Perbandingan Mortalitas Kardiak, Reinfark dan Stroke Serta Efek Perdarahan antara Heparin, Enoxaparin dan Fondaparinux pada Infark Miokard Akut ST Elevasi tanpa Reperfusi Dini

Abstract

The decrease of mortality rate in STEMI for the last two decades was related to the advent of early reperfusion strategy. However, previous studies showed that approximately 25-33% of those with STEMI were not reperfused early after the onset. This study aimed to compare the effectivity (cardiac death and MACCE) and safety due to bleeding event within hospitalization and 30 days after the onset of the infarction in those with STEMI who were not performed early reperfusion therapy. The design of the study was prospective cohort. Thirty eight patients (34,2%) were enrolled in the UFH group, while those who used enoxaparin and fondaparinux were each 34 patients (30,6%) and 38 patients (35,1%). Those in the UFH arm were given bolus dose of 60 IU/kg bodyweight and then started continuous infusion dose of 12 IU/hour in the range of 48 up to 72 hours. Those in the enoxaparin arm were given bolus dose 30 mg intravenously and then followed by dose of subcutaneus injection 60 mg fifteen minutes later, and every twelve hours thereafter up to 5 days. Those in the fondaparinux arm were given first dose 2,5 mg intravenously and then followed by subcutaneous dose 2,5 mg every 24 hours for 5 days. There was neither difference on inhospital cardiac death between enoxaparin and UFH (P = 0,66, RR = 0,60, 95% CI : 0,10-3,36), nor between fondaparinux and UFH (P = 1,00, RR = 0,68, 95% CI : 0,12-3,87). There was no difference between fondaparinux and enoxaparin, either (P = 1,00, RR = 1,15, 95% CI : 0,25-5,31). The comparison of inhospital MACCE among the three were ; no difference between enoxaparin and UFH (P = 0,66, RR = 0,59, 95% CI : 0,10-3,36), between fondaparinux and UFH with P = 0,43, RR = 0,41, 95% CI : 0,08-1,99, and between fondaparinux versus enoxaparin , either (P = 0,72, RR = 0,69, 95% CI : 0,17-2,67). Only mild bleeding (gross hematuria) was noted in this study. The event rate of gross hematuria was only noted to be significantly different between fondaparinux and UFH (P = 0,03, RR = 0,84, 95% CI : 0,71- 0,98). There were no difference in the event of cardiac death and MACCE 30 days after the onset of the infarction among the anticoagulants. The conclusion of the study was that there were no difference of cardiac death event and MACCE within hospitalization and 30 days after the onset of the infarction among the three anticoagulan in those with STEMI who were not performed early reperfusion. The bleeding events were rare among the anticoagulant with the highest rate of mild bleeding was found in those who used UFH.

Penurunan angka mortalitas IMA STE dalam 2 dekade terakhir berhubungan dengan kemajuan tindakan reperfusi dini, baik secara mekanik (IKP primer) maupun farmakologis, menggunakan regimen fibrinolitik, serta obat-obat pendukung lainnya. Meskipun begitu, sekitar 25-33% penderita IMA STE pada studi sebelumnya tidak mendapat terapi reperfusi dini. Tujuan dari penelitian ini adalah untuk membandingkan efektifitas (kejadian cardiac death dan MACCE) selama perawatan di rumah sakit dan 30 hari paska infark serta kejadian efek perdarahan antara antikoagulan unfraction heparin (UFH), enoxaparin serta fondaparinux pada penderita IMA STE yang tidak dilakukan reperfusi dini Penelitian ini bersifat kohort prospektif. Sebanyak 38 orang (34,2%) menggunakan UFH, 34 orang (30,6%) menggunakan enoxaparin serta 39 orang (35,1%) menggunakan fondaparinux. Kelompok UFH diberikan dosis bolus 60 UI/kgbb dilanjutkan dengan dosis perdrip 12 UI/jam dalam rentang waktu pemberian 48 sampai 72 jam. Kelompok enoxaparin diberikan dosis loading pertama 30 mg iv bolus yang dilanjutkan 15 menit kemudian dengan 60 mg subkutan setiap 12 jam selama 5 hari. Kelompok fondaparinux diberikan dosis pertama 2,5 mg iv bolus yang dilanjutkan dengan 2,5 mg subkutan per 24 jam selama 5 hari. Tidak ada perbedaan kejadian cardiac death di rumah sakit antara enoxaparin dengan UFH (P = 0,66, RR = 0,60, 95% IK : 0,10-3,36), antara fondaparinux dengan UFH (P = 1,00, RR = 0,68, 95% IK : 0,12-3,87) serta antara fondaparinux dengan enoxaparin (P = 1,00, RR = 1,15 ( 95% IK: 0,25-5,31). Hasil perbandingan MACCE di rumah sakit adalah tidak dijumpai perbedaan antara enoxaparin dengan UFH (P = 0,66, RR = 0,59 (95% IK : 0,10-3,36), antara fondaparinux dengan UFH (P = 0,43, RR = 0,41 (95% IK : 0,08-1,99), serta antara fondaparinux dengan enoxaparin (P = 0,72 RR = 0,69 dan 95% IK: 0,17-2,67). Hanya dijumpai perdarahan ringan berupa gross hematuria. Kejadian gross hematuria hanya berbeda secara bermakna antara fondaparinux dengan UFH (P = 0,03, RR = 0,84, 95% IK : 0,71-0,98). Tidak dijumpai perbedaan kejadian cardiac death dan MACCE selama 30 hari paska infark pada ketiga kelompok obat. Penelitian ini menunjukkan bahwa tidak ada perbedaan efektifitas antara ketiga kelompok antikoagulan pada IMA STE yang tidak dilakukan reperfusi dini. Hanya dijumpai kejadian perdarahan ringan pada studi ini yang secara bermakna lebih banyak dijumpai pada mereka yang menggunakan UFH.