SKRIPSI BARLANTY FATHANAHIYAH
STUDI PENGGUNAAN CAPTOPRIL PADA PASIEN STROKE ISKEMIK (Penelitian di Rumah Sakit Umum Daerah Sidoarjo)
PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG 2015
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KATA PENGANTAR
Bismillahirrohmanirrohim Assalamu’alaikum warohmatullahi wabarokatuh Puji syukur tercurahkan kepada ALLAh SWT, tuhan semesta alam karena berkat rahmad dan ridhonya, penulis dapat menyelesaikan skripsi yang berjudul STUDI PENGGUNAAN CAPTOPRIL PADA PASIEN STROKE ISKEMIK (Penelitian di Rumah Sakit Umum Daerah Sidoarjo). Skripsi ini diajukan untuk memenuhi syarat untuk mencapai gelar Sarjana Farmasi pada Program Studi Farmasi Fakultas Ilmu Kesehatan Universitas Muhammadiyah Malang. Dalam penyusunan skripsi ini penulis tidak terlepas dari peranan pembimbing dan bantuan dari seluruh pihak. Oleh karena itu, dengan segala kerendahan hati, penulis ingin mengucapkan banyak terima kasih kepada: 1.
ALLAH SWT, tuhan semesta alam yang memberikan rahmat, nikmat dan hidayahNYA kepada umatnya, Rosulullah SAW, yang sudah menuntun kita menuju jalan yang lurus.
2.
Bapak Yoyok Bekti Prasetyo, M.Kep., Sp. Kom selaku Dekan Fakultas Ilmu
Kesehatan Universitas Muhammadiyah
Malang
yang telah
memberikan kesempatan penulis belajar di Fakultas Ilmu Kesehatan Universitas Muhammadiyah Malang. 3.
Ibu Nailis Syifa, S.Farm., MSc., Apt selaku Ketua Program Studi Farmasi Universitas Muhammadiyah Malang yang telah memberi motivasi dan kesempatan penulis belajar di Program Studi Farmasi Universitas Muhammadiyah Malang.
4.
dr. Atok Irawan, Sp. P selaku Direktur Rumah Sakit Umum Daerah Sidoarjo beserta jajarannya yang telah memberikan kesempatan pada penulis untuk melakukan penelitian di Rumah Sakit Umum Daerah Sidoarjo.
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5.
Staf pengawai RMK RSUD Sidoarjo yang banyak membantu dalam proses pengambilan data skripsi.
6.
Ibu
Nailis
Syifa’,S.Farm.,M.Sc.,Apt.,
dan
Bapak
Drs.
Didik
Hasmono,M.S.,Apt., selaku Dosen Pembimbing I dan II, disela kesibukan Bapak dan Ibu masih bisa meluangkan waktu untuk membimbing dan memberi pengarahan dan dorongan moril sampai terselesaikannya skripsi ini. 7.
Ibu Dra. Lilik Yusetyani, Apt., Sp.FRS., dan Ibu Hidajah Rachmawati, S.Si., Apt., Sp.FRS selaku Dosen Penguji I dan II, yang telah banyak memberikan saran dan masukan demi kesempurnaan skripsi ini.
8.
Ibu Sovia Aprina Basuki, S.Farm., Apt., M. Si. selaku Dosen wali. Terima kasih banyak atas arahan, nasehat, dan bimbingannya selama ini.
9.
Untuk semua Dosen Farmasi Universitas Muhamadiyah Malang yang sudah memberikan waktunya untuk mengajarkan ilmu-ilmu yang sangat berguna, khususnya kepada Ibu Sendi Lia Yunita, S.Farm., Apt., selaku Dosen penanggung jawab skripsi yang telah susah payah membantu jalanya ujian skripsi sehingga kami dapat melaksanakan ujian skripsi dengan baik.
