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THE POSITION OF STATINS IN THE NEW GUIDELINE

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Presentation on theme: "THE POSITION OF STATINS IN THE NEW GUIDELINE"— Presentation transcript:

1 THE POSITION OF STATINS IN THE NEW GUIDELINE
Suroto Dept of Neurology, Fac of Medicine, Sebelas Maret University

2 Stroke Risk Factors—Overview
Unmodifiable Risk Factors Age Male sex Race Family history of stroke/coronary heart disease Modifiable Risk Factors Smoking Diet Sedentary lifestyle Alcohol/Drug abuse Obesity Carotid artery disease Atrial fibrillation Hypertension Diabetes Dyslipidemia Treatment Options Carotid endarterectomy Antiplatelet therapy Anticoagulation therapy Antihypertensive therapy Antidiabetic therapy Lipid-lowering therapies Unmodifiable risk factors for stroke include advancing age, male sex, Black and Hispanic race–ethnic background, and family history of stroke.1 Modifiable risk factors for stroke include lifestyle modification, such as smoking cessation, improved diet, moderate physical exercise, reducing excessive alcohol intake, and cessation of drug abuse. Weight reduction may also be recommended.1 Patients’ risk of stroke may be modified by pharmacologic therapies targeting risk factors. These therapies may include antiplatelet agents, anticoagulants, antihypertensive therapies, antidiabetic medications, or lipid-lowering (statins), as appropriate.1 In some patients, carotid endarterectomy may be recommended.1 Goldstein LB et al. Stroke. 2001;32: Reference 1. Goldstein LB, Adams R, Becker K, et al. Primary prevention of ischemic stroke: a statement for healthcare professionals from the Stroke Council of the American Heart Association. Stroke. 2001;32:

3 HISTORY Akira Endo and Masao Kuroda of Tokyo, Japan commenced research into inhibitors of HMG CoA reductase in 1971. This team reasoned that certain microorganism may produce inhibitors of the enzyme to defend themselves against other organism. The first agent isolated was Mevastatin ( ML- 236 ). The pharmaceutical company, Merck & Co showed an interest in the Japanese research in1976, and isolated Lovastatin(mevinolin, MK803), the first commercially marketed statin. Dr Endo was awarded the 2006 Japan Prize for his work on the development of statins.

4 Potential mechanisms of benefit of statins
Reduction in chylomicron and VLDL remnants, IDL, LDL-C HMG Co A reductase inhibitor Statins* Pleitrophic effect Lipid lowering effect Anti-inflammatory effects Decreased thrombosis Restore endothelial function Maintain SMC function Three paradigms are presented which might explain the benefits of statins in reducing the risk of coronary heart disease. Low-density lipoprotein cholesterol (LDL-C) reduction is integral to the efficacy of statins. However, analysis of lipid reductions in WOSCOPS with pravastatin suggest s that clinical benefit seen with pravastatin is not explained by lipid changes alone. Stains may alter one or more lipid subfractions in addition to LDL-C. These might include chylomicrons, small dense LDL-C, very low density lipoprotein remnants, or intermediate-density lipid (IDL). The combined reduction in these multiple lipid particles might explain the difference between predicted and observed event rates in patients receiving pravastatin. In addition, pravastatin has also been shown to have non-lipid effects, ie restored endothelial function, plaque stabilisation, inflammation, or decreased thrombogenicity. Research into these and other additional mechanisms of action is being actively pursued. Macrophages Lumen Lipid core Smooth muscle cells

