Therapeutic International Normalized Ratio Range Research Articles

Novel Oral Anticoagulants in Patients with Continuous Flow Left Ventricular Assist Devices

Purpose The gold standard for anticoagulation in patients with continuous flow left ventricular assist device (CF-LVADs) is warfarin. However, many patients fail warfarin therapy due to thromboembolic and bleeding events. Warfarin requires regular monitoring and dosage adjustments, and is associated with significant patient time outside recommended therapeutic INR range. Novel oral anticoagulation (NOAC) has been shown to be non-inferior compared to warfarin in stroke prevention with less intracranial hemorrhage in patients with atrial fibrillation. In this study, we sought to evaluate the safety and efficacy of NOACs in patients with CF-LVADs after failed warfarin therapy. Methods Patients who underwent CF-LVAD insertion between 2008 and 2018 were identified in a single-center database. 7 patients with either HeartMate II or HeartWare were switched from warfarin to a NOAC, either apixaban or rivaroxaban, were included. Occurrence of stroke, non-CNS embolism, pump thrombosis, and major GI bleeding or intracranial hemorrhage on warfarin and NOAC were evaluated. Results 5 of 7 patients were male, with an average BMI of 30. Common comorbidities were hypertension (100%), diabetes mellitus (57%) and ischemic cardiomyopathy (57%). There were a total of 3968 patient days on warfarin and 1459 patient days on a NOAC. Patients on warfarin therapy spent an average time of 30% within a therapeutic INR range. The rates of complications under warfarin versus NOAC therapy were: strokes 0.019 vs. 0 /patient-year, non-CNS embolism 0.019 vs. 0 /patient-year, pump thrombosis 0.01 vs. 0 /patient-year, major GI bleeding 0.02 vs. 0.07 /patient-year, and intracranial hemorrhage 0.019 vs. 0 /patient-year.(Table 1). Conclusion Increased complication rates and poor time in therapeutic INR range were present in patients receiving warfarin therapy after CF-LVAD insertion. NOAC therapy with apixaban or rivaroxaban may be a viable alternative. However, large prospective studies are necessary to confirm these results.

Anticoagulation quality and clinical outcomes in multimorbid elderly patients with acute venous thromboembolism

BackgroundMultimorbid patients with acute venous thromboembolism (VTE) are often excluded from clinical trials and little is known about their prognosis. ObjectivesTo examine whether multimorbidity is associated with adverse clinical outcomes and lower anticoagulation quality in older patients with VTE. Patients/MethodsWe studied 991 patients aged ≥65 years with acute VTE in a Swiss prospective multicenter cohort study. A modified Charlson Comorbidity Index was used to measure multimorbidity, which was defined as the presence ≥2 of 17 predefined comorbid conditions. We examined the association between multimorbidity and recurrent VTE and major bleeding, adjusting for confounders and periods of anticoagulation. We assessed whether the percentage of time spent in the therapeutic international normalized ratio (INR) range varied by the number of comorbidities present. ResultsOverall, 708 (71%) patients were multimorbid. Multimorbid patients had a higher 3-year cumulative incidence of recurrent VTE (16.8 vs. 10.8%; P = 0.056) and major bleeding (18.7 vs. 9.0%; P = 0.001) than non-multimorbid patients. After adjustment, multimorbid patients had a significantly higher risk of recurrent VTE (sub-hazard ratio [SHR] 1.66, 95% confidence interval [CI] 1.08–2.57) and a higher risk of major bleeding (SHR 1.55, 95% CI 0.96–2.50), although the latter failed to achieve statistical significance. With increasing numbers of comorbid conditions, patients spent less time in and more time above and below the therapeutic INR range. ConclusionsMultimorbid patients with acute VTE have not only a lower anticoagulation quality but also more complications. Clinical trials should explicitly enroll multimorbid patients to determine the optimal anticoagulation strategy in such patients.

