      3. Reddy CK ,
      4. Li Y , et al
      . Joint impact of clinical and behavioral variables on the risk of unplanned readmission and death after a heart failure hospitalization. PLoS One 2015;10:e0129553.doi:10.1371/journal.pone.0129553
      OpenUrl
    8. 8.↵
      2. Donzé J ,
      3. Aujesky D ,
      4. Williams D , et al
      . Potentially avoidable 30-day hospital readmissions in medical patients: derivation and validation of a prediction model. JAMA Intern Med 2013;173:632–8.doi:10.1001/jamainternmed.2013.3023
      OpenUrl
    9. 9.↵
      2. Steventon A ,
      3. Billings J
      . Preventing hospital readmissions: the importance of considering ’impactibility,' not just predicted risk. BMJ Qual Saf 2017;26:782–5.doi:10.1136/bmjqs-2017-006629
      OpenUrlFREE Full Text
    10. 10.↵
      2. van Walraven C ,
      3. Jennings A ,
      4. Forster AJ
      . A meta-analysis of hospital 30-day avoidable readmission rates. J Eval Clin Pract 2012;18:1211–8.doi:10.1111/j.1365-2753.2011.01773.x
      OpenUrlCrossRefPubMed
    11. 11.↵
      2. Nombela-Franco L ,
      3. del Trigo M ,
      4. Morrison-Polo G , et al
      . Incidence, causes, and predictors of early (≤30 days) and late unplanned hospital readmissions after transcatheter aortic valve replacement. JACC Cardiovasc Interv 2015;8:1748–57.doi:10.1016/j.jcin.2015.07.022
      OpenUrlCrossRef
    12. 12.↵
      2. Lau WCY ,
      3. Li X ,
      4. Wong ICK , et al
      . Bleeding-related hospital admissions and 30-day readmissions in patients with non-valvular atrial fibrillation treated with dabigatran versus warfarin. J Thromb Haemost 2017;15:1923–33.doi:10.1111/jth.13780
      OpenUrl
    13. 13.↵
      2. Deitelzweig S ,
      3. Bruno A ,
      4. Trocio J , et al
      . An early evaluation of bleeding-related hospital readmissions among hospitalized patients with nonvalvular atrial fibrillation treated with direct oral anticoagulants. Curr Med Res Opin 2016;32:573–82.doi:10.1185/03007995.2015.1131676
      OpenUrl
    14. 14.↵
      2. Madan S ,
      3. Shah S ,
      4. Dale P , et al
      . Use of novel oral anticoagulant agents in venous thromboembolism. Cardiovasc Diagn Ther 2016;6:570–81.doi:10.21037/cdt.2016.11.17
      OpenUrl
    15. 15.↵
      2. Beyer-Westendorf J
      . What have we learned from real-world NOAC studies in venous thromboembolism treatment? Thromb Res 2018;163:83–91.doi:10.1016/j.thromres.2018.01.034
      OpenUrl
    16. 16.↵
      2. Hirschl M ,
      3. Kundi M
      . New oral anticoagulants in the treatment of acute venous thromboembolism - a systematic review with indirect comparisons. Vasa 2014;43:353–64.doi:10.1024/0301-1526/a000373
      OpenUrlCrossRefPubMed
    17. 17.↵
      2. Weeda ER ,
      3. Wells PS ,
      4. Peacock WF , et al
      . Hospital length-of-stay and costs among pulmonary embolism patients treated with rivaroxaban versus parenteral bridging to warfarin. Intern Emerg Med 2017;12:311–8.doi:10.1007/s11739-016-1552-1
      OpenUrl
    18. 18.↵
      2. van Walraven C ,
      3. Dhalla IA ,
      4. Bell C , et al
      . Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. Can Med Assoc J 2010;182:551–7.doi:10.1503/cmaj.091117
      OpenUrlAbstract/FREE Full Text
    19. 19.↵
      Medicare C for, Baltimore MS 7500 SB, Usa M, 2018. Readmissions-reduction-program. https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/AcuteInpatientPPS/Readmissions-Reduction-Program.html (accessed 30 Mar 2018).
    20. 20.↵
      Agency for Healthcare Research and Quality, 2015. New AHRQ Database Tracks Hospital Readmission Rates. https://www.ahrq.gov/news/blog/ahrqviews/112015.html (accessed 22 Apr 2018).
