Management of Dyslipidemia: Strategies to Improve CompliancePendahuluan * Dislipidemia: faktor risiko utama PJK dan stroke, dengan angka kematian sebanyak 17,3 juta dari total 54 juta kasus mortalitas per tahunnya* + WHO (2008): dislipidemia 37% pada laki-laki dan 40% pada wanita? + Hatma RD (2011): prevalensi dislipidemia dari kalangan multietnik di Indonesia berkisar 9-25% (tertinggi pada suku Minangkabau [24,8%] untuk kadar kolesterol total >200 mg/dL)? 1. PERKENI, Pedoman Pengelolaan Dislipidemia d Indonesia. 2019, 2. Hatma RD. Indones J Intern Med, 2011;43(1):4-11,WuLNenaBte PLAQUE eccentric, Lage. Foam ctain of pe issue factor vain tei cap ilammatery onion Triggors: Physical exert, mechanical stress ‘ue to an increase in cardiac contactity. Pulse rate, blood pressure, and possiy, ‘vasoconstriction In One Picture cruiuneynann Sires of an at Fe ryeeartal ionMetabolisme Lipid Lipid merupakan substansi lemak yang terikat pada molekul protein pembawa, dikenal sebagai apolipoprotei Coe nd Type Density (g/ml) Ori ‘Major Lipids Major Apolipoproteins Size (nm) Chylomicrons <095 Tntestine 85% Triglyceride | 848, Al, AV, E, Cl, Cll CI. __~100-500 Chylomicron remnants <1.008 Derived from chylomicrons | 60% Trigiceride | 848, E ~80-125 20% Cholesterol VoL <1,006 Liver 55% Trialeride | 8100, E, Cl, Cll, Cll 3080 20% Cholesterol IDL 1.006-1.019 Derived from VLDL 35% Cholesterol | 8100, E 2535 25% Triglyceride LoL 1.019.063 Derived from IDL 60% Cholesterol | 8100 1825 5% Triglyceride HOU 1.069-1.21 Liver, intestine, plasma 25% Phospholipid | Al, All, Cl, Cll, Cll, E 512 20% Cholestero! ‘5% Triglyceride Lplad 1.05-1.09 Liver 60% Cholesterol | 8100, apola) ~30 5% Triglyceride 0, apolipoprotein; IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein; UBIaN MpOprOTSMTAT, VLDL, very low density lipoprotein, Gay F et a Williams Textbook of Endocrinology. 13" ed. 2026.Metabolic pathways of lipoproteins Metabolisme dan transpor kolesterol oe * Sebagian besar disintesis di hati * Disatukan dengan protein (contoh ApoB) dan TG> disekresi ke plasma menjadi VLDL, kemudian TG dilepaskan> hidrolisis > LDL * ApoA1 yang dikandung HDL berfungsi mentranspor lipid yang berlebih dari perifer ke hati (reverse cholesterol transport) vasclr wal Indin other Reiner Z et al. Eur H J. 2011;32:1769-1818,CENTRAL ILLUSTRATION: Remnant Lipoprotein Metabolism = . on = Bs L. Adipose enh ‘Crytomiren @ “toh LOL Remnant Chemicon ‘inane sat. @PE — @avc aval @apos100 @anovss Saeed, A. et al. J Am Coll Cardiol. 2018;72(2):156-69.Klasifikasi Dislipidemia Sedang (Hiperkolesterolemia Tipogenik dan famniial) Berat, sepet hiperkolesterolemia familial, dyslipidemia remnan, hipertrigliseridemia primer Dislipidemia Akibat kelainan sistemik, seperti hipotiroidisme, sindrom nefrotik, DM, atau sindrom metabolik Reiner Z et al. Eur H J. 2011;32:1769-1818. Effect on Uipoproteins Hert nL TEDL tapoB Fo Fail poprotein pase deficiency Fail LCAT deficiency (fch je eaze) nL sHDL FH4= fail hypercholeserotaemia HeFH = heterozygous aii hypercolesterlaemia; HoFH = homozygous fail hyperchclesterlaems HDL high density Upopreten IDL = intrmadate dens Upopretein LAT = techn cholera acyrancferse: LDL = low. densty Ipoprota: te Beers eerie etersPopulasi untuk penapisan dislipidemia * Perokok aktif (1C) * Diabetes (1C) * Hipertensi (1C) * Riwayat Penyakit Jantung Koroner (PJK) dini pada keluarga (1C) * Penyakit ginjal kronis [PGK] (1C) * Riwayat keluarga dengan hiperlipidemia (1C) * Penyakit inflamasi kronis (1C) * Lingkar perut (LP) >80 cm wanita; >90 cm laki-laki (1C) * Disfungsi ereksi (1C) * Aterosklerosis atau aneurisma aorta abdominal (1C) * Obesitas dengan IMT 25 kg/m2 * Laki-laki usia >40 tahun atau wanita >50 tahun yang sudah menopause (1C)Mekanisme kerja obat dislipidemia Hegele R et al. Circ Res. 2019;124:386-404, a MEDISOI2 ee 2) Noe . ial ‘GLYEERA J ‘APOC VOLANESORSEN aNceTa [eunacumas]SCORE [5 and ove ois seo pe ~ ee, a 10-year ik ttt| cvDn peptone High CVD riskee High EVD Risk: sigh EVO Risk: Owe 93 mara Nowe =a 7 mesa aAACE: Cholesterol Guidelines — 2017 oe Gc Kart achieving an LDL-C <70 mg/dL. ‘+ Established clinical cardiovascular disease in patients with DM, <55, <80 <70 (CKD 3/4, or HeFH + History of premature ASCVD (<55 male, <65 female) Ceca Risk factors*/10-year risk* Very high risk + Established or recent hospitalization for ACS, coronary, carotid or peripheral vascular disease, 10-year risk >20% + Diabetes or CKD 3/4 with 1 or more risk factor(s) 2 = + HeFH High risk ‘+ >2,sk factors and 10-year risk 10-20% 7 : Z + Diabetes or CKD 3/4 with no other risk factors ao ep ou Moderate risk + <2 risk factors and 10-year risk <10% <100 >130 20 Low risk + Orisk factors <130 <160 NR Jellinger PS, et al. Endocr Pract 2017,(Epub ahead of print),ADA (2016): Recommendations for Cholesterol Management in DM Cee ey cvs Risk factors Hien 50 mg/dl (1.3 mmol/L) in patients who Moderate plus ezetimibe cannot tolerate high-dose statins >75 years None Moderate ASCVD risk factors Moderate or high ASCVD High ACS and LDL cholesterol >50 mg/dl (1.3 mmol/L) in patients who Moderate plus ezetimibe cannot tolerate high-dose statins “tn addition to lifestyle therapy **ASCVD risk factors include LDL cholesterol >100 mg/dL (2.6 mmol/L), high blood pressure, smoking, overweight and obesity, and family history of premature ASCVD ‘American Diabetes Assocation Diabetes Care. 2016;39 Suppl 160-71Ce Low Moderate High Very high NLA — 2014 Lipid Guidelines ery (0-1 major ASCVD risk factors Consider ather risk indicators, if known 2 major ASCVD risk factor ‘Quantitative isk scoring recommended Consider other risk indicators 3 major ASCVD risk factors Diabetes mellitus® (type 1 or 2) + O-Lother major ASCVD risk factors, and + No evidence of end-organ damage Chronic kidney disease stage 3 or 4 LDL-C >190 MG/DI 10% 10-year hard CHD event risk ascvb* Diabetes mellitus® (type 1 or 2) + 32 other major ASCVD risk factor(s) oF + Evidence of end-organ damage Treatment goal | Consider drug therapy Pome eens <130 (<100) 2190 (2160) <130 (<100) 2160 (2130) <130 (<100) 2130 (2100) <100 {<70} 2100 (270)ACC (2016): Recommendations for Cholesterol Management Paes SB ein (ay sar DL-C TO mA onan HOLE AOD igi patents weh dbs on many trated at ee LUoyd-tones OM, ot J Aen Coll Carl 0ne68t1h92-125,Initiation of Treatment Teel 2/1) Total CV Risk (SCORE) % No No No No LSI, drug if intervention | intervention | intervention | intervention | uncontrolled No No Ls),drugif | Asi, drugif | tsi, drug if intervention | intervention | uncontrotied | uncontrolled | uncontrolled No LS drugif | Usi+drug | tSiedrug | LSI + drug intervention | uncontrolled | therapy therapy therapy si drugif | isi+drug | si+drug —siedrug | Lsi+ drug uncontrolled | therapy therapy therapy therapy ‘catapano A, ea Eur Hear | 2016372998 2058 fest interventionStrategy to Reach LDL-C Goal Risk level Low or moderate High Serv tial % LDL-C reduction to target? T Choose appro} Moderate to high High intensity intensity statin” intensity statin statin LDL target not achieved TDL target not achieved LDL-C target not achieved Up titrate statin dose High intensity statin High intensity statin + or or ezetimibe Higher intensity statin] | High intensity statin + ezetimibe *Mostly low to moderate intensityHigh, Moderate, and Low-Intensity Sta High-intensity statin therapy (mg) Daily dose lowers LDL-C on average, by approx. 250% Rosuvastatin 20-40 Atorvastatin 40-80 Moderate-intensity statin therapy (mg) Daily dose lowers LDL-C on average, by approx. 30% to <50% Atorvastatin 10-20 Rosuvastatin 5-10 Simvastatin 20-40 Pravastatin 40-80 Lovastatin 40, Fluvastatin XI 80 Fluvastatin 40 bid Pitavastatin 2-4 Therapy Low-intensity statin therapy (mg) Daily dose lowers LDL-C on average, by approx. <30% Simvastatin 10 Pravastatin 10-20 Lovastatin 20 Fluvastatin 20-40 Pitavastatin 1 Donald M. Uoydones DM, a IRCC 20166892125Algoritma Terapi Kombinasi dalam Pencapaian Target Mach Fetal. Eur H J. 2020;61:111-882016 ACC Task Force on Non-Statin Therapies For high-risk patients with ASCVD or LDL-C > 190 and failure to achieve at least a 50% reduction in LDL-C on maximally tolerated statin, non-statins may be considered Eze e, given its safety and tolerability, should be the first additional medication added Bile acid sequestrants may be used as a second-line therapy if ezetimibe is not tolerated and triglycerides are not elevated If goals of therapy are not met on maximally tolerated statin and ezetimibe, either FDA- approved PCSK9 inhibitor can be added or used to replace ezetir Given the lack of long-term safety and efficacy data on the PCSK9 inhibitor they are not recommended for use in primary prevention patients in the absence of FH LUoyel-Jones DM, etal. Am Coll Cardiol. 2016;68(1):92-125.ipid Profile i “Diabetes ‘Based upon currently available evidence CA EMAME Fenotivrate>Nicotinic Ac Fish ol ether Arial dense Cr aney ease J Sane cee Lae nd ead oan fe Bit iGaae iy aoe Pen Ce eae TG <150 mgidl andiq™™MDL-C>40 mg/dl e [vo] Priority #2 Lyfestile Implementation — Check Compliance |,_ Reduction of +COMBINATION STATIN-FENOFIBRATE"* Residual CVD RiskManagement of Hypertriglyceridemia Bordertine-high triglyceride level High triglyceride level Very high tiglycaride level (150 ~ 188 magia) (200 = 499 mg/dL) (© 500 mg/dL) | | | Initiate theurapeutic lifestyle changes, optimize glycemic contol in patients with diabetes, screen for metabolic syndrome , and search for ‘secondary or acquired causes: l | Work on reaching LDL-C goal Is patiant at or near the LDL-C goal? If triglyceride level is higher than 1000 ma/dL, initiate a very low fat det (15 % ‘oF ass of calorie intake) and aggressive body weight reduction 4 “Triglyceride level is 500 mg/dl oF lower ‘Add a statin; increase or switch statins until patient is at or near the LDL goal Consider adding a fibrat, niacin, oF fish ol to achieve the non-HDL-C goal; consider