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Bleeding Events (bleeding + event)
Selected AbstractsSafety and efficacy of nabumetone in osteoarthritis: emphasis on gastrointestinal safetyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2000Scott To compare the efficacy and gastrointestinal (GI) safety of nabumetone with two comparator non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac SR and piroxicam. Methods: Two randomized, double-blind, multicentre, parallel group trials were carried out in patients with moderate to severe osteoarthritis of the hip or knee. During the 6 month treatment phase, the safety and efficacy of nabumetone (1500,2000 mg/day) was compared to diclofenac SR (100 mg/day) or piroxicam (20,30 mg/day). GI safety was evaluated by reviewing all adverse events reported during the trials and presenting all cases of ulcers (complicated and uncomplicated), as well as other bleeding events that may have been associated with NSAID administration. Results: Most of the efficacy parameters showed no significant differences between the NSAIDs, although diclofenac SR was significantly better than nabumetone in one of 18 efficacy parameters. Nabumetone-treated patients experienced significantly fewer ulcer and bleeding events compared to patients treated with the comparator NSAIDs [1.1% (4/348) vs. 4.3% (15/346), P= 0.01]. Bleeding events, including outright upper or lower GI bleeding or a significant decline in haemoglobin, occurred in significantly fewer patients treated with nabumetone than with the comparator NSAIDs [1.1% (4/348) vs. 3.5% (12/346), P < 0.05]. More importantly, complications associated with either ulcers (perforation) or bleeding (leading to hospitalization or withdrawal) occurred in significantly fewer patients receiving nabumetone [0% (0/348)] than with comparator NSAIDs [1.4% (5/346), (P < 0.05)]. Conclusion: The results suggest that nabumetone was similar in efficacy by most criteria to diclofenac SR and piroxicam in relieving the symptoms of osteoarthritis; however, nabumetone's GI safety profile was generally superior to that of both comparator NSAIDs. In the pooled analysis, nabumetone was associated with a significantly lower total incidence of ulcers and bleeding events, and a significantly lower incidence of complications associated with these events. [source] The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjectsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2007Joachim Stangier Aims The novel direct thrombin inhibitor (DTI), dabigatran etexilate (Boehringer Ingelheim Pharma GmbH & Co. KG), shows potential as an oral antithrombotic agent. Two double-blind, randomized trials were undertaken to investigate the pharmacokinetics (PK), pharmacodynamics (PD) and tolerability of orally administered dabigatran etexilate in healthy male subjects. Methods Dabigatran etexilate or placebo was administered orally at single doses of 10,400 mg (n = 40) or at multiple doses of 50,400 mg three times daily for 6 days (n = 40). Plasma and urine samples were collected over time to determine the PK profile of dabigatran. PD activity was assessed by its effects on blood coagulation parameters: activated partial thromboplastin time (aPTT), prothrombin time (PT), reported as international normalized ratio (INR), thrombin time (TT), and ecarin clotting time (ECT). All adverse events were recorded. Results Dabigatran etexilate was rapidly absorbed with peak plasma concentrations of dabigatran reached within 2 h of administration. This was followed by a rapid distribution/elimination phase and a terminal phase, with associated estimated half-lives of 8,10 h and 14,17 h with single and multiple dose administrations, respectively. Dabigatran exhibited linear PK characteristics with dose-proportional increases observed in maximum plasma concentration and area under the curve. Steady-state conditions were reached within 3 days with multiple dosing. The mean apparent volume of distribution during the terminal phase (Vz/F) of 1860 l (range 1430,2400 l) and the apparent total clearance after oral administration (CLtot/F) of 2031 ml min,1 (range 1480,2430), were dose independent. Time curves for aPTT, INR, TT and ECT paralleled plasma concentration,time curves with values increasing rapidly and in a dose-dependent manner. At the highest dose of 400 mg administered three times daily, maximum prolongations over baseline of 3.1 (aPTT), 3.5 (INR), 29 (TT) and 9.5-fold (ECT) were observed. Dabigatran underwent conjugation with glucuronic acid to form pharmacologically active conjugates that accounted for approximately 20% of total dabigatran in plasma. Overall, variability in PK parameters was low to moderate, with an average interindividual coefficient of variation (CV) of approximately 30% and variability in PD parameters was low, with CV < 10%. Of the four assays, TT and ECT exhibited the greatest sensitivity and precision within the anticipated therapeutic dose range. Bleeding events were few and were mild-to-moderate in intensity, occurring only in