HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Reiner Körfer Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Körtke, H. Articles by Körfer, R. Search for Related Content PubMed PubMed Citation Articles by Körtke, H. Articles by Körfer, R. Related Collections Valve disease

Ann Thorac Surg 2001;72:44-48
© 2001 The Society of Thoracic Surgeons

---

Original article: cardiovascular

International normalized ratio self-management after mechanical heart valve replacement: is an early start advantageous?

Accepted for publication February 6, 2001.

Address reprint requests to Dr Körtke, Herz- und Diabeteszentrum NRW, Georgstrasse 11, 32545 Bad Oeynhausen, Germany
e-mail: hkoertke{at}hdz-nrw.de

	Abstract

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Background. Severe thromboembolic and hemorrhagic complications after mechanical heart valve replacement essentially depend on the intensity of oral anticoagulation and the fluctuation of individual international normalized ratio (INR) values.

Methods. After heart valve replacement with Medtronic Hall, St. Jude Medical, and CarboMedics implants, patients were randomly divided into two groups, one controlling INR values at home, the other being monitored by family practitioners.

Results. Almost 80% of the INR values recorded by patients at home were within the stipulated therapeutic range, INR 2.5 to 4.5, compared with just 62% of INR values recorded by family practitioners. The overall complication rate (hemorrhages and thromboembolic events) of the self-management group was significantly (p < 0.05) decreased compared with the conventional group.

Conclusions. Through INR self-management, an improvement in the quality of ongoing oral anticoagulation could be shown. Starting this form of therapeutic control early after mechanical heart valve replacement appears to effect a further reduction in anticoagulant-induced complications.

	Introduction

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Although numerous mechanical and biologic heart valves are now available after more than 30 years of continual improvement in this field, none of them fulfills all of the demands we make of an ideal replacement for a destroyed human heart valve [1]. Biologic implants show a lower thrombogeneity and therefore require no long-term anticoagulation. Because of their structural degeneration, however, their use is restricted to elderly patients. During an 11-year follow-up it was possible to show that biologic heart valve replacements involve a 40% higher explantation rate than mechanical heart valve replacements [2]. Despite progress made in the field of mechanical heart valves, thromboembolism is still a frequent complication after heart valve replacement. The risk of thromboembolism is reduced through treatment with oral anticoagulants, and yet with the newer valves it is still 1.5% in aortic position and 3% in mitral position [3, 4]. Hemorrhage rates vary in degree depending on the quality of the anticoagulation, ranging from 4.2% to 15.4% per patient-year [3, 5–9].

Thromboembolism and anticoagulant-induced hemorrhage thus continue to account for 75% of all complications after mechanical heart valve replacement [3]. These complications occur most frequently during the first 6 months after operation. The risk then becomes low where it remains constant for years [8–10].

Risk levels in conjunction with ongoing anticoagulation therapy are considerably higher in cases in which international normalized ratio (INR) values fluctuate strongly. When anticoagulant-induced complications occur, as many as 60% of the coagulation values controlled are not within the therapeutic range [11, 12].

Valid studies to find an appropriate anticoagulation intensity, ie, an intensity that results in the lowest possible morbidity (thromboembolic and hemorrhagic complications), are not available to date. Current recommended therapies are therefore largely empirically based. The previously available studies also omit inclusion of INR self-management and its goal of improved therapy compliance (oral anticoagulation) as the basis for stable anticoagulation intensity. This study investigates the extent to which INR self-management after mechanical heart valve replacement affects improved anticoagulation stability. It also examines the extent to which freshly operated on patients who are trained in INR self-management just 6 to 11 days after operation are able to effect a potential reduction in morbidity (thromboembolic and hemorrhagic complications).

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
Our so-called ESCAT study (Early Self-Controlled Anticoagulation Trial) was monocentric, randomized, and prospective. It began on February 1, 1994, and closed in October 1997, in line with the randomization, having included 1,200 patients.

Of these 1,200 patients, data from the first 600 to undergo a complete 2-year follow-up and survive were evaluated. We excluded from our analysis patients who died within the perioperative phase or immediate postoperative phase (n = 37, Figs 1 and 2) or who dropped out of the follow-up (n = 90, Figs 3 and 4). We define perioperative as during the operation and immediately postoperative as within 30 days of operation. None of the deaths was directly related to our investigation.

View larger version (20K): [in this window] [in a new window]   Fig 1. Early mortality according to valve position and study group. (AVR = aortic valve replacement; MVR = mitral valve replacement.)

View larger version (19K): [in this window] [in a new window]   Fig 2. Late mortality according to valve position and study group. (Abbreviations as in Figure 1.)

View larger version (12K): [in this window] [in a new window]   Fig 3. Distribution of study drop-outs. ***p 0.001.

