Perioperative bridging therapy with unfractionated heparin or low-molecular-weight heparin in patients with mechanical prosthetic heart valves on long-term oral anticoagulants (from the REGIMEN Registry)

Patients with mechanical prosthetic heart valves require long-term oral anticoagulant therapy (OAT). During the temporary interruption of OAT, bridging anticoagulant therapy with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) is recommended. This prespecified subgroup analysis from REGIMEN-a large, prospective, multicenter registry-compared UFH (n = 73) and LMWH (n = 172) as bridging anticoagulation in patients with mechanical heart valves on long-term OAT. Patient demographics and co-morbidities were generally similar between groups. There were more bileaflet valves in the LMWH group (67.4% vs 43.8%, p = 0.0005), but no differences in valve positions between groups. The LMWH group was less likely to undergo major surgery (33.7% vs 58.9%, p = 0.0002) and cardiothoracic surgery (7.6% vs 19.2%, p = 0.008), and to receive intraprocedural anticoagulants or thrombolytics (4.1% vs 13.7%, p = 0.007). Major adverse event rates (5.5% vs 10.3%, p = 0.23) and major bleeds (4.2% vs 8.8%, p = 0.17) were similar in the LMWH and UFH groups, respectively; 1 arterial thromboembolic event occurred in each group. More LMWH-bridged patients were treated as outpatients or discharged from the hospital in <24 hours (68.6% vs 6.8%, p <0.0001). Multivariate logistic analysis found no significant differences in major bleeds and major composite adverse events when adjusting for cardiothoracic or major surgery between groups. In conclusion, for patients with mechanical prosthetic heart valves on long-term OAT, mostly outpatient-based LMWH bridging therapy appears to be feasible for selected procedures, is as safe as UFH, and is associated with a low arterial thromboembolic rate.     

Antithrombotic therapy in patients with prosthetic heart valves

Anticoagulant therapy is an important component of treatment of patients with prosthetic heart valves. The article contains consideration of specific problems of antithrombotic therapy in patients with various types of prostheses and its tactics in different clinical situations. In the absence of national recommendations on the use of anticoagulants in these patients the authors suggest schemes of management based on recent European and American guidelines.     

Low-molecular-weight heparin in pregnant women with prosthetic heart valves

BACKGROUND AND AIM OF THE STUDY: Low-molecular-weight heparin (LMWH) is considered a recommended anticoagulation option in pregnant women with prosthetic heart valves. However, few data are available regarding the efficacy and safety of LMWH in this setting. METHODS: In 1999, the authors' institution developed a standardized anticoagulation protocol for pregnant women with prosthetic heart valves, which included LMWH administered between six and 12 weeks' gestation, and after 36 weeks, with prespecified target levels, and additional low-dose aspirin. Herein is presented the initial experience using this anticoagulation regimen. RESULTS: Among five women with prosthetic heart valves treated with LMWH during part of their pregnancy, four had uneventful pregnancies while one suffered a coronary artery embolus. A review is provided of the current state of knowledge regarding anticoagulation in pregnancy, with emphasis placed on the importance of strict monitoring of anticoagulation levels. CONCLUSION: Given the drawbacks of other forms of anticoagulation, and within the constraints of available data, LMWH appears--when administered with caution--to be an acceptable alternative in pregnant women with prosthetic heart valves.     

Low-molecular-weight heparin for the treatment of patients with mechanical heart valves

BACKGROUND: The interruption of oral anticoagulant (OAC) administration is sometimes indicated in patients with mechanical heart valves, mainly before noncardiac surgery, non-surgical interventions, and pregnancy. Unfractionated heparin (UH) is currently the substitute for selected patients. Low-molecular-weight heparin (LMWH) offers theoretical advantages over UH, but is not currently considered in clinical guidelines as an alternative to UH in patients with prosthetic valves. HYPOTHESIS: The aim of the present study was to review the data accumulated so far on the use of LMWH in this patient population and to discuss its applicability in common practice. METHODS: For this paper, the current medical literature on LMWH in patients with mechanical heart valves was extensively reviewed. RESULTS: There were eight series and six case reports. None of the studies was randomized, and only one was prospective. Data to establish the thromboembolic risk were incomplete. After excluding case reports, the following groups were constructed: (a) short-term administration, after valve insertion (n = 212); (b) short-term, perioperative (noncardiac)/periprocedural (n = 114); (c) long-term, due to intolerance to OAC (n = 16); (d) long-term, in pregnancy (n = 10). The incidence rate of thromboembolism was 0.9% for all the studies and 0.5, 0, 20, and 0% in groups a, b, c, and d, respectively; for hemorrhage, the overall rate was 3.4% (3.8, 2.6, 10, and 0% for the respective groups). CONCLUSIONS: In patients with mechanical heart valves, short-term LMWH therapy compares favorably with UH. Data on mid- and long-term LMWH administration in these patients are sparse. Further randomized studies are needed to confirm the safety and precise indications for the use of LMWH in patients with mechanical heart valves.     