Factors associated with time in therapeutic range among patients on oral anticoagulation therapy in a tertiary teaching and referral hospital in Kenya

Oral anticoagulation with warfarin is challenging owing to the drug’s narrow therapeutic index. Achievement of therapeutic range ensures safety and efficacy of warfarin therapy. A retrospective study of four hundred and six patients on warfarin anticoagulation was conducted at Kenyatta National Hospital, Kenya for the period between January 2014 and June 2016. The percentage of follow-up time spent in therapeutic international normalized ratio range was computed by Rosendaal linear interpolation method. Factors associated with this time were also explored. The mean age of the participants was 42.7±16.9 years and the ratio of females to males was 3:1. The mean percentage of time spent in therapeutic international normalized ratio range was 31.1%. Poor anticoagulation control was associated with congestive heart failure (p=0.047) and the independent predictor of time in therapeutic range was renal dysfunction (β= -13.3, 95% CI: -25.9, -0.8, p=0.038) suggesting that management of these patients needs to be intensified. Keywords: Warfarin, time in therapeutic range, oral anticoagulation

Triple therapy after PCI - Warfarin treatment quality and bleeding risk.

BackgroundA combination of warfarin, aspirin and clopidogrel is indicated after percutaneous coronary intervention (PCI) in some patients, despite the higher risk of bleeding inferred by this triple therapy.ObjectivesWhether the treatment quality of warfarin measured by iTTR (individual time within therapeutic INR range) is associated with bleeding complications during triple therapy after PCI.MethodsA retrospective register study consisting of 601 triple treated PCI patients from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). The cohort was cross-matched with the Swedish Patient Registry for background characteristics and bleeding complications up to 6 months after PCI using ICD10 codes, the Prescribed Drug Registry for ongoing medications, and the national oral anticoagulation registry Auricula for warfarin treatment quality. The patients were grouped into four iTTR groups: <50%, 50–69.9%, 70–84.9% and >85% as well as iTTR above or below 70%.ResultsOf 601 patients, 39 (6.5%) had a bleeding complication (type 2 according to BARC). Bleeding was more common for iTTR<70% compared to iTTR>70%, 28 (9.3%) vs. 11 (3.7%) (p = 0.005). The bleeding frequency increased gradually from the best group, iTTR>85% with four bleeders (3.3%) up to 17 bleeders (13.3%) in the worst group with iTTR<50% (p = 0.003), with a corresponding bleeding rate per 100 treatment years of 8.0 and 44.9, respectively. In multivariate analysis low BMI, HR 1.11 (95% CI 1.01–1.22), a medical history of anemia HR 3.17 (1.16–8.69) and iTTR < 70% HR 2.86 (1.25–6.53) increased the risk of bleeding.ConclusionTriple therapy after PCI confers a high risk of bleeding events. Warfarin treatment quality measured by iTTR as well as a medical history of anemia are strong independent predictors of bleeding in these patients. Physicians should pay more attention to iTTR after PCI.

Association between insurance status, anticoagulation quality, and clinical outcomes in patients with acute venous thromboembolism

IntroductionA higher level of health insurance coverage may be related to better quality of care and outcomes. Whether insurance status is associated with anticoagulation quality and clinical outcomes in patients with venous thromboembolism (VTE) is unknown. MethodsWe studied 819 elderly patients treated with vitamin K antagonists for VTE in a Swiss prospective multicenter cohort (09/2009–12/2013). The study outcomes were the anticoagulation quality, defined as the time spent in the therapeutic INR range, and clinical events, i.e. the time to a first VTE recurrence, major bleeding, and mortality. We assessed the association between insurance status (private vs. general), anticoagulation quality, and clinical outcomes using regression models, adjusting for potential confounders. ResultsAlthough the unadjusted mean percentage of time spent in the therapeutic INR range (2.0–3.0) was slightly higher in patients with private vs. general insurance (65% vs. 61%; p = 0.030), the adjusted difference was not statistically significant (1.53%, 95% CI −1.97 to 5.04). Patients with private insurance had a lower 36-month cumulative incidence of major bleeding (9.7% vs. 15.7%; p = 0.018). After adjustment, privately insured patients had a lower risk of major bleeding compared to patients with general insurance (sub-hazard ratio 0.57, 95% CI 0.32 to 0.98). Insurance status was not associated with recurrent VTE or mortality. ConclusionPrivately insured patients spent somewhat more time in therapeutic INR range and had a lower rate of major bleeding than generally insured patients. Basic (general) health insurance may be a marker of lower anticoagulation quality and higher risk of major bleeding.

Risk factors for ischemic stroke in patients with non-valvular atrial fibrillation and therapeutic international normalized ratio range.