the higher, multiple dose groups. Conclusions These data suggest that dabigatran etexilate is a promising novel oral DTI with predictable PK and PD characteristics and good tolerability. Further investigation of dabigatran etexilate for the treatment and prophylaxis of patients with arterial and venous thromboembolic disorders, acute coronary syndromes and other medical conditions is warranted. [source] Economic analysis of strategies in the prevention of non-steroidal anti-inflammatory drug-induced complications in the gastrointestinal tractALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2004A. Lanas Summary Background :,It is unclear what the best therapeutic approach is in patients who require non-steroidal anti-inflammatory drugs. In clinical practice, choice of prescriptions are often based on drug costs. Aim :,To evaluate costs per upper gastrointestinal bleeding avoided with different prevention strategies. Methods :,Two major strategies have been considered (coxibs vs. non-steroidal anti-inflammatory drugs plus generic/brand gastroprotective agent). The number of patients needed to treat to prevent a bleeding event, the cost of the drug and duration of treatment were used to estimate costs. Results :,Based on hospitalization costs of a bleeding event, no therapeutic strategy is cost-effective in patients without risk factors. All strategies (including omeprazole + coxib) are cost-effective in patients with bleeding ulcer history. With other risk factors, all strategies are cost-effective but prevention of events is twice as expensive in patients <75 years of age. No strategy shows superiority unless the cheapest generics are prescribed or a 50% reduction in the incidence of lower gastrointestinal complications with coxibs is confirmed. Conclusions :,Current prevention strategies to reduce serious non-steroidal anti-inflammatory drug-associated gastrointestinal events are only cost-effective in patients with risk factors. No strategy shows superiority, but coxib strategy would be more cost-effective if it were associated with a reduction of events of the lower gastrointestinal tract. [source] Management Options to Treat Gastrointestinal Bleeding in Patients Supported on Rotary Left Ventricular Assist Devices: A Single-Center ExperienceARTIFICIAL ORGANS, Issue 9 2010Helen M. Hayes Abstract Gastrointestinal (GI) bleeding in ventricular assist devices (VADs) has been reported with rotary devices. The pathophysiological mechanisms and treatments are in evolution. We performed a retrospective review of GI bleeding episodes for all VADs implanted at our institution. Five male patients experienced GI bleeding,age 63.6 ± 3.64 years. VAD type VentrAssist n = 1, Jarvik 2000 n = 2, and HeartWare n = 2. All patients were anticoagulated as per protocol with antiplatelet agents (aspirin and/or clopidogrel bisulfate [Plavix] and warfarin (therapeutic international normalized ratio 2.0,3.5). There was no prior history of gastric bleeding in this group. Ten episodes of bleeding requiring blood transfusion occurred in five patients. Some patients had multiple episodes (1 × 5, 1 × 2, 3 × 1). The events occurred at varying times post-VAD implantation (days 14, 21, 26, 107, 152, 189, 476, 582, 669, and 839). Octreotide (a long-acting somatostatin analogue that reduces splanchnic arterial and portal blood flow) was administered subcutaneously or intravenously. Three patients received infusions of adrenaline at 1 µg/min to enhance pulsatility. Anticoagulation was interrupted during bleeding episodes but successfully introduced post bleeding event. GI bleeding is a significant complication of VAD therapy. In this article, we discuss diagnosis and management options. [source] Renal surgery in the elderly: morbidity in patients aged >75 years in a contemporary seriesBJU INTERNATIONAL, Issue 6 2008Michael Staehler OBJECTIVES To evaluate the surgical complications in a contemporary group of elderly patients with renal masses, as almost a quarter of patients with newly diagnosed renal mass are aged >74 years, with the potential for significant comorbidity. PATIENTS AND METHODS From April 2004 to June 2007, of 379 surgical resections of renal tumours, we assessed 117 consecutive patients aged ,75 years, who had either radical nephrectomy (RN) or partial nephrectomy (PN) for assumed renal cell carcinoma. Also elderly patients who had nephroureterectomy (NU) for upper urothelial cancer were followed. RESULTS Fifty patients had RN, 57 PN and 10 had NU; the median (range) age of all patients was 78.1 (72.7,92.5) years and was similar in all groups. No patient died during surgery and only one died within 90 days. The complication rates during and after surgery RN, PN and NU were 12%, 15% and 20%, respectively; the major complications within 30 days were 4%, 7% and 10%; major complications included bleeding during surgery and one acute bleeding event after surgery in the PN group. CONCLUSIONS Open renal surgery in elderly patients can be done safely; there was no difference in morbidity among RN, PN and