Anticoagulation therapy in children with mechanical prosthetic cardiac valves

From 1980 through 1984, 28 children younger than 19 years (mean 7.9) underwent cardiac valve replacement with 30 mechanical prostheses. Patients were followed for a total of 471 months (mean 15.7) and received either warfarin (mean 0.16 mg/kg/day) or acetylsalicylic acid and dipyridamole (mean 6.1 and 1.9 mg/kg/day, respectively) as thromboembolism prophylaxis. The frequency and incidence of thromboembolism and hemorrhage were compared. Warfarin-treated patients were at increased risk of hemorrhage (5 of 20 [25%], or 22 per 100 patient-years, vs 0 of 10 [0%], or 0 per 100 patient-years, p less than 0.05). Three of the 5 hemorrhagic episodes were mild, and in no case was hemorrhage life-threatening. Patients who did not receive warfarin had a greater risk of thromboembolism (2 of 10 [20%], or 12 per 100 patient-years, vs 0 of 20 [0%], or 0 per 100 patient-years, p less than 0.05). Both episodes of thromboembolism were life-threatening and necessitated emergency valve replacement. Although warfarin is associated with greater risk of hemorrhage than is acetylsalicylic acid and dipyridamole, warfarin is better than antiplatelet drugs in thromboembolism prophylaxis and is indicated for anticoagulation therapy in children with mechanical cardiac prostheses.     

中国人心脏机械瓣置换后抗血栓的临床研究

目的:探讨中国人机械瓣置换后抗血栓治疗方案及不同水平的抗凝国际标准化比值(INR)的疗效及与抗凝相关事件的关系。方法:334例机械瓣置换病人,总计501病人年,4 228例次检测的INR分成INR≤1.49组(67例次),1.50~1.99组(847例次),2.00~2.59组(1420例次),2.60~3.00组 (1071例次),3.01~3.60组(254例次),>3.60组(183例次)。另INR1.8~2.0并加用阿斯匹林水溶片100mg·d-1组有386例次。观察此7组疗效,相关事件发生频率及其标准化病人年发生率。结果:重度出血仅2例,出现在INR>3.6组;中度出血36例次,与INR值、妇女年龄相关(P<0.of)。血栓事件2例.其INR分别为1.2,1.56。结论:机械瓣置换后抗血栓治疗要个体化,中国人单用华法令抗凝INR 2.0~3.0和低水平的抗凝(INR1.8~2.0)加小剂量阿斯匹林100mg·d-1的抗血栓治疗方案相关事件发生率较低,比较适合。     

Salmonella bacteremia in patients with prosthetic heart valves

During 1982 and 1983, five patients with prosthetic heart valves and documented Salmonella bacteremia were admitted to the Instituto Nacional de Cardiologia in Mexico City. The clinical and microbiologic features in this group of patients are described, as well as the therapeutic implications when Salmonella bacteremia is present in patients with heart prostheses. None of the patients had evidence of infectious endocarditis; however, all received prolonged parenteral antimicrobial therapy for at least four weeks with ampicillin or chloramphenicol, with excellent clinical response.     

Platelet survival in patients with prosthetic heart valves

Chromium-51 platelet survival studies were carried out in 20 patients with a prosthetic heart valve. Only 1 of 10 patients with a prosthetic mitral valve had a significantly shortened platelet survival time, and the mean value of 8.3 ± 0.96 (±1 standard deviation) days was not significantly different from that of normal control subjects (8.9 ± 0.75 days). Four of 10 patients with an aortic prosthesis had a shortened platelet survival time, and the mean value of 7.8 ± 0.10 days in this group differed significantly from the normal control value (P < 0.05). Treatment with aspirin did not appear to alter platelet survival but, when combined with Coumadin therapy, resulted in marked prolongation of bleeding time. Our results do not support the concept that thrombus formation on the prosthesis is the cause of the shortened platelet survival time since thrombus formation is more likely to occur in mitral than aortic prostheses. Reduced platelet survival time secondary to damage by the prosthesis, similar to the problem of hemolysis in red blood cells, is a more likely explanation.     