10. Untuk semua angggota tata usaha Program Studi Farmasi Fakultas Ilmu kesehatan Universitas Muhammadiyah Malang, yang telah banyak membantu untuk kebutuhan administrasi kelengkapan skripsi. 11. Orang Tuaku tercinta, Bapak Tri Akbari Hadi dan Ibu Sarulin, yang tiada hentinya memotivasi dalam segala hal, dengan sabar mendoakan untuk kebaikan dan kesuksesan anak-anaknya. Terima kasih banyak atas didikan dan kerja keras untuk membuat anak-anaknya bahagia serta mendapatkan ilmu yang bemanfaat. 12. Saudariku Hazra Farahiyah Ramadhani dan Albirr Rifqi Raziz, terima kasih buat motivasi dan doanya sehingga skripsi ini dapat selesai tepat waktu. 13. Sahabat seperjuanganku Dwi Qurrothul Aini, Zeni Putri A.D.T, Nifda Novi A, Siti Maslahah S, dan Bernika Ika I terima kasih atas kebersamaan,
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bantuan, motivasi, semangat kalian selama ini sebagai sahabat yang membantu dan mendukung saat senang maupun susah. 14. Teman-teman seperjuangan kelompok skripsi Dwi, Zeni, Ayu, Fina dan Alif dengan keceriaan dan semangat kalian selama ini sebagai sahabat yang membantu dan mendukung sehingga skripsi ini dapat terwujud. 15. Teman-teman Farmasi UMM 2011, khususnya Farmasi D terima kasih atas kebersamaan dan kenangan indah selama ini, terima kasih atas pelajaran hidup yang diberikan. 16. Keluarga besar kontrakan MSC AS SYFA terima kasih banyak atas kebersamaannya, dukungan, semangat, doa, dan motivasinya serta ilmu agama yang telah diajarkan kepada saya hingga Insyaallah bermanfaat nantinya. 17. Untuk semua pihak yang belum disebutkan namanya, penulis mohon maaf dan terima kasih yang sebesar-besarnya. Semua keberhasilan ini tak luput dari bantuan, doa yang telah kalian semua berikan. Jasa dari semua pihak yang telah membantu dalam penelitian ini, penulis tidak mampu membalas dengan apapun. Semoga amal baik semua pihak mendapat imbalan dari Allah SWT. Penulis menyadari bahwa skripsi ini jauh dari kesempurnaan, oleh karena itu penulis mengharapkan saran
dan kritik yang
membangun dari pembaca demi kebaikan skripsi ini. Semoga penulisan ini dapat berguna bagi penelitian berikutnya, amiin. Wassalamu’alaikum warohmatullohi wabarokatuh
Malang, 26 Juni 2015 Penyusun
(Barlanty Fathanahiyah)
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DAFTAR ISI Halaman HALAMAN JUDUL........................................................................................
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DAFTAR ISI .................................................................................................... ii DAFTAR TABEL ............................................................................................ iv DAFTAR GAMBAR ....................................................................................... v BAB I PENDAHULUAN ............................................................................. 1 1.1 Latar Belakang ............................................................................ 1 1.2 Rumusan Masalah ........................................................................ 4 1.3 Tujuan .......................................................................................... 4 1.4 Manfaat ........................................................................................ 4 BAB II TINJAUAN PUSTAKA .................................................................... 5 2.1 Tinjauan Tentang Stroke .............................................................. 5 2.1.1 Definisi ............................................................................ 5 2.1.2 Epidemiologi ................................................................... 5 2.1.3 Etiologi ............................................................................ 6 2.1.3.1 Aterosklerosis ............................................................. 6 2.1.3.2 Emboli ........................................................................ 7 2.1.3.3 Trombosis................................................................... 7 2.1.3.4 AIDS .......................................................................... 8 2.1.3.5 Infeksi ......................................................................... 8 2.1.3.6 Angiitis granulomatosa .............................................. 8 2.1.3.7 Obat-obatan ................................................................ 9 2.1.3.8 Vena atau sinus trombosis.......................................... 