(Penelitian Dilakukan di Instalasi Rawat Inap RS
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SKRIPSI Muhammad Hafiz Ansari STUDI PENGGUNAAN OBAT ACE INHIBITOR PADA PASIEN GAGAL JANTUNG (Penelitian Dilakukan di Instalasi Rawat Inap RS Muhammadiyah Lamongan) PROGRAM STUDI FARMASI FAKULTAS ILMU KESEHATAN UNIVERSITAS MUHAMMADIYAH MALANG 2016 Lembar Pengesahan STUDI PENGGUNAAN OBAT ACE INHIBITOR PADA PASIEN GAGAL JANTUNG (Penelitian Dilakukan di Instalasi Rawat Inap RS Muhammadiyah Lamongan) SKRIPSI Dibuat untuk memenuhi syarat mencapai gelar Sarjana Farmasi pada Program Studi Farmasi Fakultas Ilmu Kesehatan Universitas Muhammadiyah Malang 2016 Oleh: MUHAMMAD HAFIZ ANSARI NIM: 201210410311062 Disetujui oleh: Pembimbing I Drs. Didik Hasmono, M.S.,Apt NIP. 195809111986011001 Pembimbing II Dra. Lilik Yusetyani.,Apt.,Sp.FRS NIP UMM 114.07040450 Pembimbing III Muhtaromah.,S.Si.,AptSp.FRS NRP. 4404384 Lembar Pengujian STUDI PENGGUNAAN OBAT ACE INHIBITOR PADA PASIEN GAGAL JANTUNG (Penelitian Dilakukan di Instalasi Rawat Inap RS Muhammadiyah Lamongan) SKRIPSI Telah diuji dan dipertahankan di depan tim penguji Pada tanggal 7 Mei 2016 Oleh: MUHAMMAD HAFIZ ANSARI NIM: 201210410311062 Tim Penguji: Penguji I Drs. Didik Hasmono,Apt., MS. NIP: 195809111986011001 Penguji II Penguji III Dra. Lilik Yusetyani, Apt., Sp.FRS. NIP UMM: 114.07040450 Muhtaromah.,S.Si.,AptSp.FRS NRP. 4404384 Penguji IV Penguji V Hidajah Rachmawati, S.Si., Apt., Sp.FRS. NIP UMM: 144.0609.0449 Nailis Syifa’, S.Farm., M.Sc., Apt. NIP: 1143110522 KATA PENGANTAR Bismillahirrohmanirrohim Assalamu’alaikum warohmatullahi wabarokatuh Puji syukur tercurahkan kepada ALLAH SWT, Tuhan semesta alam karena berkat rahmat dan ridho-Nya, penulis dapat menyelesaikan skripsi yang berjudul STUDI PENGGUNAAN OBAT ACE INHIBITOR PADA PASIEN GAGAL JANTUNG (Penelitian Dilakukan di Instalasi Rawat Inap RS Muhammadiyah Lamongan) 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 memberkan rahmat, nikmat dan Karunia-Nya, Nabi Muhammad SAW yang sudah menuntun kita menuju jalan yang benar. 2. Bapak Yoyok Bekti P., M.Kep., Sp.Kom.,,selaku Dekan Fakultas Ilmu Kesehatan Universitas Muhammadiyah Malang yang telah memberikan kesempatan penulis menuntut ilmu di Fakultas Ilmu Kesehatan Universitas Muhammadiyah Malang. 3. Ibu Dr. Hj. Umi Aliyah, MARS., selaku Direktur Rumah Sakit Muhammadiyah Lamongan beserta jajarannya yang telah memberikan kesempatan pada penulis untuk melakukan penelitian di Rumah Sakit Muhammadiyah Lamongan. 4. Ibu Nailis Syifa’,S.Farm.,M.Sc.,Apt., selaku Ketua Program Studi Farmasi Universitas Muhammadiyah Malang yang telah memberi motivasi dan kesempatan penulis menuntut ilmu di Program Studi Farmasi Universitas Muhammadiyah Malang. 5. Bapak Drs. Didik Hasmono,M.S.,Apt., Ibu Dra. Lilik Yusetyani,Apt.,Sp.FRS., dan Ibu Muhtaromah.,S.Si.,Apt Sp.FRS. Selaku Dosen Pembimbing I, II dan III, disela kesibukan Bapak dan Ibu masih bisa meluangkan waktu untuk membimbing dan memberi pengarahan dan dorongan moral sampai terselesaikannya skripsi ini. 6. Ibu Hidajah Rachmawati, S.Si.,Apt.,Sp.FRS dan Ibu Nailis Syifa’,S.Farm.,M.Sc.,Apt., selaku Dosen Penguji I dan II, yang telah banyak memberikan saran dan masukan demi kesempurnaan skripsi ini. 7. Ibu Siti Rofida, S.Si., Apt.,M.Farm., Selaku dosen wali, terimakasih sudah membimbing dari awal semester hingga lulus. 8. Orang Tuaku tercinta, Syarifuddin dan Faridah yang tiada hentinya memotivasi dan sabar mendoakan untuk kebaikan dan kesuksesan anakanaknya. 9. Saudariku Sumiyati S.pd., Syarida Ulfah dan Khusnul Khatimah terima kasih atas motivasi dan doanya sehingga skripsi ini dapat selesai tepat waktu. 10. Sahabat seperjuangan skripsi klinis maupun bidang lainnya Retno, Pipit, Ana, Gitta, Akbar, Yudha, dan Iwan terima kasih atas kebersamaan, bantuan, dan semangat kerjasamanya sehingga skripsi ini dapat terwujud. 11. Teman-teman Farmasi UMM 2012, khususnya Aspirasi Pria Farmasi terima kasih atas kebersamaannya yang luar biasa. 12. Untuk semua pihak yang belum disebutkan namanya, penulis mohon maaf dan terimakasih yang sebesar-besarnya. 