5 Potential Time Course of Statin Effects in CAD / ACS
Vulnerable plaques stabilized LDL-C lowered* Inflammation reduced Cardiac events reduced* Ischemic episodes reduced Endothelial function restored Potential time course of statin effects CHD risk reduction with a statin appears to occur as a result of several related changes, including restoration of endothelial function, reduction in inflammation, and stabilization of vulnerable plaque. The time course for these antiatherosclerotic effects of statins ranges from days to years. Within weeks to months after beginning statin therapy, endothelial function of coronary arteries is restored. Concurrent with this or following by just a few months is a reduction in inflammatory markers, such as high-sensitivity C-reactive protein. These effects appear to coincide with the reduction in ischemic events demonstrated after about 18 months of statin therapy. After several years of therapy (i.e., 1.5–2.5 years), fatal and nonfatal myocardial infarction rates begin to decline in statin-treated patients, and after 5 years of therapy, significant reductions have been documented. These changes coincide somewhat with stabilization of vulnerable atherosclerotic plaque during which the lipid-rich core of plaque is replaced with connective tissue and matrix. Hours-Days Weeks-Months * Time course established

6 Statin Evidence: Expanding Benefits AFCAPS / TexCAPS/ WOSCOPS
Acute coronary event No history of CAD Unstable CAD Stable CAD 4 month AFCAPS / TexCAPS/ WOSCOPS MIRACL CARE/LIPID t = 0 4S 3 month 6 month In the 1990s, the WOSCOPS,1 AFCAPS/TexCAPS,2 4S,3 CARE,4 and LIPID5 studies demonstrated that long-term intervention with statin therapy reduces mortality and recurrent ischemic cardiovascular events both in individuals at risk for CVD and patients with stable CHD. Since this time, several trials have illustrated the benefits of statin therapy in a variety of other patient populations. The MIRACL study6 was a 16-week, multicenter, randomized, double-blind, placebo-controlled trial that showed that intensive lowering of LDL-C with atorvastatin (80 mg/day), initiated hours after an ACS, reduced the composite endpoint of death, nonfatal myocardial infarction (MI), resuscitated cardiac arrest, or recurrent symptomatic MI requiring emergency rehospitalization from 17.4% to 14.8% (P = .048) within 16 weeks of treatment. HPS7 demonstrated that, regardless of baseline LDL-C, simvastatin 40 mg/day significantly decreased the relative risk of major vascular events by 24% among patients considered to be at substantial 5-year risk of death from CHD, including patients with established CHD (primary prevention) and patients with diabetes or treated for hypertension (secondary prevention) . Moreover, there was no lower LDL-C limit at which benefits of statin therapy were not observed. ASCOT-LLA8 showed atorvastatin 10 mg significantly lowered the primary endpoint of nonfatal MI (including silent MI) and fatal CHD by 36% in a population of hypertensive patients who were only at moderate cardiovascular risk, and who would not conventionally be deemed dyslipidemic. The reductions in major cardiovascular events with atorvastatin emerged earlier than in many other statin trials. 1WOSCOPS Group. Circulation. 1998;97: 2Downs JR, et al. JAMA. 1998;279: 34S Group. Lancet. 1994;344: 4Sacks FM, et al. Circulation. 1998;97: 5LIPID Group. N Engl J Med. 1998;339: 6Schwartz GG, et al. JAMA. 2001;285: 7Heart Protection Study Collaborative Group. Lancet. 2002;360:7-22. 8Sever PS, et al. Lancet. 2003;361: HPS ASCOT-LLA Hypertension Primary prevention Secondary prevention

7 Statin in primary and secondary prevention trials ; The lower the better
4S-PBO Secondary prevention Primary prevention 25 20 LIPID-PBO 4S-Rx With CHD event (%) 15 CARE-PBO CARE-Rx HPS-PBO 10 LIPID-Rx WOS-PBO HPS-Rx WOS-Rx TNT-PBO TNT-Rx 5 AFCAPS-Rx AFCAPS-PBO 50 70 90 110 130 150 170 190 210 PBO = Placebo Rx = Treated LDL-C (mg/dL)