9 2.1.3.9 Infark lakunar ............................................................. 10 2.1.4 Klasifikasi ....................................................................... 10 2.1.5 Faktor Resiko .................................................................. 13 2.1.5.1 Usia ............................................................................ 13 2.1.5.2 Jenis kelamin .............................................................. 13 2.1.5.3 Faktor Genetik ............................................................ 14 2.1.5.4 Ras .............................................................................. 14 2.1.5.5 Hipertensi ................................................................... 15 2.1.5.6 Diabetes ...................................................................... 15 vii
2.1.5.7 Merokok ..................................................................... 16 2.1.5.8 Dislipidemia ............................................................... 16 2.1.5.9 Konsumsi Alkohol ..................................................... 17 2.1.6 Patofisiologi .................................................................... 18 2.1.7 Komplikasi ...................................................................... 20 2.1.7.1 Pneumonia, Septicemia .............................................. 21 2.1.7.2 Infark miokard, aritmia, dan gagal jantung ................ 21 2.1.7.3 DVT ........................................................................... 21 2.1.7.4 Ketidakseimbangan Cairan ........................................ 21 2.1.8 Tanda dan Gejala............................................................. 21 2.1.9 Penatalaksanaan Terapi ................................................... 22 2.1.10 Terapi Stroke Iskemik ..................................................... 24 2.1.10.1 rTPA ......................................................................... 25 2.1.10.2 Antiplatelet ............................................................... 26 2.1.10.3 Antikoagulan ............................................................ 28 2.1.10.4 Neuroprotektan ......................................................... 28 2.1.10.5 Antihipertensi ........................................................... 29 2.1.11 Rehabilitasi Setelah Stroke ............................................. 34 2.2 Tinjauan Captopril ....................................................................... 35 2.2.1 Struktur Kimia ................................................................... 35 2.2.2 Mekanisme Kerja ............................................................... 36 2.2.3 Dosis .................................................................................. 37 2.2.4 Farmakokinetik .................................................................. 37 2.2.5 Efek Samping ..................................................................... 37 2.2.6 Penggunaan Captopril pada Ischemic CVA ...................... 37 2.2.7 Sediaan ............................................................................... 38 BAB III KERANGKA KONSEP .................................................................... 39 BAB IV METODE PENELITIAN .................................................................. 42 4.1 Rancangan Penelitian ................................................................... 42 4.2 Populasi dan Sampel .................................................................... 42 4.2.1 Populasi .............................................................................. 42 4.2.2 Sampel ............................................................................... 42
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4.2.3 Kriteria Data Inklusi ......................................................... 42 4.2.4 Kriteria Data Eksklusi ........................................................ 42 4.3 Bahan penelitian .......................................................................... 43 4.4 Intrumen Penelitian ...................................................................... 43 4.5 Tempat dan Waktu penelitian ...................................................... 43 4.6 Definisi Operasional ................................................................... 43 4.7 Metode Pengumpulan Data .......................................................... 