Concurrent Use Of Anticoagulants Research Articles

Bleeding Risk from Anticoagulant Thromboprophylaxis in Patients with Multiple Myeloma

Introduction: Patients with multiple myeloma (MM) have a high risk of venous thromboembolism (VTE) due to unique disease-related (i.e., vascular inflammation, hyperviscosity) and treatment-related factors (i.e., immunomodulatory drugs [IMiDs], high-dose dexamethasone). Thromboprophylaxis is recommended for most patients starting MM therapy. Anticoagulants are preferred over aspirin except in patients at low risk for VTE. However, compliance with prophylaxis guidelines is low. The risk of bleeding from thromboprophylaxis is not well described in these patients so an excessive perceived risk may influence clinicians' practice. We conducted a real-world analysis of bleeding complications from VTE prophylaxis in MM. Methods: The IBM MarketScan Commercial Claims Database was used to identify MM cases between 2013 and 2021. Cases required MM diagnosis from 1 inpatient or 2 outpatient claims, based on ICD-9 or ICD-10 codes, and MM-specific therapy started between 7 days before and 90 days after index diagnosis code, based on HCPCS codes and prescription records. Those with preexisting VTE, atrial fibrillation or stroke were excluded. Thromboprophylaxis was defined as at least 1 prescription for warfarin, low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOAC) within 30 days of diagnosis. Major bleeding was defined as bleeding requiring hospitalization using inpatient ICD codes previously validated (Cunningham algorithm). Patients were followed from end of prophylaxis exposure window (index MM + 30 days) to first major bleeding event, disenrollment (due to death or other reasons) or December 31, 2021. Descriptive statistics were used to calculate rates of bleeding. Cox regression was used to assess the risk of bleeding from thromboprophylaxis and define risk factors associated with major bleeding. Results: We included 6,656 patients diagnosed and treated for MM, with mean age 62.7 years and 55.3% males. Although over 50% of the population would have had a high thrombotic risk based on consensus guidelines, concurrent anticoagulant prophylaxis was prescribed in only 6.6% (436). Prophylaxis agent of choice was warfarin in 23% (102), LMWH in 39% (169), and DOAC in 38% (165), respectively. There was a trend over time favoring DOAC over other agents (25% increase in DOAC use vs. other agents per year on average, p<0.01). Patients on prophylaxis had a higher rate of IMiD-based therapy (63.8% vs. 46.7%, p<0.01) and lower concomitant anti-platelet use (2.1% vs. 4.7%, p=0.01) than those not receiving prophylaxis. There were no differences in age/sex distribution, Charlson comorbidity index (CCI) or history of bleeding between groups. With a median 1.3 years follow-up, the incidence of major bleeding among MM patients receiving VTE prophylaxis was 1.4% or 7.8 bleeding events per 1,000 person-years. This was numerically but not statistically lower than the incident bleeding rate in patients not receiving prophylaxis: 1.8% or 10.1 events per 1,000 person-years. Table 1 shows risk factors for bleeding in this MM population, adjusting for age and sex, including higher age (per 10-year increase, HR 1.38), higher CCI (per SD increment, HR 1.18), history of bleeding (HR 1.54), hypertension (HR 1.87), and renal disease (HR 1.56). IMiD-based MM therapy was associated with decreased risk of bleeding (HR 0.69). Table 2 shows the estimated bleeding risk associated with prophylaxis across several models. No statistically significant association was identified between major bleeding and anticoagulant prophylaxis. Discussion: In a real-world analysis of commercial claims data, the risk of major bleeding associated with VTE prophylaxis in patients with MM undergoing cancer therapy is low and no significant increase in bleeding risk was identified for concurrent anticoagulant use. The rate of major bleeding events appears to be comparable between patients who receive VTE prophylaxis and those who do not. Nevertheless, underutilization of VTE prophylaxis is frequent. Higher CCI, bleeding history, hypertension, and renal disease were clinical factors associated bleeding risk, which may be included in models to help clinicians assess individual patient's risk and guide clinical decisions.

Proton pump inhibitors and gastroprotection in patients treated with antithrombotic drugs: A cardiologic point of view.