NU. Renal surgery in the elderly patient is safe if done at a specialized centre. Mortality and morbidity can be very low, rendering this a feasible approach in the treatment of renal masses even if the prognosis is not determined by the oncological situation but by comorbidity. [source] Considerations in the evaluation of haemophilia patients for short-term prophylactic therapy: a paediatric and adult case studyHAEMOPHILIA, Issue 1 2006L. LUCHTMAN-JONES Summary., The long-term prophylactic administration of clotting factor concentrate in patients with haemophilia reduces bleeding events, slows joint deterioration, and improves quality of life. Prophylaxis can also be effective when used short-term to prevent or reduce bleeding associated with trauma, surgery, and athletic activities. While clinical trials are needed to establish the optimal length of prophylaxis following injury, several weeks and possibly months of treatment may be needed. Discontinuing therapy prematurely can result in rebleeding in the injured area. [source] Increased Incidence of Gastrointestinal Bleeding Following Implantation of the HeartMate II LVADJOURNAL OF CARDIAC SURGERY, Issue 3 2010David R. Stern M.D. To avoid device-related thromboembolic complications, antiplatelet, and anticoagulation therapy are routinely administered. A worrisome frequency of gastrointestinal (GI) bleeding events has been observed. Methods: A retrospective review of all 33 patients undergoing long-term LVAD implantation between June 1, 2006 and July 31, 2008 at our institution for any indication was conducted. Anticoagulation consisted of heparin (intravenous or subcutaneous) followed by transition to Coumadin therapy to a target INR of two to three. Antiplatelet therapy consisted of low-dose aspirin and dipyridamole. Results: Twenty patients received the HMII and 13 patients received other devices. Eight (40%) HMII recipients suffered at least one episode of GI bleeding while no GI bleeding occurred in recipients of other devices (p = 0.012). Of 17 total bleeding episodes, no definitive source could be identified in 11 instances (65%). Conclusions: Although definitive source identification remains elusive, we believe that the majority of bleeding arises in the small bowel, possibly due to angiodysplasias, similar to the pathophysiology encountered in patients with aortic stenosis and GI bleeding. As we move toward wider use of the HMII and other axial continuous-flow devices in both bridge-to-transplant patients and for destination therapy, more studies will be necessary to understand the mechanisms of this obscure GI bleeding and develop treatment strategies to minimize its development.,(J Card Surg 2010;25:352-356) [source] Partial factor IXa inhibition with TTP889 for prevention of venous thromboembolism: an exploratory studyJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2008B. I. ERIKSSON Summary.,Background:,Inhibitors of factor (F) IXa show potent antithrombotic activity with a low risk of bleeding in preclinical models. We investigated the anticoagulant potential of oral TTP889, a small molecule that inhibits up to 90% of FIXa activity at therapeutic doses, using a clinical model of extended prophylaxis in hip fracture surgery (HFS). Methods:,In this multicenter, randomized, double-blind study, 261 patients received oral TTP889 (300 mg once daily) or placebo starting 6,10 days after HFS, and standard thromboprophylaxis for 5,9 days. Treatment was continued for 3 weeks and all patients then underwent mandatory bilateral venography. The primary efficacy outcome was venous thromboembolism (VTE; venographic or symptomatic deep vein thrombosis or pulmonary embolism) during treatment, and it was evaluated centrally by an independent adjudication panel. The main safety outcome was bleeding (major, clinically relevant non-major, and minor events). Results:,Two hundred and twelve patients with an evaluable venogram were included in the efficacy analysis. The primary efficacy outcome occurred in 32.1% (35/109) of patients who had been allocated TTP889, and 28.2% (29/103) of patients on placebo (P = 0.58). There were no major bleeding events, and only two clinically relevant non-major bleeding events with TTP889. Conclusion:,Partial FIXa inhibition with TTP889 300 mg daily was not effective for extended prevention of VTE after standard prophylaxis for up to 9 days. Coupled with the low incidence of bleeding episodes, this suggests a lack of antithrombotic potential. Further investigation of TTP889 in different clinical settings is needed. (Clinical trial registration information URL: http://www.clinicaltrials.gov. Unique identifier: NCT00119457) . [source] Initial experience with factor-Xa inhibition in percutaneous coronary intervention: the XaNADU-PCI PilotJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2004J. H. Alexander Summary.,Background:,Direct factor (F)Xa inhibition is an attractive method to limit thrombotic complications during percutaneous coronary intervention (PCI). Objectives:,To investigate drug levels