44 4.8 Analisis Data ................................................................................ 44 BAB V HASIL PENELITIAN ...................................................................... 45 5.1 Data Demografi Pasien ................................................................ 46 5.1.1 Jenis Kelamin .......................................................................... 46 5.1.2 Usia Pasien .............................................................................. 46 5.1.3 Status Pasien ........................................................................... 46 5.2 Faktor Resiko ................................................................................ 47 5.3 Profil Tekanan Darah .................................................................... 47 5.4 Diagnosis Penyerta Pasien Stroke Iskemik ................................... 48 5.5 Pola terapi pada pasien stroke iskemik ......................................... 49 5.6 Pola terapi pendukung pada pasien stroke iskemik ..................... 50 5.7 Pola terapi captopril pada pasien stroke iskemik ......................... 51 5.8 Pola Terapi Captopril Tunggal Tanpa Switch ............................... 51 5.9 Pola Switch Captopril.................................................................... 52 5.10 Kombinasi Obat Captopril dengan Antihipertensi lain ............... 52 5.11 Dosis & Frekuensi Penggunaan Captopril pada Stroke Iskemik 53 5.12 Lama Masuk Rumah Sakit (MRS).............................................. 54 5.13 Kondisi Keluar Rumah Sakit (KRS) ........................................... 55 BAB VI PEMBAHASAN................................................................................ 56 BAB VII KESIMPULAN DAN SARAN ....................................................... 69 7.1 Kesimpulan ................................................................................... 69 7.2 Saran ............................................................................................. 69 DAFTAR PUSTAKA ...................................................................................... 70 LAMPIRAN…. ................................................................................................ 77
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DAFTAR TABEL Halaman
2.1 Gejala dan tanda-tanda iskemia pada sirkulasi anterior dan posterior ...... 22 2.2 Rekomendasi farmakoterapi stroke iskemik ............................................. 24 2.3 Kriteria inklusi dan eksklusi rtPA pada stroke iskemik ............................ 26 2.4 Sediaan di Indonesia ................................................................................. 37 V.1 Jenis Kelamin Pasien Stroke Iskemik ...................................................... 46 V.2 Usia Pasien Stroke Iskemik ...................................................................... 46 V.3 Status Pasien Stroke Iskemik ................................................................... 47 V.4 Faktor Resiko Stroke Iskemik .................................................................. 47 V.5 Distribusi Tekanan Darah......................................................................... 48 V.6 Diagnosis Penyerta Stroke Iskemik.......................................................... 49 V.7 Terapi Stroke Iskemik .............................................................................. 49 V.8 Terapi Pendukung pada pasien stroke iskemik ........................................ 50 V.9 Pola Penggunaan Captopril pada pasien stroke iskemik .......................... 51 V.10 Pola Captopril Tanpa Switch .................................................................. 52 V.11 Pola Switch Captopril ............................................................................. 52 V.12 Distribusi jumlah, Dosis dan Frekuensi terapi kombinasi captopril ...... 53 V.13 Distribusi Penggunaan Dosis dan Frekuensi Captopril .......................... 54
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DAFTAR GAMBAR Halaman 2.1
Penyebab stroke...................................................................................... 8
2.2
Stroke iskemik........................................................................................ 10
2.3
Stroke hemoragik ................................................................................... 11
2.4
Klasifikasi stroke.................................................................................... 12