Aspirin, other antiplatelet agents, and anticoagulant drugs are used across a wide spectrum of cardiovascular and cerebrovascular diseases. A concomitant proton pump inhibitor (PPI) treatment is often prescribed in these patients, as gastrointestinal complications are relatively frequent. On the other hand, a potential increased risk of cardiovascular events has been suggested in patients treated with PPIs; in particular, it has been discussed whether these drugs may reduce the cardiovascular protection of clopidogrel, due to pharmacodynamic and pharmacokinetic interactions through hepatic metabolism. Previously, the concomitant use of clopidogrel and omeprazole or esomeprazole has been discouraged. In contrast, it remains less known whether PPI use may affect the clinical efficacy of ticagrelor and prasugrel, new P2Y12 receptor antagonists. Current guidelines recommend PPI use in combination with antiplatelet treatment in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids, or non-steroidal anti-inflammatory drugs, and Helicobacter pylori (H. pylori) infection. In patients taking oral anticoagulant with risk factors for gastrointestinal bleeding, PPIs could be recommended, even if their usefulness deserves further data. H. pylori infection should always be investigated and treated in patients with a history of peptic ulcer disease (with or without complication) treated with antithrombotic drugs. The present review summarizes the current knowledge regarding the widespread combined use of platelet inhibitors, anticoagulants, and PPIs, discussing consequent clinical implications.

Bleeding risk with concurrent use of anticoagulants and ibrutinib: A population-based nested case-control study.

Data regarding the safety of co-administration of ibrutinib with anticoagulants in real-life settings are scarce. Using a nationwide database, we conducted a nested case-control study in a cohort of new users of ibrutinib to assess the risk of clinically relevant bleeding (CRB) associated with anticoagulation. Cases were patients with a diagnosis of CRB, defined as hospitalization with a diagnosis of bleeding. The date of CRB constituted the index date. Up to four controls were matched on sex, age at index date and duration of follow-up. The risk of CRB associated with anticoagulation in patients receiving ibrutinib was estimated using conditional logistic regression models, providing odds ratios (OR) adjusted for risk factors of bleeding. Among 614 cases and 2407 matched controls, the risk of CRB was significantly higher in patients receiving both ibrutinib and anticoagulants (adjusted OR [aOR] 2.54, confidence interval [CI] 95% [1.94; 3.32]). When considering anticoagulant class, aOR was 1.99 (CI 95% [1.19; 3.33]) for VKA, 2.48 (CI 95% [1.76; 3.47]) for direct oral anticoagulants and 3.40 (CI 95% [2.01; 5.75]) for parenteral anticoagulants. In conclusion, this study found a 2.5-fold increased risk of CRB in patients receiving both ibrutinib and anticoagulants in real-life settings, and similar aOR among oral anticoagulants.

DS04 Clinical outcomes of the management of basal cell carcinomas in individuals aged 90 years and over

