Pengaruh Pemberian Simvastatin Pagi Versus Malam Terhadap Penurunan Kolesterol Pada Pasien Hiperkolesterolemia Pasien Rawat Jalan RS PKU Muhammadiyah

METRIKANA NOVEMBRINA, Prof. Dr. Zullies Ikawati ; dr. I Dewa Putu Pramantara S., Sp.PD., K-Ger

2015 | Tesis | S2 Ilmu Farmasi

INTISARI Latar belakang : Hiperlipidemia adalah suatu kondisi dimana terjadi peningkatan kadar kolesterol dan trigliserida yang melebihi batas normal, yakni LDL > 100 mg/dl, trigliserida > 150 mg/dl dan kolesterol total > 200 mg/dl. Hiperlipidemia dapat menyebabkan arterosklerosis atau pengerasan pembuluh darah dan dapat mengakibatkan penyumbatan aliran darah, pembentukan thrombus dan embolus yang dapat menimbulkan stroke selain penyakit jantung koroner (PJK). Pembentukan kolesterol dalam tubuh manusia mengikuti ritme sirkadian. Sejumlah penelitian menunjukkan sintesis kolesterol maksimal terjadi pada malam hari. Hal ini menjadi landasan penggunaan simvastatin pada malam hari, dengan harapan agar obat dapat langsung bekerja tepat saat pembentukan kolesterol sedang tinggi. Namun penelitian lainnya menunjukkan bahwa kadar tertinggi kolesterol bebas berada pada pukul 06.00 pagi dan terendah pada pukul 14.00-18.00. Selain itu aktivitas enzim HMG CoA reduktase yang berperan dalam sintesis kolesterol mencapai puncaknya pada pukul 04.00-08.00 pagi. Selain itu disebutkan juga penggunaan simvastatin pada pagi hari dapat meningkatkan efeknya serta mengurangi toksisitasnya terhadap otot. Tujuan penelitian ini adalah untuk mengetahui apakah penurunan kolesterol pasien hiperkolesterolemia yang diberikan simvastatin pagi tidak berbeda dari yang diberikan pada malam hari. Metode : Penelitian ini merupakan penelitian prospektif, Randomized Clinical Trial (RCT), single blind, parallel design, dimana sejumlah pasien dikelompokkan secara random ke dalam dua kelompok. Kelompok pertama menerima simvastatin 10 mg yang diminum pada malam hari dan kelompok kedua menerima simvastatin 10 mg yang diminum pada pagi hari. Satu bulan kemudian diukur kadar kolesterol masing-masing pasien dan dihitung selisihnya dari kadar kolesterol sebelum terapi. Hasilnya dianalisis dengan uji beda Student�s T-Test. Hasil : Setelah satu bulan terapi dengan simvastatin, penurunan kolesterol total dan LDL pada pasien yang minum simvastatin pagi dan malam hari berturut-turut adalah 10,45mg/dl dan 10,52mg/dl serta 11,12 mg/dl dan 10,73 mg/dl. Kesimpulan : Penurunan kadar LDL pasien yang minum simvastatin pagi hari tidak berbeda signifikan dengan penurunan kadar LDL pasien yang minum simvastatin di malam hari. Sedangkan penurunan kadar kolesterol total pasien yang minum simvastatin di malam hari lebih besar dibandingkan dengan yang minum simvastatin di pagi hari.

ABSTRACT Background : Hyperlipidemia is a condition where there is an increase in cholesterol and triglyceride levels that exceeds the normal limits, also known as LDL > 100 mg/dL, triglycerides > 150 mg/dl and total cholesterol > 200 mg/dl. Hyperlipidemia can lead to atherosclerosis or hardening of the arteries and can lead to the blockage of blood flow, the formation of thrombus and embolus which can lead to stroke in addition to coronary heart disease (CHD). The formation of cholesterol in human body's shows a circadian rhythm. Numerous studies showed that the peak of cholesterol synthesis occured at night. These studies became the foundation of the use of simvastatin in the evening. This was also intended to maximize the effect of simvastatin because the drug would be immediately worked when the formation of cholesterol was high. However, other research showed that the highest levels of free cholesterol was at 06:00 a.m and its lowest at 14:00 to 18:00 p.m. Besides that, the activity of HMG CoA reductase enzyme that plays an important role in cholesterol synthesis peaked at 04:00 to 08:00 in the morning. Other research also mentioned that the use of simvastatin in the morning could increase its effect and reduces its muscle toxicity. The aim of the research is to know if cholesterol reduction in patient with hypercholesterolemia given morning dose of simvastatin is not different to that given evening dose of simvastatin. Methods: This was a prospective, randomized, single blind, parallel research design. In this research, a number of patients were divided randomly into two testing groups. One group was given evening dose of 10 mg simvastatin as a single dose and another group was given morning dose of the same drug. Previously patient�s total cholesterol dan LDL had been taken as a baseline concentration. After one month long simvastatin therapy, patient�s total cholesterol and LDL were re-measured to observe the reduction of the cholesterol. The results were subsequently analysed by using Student�s T-Test. Results: After one month of simvastatin therapy, the mean of total cholesterol reduction in the morning dose and evening dose was 10,45 mg/dl and 11,12 mg/dl respectively. The mean of LDL reduction in the morning dose and evening dose was 10,52 mg/dl and 10,73 mg/dl respectively. Conclusions: The reduction of LDL cholesterol in patients given morning dose of simvastatin is not different to those in patient given evening dose of simvastatin. However the reduction of total cholesterol concentration in patient given evening dose of simvastatin is greater than that in patient given morning dose of simvastatin

Kata Kunci : Kata Kunci : hiperlipidemia, ritme sirkadian, simvaststin pagi dan malam, RCT