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, Penyusun (Muhammad Hafiz Ansari) DAFTAR ISI LEMBAR PENGESAHAN ................................................................................ ii LEMBAR PENGUJIAN ................................................................................... iii KATA PENGANTAR ....................................................................................... iv RINGKASAN ................................................................................................... vii ABSTRAK....................................................................................................... viii ABSTRACT ...................................................................................................... ix DAFTAR ISI ...................................................................................................... x DAFTAR TABEL ........................................................................................... xiv DAFTAR GAMBAR ....................................................................................... xvi DAFTAR LAMPIRAN ................................................................................. xviii DAFTAR SINGKATAN ................................................................................. xix BAB 1 PENDAHULUAN................................................................................... 1 1.1 Latar Belakang .......................................................................................... 1 1.2 Rumusan Masalah ..................................................................................... 4 1.3 Tujuan Penelitian ....................................................................................... 4 1.3.1 Tujuan Umum ...................................................................................... 4 1.3.2 Tujuan Khusus ..................................................................................... 4 1.4 Manfaat Penelitian ..................................................................................... 4 BAB II TINJAUAN PUSTAKA ........................................................................ 5 2.1 Definisi Gagal Jantung............................................................................... 5 2.2 Epidemiologi Gagal Jantung ...................................................................... 5 2.3 Etiologi Gagal Jantung............................................................................... 6 2.3.1 Disfungsi Miokard .............................................................................. 7 2.3.1 Overload Volume ................................................................................ 9 2.3.1 Overload Tekanan ............................................................................. 10 2.3.1 Aterosklerosis ................................................................................... 10 2.3.1 Aritmia .............................................................................................. 10 2.3.1 Infeksi ............................................................................................... 11 2.3.1 Anemia ............................................................................................. 11 2.3.1 Tirotosikosis dan Kehamilan ............................................................. 11 2.4 Klasifikasi Gagal Jantung ........................................................................ 11 2.5 Macam-macam Gagal Jantung ................................................................. 13 2.5.1 Gagal Jantung Kiri ............................................................................ 13 2.5.2 Gagal Jantung Kanan ........................................................................ 13 2.5.3 Gagal Jantung Akut ........................................................................... 13 2.5.4 Gagal Jantung Kronis ........................................................................ 13 2.5.5 Gagal Jantung Sistolik ...................................................................... 