8 NCEP - ATP Guidelines

9 The revised ATP-III was based on the review of five statin trials conducted since the release of ATP-III LDL-C <70 mg/dL considered in extremely high risk patient. LDL-C lowering drug indicated in addition to TLC if LDL-C > 100 mg/dL The intensity of LDL-lowering drug tx in high – moderately high risk patients must be sufficient to achieve at least 30-40% reduction in LDL levels Revised ATP-III 2004 se emphasis on 1st prevention inclusion of high risk groups for 2nd prevention new risk levels for major lipid measures ( LDL-C <100 mg/dL optimal level for all adults; HDL-C > 40 mg/dL and TG < 150 mg/dL ) Important secondary target were non-HDL-C in patient with TG > 200 mg/dL and metabolic syndrome New category “CHD risk equivalent” in diabetes and patients with > 20% CHD 10 year risk equivalent. Global risk score based on Framingham Heart Study used for calculation of 10 year risk ATP - III 2001 LDL-C target < 100 mg/dL Focus on 2nd Prevention Introduction of HDL-C as CHD risk ( <35 mg/dL ) TG level<200 mg/dL was normal ATP - II 1993 LDL-C target < 130 mg/dL Focus on 1st Prevention ATP - I TLC : Therapeutic Lifestyle Changes 1988

10 Comparison of Major Features of ATP II and ATP III
£ 100 mg/dL < 100 mg/dL <70mg/dL in very high risk patients ( revised ) ³ 220 mg/dL ³ 190 mg/dL < 35 mg/dL < 40 mg/dL < 200 mg/dL < 150 mg/dL Risk Factor CHD Equivalent No Yes Total-C and HDL-C Total-C, HDL-C, LDL-C, and TG LDL-C target for CHD or CHD Risk Equivalent : LDL-C level in very high cholesterol : Categorically low HDL-C : Triglycerides : Diabetes : Completion of Framingham Risk Assessment : Recommended lipid profile : Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 1993;269:3015. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486.

11 ESC/EAS Guidelines

12 ESC/EAS Guidelines for the management of dyslipidaemias
<1 >1 to <5 >5 to <10, or high risk >10 or very high risk No lipid intervention Lifestyle intervention Lifestyle intervention, consider drug consider drug if uncontrlled and immediate drug intervention Intervention strategies as a function of total CV risk and LDL-C level ESC/EAS : European Society of Cardiology /European Atherosclerosis Society European Heart Journal (2011) 32, 1769–1818

13 10-year risk of fatal CVD in populations at high CVD risk
< 1% 1% 2% 3-4% 5-9% 10-14% 15% and over 10-year risk of fatal CVD in populations at high CVD risk SCORE + 1 2 3 4 5 Age Total cardiovascular risk estimation European Heart Journal (2011) 32, 1769–1818

14 Risk will be higher than calculated in patients with additional conditions such as:
Diabetes Evidence of subclinical atherosclerosis (CalciumScore, Carotid Screening) Familial premature atherosclerotic disease Chronic Kidney Disease Increased Lp (a), AboB/ApoB1 ratio, low HDL-C, high TC

15 • In patients at very high CV risk : established CVD, type 2 diabetes or type 1 diabetes with target organ damage, moderate to severe CKD or a SCORE level ≥10 % the LDL-C goal is <1.8 mmol/L(<~70 mg/ dL) and/or a ≥ 50 % LDL-C reduction when target level cannot be reached. • In patients at high CV risk : markedly elevated single risk factors, a SCORE level ≥5 - <10% the LDL-Cgoal <2.5 mmol/L (<~100 mg/dL). • In patients at moderate risk : SCORE level >1 to ≤5% the LDL-C goal <3.0 mmol/L (<~115 mg/dL). If drug treatment is indicated to decrease LDL-C, a statin is recommended, up to the highest tolerable dose, to reach the target level.

