The contribution of patient interviews to the identification of drug‐related problems in home medication review

What is known and Objective: To determine to what extent patient interviews contribute to the identification of drug‐related problems (DRPs) in home medication reviews, in terms of number, type and clinical relevance. Methods: We performed a cross‐sectional study within the intervention arm of a randomized controlled trial. Patients were recruited from 10 Dutch community pharmacies. Patients were eligible if they were home‐dwelling, aged 65 years and over and used five or more different drugs, including at least one cardiovascular or antidiabetic drug. The community pharmacist interviewed the patient at home about the medicines and identified potential DRPs in combination with medication and clinical records. This medication review was assessed and modified by an independent pharmacist reviewers’ panel. Outcomes were the number and type of DRPs and recommendations and percentage of clinical relevant DRPs. Clinical relevance of DRPs was assessed by DRPs assigned a high priority, DRPs followed by recommendations for drug change and DRPs followed by implemented recommendations for drug change. Results: A total of 1565 potential DRPs and recommendations (10 per patient).were identified for 155 patients (median age, 76 years; 54% women). Fifty‐eight per cent of all recommendations involved a drug change; 27% of all DRPs were identified during patient interviews and 74% from medication and clinical records. Compared to DRPs identified from patient medication and clinical records, DRPs identified during patient interviews were more frequently assigned a high priority (OR = 1·8 [1·4–2·2]), were more frequently associated with recommendations for drug change (OR = 2·4 [1·9–3·1]) and were implemented recommendations for drug change (OR = 2·8 [2·1–3·7]). What is new and Conclusion: This study shows that more than a quarter of all DRPs were identified during patient interviews. DRPs identified during patient interviews were more frequently assigned a higher clinical relevance.     

Efficacy and safety of a pharmacist-managed inpatient anticoagulation service for warfarin initiation and titration

What is known and Objective: Anticoagulation consultations provided by a pharmacist‐staffed inpatient service, similar to the experience reported in outpatient anticoagulation clinics, can potentially improve anticoagulation control and outcomes. At Tan Tock Seng Hospital, a 1200‐bed acute care teaching hospital in Singapore, pharmacist‐managed anticoagulation clinics have been in place since 1997. Pharmacist‐managed services were extended to inpatient consultations in anticoagulation management from April 2006. Our objective was to assess the effect of implementing a pharmacist‐managed inpatient anticoagulation service. Methods: This was a single‐centre cohort study. Baseline data from 1 January 2006 to 31 March 2006 were collected and compared with post‐implementation data from 1 April 2006 to 31 March 2007. Patients newly started on warfarin for deep vein thrombosis, pulmonary embolism or atrial fibrillation in general medicine and surgery departments were included. The three endpoints were as follows: (i) percentage of international normalized ratios (INRs) achieving therapeutic range within 5 days, (ii) INRs more than 4 during titration and (iii) subtherapeutic INRs on discharge. Results and Discussion: A total of 26 patients in the control period were compared with 144 patients who had received dosing consultations by a pharmacist during the initiation of warfarin. The provision of pharmacist consult resulted in 88% compared to 38% (P < 0·001) of INR values achieving therapeutic range within 5 days. There was a reduction in INR values of more than 4 during titration from 27% to 2% (P < 0·001), and subtherapeutic INR values on discharge without low molecular weight heparin from 15% to 0% (P < 0·001). The mean time to therapeutic INR was reduced from 6·5 to 3·9 days (P < 0·001) and mean length of stay after initiation of warfarin from 11 to 7·7 days (P = 0·004). What is new and Conclusion: Inpatient anticoagulation care and outcomes were significantly improved by a pharmacist‐managed anticoagulation service. The time to therapeutic INR was achieved appropriately and efficiently without compromising patient’s safety.     