14 2.5.6 Gagal Jantung Diastolik .................................................................... 14 2.6 Faktor Resiko Gagal Jantung ................................................................... 16 2.6.1 Faktor Resiko Yang Dapat Dimodifikasi ........................................... 16 2.6.2 Faktor Resiko Yang Tidak Dapat Dimodifikasi ................................. 18 2.7 Patofisiologi Gagal Jantung ..................................................................... 17 2.7.1 Mekanisme Kompensasi .................................................................... 21 2.8 Manifestasi Klinik ................................................................................... 25 2.8.1 Dyspnea ............................................................................................ 16 2.8.2 Ortopnea ........................................................................................... 16 2.8.3 Paroksimal Nokturnal Dyspnea ......................................................... 16 2.9 Diagnosa dan Pemeriksaan Gagal Jantung ............................................... 25 2.10 Penatalaksanaan Terapi Gagal Jantung................................................... 27 2.10.1 Terapi NonFarmakologis ................................................................. 29 2.10.2 Terapi Farmakologis ....................................................................... 30 2.10.2.1 Diuretik .................................................................................... 32 2.10.2.2 Angiotensin Conveting Enzym Inhibitor .................................. 35 2.10.2.3 Angiotensin Reseptor Blocker ................................................... 47 2.10.2.4 β-blocker .................................................................................. 48 2.10.2.5 Digoksin .................................................................................. 49 BAB III KERANGKA KONSEPTUAL DAN OPERASIONAL ................... 52 BAB IV METODE PENELITIAN .................................................................. 54 4.1 Rancangan Penelitian............................................................................... 54 4.2 Populasi dan Sampel ................................................................................ 54 4.2.1 Populasi ............................................................................................ 54 4.2.2 Sampel .............................................................................................. 54 4.3 Kriteria Data ............................................................................................ 54 4.3.1 Kriteria Data Inklusi .......................................................................... 54 4.3.2 Kriteria Data Eksklusi ....................................................................... 54 4.4 Bahan Penelitian ...................................................................................... 55 4.5 Instrumen Penelitian ................................................................................ 55 4.6 Tempat dan Waktu Penelitian .................................................................. 55 4.7 Metode Pengumpulan Data ...................................................................... 55 4.8 Analisa Data ............................................................................................ 55 4.9 Definisi Operasional ................................................................................ 56 BAB V HASIL PENELITIAN ......................................................................... 58 5.1 Data Demografi Pasien ............................................................................ 55 5.1.1 Jenis Kelamin ..................................................................................... 59 5.1.2 Usia ................................................................................................... 59 5.1.3 Status Pasien ...................................................................................... 