Abstract
Background: Primary goal of anticoagulation treatment in patients with mechanical heart valve is the effective prevention of thromboembolism and safe avoidance of bleeding as well. Material and Method: Two-hundred and nine patients with the St. Jude Medical prosthesis operated on between 1984 and 1995, for mitral(MVR 122), aortic(AVR 39) and double mitral and aortic valve replacement(DVR 48) respectively, were studied on the practically achieved levels of anticoagulation and the clinical outcomes. Patients were on Coumadin and followed up by monthly visit to outpatient clinic for examination and prothrombin time measurement to adjust the International Normalized Ratios(INRs) within the low-intensity target range between 1.5 and 2.5. Result: A total anticoagulation follow-up period was 1082.0 patient- years(mean 62.1 months) and INRs of 10,205 measurements were available for evaluation. The accomplished INRs among the replacement groups were not significantly different and only 65% of INRs were within the target range. And, in individual patients, only 37% of patients had INRs included within the target range in more than 70% of tests during follow-up period. The levels of INRs in patients with atrial fibrillation, which was found in 57% of patients, were definitely higher than the ones measured in patients with regular rhythm(p<0.001). Thromboembolisms were experienced by 15 patients with the incidence of 1.265%/patient- year(MVR 1.412%, AVR 0.462% and DVR 1.531%/patient-year) and major bleeding by 4 patients with the incidence of 0.337%/patient-year(MVR 0.424%, AVR none and DVR 0.383%/patient-year). Frequent as well as prolonged missing of prothrombin time tests was the main risk factor strongly associated with the thromboembolic complications(odds ratio 1.99). The proportion of INRs within target range of less than 60% in individual patient was the highly significant risk factor of both thromboembolic and overall embolic and bleeding complications(p<0.004 and p<0.002 respectively). Conclusion: In conclusion, the low-intensity therapeutic target range of INRs was adequate in patients with AVR and in sinus rhythm. However, the patients with replacement of the mitral valve were more likely to require higher target range of INRs, especially in the presence of atrial fibrillation, to achieve the practical levels of anticoagulation enough to prevent thromboembolic complications effectively. For the higher therapeutic target range of INRs between 2.0∼3.0, further accumulation of clinical evidences are required. It is highly desirable to improve the patients' compliance under continuous instructions in visiting outpatient clinic and in taking daily Coumadin without omission and to keep INRs consistently within optimal range with tight control for minimization of chances and of periods of exposure to the risk of complications. And, particularly, patients with high risk of complications and with wide fluctuation of INRs should be better managed with frequent monitoring anticoagulation levels.
배경: 기계적 보철판막을 사용한 환자에서의 항응혈제 치료의 목표는 혈전전색의 효과적 예방과 출혈의 안전한 방지에 있다. 대상 및 방법: 1984년부터 1995년까지 쎈트쥬드판막으로 심장판막을 치환한 209례(승모판치환 122, 대동맥판치환 48, 중복판막치환 48)의 환자에서 실제로 수행된 항응혈제 수준과 임상적 결과를 분석하였다. 쿠마딘으로 항응혈제 치료를 개시하고 원칙적으로 월 1회의 외래 내원하여 검사와 프로트롬빈시간 측정으로 국제정상화비(International Normalized Ratio : INR)를 낮은 강도의 치료적 목표범위 1.5∼2.5 내에 조정하였다. 결과: 총 항응혈제 추적기간은 1082.0환자년(평균 62.1개월)이고 프로트롬빈시간 검사는 총 10,205회였다. 치환판막군간에 유의한 차이없이 총 측정수의 65%에서의 INR값만이 목표범위이내에 있었다. 각 환자에서 추적기간중 시행한 프로트롬빈시간 측정의 70%이상이 목표범위에 포함되었던 환자는 77례(37%)에 불과하였다. 환자의 57%에서 본 심방세동이 있던 환자에서의 INR수준은 정상동률이던 환자에서의 수준보다 분명하게 높았다(p<0.001). 혈전전색증은 15례가 경험하여 연간빈도가 1.265%/환자년(승모판치환 1.412%/환자년, 대동맥판치환 0.462%/환자년, 중복판막치환 1.531%/환자년)이고 출혈은 4례로 0.337%/환자년의 연간빈도를 보였다(승모판치환 0.424%/환자년, 대동맥판치환은 없고, 중복판막치환 0.383%/환자년). 빈번하거나 장기간의 프로트롬빈시간 측정의 탈락은 혈전전색합병증에 크게 연관된 주요 위험요소였다(대응비 1.99). 각 환자에서의 INR값이 목표범위내에 포함된 비율이 60%에 미달하였던 환자에서는 혈전전색합병증과 전색과 출혈의 종합합병증의 발생률이 높아 명확하게 큰 위험요소였다(각각 p<0.004 및 p<0.002). 결론: 낮은 강도의 치료적 목표범위가 대동맥판치환이고 정상동률인 환자에서는 적절한 수준인 듯 하다. 그러나 승모판을 치환한 환자에서 특히 심방세동을 동반할 때에는 혈전전색합병증을 효과적으로 예방하기에 충분한 실제적 항응혈제 수준을 성취하려면 보다 높은 INR의 목표범위가 필요할 듯 하며 INR 2.0∼3.0을 치료적 목표범위로 하는 임상적 결과의 축적이 필요하다. 환자가 합병증에 노출되는 기회와 기간을 최소화하려면 주기적 외래방문을 지키고 쿠마딘 복용을 빼지 않도록 계속 지도하여 환자의 순응도를 높이는 동시에 INR값을 엄격하게 적정범위 내에 일관되게 유지하여야 한다. 특히 합병증의 위험요소가 있는 환자와 INR값의 변동폭이 지나치게 넓은 환자에서는 빈번한 항응혈제 수준의 감시가 필요하다.
