Telemedicine-guided, very low-dose international normalized ratio self-control in patients with mechanical heart valve implants.

AIM: To study in patients performing international normalized ratio (INR) self-control the efficacy and safety of an INR target range of 1.6-2.1 for aortic valve replacement (AVR) and 2.0-2.5 for mitral valve replacement (MVR) or double valve replacement (DVR). METHODS AND RESULTS: In total, 1304 patients undergoing AVR, 189 undergoing MVR and 78 undergoing DVR were randomly assigned to low-dose INR self-control (LOW group) (INR target range, AVR: 1.8-2.8; MVR/DVR: 2.5-3.5) or very low-dose INR self-control once a week (VLO group) and twice a week (VLT group) (INR target range, AVR: 1.6-2.1; MVR/DVR: 2.0-2.5), with electronically guided transfer of INR values. We compared grade III complications (major bleeding and thrombotic events; primary end-points) and overall mortality (secondary end-point) across the three treatment groups. FINDINGS: Two-year freedom from bleedings in the LOW, VLO, and VLT groups was 96.3, 98.6, and 99.1%, respectively (P = 0.008). The corresponding values for thrombotic events were 99.0, 99.8, and 98.9%, respectively (P = 0.258). The risk-adjusted composite of grade III complications was in the per-protocol population (reference: LOW-dose group) as follows: hazard ratio = 0.307 (95% CI: 0.102-0.926; P = 0.036) for the VLO group and = 0.241 (95% CI: 0.070-0.836; P = 0.025) for the VLT group. The corresponding values of 2-year mortality were = 1.685 (95% CI: 0.473-5.996; P = 0.421) for the VLO group and = 4.70 (95% CI: 1.62-13.60; P = 0.004) for the VLT group. CONCLUSION: Telemedicine-guided very low-dose INR self-control is comparable with low-dose INR in thrombotic risk, and is superior in bleeding risk. Weekly testing is sufficient. Given the small number of MVR and DVR patients, results are only valid for AVR patients.

Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data.

BACKGROUND: Uptake of self-testing and self-management of oral anticoagulation [corrected] has remained inconsistent, despite good evidence of their effectiveness. To clarify the value of self-monitoring of oral anticoagulation, we did a meta-analysis of individual patient data addressing several important gaps in the evidence, including an estimate of the effect on time to death, first major haemorrhage, and thromboembolism. METHODS: We searched Ovid versions of Embase (1980-2009) and Medline (1966-2009), limiting searches to randomised trials with a maximally sensitive strategy. We approached all authors of included trials and requested individual patient data: primary outcomes were time to death, first major haemorrhage, and first thromboembolic event. We did prespecified subgroup analyses according to age, type of control-group care (anticoagulation-clinic care vs primary care), self-testing alone versus self-management, and sex. We analysed patients with mechanical heart valves or atrial fibrillation separately. We used a random-effect model method to calculate pooled hazard ratios and did tests for interaction and heterogeneity, and calculated a time-specific number needed to treat. FINDINGS: Of 1357 abstracts, we included 11 trials with data for 6417 participants and 12,800 person-years of follow-up. We reported a significant reduction in thromboembolic events in the self-monitoring group (hazard ratio 0·51; 95% CI 0·31-0·85) but not for major haemorrhagic events (0·88, 0·74-1·06) or death (0·82, 0·62-1·09). Participants younger than 55 years showed a striking reduction in thrombotic events (hazard ratio 0·33, 95% CI 0·17-0·66), as did participants with mechanical heart valve (0·52, 0·35-0·77). Analysis of major outcomes in the very elderly (age ≥85 years, n=99) showed no significant adverse effects of the intervention for all outcomes. INTERPRETATION: Our analysis showed that self-monitoring and self-management of oral coagulation is a safe option for suitable patients of all ages. Patients should also be offered the option to self-manage their disease with suitable health-care support as back-up. FUNDING: UK National Institute for Health Research (NIHR) Technology Assessment Programme, UK NIHR National School for Primary Care Research.

Survival comparison of the Ross procedure and mechanical valve replacement with optimal self-management anticoagulation therapy: propensity-matched cohort study.

BACKGROUND: It is suggested that in young adults the Ross procedure results in better late patient survival compared with mechanical prosthesis implantation. We performed a propensity score-matched study that assessed late survival in young adult patients after a Ross procedure versus that after mechanical aortic valve replacement with optimal self-management anticoagulation therapy. METHODS AND RESULTS: We selected 918 Ross patients and 406 mechanical valve patients 18 to 60 years of age without dissection, aneurysm, or mitral valve replacement who survived an elective procedure (1994 to 2008). With the use of propensity score matching, late survival was compared between the 2 groups. Two hundred fifty-three patients with a mechanical valve (mean follow-up, 6.3 years) could be propensity matched to a Ross patient (mean follow-up, 5.1 years). Mean age of the matched cohort was 47.3 years in the Ross procedure group and 48.0 years in the mechanical valve group (P=0.17); the ratio of male to female patients was 3.2 in the Ross procedure group and 2.7 in the mechanical valve group (P=0.46). Linearized all-cause mortality rate was 0.53% per patient-year in the Ross procedure group compared with 0.30% per patient-year in the mechanical valve group (matched hazard ratio, 1.86; 95% confidence interval, 0.58 to 5.91; P=0.32). Late survival was comparable to that of the general German population. CONCLUSIONS: In comparable patients, there is no late survival difference in the first postoperative decade between the Ross procedure and mechanical aortic valve implantation with optimal anticoagulation self-management. Survival in these selected young adult patients closely resembles that of the general population, possibly as a result of highly specialized anticoagulation self-management, better timing of surgery, and improved patient selection in recent years.

