A case series of the rifampin-warfarin drug interaction: focus on practical warfarin management.

PURPOSE: To provide practical guidance by providing weekly descriptions of warfarin requirements for the onset and offset of the rifampin-warfarin interaction. METHODS: A retrospective chart review within an outpatient Anticoagulation Clinic (AC). Patients were eligible for the onset phase provided they had known ambulatory-based warfarin steady-state requirements prior to rifampin initiation. For the offset phase, warfarin must be managed by the AC following rifampin discontinuation. Each phase was described separately with warfarin proportionate dose changes (median, IQR) for weeks 1, 2, and 4 as well as the change required to reach warfarin steady state. RESULTS: Ten patients with 11 courses of warfarin-rifampin were included. For onset, clinicians should anticipate proportionate warfarin dose increases of 30-80% from week 1 to week 2 and a further 20-100% from week 2 to 4, with an overall warfarin dose increase of 165% (IQR 99, 227) to reach steady state at 30 days. For offset, clinicians should anticipate proportionate warfarin dose decreases of 15-25% for both week 1 and 2, and a further 20% for both week 3 and 4, resulting in an overall warfarin decrease of 67% (IQR - 70, - 58) to reach steady state at 4 weeks for most patients. CONCLUSION: Close monitoring with at least twice weekly INRs for weeks 1 to 2 of both phases is needed to respond to substantially changing warfarin dose requirements. While inter- and intra-patient variability for proportionate warfarin dose changes for both the onset and offset of this drug interaction exists, our data provides general guidance.

Dolutegravir Dual Therapy as Maintenance Treatment in HIV-Infected Patients: A Review.

OBJECTIVE: To review available evidence for dolutegravir-based dual therapy as maintenance treatment in HIV-1 infected patients. DATA SOURCES: A literature search was conducted using PubMed, MEDLINE, and Google Scholar to the end of January 2018. Conference abstracts and article bibliographies were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language, randomized, and observational studies were included. DATA SYNTHESIS: In all, 12 studies were identified: 10 were observational, and 2 were randomized trials. Rilpivirine or lamivudine were the most common second agent used in combination with dolutegravir. Virological suppression seen in observational studies appear promising; however, the most compelling evidence to date is the 48-week results from 2 large open-label randomized trials (SWORD 1 and 2). These studies found that dual therapy with rilpivirine and dolutegravir was noninferior to 3- or 4-drug combination antiretroviral therapy (cART). The long-term efficacy, safety, and tolerability of dual therapy, as compared with usual cART, are less clear and require further data. CONCLUSIONS: Regimen switching in virally suppressed HIV-1-infected patients may be considered to reduce pill burden or dosing frequency, decrease short- or long-term toxicity, prevent or manage drug-drug interactions, and/or decrease cost. Based on available evidence, a switch to dual therapy with dolutegravir and rilpivirine appears viable for virologically suppressed patients without prior resistance mutations to these agents. Randomized studies of other dual-therapy regimens that include dolutegravir and longer-term follow-up as well as cost-effectiveness analyses are needed to provide confirmation that this strategy offers advantages to traditional cART regimens.

Anticoagulant and Antiplatelet Prescribing Patterns for Patients with Atrial Fibrillation after Percutaneous Coronary Intervention.

BACKGROUND: Current guidelines recommend triple antithrombotic therapy (TAT), defined as acetylsalicylic acid (ASA), clopidogrel, and warfarin, for patients with nonvalvular atrial fibrillation who have undergone percutaneous coronary intervention with stent implantation. The choice of anticoagulant/antiplatelet therapy in this population is ambiguous and complex, and prescribing patterns are not well documented. OBJECTIVE: To characterize local prescribing patterns for anticoagulant/antiplatelet therapy after percutaneous coronary intervention in patients with nonvalvular atrial fibrillation. METHODS: A chart review was conducted at a single quaternary cardiology centre. Patients with nonvalvular atrial fibrillation were identified via medical records, and those who underwent percutaneous coronary intervention were identified using a local clinical patient registry. Adult inpatients with nonvalvular atrial fibrillation and a CHADS2 score (based on congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) of 1 or higher who underwent percutaneous coronary intervention from 2011 to 2013 were included. Patients undergoing cardiovascular surgery or transcatheter aortic valve replacement, those with mechanical devices requiring anticoagulation, and those with an allergy to any component of TAT were excluded. RESULTS: Seventy patients were included. The median age was 75 years, and 52 (74%) were men. At discharge, 30 (43%) were receiving TAT and 27 (39%) were receiving dual antiplatelet therapy (clopidogrel and ASA). No patients received the combination of warfarin and clopidogrel. Among those who received TAT, 90% (19 of 21) who received a bare metal stent had a recommended duration of 1 month, and 75% (6 of 8) who received a drug-eluting stent had a recommended duration of 1 year. Direct-acting oral anticoagulants with 2 antiplatelet drugs were prescribed for 9% (6 of 70) of the patients, and 10% (7 of 70) received ticagrelor and ASA with or without warfarin. Overall, the combination of ASA, oral anticoagulant, and P2Y12 inhibitor was used for 54% (38/70) of the patients. CONCLUSIONS: Fewer than half of the patients in this study received TAT, and almost 20% received non-evidence-based therapy with a direct-acting oral anticoagulant or ticagrelor, alone or in combination. Despite current guideline recommendations, the rate of TAT utilization was lower than rates reported in the literature.