Abstract This retrospective cohort study examined our practice for the management of basal cell carcinoma (BCC) in the very elderly, to identify subgroups where intervention could be minimized, based on frailty and trends in survival. All patients aged ≥ 90 years with histologically confirmed BCC during 2017 and 2018 were included within the study (n = 319). Data on lesion characteristics (size, location and subtype), presence or absence of symptoms, patient characteristics (age, comorbidities, frailty score, anticoagulant use and presence of pacemaker) and treatment choice (surgery, radiotherapy, topical, systemic or observation) were collected. Overall survival was the primary endpoint. Age was the most significant predictor of survival [hazard ratio (HR) 1.10, 95% confidence interval (CI) 1.04–1.17; P = 0.001] with a maximum threshold analysis identifying 93 years as the significant age cutoff point. Median survival was 40 months for those aged ≤ 93 years and 28 months for those aged > 93 years (P = 0.002). Patients with dementia had a worse survival than those without [median survival 25 months vs. 35 months (HR 1.92, 95% CI 1.18–3.13); P = 0.009]. None of the 23 individuals with a diagnosis of dementia was alive at 5 years. There was a statistically significant difference in survival for patients who received treatment for their BCC (n = 294) compared with those observed [n = 25; median survival 34 months vs. 21 months (HR 0.54, 95% CI 0.34–0.85); P = 0.007]. There was no difference in survival in individuals with a history of cancer, cardiac or cerebrovascular disease or immunocompromise, compared with those without. Similarly, the use of anticoagulants or presence of pacemaker did not affect survival. Basal cell carcinoma subtype (nodular, infiltrative) did not impact outcomes either, although the difference between lesion size (< 10 mm, ≥ 10 mm) was approaching statistical significance (HR 1.36, 95% CI 0.98–1.87; P = 0.062). No patients required Mohs surgery in the study period. Factors that appeared to influence the preference for primary radiotherapy over surgery were the concurrent use of anticoagulants (P = 0.05) and site of lesion (P = 0.04). All 25 of the lesions treated with radiotherapy were on the head and neck. This study provides evidence in support of the active treatment of BCC in individuals aged ≥ 90 years seen in secondary care. Being fit enough to attend hospital appointments could be seen as a self-selecting process. Conservative options may be preferable in patients with dementia or those > 93 years old. While survival in this cohort is good, accurate assessment of patient frailty is key for selecting those individuals with a poor prognosis to ensure they are not referred for unnecessary intervention.

Abstract TMP47: IMPROVING Time To Anti-Coagulation Reversal For Hemorrhagic Strokes

Background: Oral anticoagulation (OAC) is a risk factor for intracerebral hemorrhage (ICH) which is an important source of disability and mortality. OAC-associated ICH (OAC-ICH) patients have worse outcomes as compared to ICH patients not on OAC, likely because of the associated larger stroke volumes, higher propensity to intraventricular hemorrhage, and a higher risk of rebleeding. Although current guidelines recommend that OAC should be reversed as quickly as possible, many health care systems have not developed a process for optimizing that aspect of care. Methods: Through the IMPROVE Stroke Care Consortium, a group of nine Hub hospitals and their regional community hospitals, a systems of care improvement project was implemented. Performance reviews identified best practices which were disseminated throughout all centers. We compared the median door-to-reversal (DTR) time before and after an institutional campaign to speed the process with a target time of 60 minutes. Results: Over two years of the study, there were 6,699 ischemic strokes, 152 subarachnoid hemorrhages, and 889 intracranial hemorrhages. During that time, 36 hemorrhagic stroke patients received reversal agents emergently. The baseline median DTR time was 123 minutes (IQR 99, 361 minutes) for all comers. By the end of the program, the median DTR time had been reduced to 92.5 minutes (IQR 59, 163 minutes) which is a trend towards 59% reduction of DTR from baseline (p=0.08). Conclusions: Utilizing an integrated stroke systems of care approach we were able to reduce DTR times for patients presenting with acute ICH and concurrent use of anticoagulants in spite of the lack of definitive guidelines as to how quickly reversing agents should be given.

Complication Rates in Patients Using Intracavernosal Injection Therapy for Erectile Dysfunction With or Without Concurrent Anticoagulant Use-A Single-Center, Retrospective Pilot Study.