IntroductionAtrial fibrillation (AF) is the most common cause of ischemic stroke (IS). Atrial fibrillation patients are recommended to use oral anticoagulants (OACs) as part of prevention against IS. However, despite having a therapeutic intensity of OAC therapy, IS can still occur in such patients. The aim of our study was to examine the configuration of IS risk factors in patients with non-valvular atrial fibrillation (NVAF) and within the therapeutic INR range (TINR).Material and methodsOur retrospective study involved 1835 patients with a recent IS. The experimental group consisted of 154 patients with acute IS, NVAF and TINR. The control group consisted of 1681 patients with acute IS but without AF.ResultsPatients with IS, NVAF and TINR were significantly older and more often female than patients with IS without NVAF (p < 0.001 and p < 0.001, respectively). In these patients, diabetes mellitus, dyslipidemia, hypertension, coronary heart disease, smoking and previous IS were significantly more frequent than in the patients with IS without NVAF (p = 0.036, p = 0.002, p < 0.001, p < 0.001, p < 0.001, p = 0.003). Based on a univariable and multivariable logistic regression model, we found that in the group of patients who suffered a stroke despite TINR compared to patients with IS without AF there were more smokers (OR = 20.337; OR = 147.589) and patients with previous stroke (OR = 6.556; OR = 11.094), hypertension (OR = 3.75; OR = 2.75) and dyslipidemia (OR = 2.318; OR = 2.294).ConclusionsThe group of patients with NVAF and TINR is significantly more burdened by other independent common risk factors for stroke.

Individual and monitoring centre influences upon anticoagulation control of AF patients on warfarin: A longitudinal multi-centre UK-based study.

Time within therapeutic INR range (TTR) predicts benefits/risk of warfarin therapy. Identification of individual- and centre-related factors that influence TTR, and addressing them to improve anticoagulation control, are important. This study examined the impact of individual and centre-related factors uponlong-term anticoagulation control in atrial fibrillation patients in seven UK-based monitoring services. Data between 2000 and 2014 on 25270 patients (equating to 203220patient years) [18120 (71.7%) in general practice, 2348 (9.3%) in hospital-based clinics and 4802 (19.0%) in domiciliary service] were analysed. TTR increased with increasing age, peaking around 77% at 70-75years, and then declined, was lower in females than males, and in dependent home-monitored patients than those attending clinic (P<0.0001). TTR, number of dose changes and INR monitoring events and the probability of TTR ≤ 65%, differed across the centres (P<0.0001). Although all the participating centres ostensively followed a standard dosing algorithm, our results indicate that variations in practice do occur between different monitoring sites. We suggest feedback on TTR for individual monitoring sites gauged against the average values reported by others would empower the individual centres to improve quality outcomes of anticoagulation therapy by identifying and adjusting contributory factors within their management system.

Premature Myocardial Infarction as the Presenting Sign of Hypercoagulable Syndrome

Introduction Premature myocardial infarction (MI) in a young patient proves to be a challenge to manage. In the absence of family history or provoking factors, etiology can be difficult to determine. Hypercoagulable syndromes should be considered as an etiology for premature MI, as future management may be influenced by the presence of these syndromes. We report the case of a young heart-kidney transplant recipient presenting with multiple thrombotic events including premature MI, LVAD thrombosis, and deep vein thrombosis (DVT) in the setting of May-Thurner Syndrome (MTS) exemplifying the importance of thorough hypercoagulability testing. Case Report Our patient is a 41-year-old male with a history of MI at age 37, resulting in ischemic cardiomyopathy complicated by cardiogenic shock requiring LVAD placement for bridge to transplant. Patient's post LVAD course was complicated by recurrent LVAD thrombosis despite adequate anticoagulation (AC) requiring two device exchanges. Hypercoagulability testing was limited due to the necessity of chronic AC. One month after undergoing heart-kidney transplant, patient presented with left lower extremity (LLE) pain and difficulty ambulating with duplex ultrasound showing DVT of LLE extending from the L common iliac vein to the L popliteal vein, requiring thrombectomy. Venography identified narrowing of the L common iliac vein confirming the diagnosis of MTS and an iliac vein stent was placed. Repeat hypercoagulability testing revealed an elevated factor VIII (FVIII) activity level to 319% of normal, warranting long-term AC with an elevated therapeutic INR range and high dose aspirin. Patient has had no recurrent thrombosis since starting this regimen. Summary Patients with multiple thrombotic events should undergo thorough hypercoagulability testing to identify risk for future thromboses and need for AC. Traditionally, elevated FVIII levels are thought to be an acute phase reactant, not necessitating AC. However, it has recently been shown that patients with an elevated FVIII level are at significant risk for thrombosis and require long-term AC. Our case highlights the importance of early FVIII level testing in hypercoagulability evaluation.