2.5
Patofisiologi stroke................................................................................. 19
2.6
Managemen stroke dan TIA ................................................................... 23
2.7
Struktur kimia captopril ......................................................................... 36
2.8
Mekanisme kerja captopril ..................................................................... 36
3.1
Skema Kerangka Konseptual ................................................................. 40
3.2
Skema Kerangka Operasional ................................................................ 41
5.1
Skema Inklusi Pasien Stroke Iskemik .................................................... 45
5.2
Distribusi Lama MRS Pasien stroke iskemik ............................................ 54
5.3
Distribusi Status KRS Pasien stroke iskemik ........................................ 55
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DAFTAR LAMPIRAN
Lampiran
Halaman
1. Daftar Riwayat Hidup .............................................................................. 77 2. Surat Pernyataan....................................................................................... 78 3. Surat Ijin Rumah Sakit ............................................................................. 79 4. Surat Ijin Bakesbangpol Provinsi ............................................................. 81 5. Surat Ijin Bakesbangpol Kabupaten ......................................................... 82 6. Harga Normal Data Labolatorik dan Klinik............................................. 84
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DAFTAR SINGKATAN
ACCESS
: Acute Candesartan Cilexetil Therapy in Stroke Survivors
ACEI
: Angiotensin-Converting Enzyme Inhibitors
ACTIVE I
: The Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events
ADP
: Adenosine Diphosphate
ADVANCE
: Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation
AHA
:American Heart Association
AIDS
: Acquired Immune Deficiency Syndrom
AIS
: Acute Ischemic Stroke
ALLHAT
: The Antihypertensive and Lipid-Lowering Treatment
APTT
: Activated Partial Thromboplastin Time
ARB
: Angiotensin Receptor Blocker
ARIC
: Atherosclerosis Risk In Communities
ASA
: American Stroke Association
ASI
: Air Susu Ibu
AT1
: Angiotensin I
BP
: Blood Pressure
BPJS PBI
: Badan Penyelenggara Jaminan Sosial Penerima Bantuan Iuran
BPJS Non PBI : Badan Penyelenggara Jaminan Sosial Non Penerima Bantuan Iuran CAPP
: Captopril Prevention Project
CAST
: Chinese Acute Stroke Trial
CBF
: Cerebral Blood Flow
CCB
: Calcium Channel Blockers
CDC
: Centers for Disease Control and Prevention
CSF
: Cairan Serebrospinal
CT-Scan
: Computerized Tomography Scan
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CVA
: Cerebrovascular Accident
DVT
: Deep Vein Thrombosis
ECASS
: European Cooperative Acute Stroke Study
GCS
: Glasgow Coma Scale
GIT
: Gastro Intestinal Tract
HDL
: High Density Lipid
HMGCoA
: 3-hydroxy-3-methylglutaryl-CoA
IGD
: Instalasi Gawat Darurat
ICH
: Intracranial Hemmorrage
INR
: International Normalized Ratio
IST
: International Stroke Trial
JNC-7
: The Seventh Report of the Joint National Committee
KRS
: Keluar Rumah Sakit
LDL
: Low Density Lipid
LMWH
: Low-Molecular-Weight Heparin
MCA
: Middle Cerebral Artery
mmHg
: millimeter merkuri Hydragyrum
MOSES
: Morbidity and Mortality After Stroke-Eprosartan vs. Nitrendipine for Secondary Prevention
MRI
: Magnetic Resonance Imaging
MRS
: Masuk Rumah Sakit
NCEP
: National Cholesterol Education Program
NIH
: National Institute of Health
NIHSS
: National Institute of Stroke Scale
NINDS
: National Institute of Neurological Disorders and Stroke
ONTARGET
: Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial
PCD
: Programmed Cell Death
PJK
: Penyakit Jantung Koroner
PNS
: Pegawai Negeri Sipil
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PROGRESS
: Perindopril Protection against Recurrent Stroke Study
RAAS
: Renin Angiotensin Aldosteron System
REGARDS
: Reasons for Geographic And Racial Differences in Stroke
RE-LY
: Randomized Evaluation of Long-Term Anticoagulant therapy
RISKESDAS
: Riset Kesehatan Dasar
RMK
: Rekam Medik Kesehatan
RSUD
: Rumah Sakit Umum Daerah
r-TPA
: Recombinant Tissue Plasminogen Activator
SAH
: Subarachnoid Hemorrage
SALSA
: Sacramento Area Latino Study on Aging
SHRsp
: Stroke-Prone Hypertensive Rats