Uptake and effectiveness of a community pharmacy intervention programme to improve asthma management

What is known and Objective: Pharmacists frequently see patients with asthma in the community who have suboptimal management. This study aimed to compare the uptake and effectiveness of pharmacist‐initiated mailed and face‐to‐face interventions for patients whose asthma may not be well managed. Methods: Seventy‐one community pharmacies in South Australia, Tasmania and Victoria (Australia) installed a software application that data‐mined dispensing records, generating a list of patients who had received six or more asthma reliever inhalers in the preceding 12 months. The pharmacists were randomized, by pharmacy, to perform either a mailed or face‐to‐face intervention, whereby these patients received educational material and a referral to their general practitioner (GP) for an asthma management review. Matching patients from each pharmacy were also randomly assigned to a control group for ‘usual care’. Results and Discussion: A total of 1483 patients were identified and grouped as follows: 510 (34·4%) mailed intervention, 480 (32·4%) face‐to‐face intervention and 493 (33·2%) controls. Significantly fewer face‐to‐face interventions were offered than mailed interventions (66·6% vs. 89·4%, respectively; χ² = 64·2, P < 0·0001). There were significant improvements in the preventer‐to‐reliever ratio after the intervention period (P < 0·0001) in each group. In a per‐protocol analysis, the magnitude of improvement in the face‐to‐face intervention group was greater than in the mailed intervention group. The reverse was true in an intention‐to‐treat analysis. The improvement in the P : R ratios was mainly due to significant decreases in reliever usage. What is new and Conclusion: Community pharmacy dispensing records can effectively identify patients with suboptimal asthma management, who can then be referred to their GP for review. Time constraints in busy pharmacies may limit the uptake and effectiveness of face‐to‐face interventions in the ‘real world’ setting, making mailed interventions an attractive option.     

Review of antithrombotic drug usage in atrial fibrillation

Background: The important prophylactic role of antithrombotic therapy against stroke in nonrheumatic atrial fibrillation (AF) has been clearly established in recent clinical trials. There have been suggestions, however, that practice has been slow to change in light of the findings of these trials Aim: To review cases of AF at the major teaching hospital in Tasmania, Australia, to determine whether the recommendations from the results of the trials had been translated into local clinical practice Methods: A retrospective review of the medical records for consecutive patients who had AF documented on ECG between 1 January and 30 June 1997 was performed. An extensive range of demographic and clinical variables were recorded for patients with chronic or paroxysmal nonrheumatic AF. These included antithrombotic and other drug therapy at admission and discharge from hospital care, risk factors for stroke, contraindications to antithrombotic use, and incidents of ischaemic stroke and bleeding complications that occurred during the period from January 1996 up to 3 months after the hospital admission that was studied Results: The 228 patients included in the study had a mean (±SD) age of 75·3±10·9 years. Sixty-eight per cent had chronic AF and 32% had paroxysmal AF. According to two risk stratification criteria, 91% and 86% of the patients with previously diagnosed chronic or paroxysmal nonrheumatic AF ( n=186) had a high risk of developing stroke at the time of admission to hospital care. However, less than one-third of these patients were receiving warfarin (or warfarin plus aspirin), with almost another one-third receiving no antithrombotic agent. Of those who were not taking warfarin, about 60% had no apparent contraindication to warfarin. For those high risk patients who had a possible contraindication to warfarin, only approximately one-third had been prescribed aspirin. Only a slight increase in the use of antithrombotic agents had occurred by the time of discharge from hospital care. The majority of international normalized ratio (INR) values on admission for patients who had been taking warfarin were subtherapeutic. The estimated annual incidence of bleeding complications in patients taking warfarin was 15·0% overall, 5·0% for major bleeds and 3·8% for intracranial haemorrhages Conclusions: While a number of published trials have demonstrated that antithrombotic agents confer substantial protection against stroke in patients with nonrheumatic AF, the drugs were underused in our setting. There is a need to improve antithrombotic use and to develop a better monitoring system for the provision of safer and more effective antithrombotic therapy.     