Warfarin Dosing According to the Genotype-guided Algorithm is Most Beneficial in Patients With Atrial Fibrillation: A Randomized Parallel Group Trial

Observational studies have indicated potential benefits of CYP2C9- and VKORC1-guided dosing of warfarin but randomized clinical trials have resulted in contradictory findings. One of the reasons for contradiction may be the negligence of possible differences between warfarin indications. This study aims to determine efficacy and safety of genotype-guided and clinically guided dosing of warfarin in atrial fibrillation (AF), deep-vein thrombosis (DVT), and pulmonary embolism (PE) within the first 5 days after the introduction of therapy. In this single-center, single-blinded, randomized, controlled trial including patients of both sexes, ≥18 years of age, and diagnosed with AF, DVT, or PE, a total of 205 consecutive patients were allocated into the group where warfarin therapy was genotype-guided pharmacogenetics guided (PHG), and where it was adjusted according to the clinical parameters non pharmacogenetics guided (NPHG). Genotyping of CYP2C9*2, *3, and VKORC1 was performed using the real-time polymerase chain reaction method. The primary outcomes were the percentage of time in the therapeutic international normalized ratio (INR) (2.0-3.0) range and the percentage of patients who achieved a stable anticoagulation defined as the INR (2.0-3.0) range in at least 2 consecutive measurements. In patients with AF, the percentage of time spent in the therapeutic range of INR was higher in the PHG group [mean = 26% (SD 25.0)] than in the NPHG group [mean = 14% (SD 18.6)], [Δ = 12; 95% confidence interval, 0-23; P = 0.040]. There was no significant difference in other 2 indications for warfarin treatment. A stable dose of warfarin was achieved in a statistically higher number of patients in the PHG group 14/30 (47%) than in the NPHG group 7/32 (22%) (odds ratio = 3.13, 95% confidence interval, 0.92-10.98; P = 0.039). CYP2C9 and VKORC1 genotype-guided dosing of warfarin may be beneficial in patients diagnosed with AF. There is no evidence for such conclusion in patients with DVT and PE.

The Influence of CYP4F2 Polymorphisms on Warfarin Doses in Korean Patients with a Variety of Diseases

Purpose We sought to determine if the CYP4F2 gene could affect warfarin maintenance dosage in Korean patients with a variety of diseases. CYP4F2 was reported to affect warfarin dose, but it was controversial. Some papers showed that CYP4F2 genotype could affect warfarin stable dose to some extent. But other papers reported that CYP4F2 genotype did not affect warfarin dose. Methods We enrolled 101 patients treated with warfarin in our registry. Non-genetic factors (clinical characteristics, stable warfarin dose, INR, medication information) and CYP4F2 polymorphisms were assessed. The definition of warfarin stable dose was the amount of medication given to maintain the patient’s INR within the target range throughout at least 3 consecutive laboratory measurements separated by at least 1 week. Each patient’s target therapeutic INR range was determined by the clinicians according to the indication for warfarin treatment. Results In our study, average patient age was 64.0± 11.9 years. Females accounted for 52% of the sample. The average warfarin maintenance dose was 3.26± 1.38 (1-9) mg/day. Compared with CYP4F2 wild type patients (GG), the patients carrying a CYP4F2 heterozygous variant (GA) or a CYP4F2 homozygous variant (AA) required higher warfarin dose. The mean warfarin dose in the patients with the CYP4F2 AA genotype was 4.1± 1.9 mg/day, while that for the patients with the CYP4F2 GA genotype was 3.3± 1.3 mg/day, and that for the patients with the CYP4F2 GG genotype was 3.0± 1.2 mg/day. The difference among them was significant (P= 0.038). Conclusion CYP4F2 polymorphisms statistically influenced the stability of warfarin maintenance dosage in Korean patients with a variety of diseases. Keywords: CYP4F2 polymorphisms, Warfarin dose, Korean

The Role of Clinical Variables and VKORC1 Polymorphism in Efficacy and Stability of Acenocoumarol in Neurological Patients.