16 2013 ACC/AHA Guideline

17 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults November 12, 2013 First new guidelines since ATP III guideline update in 2004 The most important statements or changes presented in these guidelines No longer have therapeutic targets New risk calculator Use medications proven to reduce risk, ie statins Avoid medications or supplements that may lower the cholesterol number, but have no data to decrease CV risk Circulation,published online November 12, 2013

18 Overview of the Expert Panel’s guideline

19 What has changed compared to ATP-III guideline?
Initiate either moderate-intensity or high-intensity statin therapy for patients who fall into the four categories Unlike ATP-III, Do not titrate to a specific LDL cholesterol target Measure lipids during follow-ups to assess adherence to treatment, not to achieve a specific LDL target current guidelines direct clinicians to initiate either moderate-intensity or high-intensity statin therapy for patients who fall into the four categories, without titration to a specific LDL cholesterol target Measuring lipids during follow-ups is done to assess adherence to treatment and not to see whether a specific LDL cholesterol target has been achieved Rather than use a "lowest is best" approach that combines a low dose of a statin drug along with several other cholesterol-lowering drugs, new guidelines focuses on a healthy lifestyle along with a higher dose of statins, eliminating the need for additional medications.

20 Four Major Statin Benefit Groups
Individuals with clinical ASCVD Individuals with LDL >190 Individuals with Diabetes, yo with LDL and without clinical ASCVD Individuals without clinical ASCVD or Diabetes, with LDL and estimated 10-year ASCVD risk >7.5% -Based on extensive review of the evidence, the expert panel identified 4 groups that would benefit from statin therapy: Individuals with clinical ASCVD Individuals with LDL >190 Individuals with dm, yo with LDL and without clinical ASCVD Individuals without clinical ASCVD or dm with LDL and estimated 10-year ASCVD risk >7.5% Note that Clinical ASCVD is defined by the inclusion criteria for the secondary prevention statin RCTs (acute coronary syndromes, or a history of MI, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin). ASCVD : AtheroSclerotic CardioVascular Disease

21 No Cardiovascular risk calculator Cardiovascular risk calculator
Age < 75y High-intensity statin (Moderate-intensity if not candidate for high intensity Statin) Clinical ASCVD Adults age > 21y and A candidate for Statin Tx LDL-C > 190 mg/dL Diabetes Age y > 7.5% estimated 10-y ASCVD risk Estimate 10-y ASCVD risk With Pooled Cohort Equation Moderate-to- high intensity statin Moderate-intensity statin Age > 75y or if not candidate for high intensity Statin Yes No Estimated 10-y ASCVD risk >7.5% High intensity statin No Cardiovascular risk calculator Moderate-intensity statin This algorithim summarizes the major guidelines in one page You see the 4 statin benefit groups in the middle: on top, you see the patient’s group with clinical ASCVD, below that you see the group with LDL >190, below that you see the patient’s with history of DM years old, and in the bottom, you see patients who don’t have the characteristics of the first 3 groups but their 10 year ASCD risk is greater than 7.5% For the first group: based on the guidline, if you have clinical ASCD, are younger than 75 and don’t have any history of intolerance to statin, you should be started on high intensity statin. On the other hand, if you are older than 75, or not a candidate for high intensity statin due to lets say intolerance to statins, you are a candidate for moderate-intensity statin For the second group, if your LDL is greater than 190, you need to be started on high-intensity statin, unless you have contra-indication to high dose start on moderate dose For the third group, individuals with diabetes with above mentioned group age, you need to calculate the 10 year ASCVD risk using a new equation/calculater called “pooled Cohort Equations” if the 10 year risk is greater than 7.5%, start them on high-intensity, otherwise, you can start them on moderate-intensity statin For the last group, you need to calculate patient’s risk factor and start them on moderate-to-high intensity statin if their estimated 10-y ASCVD risk is greater than 7.5% Keep that in mind that what we mean by “high intensity” statin, is the daily dose of statin that lowers the LDL by appox greater than 50%, and what we mean by moderate intensity statin, is the daily dose of statin that lowers the LDL by appox 30-50%. Cardiovascular risk calculator

22 Intensity of Statin Therapy Moderate-Intensity Statin Therapy
High-Moderate-and Low-Intensity Statin Therapy (Used in the RCTs reviewed by the Expert Panel) High-Intensity Statin Therapy Moderate-Intensity Statin Therapy Low-Intensity Daily dose lowers LDL-C on average, by approximately > 50% 30% to 50% Daily dose lowers LDL-C on average, by < 30% Atorvastatin ( 40 )- 80 mg Rosuvastatin 20 (40) mg Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin mg* Pravastatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2-4 mg Simvastatin 10 mg Pravastatin mg Lovastatin 20 mg Fluvastatin mg Pitavastatin 1 mg RCT : Randomized Control Trials Circulation,published online November 12, 2013