BackgroundIntracavernosal injection therapy (ICI) is an effective intervention used to treat erectile dysfunction (ED). It has been proposed that caution should be exercised when prescribing ICI to patients currently taking anticoagulants (AC) due to the theoretical increased risk of bleeding, however, there is limited literature describing complication rates of actively anticoagulated patients utilizing ICI.AimWe sought to determine whether there was a difference in bleeding and other complications in a cohort of patients using ICI therapy with or without concurrent AC use.MethodsWe reviewed our institutional electronic health record and identified 168 patients who were seen in our clinic from January to August 2020 who had either currently or previously utilized ICI therapy for ED treatment. These patients were surveyed regarding their ICI therapy as well as given the erectile dysfunction inventory for treatment satisfaction questionnaire. Data from 85 patients was obtained; 43 concurrently using AC during ICI therapy and 42 with no AC use. Fisher's exact test for categorical variables and a 2-tailed t-test were used with P < .05 considered to be significant.OutcomeDocumented bleeding events (eg, bruising, hematoma), complications, and mean erectile dysfunction inventory for treatment satisfaction scores were compared between the 2 groups.ResultsThere were more absolute bleeding complications in the AC group vs the no AC group, with 3 of 43 AC patients (7%, 95% confidence interval: 2.4–18.6) and 0/42 no AC patients (0%, 95% confidence interval: 0–8.4) experiencing some type of bleeding complication on ICI. However, there was no statistically significant difference found in overall or stratified documented bleeding events and complications between the 2 groups.Clinical ImplicationsPatients with concurrent AC usage on ICI therapy reported a higher rate of absolute bleeding complications than our non-AC group.Strengths and LimitationsThe strength of this study is addressing question of safety of ICI therapy in patients with concurrent AC usage. Limitations include single-center retrospective study design and underpowered sample size limiting confidence with which conclusions from data should guide future patient counseling regarding ICI risks.ConclusionFindings from a single-center cohort of patients suggest that ICI therapy may be a safe and effective treatment modality for ED in patients with concurrent anticoagulant usage, however, given the higher rate of absolute bleeding events in our AC cohort, future assessment in a higher-powered study is warranted in determining a more accurate estimation of risk or propensity for bleeding complications in patients on AC using ICI therapy.Blum KA, Mehr JP, Green T, et al. Complication Rates in Patients Using Intracavernosal Injection Therapy for Erectile Dysfunction With or Without Concurrent Anticoagulant Use—A Single-Center, Retrospective Pilot Study. Sex Med 2022;10:100535.

Review of needle electromyography complications in thrombocytopenic cancer patients.

Needle electromyography (EMG) is understood to be a relatively safe procedure based on clinical experience. There are no evidence-based guidelines for EMG procedures in thrombocytopenic patients. The purpose of this study was to determine whether there is an increased risk of bleeding complications associated with needle EMG in patients with thrombocytopenia. This retrospective study included patients with a primary cancer and thrombocytopenia who underwent needle EMG between January 1, 2016 and October 30, 2020. Patients' medical records were reviewed for demographics; diagnoses; platelet counts within a 7-day period of EMG examination; concurrent use of anticoagulants or antiplatelet medications; number of sites sampled by needle EMG, including anatomical differentiation of paraspinal and both deep and superficial limb muscles; and associated complications not limited to bleeding within 30 days of EMG examination. The initial data search identified 198 patients with a documented diagnosis of thrombocytopenia; 124 met these criteria and were included in the study. A total of 1001 muscle sample sites were documented, with 111 sites in paraspinal muscles, 876 sites in superficial limb muscles, and 14 sites within deep limb muscles. Five patients were concurrently using therapeutic anticoagulation and 3 were using antiplatelet medications. There were no clinically significant complications, but five minor incidents were documented in the medical records within 30 days post-EMG examination. Our findings suggest that bleeding complications from standard needle EMG in oncology patients with documented thrombocytopenia are rare. Testing of high-risk muscles in this patient population appears to be safe.

ANMCO/AIGO Intersocietary consensus document: Gastroprotection in patients receiving antiplatelet and/or anticoagulant drugs

Aspirin and P2Y12 receptor antagonists are widely used across the spectrum of cardiovascular and cerebrovascular diseases. Gastrointestinal complications, including ulcer and bleeding, are relatively common during antiplatelet treatment and, therefore, concomitant proton pump inhibitor (PPI) treatment is often prescribed. However, potential increased risk of cardiovascular events has been suggested for PPIs, and, in recent years, it has been discussed whether these drugs may reduce the cardiovascular protection by aspirin and, even more so, clopidogrel. Indeed, pharmacodynamic and pharmacokinetic studies suggested an interaction through CYP2C19 between PPIs and clopidogrel, which could translate into clinical inefficacy, leading to higher rates of cardiovascular events. The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. In addition, whether the use of PPIs may affect the clinical efficacy of the new P2Y12 receptor antagonists, ticagrelor and prasugrel, remains less known. According to current guidelines, PPIs in combination with antiplatelet treatment are recommended in patients with risk factors for gastrointestinal bleeding, including advanced age, concurrent use of anticoagulants, steroids or non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. Like traditional anticoagulants, novel oral anticoagulants may cause gastrointestinal bleeding. Results from both randomized clinical trials and observational studies suggest that high-dose dabigatran (150 mg bid), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of gastrointestinal bleeding as compared with warfarin. However, the usefulness of PPIs in patients receiving these anticoagulants deserves to be further demonstrated. Given the large number of patients treated with antithrombotic drugs and PPIs, even a minor reduction of platelet inhibition or anticoagulant effect potentially carries a considerable clinical impact. The present joint statement by ANMCO and AIGO summarizes the current knowledge regarding the widespread use of platelet inhibitors, anticoagulants, and PPIs in combination. Moreover, it outlines evidence supporting or opposing drug interactions between these drugs and discusses consequent clinical implications.