achieved, effect on coagulation markers, and preliminary efficacy and safety of several doses of DX-9065a, an intravenous, small molecule, direct, reversible FXa inhibitor during PCI. Patients and methods:,Patients undergoing elective, native-vessel PCI (n = 175) were randomized 4 : 1 to open-label DX-9065a or heparin in one of four sequential stages. DX-9065a regimens in stages I,III were designed to achieve concentrations of >,100 ng mL,1, >,75 ng mL,1, and >,150 ng mL,1. Stage IV used the stage III regimen but included patients recently given heparin. Results:,At 15 min median (minimum) DX-9065a plasma levels were 192 (176), 122 (117), 334 (221), and 429 (231) ng mL,1 in stages I,IV, respectively. Median whole-blood international normalized ratios (INRs) were 2.6 (interquartile range 2.5, 2.7), 1.9 (1.8, 2.0), 3.2 (3.0, 4.1), and 3.8 (3.4, 4.6), and anti-FXa levels were 0.36 (0.32, 0.38), 0.33 (0.26, 0.39), 0.45 (0.41, 0.51), and 0.62 (0.52, 0.65) U mL,1, respectively. Stage II enrollment was stopped (n = 7) after one serious thrombotic event. Ischemic and bleeding events were rare and, in this small population, showed no clear relation to DX-9065a dose. Conclusions:,Elective PCI is feasible using a direct FXa inhibitor for anticoagulation. Predictable plasma drug levels can be rapidly obtained with double-bolus and infusion DX-9065a dosing. Monitoring of DX-9065a may be possible using whole-blood INR. Direct FXa inhibition is a novel and potentially promising approach to anticoagulation during PCI that deserves further study. [source] Use of activated protein c in liver transplantation patients with septic shock,LIVER TRANSPLANTATION, Issue 11 2008Laura Rinaldi Recombinant human activated protein C (rhAPC) has been approved for use in patients with severe sepsis at high risk of death. Because of the high risk of bleeding, liver transplantation (LT) patients have been excluded from the randomized control trials that evaluated efficacy and safety of rhAPC and, thus, few data are available on the use of this drug in LT patients with severe sepsis. We describe our experience with 5 LT recipients treated for septic shock with the best conventional therapy and rhAPC. Before rhAPC therapy, all the patients showed septic shock, with ,3 organ dysfunctions and thrombocytopenia with impairment of coagulation. rhAPC therapy started within 30 hours after septic shock onset in all the patients who recovered from sepsis-induced circulatory failure, improved organ dysfunction, and completed the 96 hours of rhAPC therapy. During rhAPC infusion, 4 patients received fresh frozen plasma and/or platelet concentrates because of thrombocytopenia and severe hemostasis dysfunction. No major bleeding occurred and only 1 patient presented with minor bleeding events. Liver Transpl 14:1598,1602, 2008. © 2008 AASLD. [source] Safety and efficacy of nabumetone in osteoarthritis: emphasis on gastrointestinal safetyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2000Scott To compare the efficacy and gastrointestinal (GI) safety of nabumetone with two comparator non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac SR and piroxicam. Methods: Two randomized, double-blind, multicentre, parallel group trials were carried out in patients with moderate to severe osteoarthritis of the hip or knee. During the 6 month treatment phase, the safety and efficacy of nabumetone (1500,2000 mg/day) was compared to diclofenac SR (100 mg/day) or piroxicam (20,30 mg/day). GI safety was evaluated by reviewing all adverse events reported during the trials and presenting all cases of ulcers (complicated and uncomplicated), as well as other bleeding events that may have been associated with NSAID administration. Results: Most of the efficacy parameters showed no significant differences between the NSAIDs, although diclofenac SR was significantly better than nabumetone in one of 18 efficacy parameters. Nabumetone-treated patients experienced significantly fewer ulcer and bleeding events compared to patients treated with the comparator NSAIDs [1.1% (4/348) vs. 4.3% (15/346), P= 0.01]. Bleeding events, including outright upper or lower GI bleeding or a significant decline in haemoglobin, occurred in significantly fewer patients treated with nabumetone than with the comparator NSAIDs [1.1% (4/348) vs. 3.5% (12/346), P < 0.05]. More importantly, complications associated with either ulcers (perforation) or bleeding (leading to hospitalization or withdrawal) occurred in significantly fewer patients receiving nabumetone [0% (0/348)] than with comparator NSAIDs [1.4% (5/346), (P < 0.05)]. Conclusion: The results suggest that nabumetone was similar in efficacy by most criteria to diclofenac SR and piroxicam in relieving the symptoms of osteoarthritis; however, nabumetone's GI safety profile was generally superior to that of both comparator NSAIDs. In the pooled analysis, nabumetone was associated with a significantly lower total incidence of ulcers and bleeding events, and a significantly lower incidence of complications associated with