Effectiveness of a community pharmacist intervention in diabetes care: a randomized controlled trial

What is known and Objective: There is little evidence from well‐designed randomized controlled trials of the impact of community pharmacist intervention on the clinical management of patients with type 2 diabetes. It is also not known how sustainable any observed effects on glycaemic control are, over time. This study was initiated to address both these issues. Methods: A 6‐month, randomized, controlled parallel‐group trial in 66 community pharmacies was conducted in Belgium. Patients were randomly assigned to receive usual pharmacist care (n = 135) or a predefined pharmacist intervention (n = 153). The intervention mainly focused on correct medication use, medication adherence and healthy lifestyle promotion. Primary outcome was glycaemic control, as measured by fasting plasma glucose and HbA1c. Sustainability of changes in glycaemic control was assessed by additional glucose measurements 18 months after the end of the study. Results and Discussion: The intervention significantly reduced HbA1c (between‐group difference: 0·5%, P = 0.009). The largest impact on HbA1c was observed when pharmacotherapy changes (i.e., type and/or dose of hypoglycaemic agents) initiated by the physician were sustained with pharmaceutical care: HbA1c was reduced by 1·05% in the intervention group, whose medication was changed, compared with a reduction of 0·02% in the therapy‐modification only, group. It was also found that the diabetes education program resulted in improved self‐management and better knowledge of diabetes. Eighteen months after the end of the formal study period, the mean HbA1c of the intervention group did not differ significantly from the control group (7·4% vs. 7·2%). What is new and Conclusion: This study provides new evidence, from a randomized controlled trial, of the beneficial effect of community pharmacist intervention in the clinical management of type 2 diabetic patients. However, questions remain about the sustainability of the observed improvements.     

Impact of a self-administration of medications programme on elderly inpatients' competence to manage medications: a pilot study

What is known and objectives: Changes to medication regimens and failure to involve patients in management of their medications whilst in hospital may result in medication errors or non‐adherence at home after discharge. Self‐administration of medications programmes (SAMP) have been used to address this issue. The objective of this study was to assess the impact of a SAMP on elderly hospital inpatients’ competence to manage medications and their medication adherence behaviours. Methods: The SAMP comprised three stages: education, progressing to supervised self‐administration and finally to independent self‐administration. Decisions to progress patients to the next level, and whether they passed or failed the SAMP, were made by the ward pharmacist and nursing staff. The Drug Regimen Unassisted Grading Scale (DRUGS) was used to assess patients’ competence to manage medications at various time points. Tablet count and the Tool for Adherence Behaviour Screening (TABS) were used as adherence measures. Results and discussion: Participants (n = 24) with a mean age of 77·4 years, were mainly female and generally had a high level of functioning. They were prescribed a mean of 9·0 medications at the time of commencing the SAMP. Twenty‐two of the 24 participants successfully completed the SAMP. DRUGS scores at discharge improved significantly (P < 0·001) compared with that before commencement of medication self‐administration. Participants reported a significant decrease (P = 0·02) in non‐adherent behaviour and a trend towards improved adherent behaviour (P = 0·08) after participation in the SAMP. What is new and conclusion: An inpatient SAMP improved elderly patients’ ability to competently manage and adhere to their prescribed medications regimen. This finding needs to be confirmed in a larger controlled trial.     

Investigating general practitioner engagement with pharmacists in Home Medicines Review

Abstract

The Home Medicines Review (HMR) involves a home visit from an accredited HMR pharmacist to review a patient’s medicines, and a report to the patient’s general practitioner (GP) with recommendations for improving medicine management. Notwithstanding evidence supporting the benefits of medicines review, broad uptake by GPs in Australia remains low. We developed the 10-item Home Medicines Review Inventory (HMRI) to assess GP attitudes and behaviours regarding the HMR and modelled factors associated with the frequency of GP engagement with HMRs. Four items assessing frequency of behaviours and six items assessing attitudes related to HMR were answered by 180 GPs in a national GP survey. The HMRI’s psychometric properties were examined with exploratory factor analysis (EFA), Rasch analysis, and correlations with related instruments. Structural equation modelling was used to evaluate factors associated with HMR-related behaviours. EFA and Rasch analysis generally supported the current format of the instrument. Attitudes to HMR, gender, previous positive experiences with pharmacists, a system for working together, and participation in joint education activities predicted frequency of HMR-related behaviours. Although GPs’ attitudes to HMR were generally positive, HMR-related behaviours tended to occur with low frequency. This instrument may be used to investigate why HMR uptake has thus far been low and also help identify opportunities for building interprofessional communication and trust between GPs and pharmacists.     