Preoperative continuation of aspirin administration in patients undergoing major abdominal malignancy surgery.

In contrast to that in a nonoperative setting, it has been shown that perioperative administration of aspirin did not decrease the rate of death or myocardial infarction but increased major bleeding risk. Since these conflicting results might be due to concurrent use of anticoagulants and a lower thrombotic risk of patients, this cohort study was carried out for patients at a high thrombotic risk without concurrent use of anticoagulants. Medical records for patients who underwent major abdominal malignancy surgery and who were on a preoperative antiplatelet regimen were reviewed. The patients were divided into two groups according to perioperative antiplatelet management: administration of all preoperative antiplatelet agent-suspended (no aspirin) group and only aspirin administration-continued (aspirin) group. The incidence of symptomatic thromboembolic events, frequency of exogenous blood transfusion within 30 days after surgery and the amount of intraoperative bleeding were compared between the two groups. After propensity score matching, 105 patients of each group were matched. The incidence of perioperative thromboembolic events in the no-aspirin group was significantly higher than that in the aspirin group [7/105 (6.7%) vs 0/105 (0%), 95% CI 1.44-∞, P = 0.016]. In contrast, neither the frequency of exogenous transfusion [21.0% vs 11.4%, 95% CI 0.88-4.38 P = 0.110] nor the amount of intraoperative bleeding [median (interquartile range), ml: 230 (70-500) vs 208 (50-500), P = 0.325] was different between the two groups. Although the sample size is relatively small, our findings suggest that continuation of aspirin administration is likely to reduce the thrombotic risk but unlikely to increase the bleeding risk of patients who undergo major abdominal surgery for malignancy.

Patients’ Knowledge About Analgesic-Antipyretic Medications Purchased in Community Pharmacies: A Descriptive Study

ABSTRACTThe objective of this study was to describe the level of knowledge about paracetamol (acetaminophen), ibuprofen, and aspirin of subjects who purchased nonprescription medications containing one of these drugs. We conducted this cross-sectional descriptive study in 42 community pharmacies located in southwestern France between July and November 2013. A six-item self-administered questionnaire was used. Participants were asked to identify the active ingredient contained in 14 brand-name analgesic-antipyretics, to state the maximum daily dose of paracetamol, ibuprofen, and aspirin, the recommended first-line analgesic, and precautions of use or contraindications for paracetamol, ibuprofen, and aspirin. Among 576 participants, the identification of paracetamol ranged from 58% (for Dafalgan or Efferalgan) to 90% (for Doliprane), the identification of ibuprofen from 34% (for Nureflex) to 63% (for Nurofen), and the identification of aspirin was 70% (for Aspegic). The maximum recommended daily dose of paracetamol, ibuprofen, and aspirin was known by 58.3%, 17.7%, and 19.3% of participants, respectively, whereas 6.8%, 17.2%, and 13.2% stated supratherapeutic daily doses. Paracetamol was correctly stated as the first-line analgesic-antipyretic by 76.2% of participants. Knowledge on major precautions of use or contraindications was poor (45.8% and 53.6% for ibuprofen and aspirin use during pregnancy, and 14.1% for concurrent use of anticoagulants and ibuprofen). Purchasers of nonprescription analgesic-antipyretics had poor knowledge on the medication they purchased.