23 Risk Assessment : http://my.americanheart.org/cvriskcalculator
Sex M or F Age Years ( ) Race AA ( Afro american ) or WH ( White or others ) Total Cholesterol mg/dL ( ) HDL-Cholesterol mg/dL ( 20 – 100 ) Systolic blood pressure mmHg ( 90 – 200 ) Treatment for High blood pressure Y ( Yes ) or N ( No ) Diabetes Y ( Yes ) or N ( No ) Smoker Y ( Yes ) or N ( No )

24 Risk Assessment : Column Chart
This calculator only provides 10-year risk estimates for individuals years of age Risk Assessment : Your 10 year ASCVD Risk (%) 10 year ASCVD Risk (%) for someone with optimal risk factor ( Col E ) Your lifetime ASCVD Risk (%) Lifetime ASCVD Risk (%) for someone with optimal risk factor ( Col E ) Column Chart

25 STATIN Safety recommendations (1)
Select the appropriate dose If high or moderate intensity statin not tolerated, use the maximum tolerated dose instead Conditions that could predispose patients to statin side effect: Impaired renal or hepatic function History of previous statin intolerance or muscle disorder Age >75 Unexplained ALT elevation > 3x ULN History of hemorrhagic stroke Asian ancestry The next few slides tells you the new guidelines on the safety recommendations for statins

26 STATIN Safety recommendations (2)
Check baseline ALT prior initiating the statin (Grade B) Check LFTs if patient develops Symptoms of hepatic dysfunction (Grade E) If 2 consecutive LDL <40, Consider decreasing the statin dose (Grade C, weak recommendation) It may be harmful to initiate simvastatin 80mg, or increase the dose of simvastatin to 80mg (Grade B) Symptoms of hepatic dysfunction: unusual fatigue or weakness, loss of appetite, abdominal pain, dark colored urine, Jaundice

27 Case 1 50 year old white female Total cholesterol 180 HDL: 50 SBP: 130
taking anti-hypertension meds + diabetic + smoker Calculated 10 yr ASCVD: 9.1%

28 9.1 0.8 50.0 8.0 Your 10 year ASCVD Risk (%)
10 year ASCVD Risk (%) for someone with optimal risk factor ( Col E ) Your lifetime ASCVD Risk (%) Lifetime ASCVD Risk (%) for someone with optimal risk factor ( Col E ) 9.1 0.8 50.0 Your Lifetime ASCVD Risk (%) 8.0

29 Cardiovascular risk calculator Age < 75y Clinical ASCVD
High-intensity statin (Moderate-intensity if not candidate for high intensity Statin) Clinical ASCVD Adults age > 21y and A candidate for Statin Tx LDL-C > 190 mg/dL Diabetes Age y > 7.5% estimated 10-y ASCVD risk Estimate 10-y ASCVD risk With Pooled Cohort Equation Moderate-to- high intensity statin Moderate-intensity statin Age > 75y or if not candidate for high intensity Statin Yes No Estimated 10-y ASCVD risk >7.5% Moderate-intensity statin This algorithim summarizes the major guidelines in one page You see the 4 statin benefit groups in the middle: on top, you see the patient’s group with clinical ASCVD, below that you see the group with LDL >190, below that you see the patient’s with history of DM years old, and in the bottom, you see patients who don’t have the characteristics of the first 3 groups but their 10 year ASCD risk is greater than 7.5% For the first group: based on the guidline, if you have clinical ASCD, are younger than 75 and don’t have any history of intolerance to statin, you should be started on high intensity statin. On the other hand, if you are older than 75, or not a candidate for high intensity statin due to lets say intolerance to statins, you are a candidate for moderate-intensity statin For the second group, if your LDL is greater than 190, you need to be started on high-intensity statin, unless you have contra-indication to high dose start on moderate dose For the third group, individuals with diabetes with above mentioned group age, you need to calculate the 10 year ASCVD risk using a new equation/calculater called “pooled Cohort Equations” if the 10 year risk is greater than 7.5%, start them on high-intensity, otherwise, you can start them on moderate-intensity statin For the last group, you need to calculate patient’s risk factor and start them on moderate-to-high intensity statin if their estimated 10-y ASCVD risk is greater than 7.5% Keep that in mind that what we mean by “high intensity” statin, is the daily dose of statin that lowers the LDL by appox greater than 50%, and what we mean by moderate intensity statin, is the daily dose of statin that lowers the LDL by appox 30-50%. Cardiovascular risk calculator