Bleeding complications in patients on celecoxib and warfarin

PURPOSE: Non-selective non-steroidal anti-inflammatory drugs (nNSAIDs) used in combination with warfarin are associated with an approximately 3-fold increased risk of upper gastrointestinal bleeding (UGIB) compared with warfarin alone. Celecoxib, a selective inhibitor of cyclo-oxygenase 2 (COX-2), is associated with less gastric mucosal injury and platelet dysregulation than nNSAIDs. We compared rates of bleeding complications in patients taking celecoxib and warfarin with those taking warfarin alone. SUBJECTS AND METHODS: We performed a retrospective analysis using data from our Protime Clinic and pharmacy databases from January 2001 to April 2004. We identified 123 patients who took celecoxib and warfarin concurrently (overlap group). We compared rates of bleeding complications in this group with 1022 control patients who were taking warfarin alone. Bleeding complications were defined as major if they resulted in hospitalization, blood transfusion or death. RESULTS: During approximately 1063 months of exposure to both celecoxib and warfarin, 10 bleeding complications were identified, only one of which was considered major. No patients had UGIB. In the control group, 116 bleeding complications were identified over approximately 16 520 months of exposure to warfarin alone, with 101 minor and 15 major events, including six episodes of UGIB. The relative risk of all bleeding complications was 1.34 (95% CI: 0.70-2.57) in the overlap vs. control groups, and for major bleeds was 1.04 (95% CI: 0.14-7.85). CONCLUSIONS: There is a mild but non-significant increase in bleeding complications in patients taking celecoxib and warfarin compared with those taking warfarin alone.     

Clinical implementation of systematic medication reconciliation and review as part of the Lund Integrated Medicines Management model – impact on all‐cause emergency department revisits

What is known and objective: Interventions involving medication reconciliation and review by clinical pharmacists can reduce drug‐related problems and improve therapeutic outcomes. The objective of this study was to examine the impact of routine admission medication reconciliation and inpatient medication review on emergency department (ED) revisits after discharge. Secondary outcomes included the combined rate of post‐discharge hospital revisits or death. Methods: This prospective, controlled study included all patients hospitalized in three internal medicine wards in a university hospital, between 1 January 2006 and 31 May 2008. Medication reconciliation on admission and inpatient medication review, conducted by clinical pharmacists in a multiprofessional team, were implemented in these wards at different times during 2007 and 2008 (intervention periods). A discharge medication reconciliation was undertaken in all the study wards, during both control and intervention periods. Patients were included in the intervention group (n = 1216) if they attended a ward with medication reconciliation and review, whether they had received the intervention or not. Control patients (n = 2758) attended the wards before implementation of the intervention. Results and Discussion: No impact of medication reconciliation and reviews on ED revisits [hazard ratio (HR), 0·95; 95% confidence interval (CI), 0·86–1·04]or event‐free survival (HR, 0·96; 95% CI, 0·88–1·04) was demonstrated. In the intervention group, 594 patients (48·8%) visited the ED, compared with 1416 (51·3%) control patients. In total, 716 intervention (58·9%) and 1688 (61·2%) control patients experienced any event (ED visit, hospitalization or death). Because the time to a subsequent ED visit was longer for the control as well as the intervention groups in 2007 than in 2006 (P < 0·05), we re‐examined this cohort of patients; the proportion of patients revisiting the ED was similar in both groups in 2007 (P = 0·608). What is new and conclusion: Routine implementation of medication reconciliation and reviews on admission and during the hospital stay did not appear to have any impact on ED revisits, re‐hospitalizations or mortality over 6‐month follow‐up.     