Objective:To analyze the clinical importance of VKORC1 polymorphism and its correlation with stability of oral anticoagulation.Patients and Methods:In a hospital-based study, the patients on oral anticoagulant (OAC) were included during 2013–2016. The patients received OAC for cardioembolic stroke, cerebral venous sinus thrombosis (CVST), and prevention of deep vein thrombosis (DVT). Demographic, clinical, and neurological findings were recorded. Stability of anticoagulation was determined by percentage of time international normalized ratio (INR) values were in therapeutic range. Time in therapeutic range (TTR) >65% was defined as stable and <65% was defined unstable. VKORC 1 polymorphism was studied by polymerase chain reaction and correlated with daily dose of OAC and stability of INR.Results:A total of 157 patients with a median age of 40 years were included in the study. Ninety-two patients received OAC for secondary stroke prevention, 62 for CVST, and 3 for DVT. Out of 2976 INR reports, 1458 (49%) were in the therapeutic range, 997 (33.1%) were below the therapeutic range, and 521 (17.5%) were above the therapeutic level. Stable INR was obtained in 75 (47.77%) patients which was improved by drug modification in 3 and dietary adjustment in 12 patients. VKORC1 polymorphism revealed GG genotype in 127 (80.9%), GA genotype in 22 (14%), and AA genotype in 8 (5.1%) patients. Therapeutic range of INR was seen in 49%, below therapeutic range was seen in 31.5%, and above in 17.5%.Conclusion:VKORC1 polymorphism was related to mean daily dose of OAC but not to the stability of INR.

BRIDGING THERAPY RESULTS IN PATIENTS WITH ACUTE CALCULOUS CHOLECYSTITIS AND CONCOMITANT ISCHEMIC HEART DISEASE

Introduction. Binding or bridging therapy (BT) suggests long-term administration of short acting anticoagulants (unfractionated heparin – UFH or low-molecular-weight heparin – LMWH) during preoperative preparation and early postoperative period in patients who had been receiving anticoagulation therapy (ACT) or anti-aggregation therapy (AAT) for a long time before surgery. The generalized data on the BT technique for urgent surgical interventions, particularly, in patients with acute calculous cholecystitis (ACH) and concomitant ischemic heart disease (IHD), is currently lacking. The aim of the work – to improve the BT technique in patients with ACH and IHD and to evaluate the results of its application.&#x0D; Materials and methods. The study included 73 patients– 33 (45,2 %) women and 40 (54,8 %) men aged 57 to 81 years, on average 71,4 ± 0,7 years, who had received ACT or AAT before the hospitalization. All patients were admitted to hospital within 72 hours (from 6 to 65 hours) from the onset of the disease, on average 27.3 ± 1.5 hours. The catarrhal ACH occurred in 27 (37,0%) patients, phlegmonous – in 21 (28,8 %) patients, gangrenous – in 25 (34,2 %) patients. According to Tokyo Guidelines for the management of acute cholangitis and cholecystitis (TG13), 19 (26.0 %) patients had ACH I degree, 31 (42.5 %) patients– ACH II degree, 23 (31.5 %) patients – ACH III degree. There were 3 (4.1 %) patients with NYHA class I heart failure, 39 (53.4 %) patients with NYHA class II heart failure, 26 (35.6 %) patients with NYHA class III heart failure, and 5 (6.8 %) patients with NYHA class IV heart failure. The advanced tactics of bridging therapy was applied, which depended on several factors such as INR, aPTT, creatinine clearance, Lee-White’s bleeding time. The target points were the frequency of INR or bleeding time therapeutic range achieving, and the frequency of hemorrhagic complications.&#x0D; Results and discussion. Immediately before surgery (laparoscopic cholecystectomy), the target (therapeutic) INR range &gt;2 was obtained in 18 (90 %) patients among 20 patients who had previously received warfarin. Among them 2 (10.0 %) patients had INR in the range of 1.3-2.0, 12 (60.0%) patients had INR in the range of 2.1-3.0, and 6 (30.0 %) had INR &gt;3.1. The target value of bleeding time &gt;12 min was in 48 (90.6 %) patients among the patients (53 patients) who had received AAT earlier. The values of bleeding time in the range of 10-12 min were in 5 (9.4 %) patients, 12.1-14 min –in 42 (79.2 %) patients, &gt;14 min – in 6 (11.3 %) patients. In general, INR and bleeding time values were within the therapeutic window in 65 (90.3 %) patients, and there was no patient with signs of hypercoagulation. In the postoperative period, the dynamics of INR and bleeding time values were similar and figured out at increase in the part of patients with INR 2.1-3.0 and bleeding time 12.1-14 min respectively.