30 Moderate-Intensity Statin Therapy
High-Intensity Statin Therapy Moderate-Intensity Statin Therapy Low-Intensity Daily dose lowers LDL-C on average, by approximately > 50% 30% to 50% Daily dose lowers LDL-C on average, by < 30% Atorvastatin ( 40 )- 80 mg Rosuvastatin 20 (40) mg Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin mg* Pravastatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2-4 mg Simvastatin 10 mg Pravastatin mg Lovastatin 20 mg Fluvastatin mg Pitavastatin 1 mg

31 Case 2 48 year white female Total cholesterol 180 HDL: 55 SBP: 130
Not taking anti-hypertension meds + diabetic Non-smoker Calculated 10 yr risk ASCVD : 1.8%

32 1.8 0.7 39.0 8.0 Your 10 year ASCVD Risk (%)
10 year ASCVD Risk (%) for someone with optimal risk factor ( Col E ) Your lifetime ASCVD Risk (%) Lifetime ASCVD Risk (%) for someone with optimal risk factor ( Col E ) 1.8 0.7 39.0 8.0 Your Lifetime ASCVD Risk (%)

33 Cardiovascular risk calculator Age < 75y Clinical ASCVD
High-intensity statin (Moderate-intensity if not candidate for high intensity Statin) Clinical ASCVD Adults age > 21y and A candidate for Statin Tx LDL-C > 190 mg/dL Diabetes Age y > 7.5% estimated 10-y ASCVD risk Estimate 10-y ASCVD risk With Pooled Cohort Equation Moderate-to- high intensity statin Moderate-intensity statin Age > 75y or if not candidate for high intensity Statin Yes No Estimated 10-y ASCVD risk >7.5% High intensity statin This algorithim summarizes the major guidelines in one page You see the 4 statin benefit groups in the middle: on top, you see the patient’s group with clinical ASCVD, below that you see the group with LDL >190, below that you see the patient’s with history of DM years old, and in the bottom, you see patients who don’t have the characteristics of the first 3 groups but their 10 year ASCD risk is greater than 7.5% For the first group: based on the guidline, if you have clinical ASCD, are younger than 75 and don’t have any history of intolerance to statin, you should be started on high intensity statin. On the other hand, if you are older than 75, or not a candidate for high intensity statin due to lets say intolerance to statins, you are a candidate for moderate-intensity statin For the second group, if your LDL is greater than 190, you need to be started on high-intensity statin, unless you have contra-indication to high dose start on moderate dose For the third group, individuals with diabetes with above mentioned group age, you need to calculate the 10 year ASCVD risk using a new equation/calculater called “pooled Cohort Equations” if the 10 year risk is greater than 7.5%, start them on high-intensity, otherwise, you can start them on moderate-intensity statin For the last group, you need to calculate patient’s risk factor and start them on moderate-to-high intensity statin if their estimated 10-y ASCVD risk is greater than 7.5% Keep that in mind that what we mean by “high intensity” statin, is the daily dose of statin that lowers the LDL by appox greater than 50%, and what we mean by moderate intensity statin, is the daily dose of statin that lowers the LDL by appox 30-50%. Cardiovascular risk calculator

