Fiona Ryan

Randomized controlled trial of supervised patient self‐testing of warfarin therapy using an internet‐based expert system

Summary.  Background: Increased frequency of prothrombin time testing, facilitated by patient self‐testing (PST) of the International Normalized Ratio (INR) can improve the clinical outcomes of oral anticoagulation therapy (OAT). However, oversight of this type of management is often difficult and time‐consuming for healthcare professionals. This study reports the first randomized controlled trial of an automated direct‐to‐patient expert system, enabling remote and effective management of patients on OAT. Methods: A prospective, randomized controlled cross‐over study was performed to test the hypothesis that supervised PST using an internet‐based, direct‐to‐patient expert system could provide improved anticoagulation control as compared with that provided by an anticoagulation management service (AMS). During the 6 months of supervised PST, patients measured their INR at home using a portable meter and entered this result, along with other information, onto the internet web page. Patients received instant feedback from the system as to what dose to take and when the next test was due. During the routine care arm, patients attended the AMS at least every 4–6 weeks and were dosed by the anticoagulation pharmacist or physician. The primary outcome variable was the difference in the time in therapeutic range (TTR) between both arms. Results: One hundred and sixty‐two patients were enrolled (male 61.6%, mean age 58.7 years), and 132 patients (81.5%) completed both arms. TTR was significantly higher during PST management than during AMS management (median TTR 74% vs 58.6%; z=5.67, P < 0.001). Conclusions: The use of an internet‐based, direct‐to‐patient expert system for the management of PST improves the control of OAT as compared with AMS management.

The reliability of point‐of‐care prothrombin time testing. A comparison of CoaguChek S ® and XS ® INR measurements with hospital laboratory monitoring

The development of point‐of‐care (POC) testing devices enables patients to test their own international normalized ratio (INR) at home. However, previous studies have shown that when compared with clinical laboratory values, statistically significant differences may occur between the two methods of INR measurement. The aim of this study was to evaluate the accuracy of the CoaguChek S® and XS® POC meters relative to clinical laboratory measurements. As part of a randomized, crossover patient self‐testing (PST) study at Cork University Hospital, patients were randomized to 6 months PST or 6 months routine care by the anticoagulation management service. During the PST arm of the study, patients measured their INR at home using the CoaguChek S® or XS® POC meter. External quality control was performed at enrolment, 2 months and 4 months by comparing the POC measured INR with the laboratory determined value. One hundred and fifty‐one patients provided 673 paired samples. Good correlation was shown between the two methods of determination (r = 0.91), however, statistically significant differences did occur. A Bland–Altman plot illustrated good agreement of INR values between 2.0 and 3.5 INR units but there was increasing disagreement as the INR rose above 3.5. Eighty‐seven per cent of all dual measurements were within the recommended 0.5 INR units of each other. This study adds to the growing evidence that POC testing is a reliable and safe alternative to hospital laboratory monitoring but highlights the importance of external quality control when these devices are used for monitoring oral anticoagulation.

Managing oral anticoagulation therapy: improving clinical outcomes. A review

Many physicians are reluctant to prescribe oral anticoagulation therapy (OAT) because of the fear of haemorrhagic complications. Changes in patient health, lifestyle or diet and other drugs can alter the effectiveness of oral anticoagulants. These potential interferences, added to the fact that each individual has a different reaction to these drugs, requires that therapy is monitored regularly. This article aims to review those strategies which help to achieve optimal anticoagulation control and improve the outcomes of OAT. Relevant articles were identified through a search of MEDLINE and included publications reporting on intensity of anticoagulation, the initiation of therapy and the role of pharmacogenetics, the transition from primary to secondary care, management by specialized clinics using decision support software and home‐testing. Implementation of these strategies would increase the use of oral anticoagulants by physicians and offers the potential to improve patient safety and reduce adverse events.