Epidemiology and treatment of congenital fibrinogen deficiency

Congenital fibrinogen deficiency is a rare bleeding disorder, affecting either the quantity (afibrinogenemia, hypofibrinogenemia) or quality (dysfibrinogenemia) of circulating fibrinogen. There is a strong association between fibrinogen activity levels and clinical bleeding severity. Patients with afibrinogenemia experience frequent, often severe, spontaneous bleeds into the muscles and joints and are at significant risk of intracranial hemorrhage. Patients with hypofibrinogenemia are usually asymptomatic; however, they are vulnerable to bleeding after trauma. Dysfibrinogenemia is associated with both spontaneous bleeding and a relatively high risk of thrombosis. Fibrinogen replacement therapy is effective in treating bleeding episodes in congenital fibrinogen deficiency. Fibrinogen concentrates are the preferred treatment option and guidelines now exist for their on-demand use and to manage surgery. Prophylaxis may benefit patients with afibrinogenemia and others with a severe bleeding tendency. The dose and frequency of administration should be adjusted to maintain a fibrinogen activity level >0.5–1.0 g/L. Pregnant women with afibrinogenemia require prophylactic factor replacement as early as possible during pregnancy, continuing throughout pregnancy, and after the birth. Fibrinogen replacement should also be considered in pregnant women with other fibrinogen deficiencies. The risk of thrombosis presents an additional management challenge in these patients, often necessitating the concurrent use of anticoagulants and fibrinogen. Although basic guidelines have been developed, further studies are needed to help optimize treatment in different patient groups under different clinical circumstances and to improve our understanding of thrombotic events.

CT Guided Bone Marrow Aspiration and Core Biopsy

Hemorrhagic complications related to bone marrow aspiration and trephine biopsy are uncommon. Risk factors include thrombocytopenia, myeloproliferative disorders, concurrent use of anticoagulants, and obesity. Here we describe our technique for bone marrow aspiration and biopsy of the posterior iliac crest using CT guidance. Our technique ensures needle passage only through subcutaneous fat and bone, avoiding muscle and neurovascular structures, as well as controlled and precise needle advancement within bone. This technique should be considered for use in patients that are at increased risk for procedure related complications, particularly obese patients, where surface anatomical landmarks may prove unreliable.

Drug interactions in cancer patients receiving antidepressants are common, researchers report.

Drug interactions in cancer patients receiving antidepressants are common, researchers report.

ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines: A Focused Update of the ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use

This expert consensus document was developed by the American College of Cardiology Foundation (ACCF), the American College of Gastroenterology (ACG), and the American Heart Association (AHA). Expert consensus documents inform practitioners, payers, and other interested parties of the opinion of ACCF and document cosponsors concerning evolving areas of clinical practice or medical technologies. Expert consensus documents cover topics for which the evidence base, experience with technology, or clinical practice is not considered sufficiently well developed to be evaluated by the formal ACCF/AHA Practice Guidelines process. Often, the topic is the subject of considerable ongoing investigation. Thus, the reader should view the expert consensus document as the best attempt of the ACCF and document cosponsors to inform clinical practice in areas where rigorous evidence may not yet be available. To avoid actual, potential, or perceived conflicts of interest that may arise as a result of industry relationships or personal interests among the writing committee, all members of the writing committee, as well as peer reviewers of the document, are asked to disclose all current healthcare-related relationships and those existing 12 months before initiation of the writing effort. The ACCF Task Force on Clinical Expert Consensus Documents (CECD) reviews these disclosures to determine which companies make products (on market or in development) that pertain to the document under development. Based on this information, a writing committee is formed to include a majority of members with no relevant relationships with industry (RWI), led by a chair with no relevant RWI. Authors with relevant RWI are not permitted to draft or vote on text or recommendations pertaining to their RWI. RWI are reviewed on all conference calls and updated as changes occur. Author and peer reviewer RWI pertinent to this document are disclosed in Appendixes 1 and 2, respectively. Additionally, to ensure complete transparency, …

Concomitant Use of Gastroprotective Drugs among Elderly NSAID/COX-2 Selective Inhibitor Users