59 5.2 Distribusi Faktor Resiko .......................................................................... 60 5.3Distribusi Kelas Gagal Jantung .................................................................. 61 5.4Distribusi Diagnosa Penyerta Gagal Jantung .............................................. 61 5.5 Management Terapi Pasien Gagal Jantung ................................................ 62 5.5.1 Terapi Farmakologi Gagal Jantung Selain ACE Inhibitor ................... 62 5.5.2 Terapi Penyerta Gagal Jantung ........................................................... 63 5.5.3Penggunaan ACE Inhibitor + Antihipertensi ....................................... 63 5.6 Distribusi Kombinasi ACE Inhibitor + Antihipertensi............................... 64 5.6.1 Kombinasi ACE Inhibitor + 1 Antihipertensi ..................................... 64 5.6.2 Kombinasi ACE Inhibitor + 2 Antihipertensi ..................................... 65 5.6.3 Kombinasi ACE Inhibitor + 3 Antihipertensi ..................................... 66 5.6.4 Kombinasi ACE Inhibitor + 4 Antihipertensi ..................................... 67 5.6.5 Pola Penggunaan ACE Inhibitor......................................................... 66 5.6.6Pola Pergantiam Dosis Obat ACE Inhibitor ......................................... 68 5.6.7Pola Pergantiam Jenis Obat ACE Inhibitor .......................................... 69 5.6.8Lama Terapi ACE Inhibitor ................................................................ 69 5.7 Lama Masuk Rumah Sakit (MRS) ............................................................ 66 5.8 Kondisi Keluar Rumah Sakit (KRS) ......................................................... 67 BAB VI PEMBAHASAN ................................................................................ 71 BAB VII KESIMPULAN DAN SARAN ......................................................... 87 7.1 Kesimpulan .............................................................................................. 87 7.2 Saran ........................................................................................................ 87 DAFTAR PUSTAKA ....................................................................................... 88 LAMPIRAN ..................................................................................................... 94 DAFTAR TABEL Tabel Halaman II.1 Penyebab yang mendasari gagal jantung .................................................... 7 II.2 Klasifikasi gagal jantung menurut NYHA ................................................ 12 II.3 Faktor Resiko Gagal Jantung ................................................................... 14 II.4 Manifestasi Klinik Gagal Jantung ............................................................ 26 II.5 Penggunaan diuretik dalam pengelolaan gagal jantung............................. 34 II.6 Interaksi obat untuk ACEI ....................................................................... 39 II.7 Perbandingan golongan obat ACEI .......................................................... 46 II.8 Dosis ARB untuk terapi gagal jantung ..................................................... 47 II.9 Dosis β-blocker untuk terapi gagal jantung .............................................. 48 V.1 Jenis Kelamin Pasien Gagal Jantung ........................................................ 59 V.2 Usia Pasien .............................................................................................. 59 V.3 Distribusi Status Pasien Gagal Jantung .................................................... 60 V.4 Distribusi Faktor Resiko Gagal Jantung ................................................... 60 V.5 Distribusi Kelas Diagnosa Gagal Jantung ................................................ 61 V.6 Diagnosa Penyerta Gagal Jantung ............................................................ 61 V.7Terapi Farmakologi Gagal Jantung Selain ACE Inhibitor ............................. 62 V.8 Terapi Penyerta Gagal Jantung ................................................................ 