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Background Several variants in CYP2C9 (CYP2C9*2 and especially the CYP2C9*3 allele) and VKORC1 genes (especially the 1639G>A polymorphism) are associated with effective coumarin derivative dose. The rs2108622 polymorphism in the gene encoding cytochrome P450, family 4, subfamily F, polypeptide 2 (CYP4F2) could also influence warfarin dose with relevant effects on coumarin response. Concomitant drugs metabolised by CYP450, such as proton pump inhibitors, mainly metabolised by CYP2C19, may increase the risk of overanticoagulation in long-term oral anticoagulation therapy. Acenocoumarol pharmacokinetics may result altered with the presence of the C3435T gene polymorphism in the P-glycoprotein and has been associated to higher warfarin dose requirements in patients with deep vein thrombosis. Purpose Our aim was to evaluate the influence of VKORC1, CYP2C9-(CYP2C9*2 and CYP2C9*3 alleles), CYP4F2*2, CYP2C19*17 and MDR1-C3435T gene polymorphisms on the achievement of stable anticoagulation dose in patients treated with acenocoumarol. Materials and MethodsPatients with atrial fibrillation, pulmonary embolism, deep vein thrombosis, metallic aortic valve and metallic mitral valve prosthesis treated with acenocoumarol at a third level hospital were genotyped by Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism, direct sequencing or real time PCR. Clinical, pharmacological and socio-demographic parameters were analysed during 6 months of follow-up after starting anticoagulation therapy with acenocoumarol. Results One hundred and eighteen patients (mean age: 73 ± 12 years; 55.7% male) treated with acenocoumarol therapy and monitored for dose adjustment were recruited. The frequency of different genotypes according to stable anticoagulation status is shown in Table 1. Table 2 shows the frequency of genotypes in stable anticoagulated patients classified by stable anticoagulation dose (High: >28 mg/week; Intermediate: 7–28 mg/week; Low dose: <7 mg/week). The stable anticoagulation status was not associated to any gene polymorphism, and the stable anticoagulation dose was only associated to CYP2C9*3 (0.047). Conclusions The achievement of a stable anticoagulation status is not associated to VKORC1, CYP2C9*2, CYP4F2*2, CYP2C19*17 or MDR1-C3435T gene polymorphisms, although the stable anticoagulation dose is associated to CYP2C9*3. Abstract DGI-68 Table 1The frequency of different genotypes according to stable anticoagulation status Stable Total p-value Gene polymorphism Genotype n No Yes VKORC1*2 (rs9923231) CC 44 30 14 115 0.758 CT 57 40 17 TT 14 11 3 CYP2C9*2 (rs1799853) CC (WT) 82 61 21 117 0.223 CT 33 20 13 TT 2 2 2 0 CYP2C9*3 (rs1057910) AA (WT) 98 69 29 116 0.724 AC 18 14 4 CYP4F2*3 (rs2108622) CC (WT) 53 38 15 117 0.352 CT 50 33 17 TT 14 12 2 CYP2C19*17 (rs12248560) GG (WT) 85 59 26 113 0.729 GA 27 20 7 AA 1 1 0 ABCB1 C3435T (rs1045642) CC (WT) 31 22 9 118 0.864 CT 56 41 15 TT 31 21 10 VKORC1: Vita...

BackgroundOne of the main causes of injuries and hospital admissions in older people is falls. The risk of falling can be increased by factors such as vision and balance problems, dementia and drug consumption. In 2012, pharmacists in primary care performed an intervention, providing physicians with a list of elderly outpatients who were candidates for a clinical review because potentially inappropriate prescriptions (PIP) for sedative effect drugs was detected.PurposeTo evaluate the impact of pharmacist interventions in health outcomes of elderly patients receiving polypharmacy.Material and methodsRetrospective study at 10 primary care centres, which included polypharmacy outpatients, older than 65 years, whose pharmaceutical interventions (PI) were made in 2012 because of a PIP for sedative drugs. We evaluated acceptance by physicians checking the prescribing modifications of the pharmaceutical recommendations. We then analysed health outcomes in patients whose doctor had withdrawn the sedative effect drugs and patients without modifications in their treatment, reviewing the clinical history for a 12 month period after the intervention.Results234 PI were included. Mean patient age was 77 (±7) years. 2 of 5 patients had suffered adverse events from sedative drugs before the PI, 42% were classified as at risk of falling. The drugs involved were: tricyclic antidepressants (46%), first generation antihistamines (33%), first generation antipsychotics (16%) and 3 benzodiazepines concurrently (5%). Acceptance rate by physicians of pharmacist recommendations was 33%. We detected that 16% of patients had suffered at least one fall during the year after the intervention, of whom in 76% of cases the physician did not accept the pharmacist’s recommendation and patients had no changes in their medication, although we found no significant difference between the two groups. The falls in this group generated 15 primary care visits, 30 emergency visits and 3 hospital admissions.ConclusionAn appropriate use of sedative drugs in the elderly population could contribute to a reduction in the risk of falling and fall related injuries. A higher frequency of adverse events was found in patients without changes in their medication, as recommended by pharmacists, although future research is necessary to confirm whether these interventions are useful in reducing negative health outcomes and changing prescribing habits.References and/or AcknowledgementsThanks for your help to Dr Sam Ramsay.No conflict of interest.

Background Vitamin K antagonists (VKAs) remain the oral anticoagulant most prescribed for treatment and prevention of thrombotic disorders in atrial fibrillation (AF), despite the recent appearance of the new oral anticoagulants dabigatran, rivaroxaban and apixaban (NOACs). NOACs represent the alternative for some special cases (hypersensitivity or contraindication to VKAs; poor INR (International Normalised Ratio) control or unavailability for INR control). VKORC1-rs9923231 gene polymorphism is related to a longer time to achieve stability, higher risk of over-anticoagulation in the first months of treatment and lower doses of VKAs compared to wild-type patients, therefore exposing these patients to a higher risk of adverse reactions. Purpose To evaluate the association of VKORC1-TT genotype with the change from VKA to NOAC treatment due to poor INR control at Complejo Hospitalario de Granada. Materials and Methods Retrospective Cohort study. Patients diagnosed with AF on oral anticoagulant treatment VKORC1-rs9923231 genotype was compared between patients treated with acenocoumarol who achieved a stable dose after a minimum period of seven months and patients who were switched to NOACs after pretreatment with acenocoumarol due to poor INR control Cohorts were defined by VKORC1 TT-genotype Genotyping was performed by Polymerase Chain Reaction - Restriction Fragment Length Polymorphism for VKORC1-rs9923231. Results Seventy-nine patients fulfilled the inclusion criteria in total. Seventy-one had achieved stable doses with acenocoumarol (89.9%; 71/79) and 8 had been switched to NOACs (10.1%; 8/79). VKORC1-TT genotype was present in 13 patients, 4 switched to NOACs due to poor INR control (30.8%; 4/13). The VKORC1-C allele was present in 66 patients, 4 changed to NOACs (6.1%; 4/66). Relative risk for switching to NOACs was 5.1 (1.5-17.8; p = 0.022). Conclusions Long-term oral anticoagulant treatment in AF patients should be selected on the basis of the VKORC1-TT genotype, since they are more likely to need NOACs. No conflict of interest.