NSAIDs and cyclo-oxgenase (COX)-2-selective inhibitors have been associated with gastrointestinal (GI) complications among the elderly. It is recommended that gastroprotective drugs (i.e. misoprostol, proton pump inhibitors or high doses of histamine H2 receptor antagonists) be taken concomitantly to prevent NSAID-induced GI complications among older people. However, there are concerns that the rate of concomitant use of gastroprotective drugs in elderly NSAID users is too low. This study aimed to investigate the extent to which elderly users of NSAIDs/COX-2-selective inhibitors are concurrently taking gastroprotective drugs, and to determine the factors associated with concomitant use of gastroprotective drugs and NSAIDs/COX-2-selective inhibitors in a nationwide population of older people. We analysed data on age, sex and dispensed drugs for people>or=75 years of age registered in the Swedish Prescribed Drug Register from October to December 2005 (n=732,230) and located 41,626 NSAID/COX-2-selective inhibitor users. Logistic regression analysis was used for analysing the association between the use of different NSAIDs/COX-2-selective inhibitors and gastroprotective drugs, and between individual characteristics and use of gastroprotective drugs. Gastroprotective drugs were used by 22% of NSAID/COX-2-selective inhibitor users. Celecoxib, ketoprofen, meloxicam and etoricoxib were most commonly used concomitantly with gastroprotective drugs. Meloxicam and celecoxib were most strongly associated with gastroprotective drugs, after adjustment for age, sex and number of other drugs. Furthermore, NSAID/COX-2-selective inhibitor+oral corticosteroid users, NSAID/COX-2-selective inhibitor+selective serotonin reuptake inhibitor users and users of two or more NSAIDs/COX-2-selective inhibitors were more likely to concomitantly use gastroprotective drugs compared with NSAID/COX-2-selective inhibitor only users, after adjustment for age, sex and number of other drugs. However, users of NSAIDs/COX-2-selective inhibitors+anticoagulants (both warfarin and low-dose aspirin [acetylsalicylic acid]) did not show an increased likelihood of concomitant use of gastroprotective drugs, after adjustment for age, sex and number of other drugs. Our results indicate that gastroprotective drugs are not prescribed to elderly NSAID users according to guidelines. Furthermore, COX-2-selective inhibitors were used with gastroprotective drugs more often than were traditional NSAIDs. Greater awareness of factors contributing to NSAID/COX-2-selective inhibitor-induced GI complications is warranted, particularly with respect to advanced age and concurrent use of anticoagulants.

Final results of a phase I study of daily PI-88 as a single agent and in combination with dacarbazine (D) in patients with metastatic melanoma

8532 Background: PI-88 is a heparan sulfate mimetic that inhibits angiogenesis and metastasis directly and via release of tissue factor pathway inhibitor (TFPI). PI-88 has shown some efficacy in an intermittent dosage regimen (250 mg/day 4 days/week) in melanoma (Thomson et al, ASCO 2005). This study tested PI-88 7 days per week alone (group 1) and in combination with 3 weekly D (group 2). Methods: Eligibility included inoperable metastatic melanoma, no prior chemotherapy, PS 0–1, adequate organ function, no recent use of heparin, negative anti-heparin antibody (AHA), no concurrent use of anti-coagulants or anti-platelet agents, no history of GI bleeding. Group 1 cohorts received daily PI-88 in doses of 140 mg, 190 mg and 250 mg. Group 2 received PI-88 commencing at the level below the single agent MTD plus D 1,000 mg/m2 every 21 days. Group 1 pts who had PD could continue PI-88 with the addition of D. FDG-PET scans were performed prior to and after 6 weeks PI-88 in Group 1. Free TFPI was measured in serum prior to and up to 2hr post first dose PI-88 in group 1. Results: Group 1 - DLT occurred in 0/3 (140 mg), 0/3 (190 mg) and 2/3 (250 mg) pts. Group 2 - DLT occurred in 1/6 (140 mg) and 0/4 (190 mg) pts. All DLTs were AHA positive grade III/IV thrombocytopenia with in 1 pt (250 mg) cerebral venous sinus thrombosis. No other major toxicities and no increase in expected DTIC toxicities were observed. 4 group 1 pts had pre/post PET scans. One pt had 50% fall in SUVmax with radiologic SD for 4 months. No radiologic responses occurred with PI-88 alone. 3/9 pts in group 2 had radiologic PR. 2/5 group1 pts who had D added to PI-88 had PR. Free TFPI increased from 6.9 ± 1.9 ng/ml just prior PI-88 to 56.1 ± 19.4 30 min post PI-88. The elevated levels were maintained at 60 and 120 min. Elevation of free TFPI did not correlate with PI-88 dose. Conclusion: The recommended phase II dose of continuous daily PI-88 is 190mg alone and in combination with D 1,000 mg/m2 every 3 weeks. An ongoing randomised study is comparing D 1,000 mg/m2 plus PI-88 190mg/day to single-agent D. No significant financial relationships to disclose.

