METHODS: We searched PubMed, EMBASE and Cochrane library from inception to Feb 24th, 2017, to identify systematic reviews and meta-analyses of randomized controlled trials that assessed interventions or strategies to improve oral anticoagulant use in AF patients.
RESULTS: Thirty-four systematic reviews were eligible for inclusion but only 11 were included in the qualitative analyses, corresponding to 40 unique meta-analyses, as the remaining systematic reviews had overlapping primary studies. There was insufficient evidence to support the efficacy of genotype-guided dosing and pharmacist-managed anticoagulation clinics for stroke prevention in AF patients. Conversely, patient's self-management and novel oral anticoagulants (NOACs), in general were superior to warfarin for preventing stroke and reducing mortality. All interventions showed comparable risk of major bleeding with warfarin.
CONCLUSION: Findings from this overview support the superiority of NOACs and patient's self-management for preventing stroke in AF patients. However, uncertainties remain on the benefits of genotype-guided dosing and pharmacist-managed anticoagulation clinics due to poor quality evidence, and future research is warranted.
AREAS COVERED: A review of articles that evaluated the cost of prescribing conventional (e.g. vitamin K antagonists) and NOACs (e.g. direct thrombin inhibitors and direct factor Xa inhibitors) in older adults.
EXPERT COMMENTARY: While the use of NOACs significantly increases the cost of the initial treatment for thromboembolic disorders, they are still considered cost-effective relative to warfarin since they offer reduced risk of intracranial haemorrhagic events. The optimum anticoagulation with warfarin can be achieved by providing specialised care; clinics managed by pharmacists have been shown to be cost-effective relative to usual care. There are suggestions that genotyping the CYP2C9 and VKORC1 genes is useful for determining a more appropriate initial dose and thereby increasing the effectiveness and safety of warfarin.
METHODS: In this non-interventional study involving 49 sites across five countries in Southeast Asia and South Korea, 379 stable NVAF patients who switched from VKA therapy to dabigatran during routine clinical practice were recruited and followed up for 6 months. Treatment convenience and satisfaction were evaluated using Perception on Anticoagulant Treatment Questionnaire-2 (PACT-Q2). Through post hoc analysis, factors associated with improved treatment convenience scores at visit 2 were described.
RESULTS: Treatment convenience and satisfaction significantly improved after switching from VKAs to dabigatran at visit 2 and visit 3 (convenience: p<0.001 each vs baseline; satisfaction: p=0.0174 (visit 2), p=0.0004 (visit 3) compared with baseline). Factors predictive of higher (>80th percentile) response on treatment convenience were female sex, younger age (<75 years), higher baseline stroke risk, higher creatinine clearance and absence of concomitant hypertension, stroke or gastrointestinal diseases.
CONCLUSION: Dabigatran was associated with a significant improvement in treatment convenience and satisfaction after switching from VKAs when used for stroke prevention in NVAF patients from Southeast Asia and South Korea.
METHODS: This was a randomized control, open-label trial. Women underwent major gynecological surgery were randomized to receive either subcutaneous 50 mg of Na-PPS twice daily or subcutaneous enoxaparin 40 mg once daily. Fondaparinux 2.5 mg once daily was given to Muslim women as an alternative to enoxaparin. The treatment was started 6 h postoperatively, for at least 3 days. All the patients received thromboembolic deterrent stockings. The primary efficacy outcome was venous thromboembolism up to 3 days postsurgery. The main safety outcomes were minor and major bleeding.
RESULTS: Among 109 participants, there was no incidence of venous thromboembolism. None of the women developed major bleeding. Minor bleeding was observed in 28.3% (15/53) and 5.4% (3/56) of Na-PPS and standard thromboprophylaxis group, respectively (P = 0.001).
CONCLUSION: Na-PPS was associated with increased risk of minor bleeding. There was insufficient data to conclude its efficacy as thromboprophylaxis. Further research is needed to evaluate Na-PPS safety as a standard thromboprophylactic agent.
OBJECTIVE: The aim of this study was to determine the rate, factors, and medications associated with ADR-related hospitalisations among HF patients.
SETTING: Two government hospitals in Dubai, United Arab Emirates.
METHODS: This was a prospective, observational study. Consecutive adult HF patients who were admitted between December 2011 and November 2012 to the cardiology units were included in this study. The circumstances of their admission were analysed.
MAIN OUTCOME MEASURES: ADRs-related admissions of HF patients to cardiology units were identified and further assessed for their nature, causality, and preventability.