SHS
: Study Strong Heart
SPARCL
: Stroke Prevention by Aggressive Reduction in Cholesterol
SSP
: Sistem Saraf Pusat
Syst-Eur
: The Systolic Hypertension in Europe
TD
: Tekanan Darah
TIA
: Transcient ischemic attack
TNI
: Tentara Nasional Indonesia
TOAST
: Trial of Organon 10172 in Acute Stroke Treatment
UK
: United Kingdom
UFG
: Universidade Federal de Goiás
UU SJSN
: Undang-UNdang Sistem Jaminan Sosial Nasional
VALUE
: Valsartan Antihypertensive Long-term Use Evaluation
WHO
: World Health Organization
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DAFTAR PUSTAKA Adams, H.P., Zoppo, G., Alberts, M.J., Bhatt, D.L., Brass, L., Furlan, A. 2007. Guidelines for The Early Management of Adults With Ischemic Stroke. AHA Journal, Vol:38, pp:1655-1711. Adams Jr., Harold P., et al. 2009. Guidelines on the Management of Hypertention for the Prevention and Treatment Strokes. Plos One Journal. New York: Mcmahon Publishing. Aminoff, M.J., Greenberg, David A., Simon, Roger P., 2009. Clinical Neurology, 7th edition. USA: The McGraw-Hill Companies. Electronic version. pp: 293–397. Anonim, 2012. Peraturan Bupati Sidoarjo Nomor 36 tahun 2012. 2012. Sidoarjo. Anonim, 2013. MIMS Edisi Bahasa Indonesia. Jakarta. BIP Kelompok Gramedia. pp: 47–51. Anonim, 2014. Buku Pegangan Sosialisasi Jaminan Kesehatan Nasional (JKN) dalam Sistem Jaminan Sosial Nasional. Jakarta: Pusat Komunikasi Publik Kementerian Kesehatan RI Anonim, 2014. World Health Statistics 2014. Italy: WHO Library Cataloguing-inPublication Data, ISBN 978 92 4 069267 1. Aronson, J.K., 2009. Meyler’s Side Effects of Cardiovascular Drugs. UK: Elsevier Publications Data, ISBN: 978-044-453268-8. pp: 11–20. Azizi, Michel MD, PhD., and Menard, Joel, MD. 2004. Combined Blockade of the Renin Angiotensin System With Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Type 1 Receptor Antagonists. AHA Journal, Vol:276, pp: 2492-2499 Black, Henry R. et al. 2007. Hypertension : A Companion to Braunwald’s Heart Disease 1st Edition. USA: Elsevier Inc. pp: 239–251. Brenner D.A,M.D., Zwefler R.M.,M.D., Gomez C.R.,M.D.,MBA., Kissela B.M.,M.D., Levine M.D., Howard G. DR.,P.H., Coull B. M.D., Howard V.J., Ph.D., 2009. Awareness, Treatment, and Control of Vascular Risk Factors Among Stroke Survivors. NIH Journal. Vol. 19(4), pp: 311–320. Cannon, Christopher P., O’gara Patrick T., et al. 2007. Critical Pathways in Cardiovascular Medicine, 2nd edition. Usa: Lippincott Williams & Wilkins. pp: 64–79.
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Caulfield, A.F. dan Wijman, C.A.C. 2008. Management of Acute Ischemic Stroke. Neurology Clinical Journal. Vol. 26. pp:345-371. Chandrasoma, Prakarma et al., 2006. Patologi Anatomi Edisi 2.Jakarta: EGC. Chobanian, A.V., Bakris, G.L., Black, H.R., Cushman, W.C., Green, L.A., Izzo, J.L et.al., 2004. The Seventh Report of theJoint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA, 289:2560 –2572.
Connolly, S., Ezekowitz, M., Yusuf, S., Eikelboom, J., Oldgren, J., Parekh, A. et al. (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med, Vol.361, pp: 1139-1151. Culyer, Virginia et al., 2013. Antihypertensives Are Administered Selectively in Emergency Department Patients with Subarachnoid Hemorrhage. NIH Journal. Vol. 22(8). Diener, H., Connolly, S., Ezekowitz, M., Wallentin, L., Reilly, P., Yang, S. et al. (2010) Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY Trial. Lancet Neurol. Vol. 9, pp: 1157–1163. Dipiro, Joseph T., Talbert, Robert L.,Yee, Gary C., Matzke, Gary A., Wells, Barbara G., Posey, Michael, 2011. Pharmacotherapy A Pathophysiologic Approach, 8th edition. New York: The McGraw-Hill Companies ISBN: 978-0-07-1643269. Chapter 27. Feng, Wuwei., Belagaje, Samir R., Neurol, Semin., 2013. Recent Advances in Stroke Recovery and Rehabilitation. Medscape Journal Vol. 33(5), pp: 498-506. Furie , Karen L., Kasner, Scott E., Adams, Robert J., Albers, Gregory W., Bush, Ruth L., Fagan, Susan C.,Halperin, jonathan L., Johnston, S Claiborne., Katzan, Irene., Keman, Walter N., Mitchell, Pamela H., Oybiagele, Bruce., Palesch, Yuko Y, Sacco, Ralph L., Schamm, Lee H., Sylvia, Wassertheil-Smoller., Turan, Tanya N., and Wentworth, Deidre. 2011. Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. AHA Journal, Vol:42, pp:227-276. Ginsberg. L, 2008.Lecture Note Neurologi. Jakarta: penerbit Erlangga. Hal 89-99.
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