Economic evaluation of a randomized controlled trial of pharmacist‐supervized patient self‐testing of warfarin therapy

The increase in numbers of patients requiring oral anti‐coagulation testing in outpatient clinics has focused attention on alternative flexible systems of anti‐coagulation management. One option is pharmacist led patient self‐testing (PST) of international normalised ratio (INR) levels. PST has demonstrated improvements in anti‐coagulation control, but its cost‐effectiveness is inconclusive. This study reports the first cost‐effectiveness evaluation of a randomized controlled trial of an automated direct‐to‐patient expert system, enabling remote and effective management of patients on oral anti‐coagulation therapy.

B-Type Natriuretic Peptide and Ventricular Dysfunction in the Prediction of Cardiovascular Events and Death in Hypertension

BACKGROUND The prevalence and morbidity of hypertension continues to grow globally and improved methods of stratifying risk and identifying organ damage earlier are required. Methods such as echocardiography and population-based risk scores are suggested by guidelines as approaches to aid in risk stratification. However, biomarkers such as natriuretic peptides may help provide such an approach. METHODS We analyzed data from the screening to prevent heart failure cohort including participants with hypertension with and without a history of a cardiovascular (CV) event at baseline. We investigated the ability of ventricular dysfunction on echocardiography at baseline and of B-type natriuretic peptide (BNP) levels in predicting future major adverse CV events (MACE) and death. We also investigated the use of Systematic COronary Risk Evaluation (SCORE) to predict these events in the uncomplicated cohort. RESULTS In total, 572 patients (427 with uncomplicated hypertension) were included. Thirty-three patients had MACE or died during follow up. In a univariate analysis, BNP was predictive of MACE and death in all groups. Ventricular dysfunction was not predictive of MACE and death in any group. Both BNP and SCORE had predictive value in this category. However, the magnitude and strength of the continuous association between BNP and events is higher and BNP adds significantly to the predictive value of SCORE as determined by likelihood ratios. The net reclassification improvement for BNP compared to stage B heart failure was 0.20. CONCLUSION This study demonstrates that in patients with hypertension, BNP is superior to ventricular dysfunction on echocardiography in the prediction of risk of MACE and death in a community-based cohort of patients with complicated and uncomplicated hypertension.

In vivo impact of prodrug isosorbide-5-nicotinate-2-aspirinate on lipids and prostaglandin D2: is this a new immediate-release therapeutic option for niacin?

OBJECTIVES To evaluate the pharmacokinetics and effects of the first immediate-release (IR) niacin-aspirin prodrug (ST0702) on lipid, prostaglandin and thromboxane levels in non-human primates (NHPs). METHODS We compared 28 mg/kg crystalline IR niacin, equimolar doses of crystalline IR ST0702 and control on low density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB) and triglycerides (Tg) in NHPs (6 per group) over 48 h (daily oral gavage). In addition, we compared IR niacin and ST0702 effects on prostaglandin (PG)D(2), ex vivo thromboxane B(2) (TXB(2)) levels and plasma pharmacokinetics. RESULTS ST0702 is metabolised in vivo to aspirin, niacin and salicylic acid with T(max) values of 30, 45 and 95 min respectively using a non-compartmental model. ST0702 resulted in 38% and 40% reductions in LDL-C and ApoB levels compared to control over the 48 h period (p = 0.027 and p = 0.012 respectively). Corresponding values were 32% and 25% for niacin (both p = NS vs control). ST0702, but not niacin, decreased Tg levels (p = 0.017 for between group difference). Post prandial glycaemia was attenuated vs baseline in the ST0702 group only. Ex vivo serum TXB(2) generation was suppressed at 15 min and complete suppression of TXB(2) was sustained at 24h (p<0.01 vs niacin). ST0702 suppressed PGD(2) exposure eightfold (p = 0.012) compared to niacin over the first 24h. CONCLUSIONS This two-dose study in NHPs suggests that ST0702 is more effective than IR niacin on lipid profiles, while suppressing TXB(2) and PGD(2) increases and prevents post-prandial glycaemia. ST0702 shows promise as a new IR therapeutic option for niacin.