Should We Always Perform TEE Before Direct Current Cardioversion?

Spontaneous or intended conversion of atrial fibrillation (AF) to sinus rhythm is associated with a short-term increase from baseline risk of clinical thromboembolism. Guidelines suggest performing cardioversion without prior execution of trans esophageal echo (TEE) if the patient has completed a month of anticoagulation with warfarin (in the therapeutic international normalized ratio range) or non-vitamin K antagonist oral anticoagulants (NOACs).

Use of neutrophil-lymphocyte ratio for risk stratification and relationship with time in therapeutic range in patients with nonvalvular atrial fibrillation: A pilot study.

Atrial fibrillation is one of the most common abnormal heart rhythms. Neutrophil-lymphocyte ratio (NLR) has emerged as a potential marker for the level of inflammation in cardiac disorders. NLR might be associated with thrombosis and bleeding risk scores and might predict cardioembolic risk in nonvalvular atrial fibrillation (NVAF) patients within the therapeutic international normalized ratio (INR). We enrolled 272 patients taking warfarin for NVAF and classified them into 2 groups: Group A consisted of patients (n = 132) whose time in therapeutic range (TTR) was ≥65%, and Group B comprised patients (n = 139) whose TTR was <65%. NLR values were higher in group B than in group A (P < 0.0001). Patients classified as high risk according to CHA2 DS2 -VASc score had significantly higher NLR levels (P = 0.002) than those classified as low and intermediate risk. Furthermore, NLR levels were significantly correlated with CHA2 DS2 -VASc and HAS-BLED scores (P < 0.001 and P < 0.0001, respectively). NLR predicted patients within therapeutic INR range (TTR ≥65%) with sensitivity of 81% and specificity of 71% in a receiver operator characteristic curve analysis, using a cutoff value of 2.17. Area under the curve for NLR was 0.81 (P < 0.0001). To our knowledge, this is the first study showing correlation of NLR with both CHA2 DS2 -VASc and HAS-BLED risk scores. NLR might represent a useful marker to identify patients with high risks of stroke and bleeding and may have predictive value in identifying patients within the therapeutic INR range.

Oral anticoagulation cost in primary antiphospholipid syndrome: comparison between warfarin and hypothetical rivaroxaban.

: The objective of the study is to perform a cost comparison of 1 year of oral anticoagulation management with warfarin vs. hypothetical rivaroxaban (RRX) in thrombotic primary antiphospholipid syndrome. Longitudinal study on 20 primary antiphospholipid syndrome patients followed-up for 1 year after anticoagulation stabilisation with warfarin: a dedicated software calculated number of clinic visits, time in therapeutic range and warfarin consumption for each patient; for RRX, we considered a visit every 3 months (baseline done in hospital before attending anticoagulant clinic); knowing the cost of both anticoagulants, the laboratory cost and the human cost we calculated and compared the yearly expenditure. Average time in therapeutic international normalized ratio range was 69 ± 11%: warfarin management required a total of 375 of visits compared with the 60 for RRX; the yearly cost of RRX was superior to that of warfarin (12 012 vs. 446.4 euros, P < 0.0001), and in spite of lower laboratory (738 vs. 1853 euros, P < 0.0001) and human costs (774.6 vs. 4841 euros), RRX thromboprophylaxis still yielded a hefty bill (13 525 vs. 7140 euros, P < 0.0001). Switching from warfarin to RRX will be 48% more expensive to our Healthcare Authority; unless ongoing clinical trials demonstrate improved long-term outcomes for RRX over warfarin, we feel that a 69% time in therapeutic range does not warrant a change to RRX at a 48% increased cost.