心脏机械瓣置换后特殊情况抗血栓治疗的临床研究

目的:探讨机械瓣置换后特殊情况抗血栓治疗方案的疗效和安全性。方法:对于机械瓣置换后病人妊娠、分娩,INR在目标值范围内月经过多,人流手术等不同特殊情况制定不同的抗血栓治疗方案。妊娠在头6～12周改为低分子肝素,每次0.01 ml·kg-1,1日2次,皮下注射,剖腹产前1周停华法令,前4天改为低分子肝素,后3天改为普通肝素持续静脉泵入,按APTT为正常值的2～3倍来调整剂量,术前6～12小时停用普通肝素,手术后无出血24小时内服用华法令。血栓高危患者择期大手术、人流手术按剖腹产术前准备。急性兰尾炎手术给予小剂量维生素K。INR在目标值范围的妇女月经过多者,在月经的第1天停用华法令1次。眼科白内障手术、拔牙手术及皮肤癌手术无需调整INR。结果:剖腹产围手术期顺利,新生儿健康。所有手术无大出血和血栓事件。INR在目标值范围月经过多的妇女,有效率达94％（32/34例）。结论:本组为机械瓣置换后特殊情况所制定的抗血栓方案疗效满意;是否为较成熟方案,尚需临床实践进一步证实。     

Evaluation of hemolysis in patients with prosthetic heart valves

The primary mechanism and most common cause of hemolytic disease in patients with prosthetic heart valves are mechanical trauma to red blood cells and paraprosthetic valvular regurgitation, respectively. Presenting features in patients with this condition include anemia, congestive heart failure, fatigue, jaundice, dark urine, and a regurgitant murmur. Various laboratory studies can be utilized to diagnose hemolytic anemia and to assess the severity of hemolysis. Transthoracic echocardiography, transesophageal echocardiography, and Doppler studies including color Doppler are useful imaging methods to assess valve function. Treatment is usually medical (oral iron); however, in patients with paravalvular regurgitation, surgery is often required to correct the anemia.     

Measurement of haemolysis in patients with prosthetic heart valves

Haemolysis following prosthetic heart valve insertion can be precisely and sensitively measured by means of a 59Fe ferrokinetic technique. Results obtained in a small series of patients with either Starr-Edwards or Brunwald-Cutter valve replacement are presented.     

Anticoagulation in pregnancy with mechanical heart valves: 10-year experience

Anticoagulation in pregnancy was evaluated in 33 women with a mechanical heart valve prosthesis who had 53 pregnancies between 1994 and 2006. Their mean age at valve operation was 24.4 +/- 5.4 years, and 22 (67%) had isolated mitral valve disease. Of these patients, 22 had a single pregnancy, 5 had 2 pregnancies, 3 had 3, and 3 had 4. In 43 pregnancies, the patients took warfarin throughout; in the other 10, heparin was used in the first trimester followed by warfarin until the last 15 days. Mean international normalized ratio and warfarin levels before, during, and after pregnancy were similar. Complications occurred in 3 (6%) women who had thrombosed valves: 2 (20%) in the heparin group and 1 (2%) who had warfarin only. Live births resulted from 37 (70%) pregnancies. There were significantly more abortions in the heparin group (6; 60%) than the warfarin group (8; 19%). Hemorrhage requiring transfusion occurred in 2 (5%) patients in the warfarin group. All live births resulted in healthy babies. It was concluded that anticoagulation with warfarin is safe during pregnancy in women with mechanical heart valves.     