63 V.9Penggunaan ACE Inhibitor + Antihipertensi ................................................ 64 V.10 DistribusiDistribusi Kombinasi ACE Inhibitor + Antihipertensi ................ 64 V.11Kombinasi ACE Inhibitor + 1 Antihipertensi.............................................. 65 V.12 Kombinasi ACE Inhibitor + 2 Antihipertensi........................................... 65 V.13 Kombinasi ACE Inhibitor + 3 Antihipertensi........................................... 67 V.14 Kombinasi ACE Inhibitor + 4 Antihipertensi........................................... 67 V.15Pola Penggunaan Obat ACE Inhibitor ....................................................... 68 V.16 Pola Pergantian Dosis Obat ACE Inhibitor ............................................. 68 V.17 PolaPergantian Jenis Obat ACE Inhibitor ............................................... 69 V.18 Lama Terapi ACE Inhibitor Pada Pasien Gagal Jantung .......................... 69 V.19Lama MRS pasien Gagal Jantung ............................................................... 70 DAFTAR GAMBAR Gambar Halaman 2.1 Gagal Jantung............................................................................................. 7 2.2 Patofisiologi Gagal Jantung ...................................................................... 20 2.3 Sistem Renin Angiotensin Aldosteron (RAAS) ........................................ 24 2.4 Mekanisme aktivasi sistem syaraf simpatik dan parasimpatik pada gagal jantung ..................................................................................................... 25 2.5 Manifestassi Klonik Gagal Jantung .......................................................... 26 2.6 Alrogitma Diagnostik Gagal Jantung ........................................................ 29 2.7 Manajemen Terapi Gagal Jantung ............................................................ 31 2.8 Terapi Farmakologi Gagal Jantung ........................................................... 32 2.9 Sistem Transpor Tubulus dan Tempat kerja Diuretik ............................... 33 2.10 Mekanisme Aksi ACEI............................................................................ 35 2.11 Efek Angiotensin II dan Aksi Protektif Bradikinin................................... 36 2.12 Hubungan Struktur Kimia dan Aktifitas ACEI......................................... 37 2.13 Struktur Kimia Captopril ......................................................................... 41 2.14 Tempat aksi Captopril ............................................................................. 41 2.15 Struktur Kimia Enalapril ......................................................................... 42 2.16 Struktur kimia Lisonopril ........................................................................ 42 2.17 Struktur Kimia Benazepril ....................................................................... 42 2.18 Struktur Kimia Fosinopril ........................................................................ 44 2.19 Struktur Kimia Ramipril .......................................................................... 45 2.20 Struktur kimia digoxin ............................................................................. 50 2.21 Mekanisme kerja digoxin ........................................................................ 51 3.1 Skema Kerangka Konseptual ................................................................... 52 3.2 Skema Kerangka Operasional .................................................................. 53 5.1 Skema Kriteria Inklusi dan Eksklusi Penelitian pada Pasien Gagal Jantung 58 5.2 Kondisi KRS Pasien Gagal Jantung .......................................................... 70 DAFTAR LAMPIRAN Lampiran Halaman 1 Daftar Riwayat Hidup ......................................................................... 94 2 Surat Pernyataan Keaslian Tulisan ...................................................... 95 3 Anggaran Biaya Skripsi ....................................................................... 96 4 Jadwal Penelitian ................................................................................. 