View larger version (23K): [in this window] [in a new window]   Fig 4. Reasons for study drop-outs.

In accordance with the study protocol, 295 patients were included in the so-called conventional group (group A) and 305 patients in the INR self-management group (group B). The patients in group B were trained in INR self-management 6 to 11 days after operation. After successful training, each of them received a coagulation monitor, initially Biotrack from the Ciba Coming company, later to be renamed CoaguChek plus from the Roche Diagnostics company (Roche Diagnostics GmbH, Mannheim, Germany). Randomization was conducted in accordance with the Masters Random list. The two groups were comparable with regard to age, rhythm, valve distribution, and risk factors (Fig 5). Every month the study center received by post the INR values recorded in group A by family practitioners and the INR values recorded in group B by the patients themselves. Within the framework of the study, patients were also asked to record any complications (thromboembolism, hemorrhage) themselves, these records then being double-checked by the study center. All patients were required to visit the study center as outpatients for a cardiologic check-up every 6 months, including coagulation controls. Each patient therefore underwent four outpatient controls during the 2-year follow-up. All patients had been checked with the ultrasound system Sonos 2500/5500 from Hewlett-Packard (Agilent Technologies, Böblingen, Germany).

View larger version (16K): [in this window] [in a new window]   Fig 5. Distribution of risk factors between the two groups. 1 Men, body weight 15% higher than normal; women, body weight 10% higher than normal. 2 Blood pressure greater than 150/60 mm Hg. (AF = artrial fibrillation; n.s. = not significant.) *p 0.05.

Thromboembolism

Grade I Questionable events (eg, dizziness) not requiring medical treatment.

Grade II Complaints presumably connected with the ongoing anticoagulation, requiring outpatient treatment and causing no lasting impediments.

Grade III Prosthetic thrombosis, severe thromboembolism requiring inpatient treatment and causing long-term impediments (including transient ischemic attacks).

Bleeding

Grade I Mild bleeding (eg, of the gums) not requiring medical treatment.

Grade II Hemorrhage leading to outpatient medical care, not requiring surgical or endoscopic intervention.

Grade III Severe hemorrhage, requiring transfusion, surgical or endoscopic intervention and inpatient care. Long-term impediments.

Statistics
The statistical calculations were performed using SPSS 7.5 (SPSS GmbH Software, Munich, Germany) and represent our descriptive evaluations as of November 28, 1998. All results refer to the number of patients included and not the number of documented coagulation controls as this would distort the results considerably, the number of results submitted varying considerably from patient to patient. Variable independence was tested using Fisher’s exact test.

	Results

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
In all patients recruited for the ESCAT study since it began in 1994, oral anticoagulation was monitored using INR values. As shown in Figure 6, the observation period ranged from 25 to 51 months (mean, 38.32 months). This corresponds to an overall observation period of 1,916 patient-years (conventional group, 943 patient-years; self-management group, 973 patient-years).

View larger version (13K): [in this window] [in a new window]   Fig 6. ESCAT-1 observation period for 600 patients.

In our study, an anticoagulation intensity of INR 2.5 to 4.5 was selected as generally acceptable, regardless of prosthesis distribution. During the entire investigation period, a total of 28,292 (23,693 self-management; 4,599 conventional) workable INR values were submitted to our study center. The intensity distribution is shown in Figure 7.

View larger version (17K): [in this window] [in a new window]   Fig 7. Percentages within the therapeutic international normalized ratio (INR) range. (**p 0.01; ***p 0.001.)

Taken together for the entire observation period, grade III hemorrhagic and thromboembolic complications amounted to 74 events (Table 1). A statistically significant difference (p = 0.04) could be observed in favor of INR self-management (Fig 8). A high proportion of the complications in both therapeutic groups were hemorrhagic. The number of hemorrhagic complications was not significantly different between the two groups, the same as the number of thromboembolic complications.

View larger version (12K): [in this window] [in a new window]   Fig 8. Grade III complications, with a significant difference (*p = 0.04) between the two groups.

View larger version (13K): [in this window] [in a new window]   Fig 9. Freedom from grade III thromboembolic or hemorrhagic complications. (post op = postoperative; cum. = cumulative.)

View larger version (24K): [in this window] [in a new window]   Fig 10. Course of grade III complications during 24 months postoperatively.

	Comment

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

This improvement in the quality of ongoing anticoagulation was in itself sufficient to reduce the incidence of severe thromboembolic and hemorrhagic complications after mechanical heart valve replacement, with a statistical significance of p = 0.04. The considerable benefit to the patient was particularly noticeable in the first year of therapy, confirming indications for starting INR self-management early. Because of the relatively small amount of emerging anticoagulation-related complications accorded grade III, we have not differentiated between thromboembolic and hemorrhagic events. A detailed and secure statement about this issue is anticipated with the final evaluation of the ESCAT I study.