Collagen- versus gelatine-coated Dacron versus stretch PTFE bifurcation grafts for aortoiliac occlusive disease: long-term results of a prospective, randomized multicenter trial.

BACKGROUND: In this prospective randomized multicenter trial, knitted gelatine-coated Dacron, knitted collagen-coated Dacron, and stretch polytetrafluoroethylene (PTFE) aortic bifurcation grafts were compared for their long-term results. METHODS: Between 1991 and 1998, 149 patients undergoing elective revascularization for aortoiliac occlusive disease were prospectively randomized at 3 tertiary referral centers of vascular surgery. The patients received either gelatine-coated Dacron (GEL-D) grafts (n = 52), collagen-coated Dacron (COL-D) grafts (n = 49), or stretch PTFE grafts (n = 48). RESULTS: No intraoperative deaths were recorded. The 30-day mortality was 4%. The mean follow-up time was 97 months. Primary patency rates were 77% for GEL-D, 78% for COL-D, and 79% for PTFE at 8 years. The differences were not different (P >.8). Secondary corrected 8-year patency rates were also not significantly different (P >.5): 91% for GEL-D, 96% for COL-Dm and 90% for PTFE. Five Dacron and 1 PTFE grafts were affected by infections. CONCLUSIONS: Bifurcation grafts for revascularization of aortoiliac occlusive disease using these 3 materials were comparable in terms of primary and secondary patency and long-term complication rates.

Efficacy and safety of very low-dose self-management of oral anticoagulation in patients with mechanical heart valve replacement.

BACKGROUND: Self-management improves oral anticoagulation control. Here we provide data of a preplanned interim analysis of very low-dose early self-controlled anticoagulation. METHODS: In a prospective, randomized, multicenter trial, 1,137 patients performed low-dose international normalized ratio (INR) self-management with a target INR range of 1.8. to 2.8 for aortic valve replacement recipients and 2.5 to 3.5 for mitral or double valve replacement recipients for the first six postoperative months. Thereafter, 379 patients continued to achieve the aforementioned INR target range (LOW group), whereas the INR target value was set at 2.0 (range, 1.6 to 2.1) for the remaining patients with aortic valve replacement and 2.3 (range, 2.0 to 2.5) for the remaining patients with mitral valve or double valve replacement. One half of this latter group had to check their INR values once a week (VL1 group) the other half twice a week (VL2 group). Patients were followed up for 24 months. RESULTS: Beyond study month six, the incidence of thromboembolic events that required hospital admission was 0.58%, 0.0%, and 0.58% in the LOW, VL1, and VL2 groups, respectively (p = 0.368). The incidence of bleeding events per patient-year was 1.16%, 1.07%, and 0.58% in the LOW, VL1, and VL2 groups, respectively (p = 0.665). Mortality rate did not differ among study groups. CONCLUSIONS: Data demonstrate the efficacy and safety of very low-dose INR self-management.

International normalized ratio self-management lowers the risk of thromboembolic events after prosthetic heart valve replacement.

BACKGROUND: Although prosthetic valves are durable and easy to implant, the need for lifetime warfarin-based anticoagulation restricts their exclusive usage. We investigated if anticoagulation self-management improves outcome in a single-center series. METHODS: Between 1994 and 1998, 765 patients with prosthetic valve replacements were prospectively enrolled and randomized to receive conventional anticoagulation management by their primary physician (group 1, n = 295) or to pursue anticoagulation self-management (group 2, n = 470). A study head office was implemented to coordinate and monitor anticoagulation protocols, international normalized ratios (INR), and adverse events. Patients were instructed on how to obtain and test their own blood samples and to adjust warfarin dosages according to the measured INR (target range, 2.5 to 4). RESULTS: Mean INR values were slightly yet significantly smaller in group 1 than in group 2 (2.8 +/- 0.7 vs 3.0 +/- .6, p < 0.001). Moreover, INR values of patients with conventional INR management were frequently measured outside the INR target range, whereas those with anticoagulation self-management mostly remained within the range (35% vs 21%, p < 0.001). In addition, the scatter of INR values was smaller if self-managed. Freedom from thromboembolism at 3, 12, and 24 months, respectively, was 99%, 95%, and 91% in group 1 compared with 99%, 98%, and 96% in group 2 (p = 0.008). Bleeding events were similar in both groups. Time-related multivariate analysis identified INR self-management and higher INR as independent predictors for better outcome. CONCLUSIONS: Anticoagulation self-management can improve INR profiles up to 2 years after prosthetic valve replacement and reduce adverse events. Current indications of prosthetic rather than biologic valve implantations may be extended if the benefit of INR self-management is shown by future studies with longer follow-up.