Retrospective evaluation of medication appropriateness and clinical pharmacist drug therapy recommendations for home-based primary care veterans

Background:The Medication Appropriateness Index (MAI) has demonstrated reliability in several outpatient settings. Clinical pharmacists play key roles as members of an interdisciplinary team in determining medication appropriateness.Objective:The goal of this study was to examine medication appropriateness using the MAI and the degree of recommendation acceptance associated with clinical pharmacist medication reviews for veterans enrolled in the Home-Based Primary Care (HBPC) program.Methods:A retrospective analysis of clinical pharmacist medication reviews was performed by accessing the computerized patient medical record. Patients included in the study were enrolled in the HBPC program between March 2002 and January 2004. The data were examined to determine a total MAI score associated with medication recommendations after each review. The number and types of pharmacist recommendations, their acceptance rate, and the total number of medications discontinued were also evaluated.Results:Seventy-nine patients (mean [SD] age, 75.3 [10.3] years) identified through the pharmacy database met the inclusion criteria and were included in the study. No patients identified were excluded from the analysis. A statistically significant decrease in the overall MAI score was observed from the initial review to the end of the study (P < 0.001). Recommendations to patients' primary care providers included medication initiation/discontinuation, laboratory monitoring, dosage adjustment, and other issues associated with appropriate prescribing that could be categorized using the MAI. Recommendations to home health nurses included monitoring for medication adherence, efficacy, and adverse events. Pharmacist recommendation acceptance rates for primary care providers and home health nurses were 69% and 56%, respectively. Overall, 121 medications were discontinued during the study period.Conclusions:By using the MAI for evaluation, pharmacist recommendations significantly improved the appropriateness of medication use among veterans receiving home health care. A majority of pharmacist recommendations were accepted.     

A survey of patients with prostate cancer attitudes concerning being cared for closer to home

Recent guidance recommends that men with prostate cancer on watchful waiting and men who have a stable prostate specific antigen, with no significant complications at least 2 years following treatment, should be offered follow‐up outside hospital. The study presented here represents the views of 442 men in the North East of England who fall into this group. It shows that 70·7% of the men surveyed preferred to be followed up at their local district general hospital, compared to 18·1% preferring to be followed up at their general practitioner (GP) practice. Almost 63·8% of patients in this study preferred to be followed up by the nurse specialist in comparison with 23·9% of patients preferring to be reviewed by a consultant and 9·4% choosing their GP. Patients who live in rural areas with a long journey time to the hospital were more likely to choose to be followed up by their GP. There has been no preparation of patients to change their expectations of lifelong follow‐up in secondary care. Patient survivorship information needs to be developed, so that patients are prepared and supported through this change in follow‐up care. This survey demonstrates that the patients within this particular National Health Service (NHS) Trust are happy with the current system of being followed up by the nurse specialist at their local district general hospital.     

Performance outcomes of a pharmacist‐managed anticoagulation clinic in the rural,resource‐constrained setting of Eldoret,Kenya