34 Moderate-Intensity Statin Therapy
High-Intensity Statin Therapy Moderate-Intensity Statin Therapy Low-Intensity Daily dose lowers LDL-C on average, by approximately > 50% 30% to 50% Daily dose lowers LDL-C on average, by < 30% Atorvastatin ( 40 )- 80 mg Rosuvastatin 20 (40) mg Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin mg* Pravastatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2-4 mg Simvastatin 10 mg Pravastatin mg Lovastatin 20 mg Fluvastatin mg Pitavastatin 1 mg

35 Case 3 22 year white male LDL- cholesterol 195 SBP: 120
Not taking anti-hypertension meds Non-diabetic Non-smoker

36 No Cardiovascular risk calculator Age < 75y Clinical ASCVD
High-intensity statin (Moderate-intensity if not candidate for high intensity Statin) Clinical ASCVD Adults age > 21y and A candidate for Statin Tx LDL-C > 190 mg/dL Diabetes Age y > 7.5% estimated 10-y ASCVD risk Estimate 10-y ASCVD risk With Pooled Cohort Equation Moderate-to- high intensity statin Moderate-intensity statin Age > 75y or if not candidate for high intensity Statin Yes No Estimated 10-y ASCVD risk >7.5% High intensity statin No Cardiovascular risk calculator This algorithim summarizes the major guidelines in one page You see the 4 statin benefit groups in the middle: on top, you see the patient’s group with clinical ASCVD, below that you see the group with LDL >190, below that you see the patient’s with history of DM years old, and in the bottom, you see patients who don’t have the characteristics of the first 3 groups but their 10 year ASCD risk is greater than 7.5% For the first group: based on the guidline, if you have clinical ASCD, are younger than 75 and don’t have any history of intolerance to statin, you should be started on high intensity statin. On the other hand, if you are older than 75, or not a candidate for high intensity statin due to lets say intolerance to statins, you are a candidate for moderate-intensity statin For the second group, if your LDL is greater than 190, you need to be started on high-intensity statin, unless you have contra-indication to high dose start on moderate dose For the third group, individuals with diabetes with above mentioned group age, you need to calculate the 10 year ASCVD risk using a new equation/calculater called “pooled Cohort Equations” if the 10 year risk is greater than 7.5%, start them on high-intensity, otherwise, you can start them on moderate-intensity statin For the last group, you need to calculate patient’s risk factor and start them on moderate-to-high intensity statin if their estimated 10-y ASCVD risk is greater than 7.5% Keep that in mind that what we mean by “high intensity” statin, is the daily dose of statin that lowers the LDL by appox greater than 50%, and what we mean by moderate intensity statin, is the daily dose of statin that lowers the LDL by appox 30-50%.

37 Moderate-Intensity Statin Therapy
High-Intensity Statin Therapy Moderate-Intensity Statin Therapy Low-Intensity Daily dose lowers LDL-C on average, by approximately > 50% 30% to 50% Daily dose lowers LDL-C on average, by < 30% Atorvastatin ( 40 )- 80 mg Rosuvastatin 20 (40) mg Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin mg* Pravastatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2-4 mg Simvastatin 10 mg Pravastatin mg Lovastatin 20 mg Fluvastatin mg Pitavastatin 1 mg

38 Summary The statins (or HMG-CoA reductase inhibitors) form a class of Hypolipidemic drugs used to lower cholesterol levels in people with or at risk of Cardiovascular disease. Based on clinical trials (RCT), the National Cholesterol Education Program / Adult Treatment Panel (NCEP-ATP) had developed guidelines, focus on aggressively lowering LDL-cholesterol. The statins continue to play an important role in both the primary and secondary prevention of ASCVD. End of 2013 the ACC and AHA , collaborate with the National Heart, Lung, and Blood Institute (NHLBI) develop new clinical practice guidelines for assessment of CV risk, lifestyle modifications to reduce CV risk, and management of blood cholesterol. This guideline focuses on treatments to reduce ASCVD events. ASCVD : AtheroSclerotic CardioVascular Disease RCT : Randomized Control Trial

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