Anticoagulation therapy: patients attitude, knowledge, and concerns regarding their effects on the international normalized ratio (INR) in Saudi Arabia

Introduction: Thoughtful evaluation of patients’ knowledge, satisfaction, and concerns in Anticoagulation clinics will help to understand areas of improvement. Our study aimed to examine patients’ drug knowledge, satisfaction and concerns with provided anticoagulation services. Patients and Methods: We designed our study as a cross-sectional survey that was developed and conducted in a regional anticoagulation clinic with good number of patients. Two hundred sixty eight were recruited in the survey. Patients’ warfarin refill records and time within the therapeutic INR range were retrieved from hospital databases. Results: Adequate knowledge of warfarin-food and warfarin-drug interactions was lacking in about 50% of patients. Satisfaction with provided service was not optimal, Concerns associated with warfarin was bothersome to many patients due to possible drug-drug interactions (41.42%), missed doses impact (29.10%), adverse drug reactions (29.85%). All of which might lead to unfavorable consequences. Higher satisfaction was associated with better knowledge (r=0.27, p=0.001) and fewer concerns (rs=-0.26, p=0.002). Improved drug related knowledge and higher satisfaction were positively reflected in these patients’ attitude toward drug use compliance in knowledge (rs=0.23, p=0.01) and satisfaction (rs=0.19, p=0.041). Eventually, good INR control was shown more with better knowledge, higher satisfaction, and better warfarin adherence (p=0.004, 0.03, 0.04 and 0.004, respectively). Conclusion: There is a deficit in patients’ knowledge and satisfaction with warfarin therapy. Such deficits lifted the threshold of concerns with warfarin use and negatively affected INR control.

Characteristics and quality of oral anticoagulation treatment in pediatric patients in the Netherlands based on the CAPS cohort

Background The use of vitamin-K antagonists in pediatric patients is rare and information on the quality and safety of treatment with acenocoumarol and phenprocoumon is limited. Objectives To assess the quality, safety and effectiveness during the first year of acenocoumarol and phenprocoumon treatment in pediatric patients in the Netherlands. Methods The Children Anticoagulation and Pharmacogenetics Study (CAPS) was designed as a multicenter retrospective follow-up study. Patients who used acenocoumarol or phenprocoumon at an age of ≤ 18 years, were selected from four pediatric hospitals and one anticoagulation clinic in the Netherlands. The quality of treatment was assessed by calculating the percentage of time in therapeutic INR range (TTR) for the first month and for every 3 months of use during the first year of treatment. Effectiveness and safety were assessed by the number of thromboembolic and bleeding events. Results In total, 213 patients participated, of whom 187 (155 acenocoumarol; 32 phenprocoumon) were included in this analysis. The mean TTR was 47.0% and 51.4% in the first month of use for acenocoumarol and phenprocoumon, respectively. After the first 3 months the mean TTR for both VKAs was above 64%. In 14.6% (acenocoumarol) and 31.3% (phenprocoumon) of the patients a bleeding event occurred during the first year of treatment; no thromboembolic events were reported. Conclusions The quality of anticoagulation treatment was low during the first month of use and leaves room for improvement. After the first month it increased to an acceptable level. However, bleeding events occurred frequently during the first year.

Compare the clinical management of warfarin among physician versus pharmacist-led coagulation clinic: structured systematic review

The aim of the study was to assess the management of INR therapeutic range as an estimate for achieving therapeutic outcome and estimate sub/supra-therapeutic INR's among physician versus pharmacist-led clinics. Articles were searched in: PubMed, Cochrane, Springer, Science Direct, and Wiley. The search was limited to the English language from 2010 to 2016. The inclusion criteria of the articles keywords such as warfarin, management, pharmacist, physician, therapy, clinic, and anticoagulation were used and GRACE guideline was used to assess the quality of these research articles. A total of 1050 articles were found with the relative subject, after excluding the duplicates more than 50% have been excluded, following the title and reviewing the abstract another 133 (12.67%) were ruled out, and 6 studies were included in the systematic review. In multiple studies pharmacist-Led coagulant clinic showed better outcomes with warfarin anticoagulant therapy. Patients exhibits high satisfaction levels and least warfarin induced complications in comparison with those results obtained with physician-led clinic. It is found that patients-oriented care has not been reported in the retrieved literature, which might open a room for researcher to determine the impact of services provided by pharmacists on individual patient-centered outcomes.

Effect of Standardized Warfarin Treatment Protocol on Anticoagulant Effect: Comparison of a Warfarin Medication Therapy Adherence Clinic with Usual Medical Care.