    21. 21.↵
      2. Ryan AM ,
      3. Krinsky S ,
      4. Maurer KA , et al
      . Changes in hospital quality associated with hospital value-based purchasing. N Engl J Med 2017;376:2358–66.doi:10.1056/NEJMsa1613412
      OpenUrlCrossRefPubMed
    22. 22.↵
      2. Ageno W ,
      3. Mantovani LG ,
      4. Haas S , et al
      . Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. Lancet Haematol 2016;3:e12–e21.doi:10.1016/S2352-3026(15)00257-4
      OpenUrlCrossRef
    23. 23.↵
      2. Kakkos SK ,
      3. Kirkilesis GI ,
      4. Tsolakis IA
      . Editor’s choice - efficacy and safety of the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban in the treatment and secondary prevention of venous thromboembolism: a systematic review and meta-analysis of phase III trials. Eur J Vasc Endovasc Surg 2014;48:565–75.doi:10.1016/j.ejvs.2014.05.001
      OpenUrlPubMed
    24. 24.↵
      2. Chai-Adisaksopha C ,
      3. Crowther M ,
      4. Isayama T , et al
      . The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood 2014;124:2450–8.doi:10.1182/blood-2014-07-590323
      OpenUrlAbstract/FREE Full Text
    25. 25.↵
      2. Kohn CG ,
      3. Fermann GJ ,
      4. Peacock WF , et al
      . Association between rivaroxaban use and length of hospital stay, treatment costs and early outcomes in patients with pulmonary embolism: a systematic review of real-world studies. Curr Med Res Opin 2017;33:1697–703.doi:10.1080/03007995.2017.1349659
      OpenUrl
    26. 26.↵
      2. Lippi G ,
      3. Mattiuzzi C ,
      4. Cervellin G , et al
      . Direct oral anticoagulants: analysis of worldwide use and popularity using Google Trends. Ann Transl Med 2017;5:322.doi:10.21037/atm.2017.06.65
      OpenUrl
    27. 27.↵
      2. Budlong H ,
      3. Brummel A ,
      4. Rhodes A , et al
      . Impact of Comprehensive Medication Management on Hospital Readmission Rates. Popul Health Manag 2018.doi:10.1089/pop.2017.0167
    28. 28.↵
      2. Moye PM ,
      3. Chu PS ,
      4. Pounds T , et al
      . Impact of a pharmacy team-led intervention program on the readmission rate of elderly patients with heart failure. Am J Health Syst Pharm 2018;75:183–90.doi:10.2146/ajhp170256
      OpenUrlAbstract/FREE Full Text
    29. 29.↵
      2. Lutz J ,
      3. Jurk K ,
      4. Schinzel H
      . Direct oral anticoagulants in patients with chronic kidney disease: patient selection and special considerations. Int J Nephrol Renovasc Dis 2017;10:135–43.doi:10.2147/IJNRD.S105771
      OpenUrl
    30. 30.↵
      2. Martin K ,
      3. Beyer-Westendorf J ,
      4. Davidson BL , et al
      . Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. J Thromb Haemost 2016;14:1308–13.doi:10.1111/jth.13323
      OpenUrlCrossRefPubMed
    31. 31.↵
      2. Riley P ,
      3. Maan A ,
      4. Korr KS
      . Direct Oral Anticoagulants (DOACs): Current Status Among Distinct Patient Subgroups. R I Med J 2017;100:18–22.
      OpenUrl
    32. 32.↵
      2. Hansen ML ,
      3. Sørensen R ,
      4. Clausen MT , et al
      . Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 2010;170:1433–41.doi:10.1001/archinternmed.2010.271
      OpenUrlCrossRefPubMedWeb of Science
    33. 33.↵
      2. Gibson CM ,
      3. Mehran R ,
      4. Bode C , et al
      . Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med 2016;375:2423–34.doi:10.1056/NEJMoa1611594
      OpenUrl

    Footnotes

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient consent Not required.

    • Ethics approval Springfield Committee for Research Involving Human Subjects.

    • Provenance and peer review Not commissioned; externally peer reviewed.