Animal experiments and clinical trials have shown that thrombi can occur intraoperatively, during the implantation of a valve replacement. Reasons for this are valvular and mural endocardial lesions on the one hand, and the polyethylene terephthalate fiber (Dacron) ring (DuPont Company, Wilmington, DE), anchoring the valve replacement and sewn with it into the surrounding tissue, on the other. Thrombocytes marked with indium-III are able to show that thrombocytes can be deposited around the valve ring as early as the first 24 hours after operation [13, 14]. This is further confirmation of the advantages of starting INR self-management early after mechanical heart valve replacement.

The quality of the anticoagulation can be considerably increased through the introduction of INR self-management. Our results show that INR self-management should commence immediately after the onset of anticoagulation therapy.

	Acknowledgments

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 
We thank all surgeons for their cooperation and also Mr. Otto Wagner for his support with the data management and statistics.

	References

Top Abstract Introduction Patients and methods Results Comment Acknowledgments References

 

1. Roberts W.C. Choosing a substitute cardiac valve; type, size, surgeon. Am J Cardiol 1976;38:633-644.[Medline]
2. Hammermeister K.E., Gulshan S., William G., Oprian C., Tai K., Shahbudin R. A comparison of outcomes in men 11 years after heart valve replacement with a mechanical or bioprosthesis. N Engl J Med 1993;328:1289-1296.[Abstract/Free Full Text]
3. Edmunds L.H. Thrombotic and bleeding complications of prosthetic heart valves. Ann Thorac Surg 1987;44:430-445.[Abstract]
4. Butchart E.G. Prosthesis-specific and patient-specific anticoagulation. In: Butchart E.G., Bodnar E., eds. Thrombosis, embolism and bleeding. London: ICR Publishers, 1992:293-317.
5. Forfar J.C. A 7-year analysis of haemorrhage in patients on long-term anticoagulant therapy. Br Heart J 1979;42:128-132.[Free Full Text]
6. Gaudel G., Fourchard J. Complications du traitment anticoagulant; a propos de 98 accidents et incidents. Sem Höp Paris 1979;55:1340-1345.[Medline]
7. Halhuber C. Quickwert-Selbstbestimmung durch den Pati-enten nach Herzklappenersatz. Herz Gefaesse 1987;7:240-246.
8. Davies F.B., Estruch M.T., Samson-Corvera E.B., Voigt G.C., Tobin J.D. Management of anticoagulation in outpatients, experience with an anticoagulation service in a municipal hospital setting. Arch Intern Med 1977;137:197-202.[Abstract]
9. Husted S., Andreasen F. Problems encountered in long-term treatment with anticoagulants. Acta Med Scand 1976;200:379-384.[Medline]
10. Second report of the Sixty Plus Reinfarction Study Research Group. Risks of long-term oral anticoagulant therapy in elderly patients after myocardial infarction. Lancet 1982;1:64–68.
11. Stein P.D., Albert J.S., Copeland J.M.G., Dalen J.E., Goldmann S., Turpie A.G.G. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. Chest 1995;108(Suppl):371S-379S.[Free Full Text]
12. Karnofsky D.A., Burchenal J.H. The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod C.M., ed. New York Academy of Medicine. Section on Microbiology. Symposia No. 2. New York: Columbia University Press, 1949:191-205.
13. Dewnjee M.K., Fuster V., Rao S.A., Forsham P., Kaye M. Non-invasive radioisotopic technique for detection of platelet deposition in mitral valve prostheses and quantification of visceral microembolism in dogs. Mayo Clin Proc 1983;58:307-314.[Medline]
14. Winter R. Antikoagulationstherapie mit Phenprocoumon unter besonderer Berücksichfigung der Komplikationen. Herz Med 1984;10:14-16.

This article has been cited by other articles:

				J. Ansell, J. Hirsh, E. Hylek, A. Jacobson, M. Crowther, and G. Palareti Pharmacology and Management of the Vitamin K Antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 160S - 198S. [Abstract] [Full Text] [PDF]

				R. W. Emery, A. M. Emery, A. Knutsen, and G. V. Raikar Aortic Valve Replacement with a Mechanical Cardiac Valve Prosthesis Card. Surg. Adult, January 1, 2008; 3(2008): 841 - 856. [Full Text]

				P. Herijgers and P. Verhamme Improving the quality of anticoagulant therapy in patients with mechanical heart valves: what are we waiting for? Eur. Heart J., October 2, 2007; 28(20): 2424 - 2426. [Full Text] [PDF]