Summary. Background: It is recommended that warfarin therapy should be managed through an anticoagulation monitoring service to minimize the risk of bleeding and subsequent thromboembolic events. There are few studies in Sub‐Saharan Africa that describe warfarin management in spite of the high incidence of venous thromboembolism (VTE) and rheumatic heart disease. Objective: To examine the feasibility of the Moi Teaching and Referral Hospital anticoagulation monitoring service and compare its performance with clinics in resource‐rich settings. Methods: A retrospective chart review compared the percentage time in the therapeutic range (TTR) and rates of bleeding and thromboembolic events to published performance targets using the inference on proportions test. Wilcoxon’s rank sum analyses were used to establish predictors of TTR. Results: For the 178 patients enrolled, the mean TTR was 64.6% whereas the rates of major bleeds and thromboembolic events per year were 1.25% and 5%, respectively. In the primary analysis, no statistically significant differences were found between the results of TTR, major bleeds and thromboembolic events for the clinic and published performance rates. In the secondary analysis, having an artificial heart valve and a duration of follow‐up of > 120 days were positively associated with a higher TTR (P < 0.05) whereas venous thromboembolism, history of tuberculosis, HIV and a duration of follow‐up of < 120 days were associated with having a lower TTR (P < 0.05). Conclusions: The performance of the MTRH anticoagulation clinic is non‐inferior to published metrics on the performance of clinics in resource‐rich settings.     

Effectiveness of pharmacist‐participated warfarin therapy management: a systematic review and meta‐analysis

Summary. Objective: Although pharmacist‐participated warfarin therapy management (PWTM) has been accepted and implemented in various parts of the world, the evidence demonstrating the effects of PWTM compared with usual care on clinical outcomes is lacking. We performed a systematic review and meta‐analysis to compare the effects of PWTM with usual care on bleeding and thromboembolic outcomes. Methods: We searched MEDLINE, SCOPUS, EMBASE, IPA, CINAHL, Cochrane CENTRAL, Thai Index Medicus and Thai Medical Index, and reference lists of studies, without language restriction. Databases were searched from their inception to July 2009. The studies using warfarin as an anticoagulant with sufficient data for compilation of 2 × 2 tables were included. Both randomized controlled trials (RCTs) and non‐RCTs were considered. Two authors independently reviewed each study, assigned quality scores and extracted data for all outcomes using a standardized form. Pooled effect estimates (risk ratio; RR) were obtained using a random effects model. Result: Of 661 articles identified, 24 studies with 728,377 patients were included. In the random‐effects meta‐analysis of RCTs, the PWTM group had statistically significant effects on the prevention of total bleeding [RR, 0.51; 95% confidence interval (CI), 0.28–0.94]. However, the effects on major bleeding (RR, 0.64; 95% CI, 0.18–2.36), thromboembolic events (RR, 0.79; 95% CI, 0.33–1.93), all‐cause mortality (RR, 0.93; 95% CI, 0.41–2.13) and warfarin‐related mortality (RR, 0.65; 95% CI, 0.18–2.42) were not significant. Conclusion: Pharmacist’s participation in the management of warfarin therapy significantly reduces total bleeding, with a non‐significant trend towards decreases in other warfarin‐related complications.     

Prochlorperazine tablets repackaged into dose administration aids: can the patient be assured of quality?

Background and objective: Patients are increasingly requiring their medications to be repackaged into dose administration aids because of the positive outcomes associated with reduction in medication related hospitalization and adverse effects due to improved medicines management. Since the stability of these repackaged medications is not the responsibility of manufacturer, it is important that drug substances with potential stability issues be identified. Thus the objective of this study was to evaluate the stability of prochlorperazine, a light sensitive drug repackaged into dose administration aids (DAAs), in order to provide guidelines to the pharmacist and advice to the patient on appropriate storage. Methods: Prochlorperazine tablets were stored repackaged in DAAs and in their original packaging for 8 weeks at ambient (25 ± 1 °C; 60 ± 1·5% RH), accelerated (40 ± 1 °C; 75 ± 1·5% RH) and in‐use conditions encountered in situ both in a pharmacy and the patients’ home. They were assessed for both chemical (using a validated HPLC method) and physical stability according to British Pharmacopoeial (BP) standards. In addition, photostability testing was undertaken under ICH conditions. Results and discussion: Chemical and physical stability was confirmed to be within BP Limits.
There were, however, noticeable organoleptic changes in the tablets stored under in‐use conditions with a progressive grey discolouration over the 8 weeks, starting in week 2. Conclusion: Despite the confirmation of physical and chemical stability within BP limits, the discoloration and the potential for photodegradants to cause adverse effects in patients must lead us to draw the conclusion that the quality of this medication has been compromised. Pharmacists thus need to take this into account in repackaging and storage of prochlorperazine in DAAs and advise patients to store their DAA protected from light, heat and humidity.     