Management of anticoagulant therapy for patients with prosthetic heart valves or atrial fibrillation

There is a wide array of recommendations for the management of anticoagulant therapy in patients with mechanical heart valves. Especially the optimal intensity of vitamin K antagonists (VKA) is a ongoing matter of debate. On the basis of several studies, recommendations for daily clinical practice can be made. In this review, we discussed the studies and the different guidelines. Guidelines for the prevention of thromboembolic complications in patients with atrial fibrillation are more stringent. VKA with a target INR between 2.0 and 3.0 is more effective in the prevention of stroke than aspirin, especially in the presence of riskfactors for thromboembolism (age above 65, previous thromboembolism, history of hypertension and diabetes, enlarged left atrial diameter and left ventricular dysfunction). In the absence of clinical or echocardiographical riskfactors for thromboembolism, patients may be safely treated with aspirin.     

Costs and clinical outcomes associated with low-molecular-weight heparin vs unfractionated heparin for perioperative bridging in patients receiving long-term oral anticoagulant therapy

STUDY OBJECTIVES: There have been no health-care cost evaluations comparing the use of low-molecular-weight heparin (LMWH) to unfractionated heparin (UH) as "bridge therapy" in the perioperative period in patients receiving long-term oral anticoagulant (OAC) therapy who need interruption of therapy to undergo an elective surgical procedure. We performed a retrospective analysis of the medical and administrative records of health plan members in a managed care organization who underwent bridge therapy perioperatively with either i.v. UH, administered in a hospital setting, or LMWH, administered primarily in the outpatient setting using disease management guidelines. DESIGN: A retrospective analysis of medical and administrative records of treated health plan members meeting inclusion/exclusion criteria during the two study periods (ie, from 1994 to 1996 and from 1998 to 2000). SETTING: Staff-model health maintenance organization serving New Mexico. PATIENTS: The UH group included persons receiving long-term warfarin therapy from 1994 to 1996 (26 patients), and the LMWH group included persons receiving long-term warfarin therapy from 1998 to 2000 (40 patients) with perioperative use of heparin (either UH or LMWH) as bridge therapy for an elective surgical procedure. INTERVENTIONS: Costs were calculated for the period from 10 days before the procedure through 30 days after the procedure. The rates of adverse events (ie, valvular or mural thrombus, intracranial event, transient ischemic attack, peripheral arterial event, venous thromboembolic event, major and minor bleeding, thrombocytopenia, and death) occurring 1 to 30 days postprocedure were determined. MEASUREMENTS AND RESULTS: The groups were similar in age, sex, Charlson score, indication for long-term warfarin therapy (ie, arterial/cardiac vs venous), mean international normalized ratio prior to procedure, procedure duration, use of intraprocedural anticoagulant agents or thrombolytic agents, and use of general anesthesia during the procedure (all p > 0.05). A total of 34.6% of UH patients and 40.0% of LMWH patients experienced one or more clinical adverse events within 30 days of the postoperative period, a difference that was not statistically significant (p = 0.67). The mean total health-care costs were 31,625 dollars in the UH group and 18,511 dollars in the LMWH group (p < 0.01). The mean inpatient costs were 28,515 dollars in the UH group and 14,330 dollars in the LMWH group (p < 0.01). Outpatient surgery costs (1,159 dollars vs 53 dollars, respectively; p = 0.01) and pharmacy costs (639 dollars vs 133 dollars, respectively; p < 0.01) were higher in the LMWH group. CONCLUSIONS: The mean total health-care costs in the perioperative period were significantly lower (by 13,114 dollars) in patients receiving long-term OAC therapy using LMWH compared to those receiving it using UH for an elective surgical procedure. The cost savings associated with LMWH use were accomplished through the avoidance or minimization of inpatient stays and no increase in the overall rate of clinical adverse events in the postoperative period.     

Benefits of endocarditis prevention in patients with prosthetic heart valves

The beneficial effect of prophylaxis for IE was studied in 229 patients with prosthetic heart valves in whom 287 diagnostic or therapeutic interventions were performed. The prevention used was similar to that recommended by the American Heart Association. Prosthetic valve endocarditis was not observed in any of these patients. This result was compared with that of 304 patients with prosthetic heart valves, in whom without any prevention 390 similar interventions were performed during the same observation period. The incidence of prosthetic valve endocarditis occurring within 14 days after the intervention was 1.5/100 interventions (n = 6). All patients had to be reoperated. One patient died perioperatively. Two more patients developed prosthetic valve endocarditis 8 and 13 weeks, respectively, after the initial intervention. This retrospective study documents the benefit of the prophylaxis for IE used.