				H. Koertke, A. Zittermann, O. Wagner, and R. Koerfer Self-Management of Oral Anticoagulation Therapy Improves Long-Term Survival in Patients With Mechanical Heart Valve Replacement Ann. Thorac. Surg., January 1, 2007; 83(1): 24 - 29. [Abstract] [Full Text] [PDF]

				K. L. Scolaro, P. L. Stamm, and K. B. Lloyd Devices for ambulatory and home monitoring of blood pressure, lipids, coagulation, and weight management, part 2 Am. J. Health Syst. Pharm., September 15, 2005; 62(18): 1894 - 1903. [Abstract] [Full Text] [PDF]

				F. Dagenais, P. Cartier, P. Voisine, D. Desaulniers, J. Perron, R. Baillot, G. Raymond, J. Metras, D. Doyle, and P. Mathieu Which biologic valve should we select for the 45- to 65-year-old age group requiring aortic valve replacement? J. Thorac. Cardiovasc. Surg., May 1, 2005; 129(5): 1041 - 1049. [Abstract] [Full Text] [PDF]

				S. Schulman and R. J. Beyth Risk of bleeding with long-term antithrombotic therapy in atrial fibrillation Eur. Heart J. Suppl., May 1, 2005; 7(suppl_C): C34 - C40. [Abstract] [Full Text] [PDF]

				B. Menendez-Jandula, J. C. Souto, A. Oliver, I. Montserrat, M. Quintana, I. Gich, X. Bonfill, and J. Fontcuberta Comparing Self-Management of Oral Anticoagulant Therapy with Clinic Management: A Randomized Trial Ann Intern Med, January 4, 2005; 142(1): 1 - 10. [Abstract] [Full Text] [PDF]

				J. Ansell, J. Hirsh, L. Poller, H. Bussey, A. Jacobson, and E. Hylek The Pharmacology and Management of the Vitamin K Antagonists: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 204S - 233S. [Abstract] [Full Text] [PDF]

				M. N. Levine, G. Raskob, R. J. Beyth, C. Kearon, and S. Schulman Hemorrhagic Complications of Anticoagulant Treatment: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 287S - 310S. [Abstract] [Full Text] [PDF]

				H. Koertke, K. Minami, D. Boethig, Th. Breymann, D. Seifert, O. Wagner, N. Atmacha, A. Krian, J. Ennker, U. Taborski, et al. INR Self-Management Permits Lower Anticoagulation Levels After Mechanical Heart Valve Replacement Circulation, September 9, 2003; 108(90101): II-75 - 78. [Abstract] [Full Text] [PDF]

				C. Hagl, J. T. Strauch, D. Spielvogel, J. D. Galla, S. L. Lansman, R. Squitieri, C. A. Bodian, and R. B. Griepp Is the bentall procedure for ascending aorta or aortic valve replacement the best approach for long-term event-free survival? Ann. Thorac. Surg., September 1, 2003; 76(3): 698 - 703. [Abstract] [Full Text] [PDF]

				S. Schulman Care of Patients Receiving Long-Term Anticoagulant Therapy N. Engl. J. Med., August 14, 2003; 349(7): 675 - 683. [Full Text] [PDF]

				H. Koertke, A. Hoffmann-Koch, D. Boethig, K. Minami, T. Breymann, M. El-Arousy, D. Seifert, and R. Koerfer Does the noise of mechanical heart valve prostheses affect quality of life as measured by the SF-36(R) questionnaire? Eur. J. Cardiothorac. Surg., July 1, 2003; 24(1): 52 - 58. [Abstract] [Full Text] [PDF]

				J. Hirsh, V. Fuster, J. Ansell, and J. L. Halperin American Heart Association/American College of Cardiology Foundation guide to warfarin therapy J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1633 - 1652. [Full Text] [PDF]

				J. Hirsh, V. Fuster, J. Ansell, and J. L. Halperin American Heart Association/American College of Cardiology Foundation Guide to Warfarin Therapy Circulation, April 1, 2003; 107(12): 1692 - 1711. [Full Text] [PDF]

				T. D. Christensen, N. T. Andersen, J. Attermann, V. E. Hjortdal, M. Maegaard, and J. M. Hasenkam Mechanical heart valve patients can manage oral anticoagulant therapy themselves Eur. J. Cardiothorac. Surg., March 1, 2003; 23(3): 292 - 298. [Abstract] [Full Text] [PDF]

				H. Voller, C. Dovifat, and J. Glatz Home management of anticoagulation Eur. Heart J. Suppl., December 1, 2001; 3(suppl_Q): Q44 - Q49. [Abstract] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Reiner Körfer Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Körtke, H. Articles by Körfer, R. Search for Related Content PubMed PubMed Citation Articles by Körtke, H. Articles by Körfer, R. Related Collections Valve disease