Prevalence of medication-related problems among patients with renal compromise in an Indian hospital

What is known and Objective: Patients suffering from renal dysfunction often have multiple medical conditions either as a cause or as a consequence of their renal disease. These patients receive an average of 10–12 medications daily leading to complex dosing schedules and are more likely to develop medication‐related problems (MRPs). The objectives of this study were to determine the nature and extent of MRPs in renally compromised patients and to explore the potential clinical significance of the MRPs. The potential for a clinical pharmacist to contribute towards resolving or preventing some of these MRPs was also explored. Methods: A prospective study was conducted for a period of 9 months in the renal unit of Jagadguru Shri Shivaratheeshwara (JSS) Medical College Hospital, Mysore, India. Patients undergoing dialysis on outpatient basis and patients who were admitted under the care of or referred to the nephrologists for renal dysfunction from other specialties were reviewed. Patterns of the MRPs were identified using an adapted Hepler and Strand criteria. The potential clinical significance of the MRPs and the contribution of the clinical pharmacist in resolving or minimizing some of the MRPs were also explored. Results and Discussion: Three hundred and twenty‐seven MRPs were identified with 308 patients reviewed. The incidence of MRPs was found to be 1·06 ± 0·85 per patient reviewed. The most common MRP identified in our study was overdose (19·3%) followed by adverse drug reactions (19·0%). Cardiovascular agents (33·6%) followed by anti‐infective agents (26·3%) were the most common therapeutic classes of medication implicated in causing MRPs. Twenty‐six per cent of the MRPs identified were explored to be potentially moderate or major in clinical significance. The clinical pharmacists’ recommendations were accepted in 97% of the cases, which resulted in a change in therapy in 83% of the cases. What is new and Conclusion: Medication‐related problems are frequent in renally compromised patients in our patient population. The high level of acceptance of clinical pharmacist’s recommendations by the nephrologists demonstrates that clinical pharmacists may help improve overall patient care in this setting.     

PRODIGE: a randomized placebo‐controlled trial of dalteparin low‐molecular‐weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma

Summary. Background and objectives: Venous thromboembolism (VTE) occurs in 20–30% of patients with malignant glioma per year of survival. We tested the efficacy of long‐term dalteparin low‐molecular‐weight heparin (LMWH) for prevention of VTE in these patients. Patients/methods: Adults with newly diagnosed malignant glioma were randomized to receive dalteparin 5000 anti‐Xa units or placebo, both subcutaneously once daily for 6 months starting within 4 weeks of surgery. Treatment continued for up to 12 months. The primary outcome was the cumulative risk of VTE over 6 months. The target sample size was 512 patients. Events were adjudicated by a committee unaware of treatment. Results: The trial began in 2002 and closed in May 2006 because of expiration of study medication. Ninety‐nine patients were randomized to LMWH and 87 to placebo. Twenty‐two patients developed VTE in the first 6 months: nine in the LMWH group and 13 in the placebo group [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.19–1.4, P = 0.29]. At 6 months, there were three major bleeds on LMWH and none on placebo; at 12 months, 5 (5.1%) major bleeds on LMWH and 1 (1.2%) on placebo occurred (HR = 4.2, 95% CI: 0.48–36, P = 0.22). All major bleeds were intracranial and occurred while on study medication. The 12‐month mortality rates were 47.8% for LMWH and 45.4% for placebo (HR = 1.2, 95% CI: 0.73–2.0, P = 0.48). Conclusions: Trends suggesting reduced VTE and increased intracranial bleeding were seen in the LMWH thromboprophylaxis group. The role of long‐term anticoagulant thromboprophylaxis in patients with brain tumors remains uncertain.