RESULTS: Of 511 admissions, 34 were due to ADR-related hospitalisation (6.65, 95 % confidence interval 4.8-8.5 %). Number of medications taken by HF patients was the only predictors of ADR-related hospitalisations, where higher number of medications was associated with the odd ratio of 1.11 (95 % CI, 1.03-1.20, P = 0.005). More than one-third of ADR-related hospitalisations (35 %) were preventable The most frequent drugs causing ADR-related hospitalisation were diuretics (32 %), followed by non-steroidal anti-inflammatory drugs (15 %), thiazolidinediones (9 %), anticoagulants (9 %), antiplatelets (6 %), and aldosterone blockers (6 %).
CONCLUSION: ADR-related hospitalisations account for 6.7 % of admissions of HF patients to cardiac units, one-third of which are preventable. Number of medications taken by HF patients is the only predictors of ADR-related hospitalisations. Diuretic induced volume depletion, and sodium and water retention caused by thiazolidinediones and NSAIDs medications are the major causes of ADR-related hospitalisations of HF patients.
PURPOSE: The aim was to determine the metabolic fingerprint that predicts warfarin response based on the international normalized ratio (INR) in patients who are already receiving warfarin (phase I: identification) and to ascertain the metabolic fingerprint that discriminates stable from unstable INR in patients starting treatment with warfarin (phase II: validation).
EXPERIMENTAL APPROACH: A total of 94 blood samples were collected for phase I: 44 patients with stable INR and 50 with unstable INR. Meanwhile, 23 samples were collected for phase II: nine patients with stable INR and 14 with unstable INR. Data analysis was performed using multivariate analysis including principal component analysis and partial least square-discriminate analysis (PLS-DA), followed by univariate and multivariate logistic regression (MVLR) to develop a model to identify unstable INR biomarkers.
KEY RESULTS: For phase I, the PLS-DA model showed the following results: sensitivity 93.18%, specificity 91.49% and accuracy 92.31%. In the MVLR analysis of phase I, ten regions were associated with unstable INR. For phase II, the PLS-DA model showed the following results: sensitivity 66.67%, specificity 61.54% and accuracy 63.64%.
CONCLUSIONS AND IMPLICATIONS: We have shown that the pharmacometabonomics technique was able to differentiate between unstable and stable INR with good accuracy. NMR-based pharmacometabonomics has the potential to identify novel biomarkers in plasma, which can be useful in individualizing treatment and controlling warfarin side effects, thus, minimizing undesirable effects in the future.
METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation.
RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).
CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.
HYPOTHESIS: There is wide variability in AMP use for ACS management in Asia.
METHODS: EPICOR Asia (NCT01361386) is a prospective observational study of patients discharged after hospitalization for an ACS in eight countries/regions in Asia, followed up for 2 years. Here, we describe AMPs used and present an exploratory analysis of characteristics and outcomes in patients who received DAPT for ≤12 months post discharge compared with >12 months.
RESULTS: Data were available for 12 922 patients; of 11 639 patients discharged on DAPT, 2364 (20.3%) received DAPT for ≤12 months and 9275 (79.7%) for >12 months, with approximately 60% still on DAPT at 2 years. Patients who received DAPT for >12 months were more likely to be younger, obese, lower Killip class, resident in India (vs China), and to have received invasive reperfusion. Clinical event rates during year 2 of follow-up were lower in patients with DAPT >12 vs ≤12 months, but no causal association can be implied in this non-randomized study.
CONCLUSIONS: Most ACS patients remained on DAPT up to 1 year, in accordance with current guidelines, and over half remained on DAPT at 2 years post discharge. Patients not on DAPT at 12 months are a higher risk group requiring careful monitoring.
METHODS: EPICOR Asia (Long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients in Asia) (NCT01361386) is a prospective, multinational, observational study of patients discharged after hospitalization for an ACS, with 2-year follow-up. The aim is to describe short- and long-term (up to 2 years post-index event) AMPs in patients hospitalized for ACS and to record clinical outcomes, healthcare resource use, and self-reported health status. Pre- and in-hospital management, AMPs, and associated outcomes, with particular focus on ischemic and bleeding events, will be recorded during the 2-year follow up.
RESULTS: Between June 2011 and May 2012, 13 005 patients were enrolled. From these, 12 922 patients surviving an ACS (6616 with STEMI, 2570 with NSTEMI, and 3736 with UA) were eligible for inclusion from 219 hospitals across 8 countries and regions in Asia: China (n = 8214), Hong Kong (n = 177), India (n = 2468), Malaysia (n = 100), Singapore (n = 93), South Korea (n = 705), Thailand (n = 957), and Vietnam (n = 208).
CONCLUSIONS: EPICOR Asia will provide information regarding clinical management and AMPs for ACS patients in Asia. Impact of AMPs on clinical outcomes, healthcare resource use, and self-reported health status both during hospitalization and up to 2 years after discharge will also be described.