statins first {for moderate-o high-risk patients (risk of myopathy is increased with a stain plus a fibrate) ‘Add a fibrate or niacin: Consider adding fish ol Work on reaching LOL-C goal Jeatal Oh Sembend Wine Wve SUNNNeL Wek LDLAT gute We eueindenrenyetereeNnNeN eels be eeUNNGN HERIOT gN ROL AAR)Monitoring dan AE pada Terapi Dislipidemia How often should ips be teste? lr sorsg ip omg rig eae eat no ‘earns sol be mace wh a ean of 112 was ‘wee ecepton of earns wre nmodste resem t egesad thas MACS How often sould patients Ips be ested after staring d-owerng treatment (fiw er sre geese 8 (24) wel raises weve unl wen de ree How often sould cholestralo pis be tested once a allen has reached target or optima ehaesterot hana ces ere sade poem or ter phe reson or mor eu oe). Mach F et al. Eur HJ. 2020;41:111-88. How often should iver enzymes (ALT) be routinely msrp king powering rg! weak ater ring drug exon or er any doe nrete + Analy hereafter er zymes are XUN, ‘What if iver enzymes become rsd na person taking ipld-owering drugs! Heute + Comins thorgy Recheck ne nye in 4-6 weeks ale eto aXULN = Sep san or reduce ote, rchack ver enzymes win 4-6 weeks + Cautious eincoducon of herapy maybe considered ar ALT as How often should CK be measure npn aking p= lowering rugs! Perea aoe sring ene bslne Ck lel >SULN do ot ar rg hap ahh Mating Route mona of Ck re recesary + Check CK patent doops malas rere sere: rede myo nd CK slesonin tnt 2 Poca ele ere conor tate ey mae wnat # CX becomes rased na prion aking powering rugs ifoSeuane * Sopot. heck rem nczon nd mentor CK ery 2 wee Caner the oul of ans CX ton or he rane ‘achat ran ron + Canader seen ues of mops #CK ro ated eo made sept. conine sn peso be serio reper oyna coir father ces of CK) + Hrmnce plans mentor sypn and CK repiyPemantauan Myopati pada Terapi Statin Mach F et al. Eur HJ. 2020;41:111-88.Pemantauan efek samping er ed cy Cee’ norms oer 20 | nee | eo os “Menonvtonmn mn ons oe ‘emer oe Boneless = Nace ten pancoes 1 oes Use new Css Semmes | rte Hveeoate | Uae eer Sees cel eee Pere maw [igeeee oe =e = —— Ear —eal= Se =o = = eee aaa i ceomms [SES eee | ae |e tease, ie Suing mace yt Sante amin yA a tne ec Oe ‘Grundy SM et al.J Am Col Cardiol. 2038.Table 10 Drugs potentially interacting with statins metabolized by cytochrome P450 3A4 leading to increased risk of myopathy and rhabdomyolysis Anti-infective Calcium agents antagonists Interaksi Obat pada smo aoe . : Ketoconazole Diltiazem. Pemberian Statin Posaconazole ‘Amlodipine Erythromycin Clarithromycin Telithromycin HIV protease inhibitors ‘Adapted from Egan and Colman,” and Wiklund et al?5® HIV = human immunodeficiency virus. ‘Mach Fet al. Eur H J. 2020;41:111-88, Other Ciclosporin Danazol Amiodarone Ranolazine Grapefruit juice 2 Nefazodone Gemfibrozit ESC 20Personalized Medicine May Be Necessary to Address Residual Vascular Risk CARDIOMETABOLIC RISK TODAY REDUCTION 7 STEP Statins, ACE inhibitors-ARBs, OAD ME Raeehes rea eycnt EFFECTIVE SUPPORTED BY GUIDELINES across gender, age and CVD risk groups ete Rye tohi ese) eel Dtcimt yD) aaa 4 ROMP ORC CE Mora Pens RESIDUAL CV RISK REDUCTION (.e. combination statin and fenofibrate) INDIVIDUALIZED SELECTED SUBGROUPS of PATIENTS Pan melted ee Pobre ttm O00) 10) Zambon A. - Restdual Risk Reduction Inative 2010r= Pee a.