97 5 Ethical Clearence ................................................................................ 98 6 Daftar Nilai Normal Data Klinik dan Data Laboratorium ..................... 99 7 Tabel Data Induk Penyakit Gagal Jantung ............................................ 100 8 Lembar Pengumpulan Data Pasien Penyakit Gagal Jantung ................. 126 DAFTAR SINGKATAN ACC : American College of Cardiology ACE : Angiotensin Converting Enzym ACEI : Angiotensin Converting Enzym Inhibitor ADH : Anti Diuretic Hormone AHA : American Heart Association ARB : Angiotensin Reseptor Blocker As : Asam AT1 : Angiotensin Tipe 1 AT2 : Angiotensin Tipe 2 ATP : Adhenosi Tri Phosphate AV : Atrioventricular β-blocker : Beta-blocker B1 : Bradikinin Tipe 1 B2 : Bradikinin Tipe 2 BUN : Blood Urea Nitrogen BNP : B-type Natriuretic Peptide Ca2+ : Calsium CAD : Coronary Artery Disease CASS : Coronary Artery Surgery Study CBC : Complete Blood Count CABG : Coronary Artery Bypass Grafting CHF : Congesive Heart Failure - Cl : Chlorida CrCl : Clreatinine Clearance cGMP : Cyclic Guanosine Monophosphate CK-MB : Creatine Kinase-Muscle Brain CONSENSUS : Cooperative North Scandinavian Enalapril Survival Study COP : Cardiac Out Put CRT : Cardiacn Resynchronization Therapy CVD : Cardiovascular Disease CVP : Central vena Pressure DIG : Digitalis Investigation Group DM : Diabetes Melitus ECG : Echocardiographic EDP : End-diastolic pressure EKG : Electrocardiogram ESC : Eropa Society of Cardiology + H : Hidrogen H2O : Hidrogen Oksida Hb : Hemoglobin HCT : Hematokrit HDL : Low High Lipoprotein HF : Heart Failure HFSA : Heart failure Society of America HLD : Hyperlipidemia HR : Heart Rate HTN : Hipertensi ICAM-1 : Intercellular Adhesion Protein-1 ICDs : Implantable Cardioverter Defibrillators g : Gram K+ : Kalium Kep : Kepulauan Kemenkes RI : Kementrian Kesehatan Republik Indonesia KgBB : Kilogram Berat Badan KRS : Keluar Rumah Sakit LA : Left Atrium LAP : Left Atrium Pressure LDL : Low Density Lipoprotein LED : Laju Endap Darah LEDV : Left End Diastolik Ventricle LFT : Liver Function Tests LVEDP : Left Ventricle End Diastolic Pressure t-PA : Tissue plasminogen activator LPD : Lembar Pengumpulan Data LV : Left Ventricle LVEF : Left Ventricle Ejection Fraction LVH : Left Ventricle Hipertrofi MAP : Mean Arterial Pressure MCH : Mean Cospucular Hemoglobin MCHC : Mean Cospucular Hemoglobin Concentration MCV : Mean Cospucular Volume µg : Mikrigram Mg2+ : Magnesium ml : Milliliter MPV : Mean Platelet Volume MR : Mitral Regurgitasi MRI : Coronary Magnetic Resonance Imaging MRS : Masuk Rumah Sakit Na+ : Natrium NE : Norepinefrin ng : Nanogram NO : Nitrit Oksida NSIDs : Non Steroid Inflamatory Drugs NT-proBNP : N-Terminal Pro-Tipe B NYHA : New York Heart Association O2 : Oksigen PAI-1 : Plasminogen Activator Inhibitor 1 PCI : Percutaneous Coronary Intervention pg : Picogram PG : Prostaglandin PJK : Penyakit Jantung Koroner PND : Paroxysmal nocturnal dyspnea PO : Per Oral Protein G : Protein Globulin RAAS : Renin Angiotensin Aldosterone System RBC : Red Blood Cell RMK : Rekam Medik Kesehatan RR : Respiratory Rate RS : Rumah Sakit SH : Sulfhidril SOLVD : Studies Of Left Ventricular Dysfunction SV : Stroke Volume SVR : Systemic Vascular Resistance TSH : Thyroid StimulatingHormone UA : Urinalysis Vs : Versus WBC : White Blood Cell WHO : World Health Organization Zn+ : Zink DAFTAR PUSTAKA Aaronson and Ward,2010. At a Glance Sistem Kardiovaskular.Edisi ke-3, Jakarta: Erlangga, pp. 101-74. Alan Vainrib, Asa William Peter Viccellio, and Henry H Ooi., 2014. Restrictive Cardiomyopathy. http://emedicine.medscape.com/article/153062-overview. Diakses tanggal 28 Januari 2016. Aldredge, K. Brian., Corelli, L. Robbin., Ernest, E. Michael., 2013. Applied therapeutics, Ed. 10th, Philadelpia: Wolter Kluwers Health., pp 436. Allen Patrick Burke., 2015. Dilated Cardiomyopathy Pathology. http://emedicine.medscape.com/article/2017823-overview. Diakses tanggal 28 Januari 2016. Anh L. Bui., Tamara B. Horwich., and Gregg C. Fonarow., 