these events. [source] Latest news and product developmentsPRESCRIBER, Issue 5 2008Article first published online: 3 APR 200 Newer antidepressants no better than placebo? A new meta-analysis suggests that newer antidepressants are no superior to placebo in most patients with depression , the exception being those with very severe depression, who can expect a small benefit. Writing in the online-only open access journal PLoS Medicine (5:e45.doi:10.1371/ journal.pmed.0050045), researchers from Hull and the US analysed published and unpublished trials submitted to the Food and Drug Administration in marketing applications for fluoxetine, paroxetine, venlafaxine (Efexor) and nefazodone (no longer available). Using the Hamilton Rating Scale for Depression (HRSD) score as an endpoint, meta-analysis of 35 trials involving 5133 patients and lasting six to eight weeks showed that mean HRSD score improved by 9.6 points with drug treatment and 7.8 with placebo. The authors say the difference of 1.8 was statistically significant but below the criterion for clinical significance (3.0) set by NICE in its clinical guideline on depression. A review of the study by the NHS Knowledge Service (www.nhs.uk) points out that it omits trials published after the drugs were licensed (1999) and those not sponsored by the pharmaceutical industry. It did not include any patients with severe depression and only one trial in patients with moderate depression. An earlier US study of data submitted to the FDA (N Eng J Med 2008;358:25260) showed that published trials of antidepressants were more likely to be positive (37/38) than unpublished ones (3/25). Further, FDA analysts concluded that 51 per cent of trials (published and unpublished) demonstrated positive findings compared with 94 per cent of those that were published. Audit reveals variations in hospital psoriasis care There are unacceptably large variations in the quality of care for patients with psoriasis in UK hospitals, a report by the British Association of Dermatologists and the Royal College of Physicians reveals. The audit of 100 hospital units found that 39 per cent restricted access to biological therapies because of cost, and over one-third of pharmacies could not supply ,specials' such as topical coal tar preparations. More positively, the units are adequately resourced to provide timely communication with GPs. RCGP responds to Public Accounts Committee The Royal College of General Practitioners has agreed with the Commons Public Accounts Committee that drug package labelling should include the cost of the medication. The suggestion was made by the Committee in its report Prescribing Costs in Primary Care. While recognising the importance of generic prescribing, the RCGP cautions against frequent medication switches because it may unsettle patients. ,Any changes must be carried out for sound clinical reasons with good communication between GPs and their patients,' it adds. Statins for patients with kidney disease? Statins reduce cardiovascular risk in people with chronic kidney disease, a new study suggests, but their effects on renal function remain unclear (BMJ 2008; published online doi: 10.1136/bmj. 39472.580984.AE). The meta-analysis of 50 trials involving a total of 30 144 patients found that statins reduced lipids and cardiovascular events regardless of the severity of kidney disease. However, all-cause mortality was unaffected and, although proteinuria improved slightly, there was no change in the rate of decline of glomerular filtration rate. An accompanying editorial (BMJ 2008; published online doi:10.1136/ bmj.39483.665139.80) suggests that the indications for statin therapy to reduce cardiovascular risk in patients with chronic kidney disease should be the same as for those with normal renal function. New NICE guidance New clinical guidelines from NICE (see New from NICE, pages 14,15) include the diagnosis and management of irritable bowel syndrome in adults in primary care, the care and management of osteoarthritis in adults, and the diagnosis and treatment of prostate cancer. In a public health guideline on smoking cessation services, NICE endorses the use of nicotine replacement patches for 12,17 year olds. Suspect additives in children's medicines The Food Commission (www.foodcomm.org.uk) has drawn attention to the presence in children's medicines of food additives it says are linked with hyperactivity. The Commission, a national nonprofit organisation campaigning for ,the right to safe, wholesome food', says that seven common additives (including tartrazine, sodium benzoate and Ponceau 4R) are associated with hyperactivity in susceptible children. Checking the SPCs, it found that 28 of 70 children's medicines , including formulations of paracetamol, ibuprofen, amoxicillin, erythromycin and codeine phosphate throat linctus , contain at least one suspect additive. Digoxin may increase mortality in AF patients An observational study has suggested that digoxin may increase deaths in patients with atrial fibrillation (Heart 2008;94:191,6). The