This Month in Gastroenterology

This Month in Gastroenterology

Adverse Reactions and Interactions with Aspirin Considerations in the Treatment of the Elderly Patient

Aspirin (acetylsalicylic acid) is probably the most frequently used medication, and its use is generally uneventful. However, aspirin is also noted for numerous side effects and drug interactions that can complicate the course of therapy. The elderly, especially those with complicated medical histories, are more prone to the adverse effects of salicylates and may develop gastrointestinal tract bleeding, renal insufficiency, asthma and CNS toxicity. In the clinical situation, important drug interactions can occur with concurrent use of anticoagulants, sulphonylureas, diuretics, methotrexate and antacids. In long term aspirin therapy, enteric-coated or nonacetylated forms of aspirin are associated with fewer side effects and may be better tolerated. Monitoring of therapy (especially in the higher risk patient), with frequent assessments of the clinical state and measurements of serum creatinine, electrolytes and salicylate concentrations, may diminish the likelihood of toxicity.

Non surgical treatment of subdural hematoma in a hemodialysis patient

The development of subdural hematoma in the course of hemodialysis treatment has been well documented in the literature. We report a case of a subdural hematoma in a patient on hemodialysis, in whom surgery was contraindicated, due to her concurrent use of anticoagulants. Good recovery was achieved by steroid treatment. Although surgical removal constitutes the essential therapeutic approach for subdural hematoma, we emphasize the importance of medical management in special cases where surgery is contraindicated.

An evaluation of the safety and tolerance of Timentin.

The safety and tolerance of four intravenous formulations of Timentin (ticarcillin + clavulanic acid) have been evaluated in 1659 patients (1512 adults and 147 paediatric) included in clinical trials conducted in Europe and U.S.A. Timentin 3.2 and 5.2 g were administered respectively to 877 and 635 adults and Timentin 1.6 and 2.6 g to 117 and 30 paediatric patients three, four or six times daily for between 7.7 and 9.0 days in adults and 8.0 and 12.0 days in paediatric cases. Patients with septicaemia were 16%, 14% and 28% respectively of the Timentin 3.2, 5.2 g and paediatric groups, which together with respiratory tract and other serious miscellaneous infections accounted for the majority of cases treated within these three groups. Of the 1659 patients studied, 161 adverse reactions were reported from 151 patients (9.1%), 36 of which (2.2%) resulted in discontinuation of treatment. The reactions were at the injection site in 86 cases (5.2%), hypersensitivity in 35 (2.1%) and miscellaneous systemic symptoms in 40 cases (2.4%). Local reactions, i.e. phlebitis, pain and erythema, were self-limiting and did not necessitate early cessation of treatment. Hypersensitivity reactions occurred equally in all groups and necessitated cessation of treatment in about half of the patients. Gastro-intestinal disturbances were observed in eight, four and one patient within the Timentin 3.2, 5.2 g and paediatric groups. Changes in haemostatic status were reported in nine patients treated with Timentin. In all cases they were associated with contributory pathology and/or concurrent use of anticoagulants. Laboratory monitoring revealed transient variations in haemoglobin, blood cellular or plasma composition and plasma enzymatic activity.(ABSTRACT TRUNCATED AT 250 WORDS)