thrombolysis versus anticoagulation for the initial treatment of moderate pulmonary embolism: a...
TRANSCRIPT
![Page 1: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/1.jpg)
Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism:
A Meta-Analysis of Randomized Controlled TrialsChen H, Ren C, Chen H
Respir Care 2014;59(12):1880–1887
Ferdy Ferdian, dr
Penilai: Dr. Ria Bandiara, dr, SpPD-KGH
Pembimbing: Lilik Sukesi, dr, SpPD-KIC
Pembacaan jurnal
5 Mei 2015
![Page 2: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/2.jpg)
Latar belakang
• Emboli paru atau Pulmonary Embolism (PE) merupakan penyakit penyumbatan pembuluh darah paru yang mengancam nyawa. Diperkirakan insiden PE adalah 6-7 per 10.000 orang dan angka mortalitas 3 bulan sampai 17% 1,2
1 Aujesky et al, 2009. Circulation 2009;119(7):962-9682 Laporte et al, 2008, Circulation 2008;117(13):1711-1716
![Page 3: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/3.jpg)
Latar belakang
• Sampai saat ini penggunaan trombolitik sebagai terapi awal pada moderate PE masih menjadi kontroversi. Penelitian-penelitian, metaanalisis bahkan guideline sebelumnya mengatakan bahwa trombolitik tidak memberikan manfaat dalam menurunkan mortalitas ataupun rekurensi PE 3
3 Respir Care 2014;59(12):1880–1887
![Page 4: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/4.jpg)
Apa itu moderate PE?
4 Eur Heart J 2000; 21: 1301-36.5 European Heart Journal (2008) 29, 2276–2315
Non highrisk (intermedite) PE
![Page 5: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/5.jpg)
Latar belakang
• Metaanalisis ini bertujuan untuk memberikan informasi terkini yang membandingkan peran trombolisis dan antikoagulan pada penderita moderate PE 3
3 Respir Care 2014;59(12):1880–1887
![Page 6: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/6.jpg)
Metodologi penelitian
• Pencarian melalui Pubmed, Embase, Cochrane library, Wanfang dan database CNKI
• Studi dari awal Januari 1980 – Juni 2013
• Inklusi : RCT, PE dgn hemodinamik stabil, terapi trombolitik vs antikoagulan, keluaran yang sesuai
• Eksklusi : usia <18 tahun, hamil menyusui, PE massive 3
3 Respir Care 2014;59(12):1880–1887
![Page 7: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/7.jpg)
Metodologi penelitian
• Keluaran penelitian
– Keluaran primer
• Rekurensi PE dan mortalitas
– Keluaran sekunder
• Keamanan terapi berupa perdarahan mayor dan nonmayor 3
3 Respir Care 2014;59(12):1880–1887
![Page 8: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/8.jpg)
Metodologi penelitian
• Analisa statistik
– Heterogenitas dengan Cocran Q test
– Odd ratio (OR) dgn 95% confidence interval (CI)
– Hasil akan ditampilkan berupa forrest plot
– Bias dievaluasi dengan funnel plot
– Signifikan P <0.05 3
3 Respir Care 2014;59(12):1880–1887
![Page 9: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/9.jpg)
Hasil penelitian
• 1469 artikel ditemukan
• 15 RCT dimasukkan berdasarkan kriteria inklusi dengan total sampel 1247 pasien 3
3 Respir Care 2014;59(12):1880–1887
![Page 10: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/10.jpg)
3 Respir Care 2014;59(12):1880–1887
![Page 11: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/11.jpg)
3 Respir Care 2014;59(12):1880–1887
Terapi trombolitik pada moderate PE bila dibandingkan dengan terapi antikoagulanterapi trombolitik dapat menurunkan angka kematian secara keseluruhan dan rekurensi terjadinya PE secara signifikan (1.94% vs 5.87% Odds Ratio (OR) 0.37, 95% CI 0.21–0.66p for heterogenity 0.49Test for overall effect Z =3.35, P = 0.0008) 3
![Page 12: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/12.jpg)
Respir Care 2014;59(12):1880–1887
Terapi trombolitik pada moderate PE bila dibandingkan dengan terapi antikoagulanterapi trombolitik dapat meningkatkan resiko perdarahan mayor secara tidak signifikan (3.57% vs 2.67%, OR 1.34, 95% CI 0.70 –2.58) terapi trombolitik dapat meningkatkan resiko perdarahan minor secara signifikan (12.78% vs 3.65%, OR 4.12, 95% CI 2.37–7.17)
Hasil penelitian
![Page 13: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/13.jpg)
Diskusi
• Metaanalisis ini menunjukan bahwa penggunaan trombolitik sebagai terapi inisial pada moderate PE dapat menurunkan mortalitas dan rekurensi PE bila dibandingkan dengan terapi antikoagulan 3
3 Respir Care 2014;59(12):1880–1887
![Page 14: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/14.jpg)
Diskusi• Wan et al, 2004, metaanalisis dengan jumlah sampel
sebesar 748 pasien PE, didapatkan bhw terapi trombolitik hanya bermanfaat pd highrisk PE 6
• Ramakhrisnan et al, 2007, metaanalisis dengan jumlah sampel sebesar 494 pasien submasive PE, didapatkan bhw terapi trombolitik tidak berbeda bermakna dengan terapi antikoagulan dalam mencegah rekurensi PE 76 Wan et al, 2004, Circulation. 2004;110:744-7497 Ramakhrisnan et al, 2007. Crit Care Resusc 2007; 9: 357–363
![Page 15: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/15.jpg)
Non highrisk (intermedite) PE
8 Konstantinides S. N Engl J Med 2008;359:2804-13.
![Page 16: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/16.jpg)
![Page 17: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/17.jpg)
Apakah terdapat syok / hipotensi?