study was a planned subgroup analysis of a trial evaluating anticoagulant therapy in 7329 patients with atrial fibrillation. Of these, 53 per cent were treated with digoxin. Mortality was significantly higher among digoxin users than nonusers (4.22 vs 2.66 per cent per year); myocardial infarction and other vascular deaths (but not stroke, systemic embolic episodes and major bleeding events) were significantly more frequent with digoxin. Poor communications cause readmission Elderly hospital patients are often discharged with inadequate information or arrangements for care, causing almost three-quarters to be readmitted within a week, say investigators from Nottingham (Qual Safety Health Care 2008;17:71,5). Retrospective review of records for 108 consecutive patients aged over 75 found that readmission was related to medication in 38 per cent and, of these, 61 per cent were considered avoidable. Almost two-thirds had no discharge letter or were readmitted before the letter was typed; two-thirds of discharge letters had incomplete documentation of medication changes. Copyright © 2008 Wiley Interface Ltd [source] Valproate induces reversible factor XIII deficiency with risk of perioperative bleedingACTA NEUROLOGICA SCANDINAVICA, Issue 2 2003B. Pohlmann-Eden The antiepileptic drug valproic acid (VPA) induces subclinical changes in both the intrinsic and extrinsic coagulation system. However, fatal bleeding is very rare. This study reports a 39-year-old patient who underwent selective amygdalohippocampectomy because of drug-resistant temporal lobe epilepsy. Preoperatively, the patient was on a combined therapy with VPA and topiramate, and routine coagulation laboratory parameters were entirely normal. Epilepsy surgery was immediately followed by severe intracranial bleeding events which promped repeated craniectomy. Extensive laboratory analyses revealed a factor XIII activity level of 17%, indicating factor XIII deficiency confirmed by a reduced XIIIA-antigen. After termination of treatment with VPA, factor XIII levels returned to normal. Control examinations after 9 and 24 months showed normal range values for all coagulation parameters, including factor XIII, platelet function, and von Willebrand factor. To our knowledge, this case is the first description of a well-documented, clinically relevant transient factor XIII-deficiency syndrome related to VPA treatment. [source] What influence do anticoagulants have on oral implant therapy?CLINICAL ORAL IMPLANTS RESEARCH, Issue 2009A systematic review Abstract Objectives: This systematic review aims to assess the risks (both thromboembolic and bleeding) of an oral anticoagulation therapy (OAT) patient undergoing implant therapy and to provide a management protocol to patients under OAT undergoing implant therapy. Material and methods: Medline, Cochrane Data Base of Systematic Reviews, the Cochrane Central Register of Controlled Trials and EMBASE (from 1980 to December 2008) were searched for English-language articles published between 1966 and 2008. This search was completed by a hand research accessing the references cited in all identified publications. Results: Nineteen studies were identified reporting outcomes after oral surgery procedures (mostly dental extractions in patients on OAT following different management protocols and haemostatic therapies). Five studies were randomized-controlled trials (RCTs), 11 were controlled clinical trials (CCTs) and three were prospective case series. The OAT management strategies as well as the protocols during and after surgery were different. This heterogeneity prevented any possible data aggregation and synthesis. The results from these studies are very homogeneous, reporting minor bleeding in very few patients, without a significant difference between the OAT patients who continue with the vitamin K antagonists vs. the patients who stopped this medication before surgery. These post-operative bleeding events were controlled only with local haemostatic measures: tranexamic acid mouthwashes, gelatine sponges and cellulose gauzes's application were effective. Post-operative bleeding did not correlate with the international normalised ratio (INR) status. In none of the studies was a thromboembolic event reported. Conclusions: OAT patients (INR 2,4) who do not discontinue the AC medication do not have a significantly higher risk of post-operative bleeding than non-OAT patients and they also do not have a higher risk of post-operative bleeding than OAT patients who discontinue the medication. In patients with OAT (INR 2,4) without discontinuation, topical haemostatic agents were effective in preventing post-operative bleeding. OAT discontinuation is not recommended for minor oral surgery, such as single tooth extraction or implant placement, provided that this does not involve autogenous bone grafts, extensive flaps or osteotomy preparations extending outside the bony envelope. Evidence does not support that dental implant placement in patients on OAT is contraindicated. [source] | ||||||||||