CONTEXTE: Les lignes directrices actuelles recommandent une trithérapie antithrombotique, composée d'acide acétylsalicylique (AAS), de clopidogrel et de warfarine, pour les patients atteints de fibrillation auriculaire non valvulaire qui ont subi l'implantation d'une endoprothèse par intervention coronarienne percutanée. Le choix de traitement par anticoagulant ou antiplaquettaire pour cette population est ambigu et complexe. De plus, les habitudes de prescription ne sont pas bien documentées. OBJECTIF: Offrir un portrait des habitudes locales de prescription de traitements par anticoagulant ou antiplaquettaire suite à une intervention coronarienne percutanée chez les patients atteints de fibrillation auriculaire non valvulaire. MÉTHODES: Une analyse des dossiers médicaux a été menée dans un seul centre quaternaire de cardiologie. Les patients atteints de fibrillation auriculaire non valvulaire ont été identifiés à l'aide de leurs dossiers médicaux. Ceux qui avaient subi une intervention coronarienne percutanée ont été trouvés en consultant un registre local de patients. Les patients adultes hospitalisés qui souffraient d'une fibrillation auriculaire non valvulaire, qui présentaient un score CHADS2 de 1 ou plus (calculé en fonction de la présence d'insuffisance cardiaque congestive, d'hypertension, d'âge égal ou supérieur à 75 ans, de diabète et d'accident vasculaire cérébral antérieur) et qui avaient subi une intervention coronarienne percutanée entre 2011 et 2013 ont été admis. Les patients qui avaient subi une chirurgie cardiovasculaire ou un remplacement valvulaire aortique par cathéter, ceux dotés de prothèses mécaniques nécessitant une anticoagulothérapie et ceux allergiques à un ou plusieurs éléments de la trithérapie antithrombotique ont été exclus. RÉSULTATS: L'âge médian des 70 patients admis était de 75 ans et 52 d'entre eux étaient des hommes. Au moment du congé, 30 (43 %) recevaient une trithérapie antithrombotique et 27 (39 %) recevaient une bithérapie antiplaquettaire (AAS et clopidogrel). Aucun patient n'a reçu une association de warfarine et de clopidogrel. Parmi ceux qui ont reçu une trithérapie antithrombotique, la durée recommandée du traitement était d'un mois pour 90 % (19 sur 21) de ceux qui ont reçu une endoprothèse métallique nue et d'un an pour 75 % (6 sur 8) de ceux qui ont reçu une endoprothèse à élution de médicaments. On a prescrit pour 9 % (6 sur 70) des patients un anticoagulant oral direct accompagné de deux antiplaquettaires. De plus, 10 % (7 sur 70) des patients ont reçu du ticagrelor et de l'AAS avec ou sans warfarine. Dans l'ensemble, la combinaison d'AAS, d'un anticoagulant oral et d'un inhibiteur du P2Y12 a été employée chez 54 % (38 sur 70) des patients. CONCLUSIONS: Moins de la moitié des patients de la présente étude ont reçu une trithérapie antithrombotique et près de 20 % ont reçu un traitement non fondé sur des données probantes composé d'un anticoagulant oral direct ou de ticagrelor, employés seuls ou en association. Malgré les recommandations des lignes directrices actuelles, le taux de recours à la trithérapie antithrombotique était plus faible que les pourcentages présentés dans la littérature.