2010. Epidemiology and risk profile of heart failure.Nat Rev Cardiol, Vol. 8 No. 2, pp.24-1. Anonim, 2015. Heart Failure Fact Sheet. Centers for Disease Control and Prevention..http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_he art_failure.htm. Diakses tanggal 14 oktober 2015. Anonim, 2012. Cardiovascular disease risk factors. World Heart Federation.http://www.world-heart-federation.org/cardiovascularhealth/cardiovascular-disease-risk-factors/. Diakses tanggal 14 oktober 2015. Betram G. Katzung, Susan B. Masters, Anthony J. Trevor, 2012. Basic and Clinical Pharmacology. Ed. 13, New York: Mc Graw Hill Education., pp. 211-225. Borton Chloe, Rull Gurvinder, and Huins Helen, 2013. Diuretics. EMIS : Vol. 6, No. 315, pp. 6-1. Csaba Andras Dezsi, 2014. Differences in the Clinical Effects of AngiotensinConverting Enzyme Inhibitors and Angiotensin Receptor Blockers:A Critical Review of the Evidence. Am J Cardiovasc Drugs: No.14 pp 173-147. Clyde W. Yancy, Mariell Jessup, Biykem Bozkurt, Javed Butler, Donald E. Casey, Jr, Mark H. Drazner, Gregg C. Fonarow, Stephen A. Geraci, Tamara Horwich, James L., Januzzi, Maryl R. Johnson, Edward K. Kasper, Wayne C. Levy, Frederick A. Masoudi, Patrick E. McBride, John J.V. McMurray, Judith E. Mitchell, Pamela N., Peterson, Barbara Riegel, Flora Sam, Lynne W. Stevenson, W.H. Wilson Tang, Emily J. Tsai, Bruce L. Wilkoff, 2013. ACCF/AHA Guideline for the Management of Heart Failure A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.Circulation: pp.e299e243. Connor A. Emdin, Tom Callender, Jun Cao, John J.V. McMurray, and Kazem Rahimi, 2015. Meta-Analysis of Large-Scale Randomized Trials to Determine the Effectiveness of Inhibition of the Renin-Angiotensin Aldosterone System in Heart Failure. Am J Cardiol Vol. 52 No. 3, pp. 155-161. Darmadi, 2013. Pathophysiology And Management Of Cadiac Remodeling. Cardiac Remodeling, Vol. 40 No. 9, pp. 654-651. Davey P., 2006. At a Glance Medicine, Jakarta: Erlangga, pp. 168-114. Dipiro, T. Joseph., Albert, L. Robert., Yee, C. Garry., 2011. Pharmacoteraphy, Ed. 8th, New York: The McGraw Hill Companies., pp 212-174. Dunlay Shannon M., Weston Susan A., JacobsenSteven J., and RogerVéronique L., 2010. Risk Factors for Heart Failure: A Population-Based Case-Control Study. Am J Med: Vol.122, No. 11, pp. 1028–1023. Fauci., Kasper., Hauser., Longo., Jameson, Loscalgo., 2015. Horison’s principles of Internal Medicine Ed. 19th, New York: McGraw Hill Education., pp 1504-1502. Gunawan Sulistia G, Nafrialdi Rianto S, Elysabeth, 2011. Farmakologi dan Terapi, Edisi ke-5, Jakarta: Balai Penerbit FKUI., pp. 313-299. Hardman G. Joel and Limbird E. Lee., 2012. Gilman, Goodman. Alferd (Eds). Goodman and Gilmans Dasar Farmakologi Terapi. Edisi ke-10, Jakarta: Buku Kedokteran EGC., hal 875. Hean Teik Ong, Loke Meng Ong, and Jacqueline Judith Ho, 2013. AngiotensinConverting Enzyme Inhibitors (ACEIs) and Angiotensin-Receptor Blockers (ARBs) in Patients at High Risk of Cardiovascular Events: A Meta-Analysis of 10 Randomised Placebo-Controlled Trials. ISRN Cardiology: Vol.2013, pp. 8-1. Ioana Dumitru, and Henry H Ooi., 2015. Heart http://emedicine.medscape.com/article/163062-overview. Failure. Diakses tanggal 11 Mei 2015. Irmalita, Dafsah A Juzar, Andrianto, Budi Yuli Setianto, Daniel PL Tobing, Doni Firman, Isman Firdaus, 2015. Pedoman Tatalaksana Sindrom Koroner Akut. Edisi ke-3, Perhimpunan Dokter Spesialis KardiovaskularIndonesia : pp. 70-1. James C. Coons, Molly McGraw, Srinivas Murali, 2011. Pharmacotherapy for Acute Heart Failure Syndromes. Am J Health Syst Pharm. Vol. 68 No. 1, pp. 21-35. John S. Floras,2009. Sympathetic Nervous System Activation in Human Heart Failure. Heart Failure, Vol. 54, No. 5, 2009. 54, pp. 382-375. Karl T. Weber, 2001. Aldosterone In Congestive Heart Failure. Mechanisms Of Disease. Mechanisms Of Disease. Vol. 345, No. 23, pp. 8-1. Kenneth Dickstein, Alain Cohen-Solal , Gerasimos Filippatos, John J.V. McdMurray, Piotr Ponikowski, Philip Alexander Poole-Wilson, Anna Stro¨mberg, Dirk J. van Veldhuisen, Dan Atar, Arno W. Hoes, Andre Keren, Alexandre Mebazaa, Markku Nieminen, Silvia Giuliana Priori, Karl Swedberg, 2008. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal: pp. 2434-2388. Laurence L. Brunton, 2011. Bruce A. Chabner and Bjorn C. Knollmann (Eds). Goodman & Gilman’s The Pharmacological Basis of Therapeutics. Ed. 13th, New York: Mc Graw Hill Education., pp. 772-754. Lilly LS., 2011. Phatophysiology of Heart Diseaase, Ed. 15, US: Wolters Kluwer Health., pp. 229-224. Limen Merry Pricilia, Palandeng Ora, TumbelRonny, 2013. Epistaksis Di Poliklinik Tht-Kl Blu Rsup Prof. Dr. R. D. Kandou Manado Periode Januari 2010-Desember 2012.. Jurnal e-Biomedik (eBM), Vol. 1, No. 1, pp. 478-483. Luntungan L.Z., Fatimawali, and BodhiWiddhi, 2012. Studi Karakteristik Dan Penggunaan Obat Pada Penderita Hepatitis B Di Rumah Sakit Pemerintah Kota Manado Periode Januari 2011 – Desember 2012. Pharmacon : Vol. 2, No. 3, pp. 70-67. Maarten,FerketB.S., Steyerberg E.W., Kavousi M, Deckers J.W., NieboerDaan, Heeringa Jan, Hofman A.M., Ikram M.A., Hunink M., Franco O.H., Stricker B.H., Witteman J.C.M., and Hesselink J.W.R.., 2014. Sex differences in lifetime risk and first manifestation of cardiovascular disease: prospective population based cohort study. BMJ : Vol. 10, No. 1136, pp 13-1. Mashitisho, 2012. The use of angiotensin-converting enzyme inhibitors in general medicine. S Afr Fam Pract: Vol. 54 No. 4. Pp. 315-313. M. Maurer, M. Bader, M. Bas, F. Bossi, M. Cicardi , M. Cugno, P. Howarth, A. Kaplan8, G. Kojda, F. Leeb-Lundberg, J. Lo¨ tvall and M. Magerl, 2011. New topics in bradykinin research. Allergy:Vol.66, pp. 1406-1397. Michael king, Joe Kingery, and Baretta Casey, 2012. Diagnosis and Evaluation of Heart Failure. Heart Failure:Vol. 85, No. 12,pp. 1167-1161. Mpe M.T., Klug E.Q., Sliwa K.S., Hitzeroth J., andSmith D.A., 2013. Heart Failure Society of South Africa (HeFSSA) perspective on the European Society of Cardiology (ESC) 2012 chronic heart failure guideline.S Afr Med J: Vol. 103, pp. 667-661. Rajeev Kumar, Ramji Sharma, Khemraj Bairwa, Ram Kumar Roy, Arun Kumar, Atul Baruwa, 2010.Modern Development in ACE inhibitors. Der Pharmacia Lettre: Vol. 2 No. 3, pp. 419-388. Richard E. Klabunde, 2014. Cardiovascular Physiology Concepts. http://cvphysiology.com/Heart%20Failure/HF002.htm. Diakses tanggal 23 Oktober 2015. Rilantono LI., Baraas F., Karo SK., Roebiono PS., 2001. Buku Ajar Kardiologi. Jakarta: Gaya Baru, pp. 125-115. Robert J.Straka., 2012, Comparison Of Approved Ace Inhibitors. University of MN, College of Pharmacy. pp. 2-1. Sakata Yasuhiko and Shimokawa Hiroaki, 2013. Epidemiology of Heart Failure in Asia. Circulation Journal : Vol.77, pp. 2217-2209. Sandy N Shah and Henry H Ooi., 2016. Hypertrophic Cardiomyopathy. http://emedicine.medscape.com/article/152913-overview#a1. Diakses tanggal 28 Januari 2016. Shargel Leon, Wu-Pong S., and Yu Andrew B.C., 2012. Biofarmasetika dann Farmakokinetika Terapan. Edisi Ke-5, Airlangga Univercity Press : pp. 715-709. Siswanto BB, Hersunarti Nani, Erwinanto, Barack Rossana, Pratikto R.S., Nauli S.E., Lubis A.C., 2015. Pedoman Tatalaksana Gagal Jantung.Edisi Ke1.Perhimpunan Dokter Spesialis Kardiovaskular Indonesia : pp 47-1. S. Reddy, A. Bahl and K.K. Talwar., 2010. Congestive heart failure in Indians: How do we improve diagnosis & management. Indian J Med Res: No.132, pp. 260-249. Syamsudin,2011. Farmakoterapi Kardiovaskular dan Renal. Ed. 1, Jakarta: Salemba Medika Press, hal 51-32. Trihono, 2013. Riset Kesehatan Dasar. Jakarta: Badan Penelitian Dan Pengembangan Kesehatan Kementerian Kesehatan RI. Valentin Fuster, Richard A. Walsh, Robert A. Harrington, 2011. Sharon A. Hunt, Eric N. Prystowsky, Spencer B. King III, Robert Roberts, Eric Rose (Eds). Hurst's The Heart, Ed. 13th Vol. 1, New York: Mc Graw Hill Education., pp. 775-748. Wanda Lockwood, 2015. Heart Failure : RN.ORG., pp 17-1. Wulandhari Intan, 2014. Studi Penggunaan Obat Golongan ACE Inhibitor Pada Pasien Gagal Jantung (Penelitian di Rumah Sakit Umum Dr. Saiful Anwar Malang). Malang : Skripsi.