Self-management of oral anticoagulation therapy improves long-term survival in patients with mechanical heart valve replacement.

BACKGROUND: The Early Self-Controlled Anticoagulation Trial has demonstrated that in patients with mechanical heart valve replacement self-management of oral anticoagulation results in less major thromboembolic events than conventional measurement by the general practitioner. However, the effects of self-management on long-term survival are currently not known. METHODS: Nine hundred thirty patients participated in a follow-up study of the aforementioned trial (488 from the self-management group and 442 from the conventional group). Long-term survival was assessed 12 years after the study began using the intent-to treat analysis as well as the per protocol analysis. Univariate and multivariate analyses were performed in order to assess independent predictors of survival. RESULTS: In total, the 930 patients accrued 8,315 patient-years of observation. During follow-up, 236 patients died. According to the intent-to treat analysis, 10-year survival was 76.1% in the conventional group and 84.5% in the self-management group. The corresponding values for the per protocol analysis were 67.7% and 80.6%, respectively. Age, kind of valve surgery, and study group were independent predictors of survival. Self-management of oral anticoagulation increased long-term survival by 23% (intent-to-treat analysis) and 33% (per protocol analysis), respectively, compared with conventional measurement by the general practitioner. Possible reasons for these advantageous results in the self-management group are fewer thromboembolic events due to a higher percentage of international normalized ratio values lying in the target range compared with the conventional group. CONCLUSIONS: Data indicate that self-management of oral anticoagulation is a promising strategy in order to increase long-term survival in patients with mechanical prosthetic valves.

Low-dose oral anticoagulation in patients with mechanical heart valve prostheses: final report from the early self-management anticoagulation trial II.

AIMS: In mechanical heart valve recipients, low-dose international normalized ratio (INR) self-management of oral anticoagulants can reduce the risk of developing thrombo-embolic events and improve long-term survival compared with INR control by a general practitioner. Here, we present data on the safety of low-dose INR self-management. METHODS AND RESULTS: In a prospective, randomized multi-centre trial, 1346 patients with a target INR range of 2.5-4.5 and 1327 patients with a target INR range of 1.8-2.8 for aortic valve recipients and an INR range of 2.5-3.5 for mitral or double valve recipients were followed up for 24 months. The incidence of thrombo-embolic events that required hospital admission was 0.37 and 0.19% per patient year in the conventional and low-dose groups, respectively (P = 0.79). No thrombo-embolic events occurred in the subgroups of patients with mitral or double valve replacement. The incidence of bleeding events that required hospital admission was 1.52 and 1.42%, respectively (P = 0.69). In the majority of patients with bleeding events, INR values were < 3.0. Mortality rate did not differ between the study groups. CONCLUSION: Data demonstrate that low-dose INR self-management does not increase the risk of thrombo-embolic events compared with conventional dose INR self-management. Even in patients with low INR target range, the risk of bleeding events is still higher than the risk of thrombo-embolism.

Low-dose international normalized ratio self-management: a promising tool to achieve low complication rates after mechanical heart valve replacement.

BACKGROUND: International normalized ratio (INR) self-management can significantly reduce INR fluctuations, bleeding, and thromboembolic events compared with INR control managed by general practitioners. However, even patients with INR self-management may have an increased risk of bleeding if their INR value is above 3.5. This study evaluated the compliance, clinical complications, and survival of patients after mechanical heart valve replacement with low-dose INR self-management compared with conventional-dose anticoagulation. METHODS: Group 1 (n = 908) received low-dose anticoagulation with a target INR range of 1.8 to 2.8 for aortic valve replacement and 2.5 to 3.5 for mitral or double valve replacement. Group 2 (n = 910) received conventional-dose anticoagulation with a target INR range of 2.5 to 4.5 for all heart valve prostheses. RESULTS: In groups 1 and 2, 76% and 75% of INR values, respectively, were in the target range. Results did not differ according to schooling and age. The rate of thromboembolic events per patient year was 0.18% in group 1 and 0.40% in group 2 (p = 0.210). The rate of bleeding complications was 0.74% for group 1 and 1.20% for group 2 (p = 0.502). In most patients with clinically relevant bleeding, these complications occurred although their measured INR values were below 3.5. The survival rate did not differ between the study groups (p = 0.495). CONCLUSIONS: Low-dose INR self-management is a promising tool to achieve low hemorrhagic complications without increasing the risk of thromboembolic complications. INR self-management is applicable for all patients in whom permanent anticoagulation therapy is indicated. Even INR values below 3.5 can bear the risk of bleeding complications.