Bila ya, masuk highrisk PEDan dapat diberikan terapi trombolitik
Bila tidak, masuk non highrisk PE
Hitung PESI
Bila PESI score class 3 sampai 5Periksakan 1) Echo / CTA untuk menilai right ventricel2) Biomarker (troponin T / BNP)
Bila keduanya positifPasien merupakan pasien intermediete highrisk PEyang dapat menjadi kandidat untuk trombolisisAsalkan tidak ada kontraindikasi
9 Konstantinides et al, 2014. Eur Heart J 2014 Aug 29.
![Page 18: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/18.jpg)
Bagaimana posisi meta analisis ini ?
![Page 19: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/19.jpg)
Diskusi• Penggunaan trombolitik meningkatkan resiko
perdarahan non mayor secara signifikan 3
3 Respir Care 2014;59(12):1880–188710 NICE 2010 clinical guideline
![Page 20: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/20.jpg)
Diskusi
• Metaanalisis ini mengikutsertakan penelitian RCT dengan jumlah terbanyak bila dibandingkan metanalisis sebelumnya
• Subanalisis penelitian mengatakan bahwa penelitian RCT asing maupun RCT dalam Cina sama sama bermakna dalam hal primary dan secondary outcome 3
3 Respir Care 2014;59(12):1880–1887
![Page 21: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/21.jpg)
Kesimpulan• Moderate PE adalah PE dengan hemodinamik stabil
dimana sudah didapatkan disfungsi RV atau peningkatan biomarker kerusakan miocard
• Moderate PE dapat diberikan trombolisis dengan pertimbangan khusus, mengingat metaanalisis membuktikan bahwa resiko perdarahan meningkat pada pasien yang diberikan terapi trombolisis 3
3 Respir Care 2014;59(12):1880–1887
![Page 22: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/22.jpg)
Critical appraisalAre the results of this meta-analysis valid?
• Is this a meta-analysis of randomized trials?
– Ya. Peneliti hanya memasukan penelitian RCT
• Does it describe a comprehensive and detailed search for relevant trials ?
– Ya. Peneliti melakukan pencarian dari database PubMed, Embase, Cochrane library, Wanfang dan database CNKI. Tidak ada batasan bahasa dalam pencarian.
– Pencarian dilakukan dari awal Januari 1980 – Juni 2013. Pencarian juga dilakukan terhadap referensi artikel dan review-review sebelumnya
• Were the individual studies assessed for validity ?
– Peneliti menggunakan Cochrane Collaboration tool untuk menilai risiko bias dari masing-masing studi dan bias di antara studi
PENELITIAN INI VALID
![Page 23: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/23.jpg)
Critical appraisalIs the valid results of this study important?
• Are the results consistent across studies ?
– Tidak. Tidak semua studi mendukung terapi trombolitik pada moderate PE bila dibandingkan dengan antikoagulan, namun setelah dilakukan metaanalisis didapatkan hasil bahwa terapi trombolitik dapat menurunkan kematian secara keseluruhan dan rekurensi PE
• What is the magnitude of the treatment effect ?
– Terapi trombolitik pada moderate PE bila dibandingkan dengan terapi antikoagulan, terapi trombolitik dapat menurunkan angka kematian secara keseluruhan dan rekurensi terjadinya PE secara signifikan (1.94% vs 5.87%, Odds Ratio (OR) 0.37, 95% CI 0.21–0.66, P for heterogeneity = 0.49)
• How precise is the treatment effect ?
– 95% confident interval CI 0.21– 0.66. CI memiliki rentang nilai yang sempit
![Page 24: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/24.jpg)
Critical appraisalIs the valid results of this study really important?
PENELITIAN INI TIDAK PENTING
![Page 25: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/25.jpg)
Critical appraisalAre the valid result of this study applicable to our patients?
• Is our patient so different from those in the study that its results cannot apply?
– Tidak, populasi studi dengan moderate PE
• Is the treatment feasible in our setting ?
– Ya, pemberian trombolitik dapat dilakukan di RSHS
• What are our patient’s potential benefits and harms from the therapy?
– Pemberian terapi trombolitik dipertimbangkan pada penderita moderate highrisk PE, karena dapat menurunkan angka kematian dan rekurensi PE. Pemberian terapi trombolitik meningkatkan resiko perdarahan sehingga penggunaannya harus tetap berhati hati
PENELITIAN INI DAPAT DITERAPKAN
![Page 26: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/26.jpg)
Sekian dan terimakasih
Yin & Yang
Be strong, but not rude
Be kind, but not weak
Be bold, but don't bully
Be humble, but not shy
Be confident, but not arrogant
![Page 27: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/27.jpg)
Funnel plot
![Page 28: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/28.jpg)
Disfungsi RV berdasarkan echo
![Page 29: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/29.jpg)
Konstantinides S. N Engl J Med 2008;359:2804-13.
![Page 30: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/30.jpg)
Konstantinides S. N Engl J Med 2008;359:2804-13.
![Page 31: Thrombolysis Versus Anticoagulation for the Initial Treatment of Moderate Pulmonary Embolism: A Meta-Analysis of Randomized Controlled Trials](https://reader033.vdocuments.us/reader033/viewer/2022052602/55a975301a28abba2a8b484e/html5/thumbnails/31.jpg)
Diskusi