Objective: To evaluate the impact of pharmacist-led warfarin management and standardized treatment protocol.Methods: A retrospective cohort study was carried out in a cardiology referral hospital located in central Kuala Lumpur, Malaysia, from 2009 to 2014. The inclusion criteria were: adult patients who were diagnosed and treated for atrial fibrillation (AF) with warfarin, attended the warfarin medication therapy adherence clinic (WMTAC) for at least 12 weeks, and with at least four international normalized ratio (INR) readings. The electronic medical records were reviewed for demographics, type of AF, warfarin dose, INRs, adverse events, co-morbidities, and drug–drug interactions. The outcome measures included the mean time to therapeutic INR, the mean percentage of time in therapeutic range (TTR), bleeding events, and common drug interactions.Results: Out of 473 patients, 151 patients fulfilled the inclusion criteria. The findings revealed that there were significant associations between the usual medical care (UMC) group and pharmacist-led WMTAC in terms of TTR (p = 0.01) and INR (p = 0.02) levels. A positive impact of pharmacists’ involvement in the WMTAC clinic was where the “pharmacist’s recommendation accepted” (p = 0.01) and “expanded therapeutic INR range” (p = 0.04) were statistically significantly higher in the WMTAC group.Conclusion: There was a significant positive association between the pharmacist-led WMTAC and anticoagulation effect (therapeutic TTR, INR). The identified findings revealed that expanded role of pharmacist in pharmacist-managed warfarin therapy is beneficial to optimize the warfarin therapy. This study also highlighted the critical roles that pharmacists can actively play to ensure optimal anticoagulation pharmaceutical care.Key messages:What is already known on this subject?• Pharmacist-managed warfarin therapy is beneficial for optimizing warfarin therapy. In such therapy, recommendations such as dose adjustment and safer alternative drugs (given drug–drug interactions and/or food–drug interactions) are made.• The active involvement of pharmacists in warfarin adherence clinics could significantly improve adherence.• However, the warfarin treatment outcomes from UMC, pharmacist-and-physician-led care and pharmacist-led care have not been studied.• The impact of the implementation of the standardized protocol for the warfarin adherence clinic has not been assessed.What this study adds?• INR levels among UMC group and WMTAC group were significantly different.• Though the TTR level for the WMTAC group was not significantly different than the UMC group, it was higher and close to the targeted 60% level.• The identified findings show that pharmacists’ focus on intervention for missed doses, adherence and dose adjustment provide positive impact on patients’ warfarin therapy.

Renal function in patients receiving long-term warfarin therapy: A five-year prospective follow-up

To investigate the prognostic value of renal function and to estimate glomerular filtration rate (GFR) changes during a 5-year follow-up of patients receiving warfarin therapy. 200 patients (124 men, 76 women) mainly from a group at high risk for thromboembolic events (mean CHA2DS2-VASc scores, 3.25±1.89) were examined. The patients' mean age was 62.3±9.4 years; the follow-up period was 5 years. 74% of the patients received warfarin monotherapy (international normalized ratio (INR) 2.0 to 3.0); 36% took vitamin K antagonists in combination with one or two antiplatelet agents. The CKD-EPI formula was used to estimate GFR in all the patients at baseline and throughout the investigation once a year. GFR less than 70.9 ml/min/1.73 m2 was found to be a predictor of fatal and nonfatal thrombotic events. The decreased GFR was unassociated with the development of major and clinically relevant hemorrhagic complications within 5 years of warfarin therapy. The initial decline in renal function (GFR <70.9 ml/min/1.73 m2) was associated only with an increased rate of recurrent minor hemorrhagic complications. During 5-year warfarin therapy, there was a significant decrease in GFR from 97.1±24.85 to 91.9±28.9 ml/min/1.73 m2; at the same time, a rapidly progressive loss of renal function (GFR ≥3 ml/min/1.73 m2/year) was recorded in 25.9% of the patients. Discriminant analysis showed that a baseline left ventricular ejection fraction of <40% was a predictor for the rapidly progressive loss of kidney function. Long-term warfarin therapy achieved the therapeutic range for INR is safe in the environment of the created patronage system. The initial decrease in GFR is a predictor of thrombotic events and is unassociated with an increased risk of bleeding.