Isn't Xstatin 10mg good enough for the control of lipids for my patient? Do we need more?

Transcription

1 Isn't Xstatin 10mg good enough for the control of lipids for my patient? Do we need more? Singhealth GP CME Symposium 2018 ~ Keep Well, Age Well Pan Pacific Hotel, Singapore 12 May 2018 Dr Farhad Fakhrudin Vasanwala Head, Department of Family Medicine, Sengkang General Hospital Senior Consultant BSc(Hons)NUS, FCFP, FRCP(Edin), FAMS

2 OUTLINE Case Scenario What Is Hyperlipidemia And Long Term Sequelae Of Raised Levels? Major Risk Factors For Cardiovascular Disease Sobering Facts Of Hyperlipidemia Control In Singapore 2013 ACC/AHA Guideline: Cholesterol Treatment to Reduce ASCVD Risk In Adults Heavyweight Statins, Ezetimibe And PCSK9 Inhibitors Singapore CPG Lipid Guidelines 2016 Critical Role Of Diet And Exercise Answer To Case Scenario Quiz Questions

3 Case Scenario: Another Day With A Typical Patient With Multiple Chronic Diseases You see an elderly 72 year old Malay gentleman with Diabetes, Hyperlipidemia, and Ischaemic Heart Disease with PCI done referred from a RH for follow up of his chronic medical issues. Latest lipids LDL 2.2 mmol/l, HDL 1.1 mmol/l, TG 1.0 mmol/l, HbA1C 6.8 %,LFT, CK normal, BP 120/80 mmhg. Excellent diet control and exercise. Compliant with medication. No drug allergy. Currently on: Metformin 500 mg bd Losartan 50 mg om Lovastatin 10 mg on Aspirin 100 mg om Famotidine 40 mg om What are you going to do with regards to the statins dose? Are you going to: a. Keep it to Lovastatin 10mg on? b. Reduce the dose to Lovastatin 5mg on? c. Change to Simvastatin 40mg on? d. Change to Atorvastatin 40mg on?

4 OUTLINE Case Scenario What Is Hyperlipidemia And Long Term Sequelae Of Raised Levels? Major Risk Factors For Cardiovascular Disease Sobering Facts Of Hyperlipidemia Control In Singapore 2013 ACC/AHA Guideline: Cholesterol Treatment to Reduce ASCVD Risk In Adults Heavyweight Statins, Ezetimibe And PCSK9 Inhibitors Singapore CPG Lipid Guidelines 2016 Critical Role Of Diet And Exercise Answer To Case Scenario Quiz Questions

5 What Is Hyperlipidemia? An abnormally elevated plasma lipid level. It is a significant risk factor for coronary artery disease (ischaemic heart disease) which can be familial or acquired (largely through lifestyle, especially high-fat diet) or due to secondary causes, e.g. hypothyroidism. The condition is asymptomatic and only diagnosed by a screening blood test or following a cardiac event, or cerebrovascular event.

6 What Is The Long Term Sequelae Of Raised Levels of Hyperlipidemia? Lipid and lipoprotein abnormalities are very common in the general population, and are regarded as a modifiable risk factor for cardiovascular disease due to their influence on atherosclerosis. In addition, some forms may predispose to acute pancreatitis.

7 What Is The Long Term Sequelae Of Hyperlipidemia? Pathogenesis of Atherosclerosis

8 What Is The Long Term Sequelae Of Hyperlipidemia? Manifestations of Hyperlipidemia On The Skin Eruptive Xanthomas Palmar Xanthomas Tendon Xanthomas Xanthelasma

9 OUTLINE Case Scenario What Is Hyperlipidemia And Long Term Sequelae Of Raised Levels? Major Risk Factors For Cardiovascular Disease Sobering Facts Of Hyperlipidemia Control In Singapore 2013 ACC/AHA Guideline: Cholesterol Treatment to Reduce ASCVD Risk In Adults Heavyweight Statins, Ezetimibe And PCSK9 Inhibitors Singapore CPG Lipid Guidelines 2016 Critical Role Of Diet And Exercise Answer To Case Scenario Quiz Questions

10 Major Risk Factors For Cardiovascular Disease Adverse Lifestyle Cigarette Smoking Physical Inactivity Atherogenic Diet High Risk Diseases Hypertension Diabetes Hyperlipidemia Obesity Non-Modifiable Factors Age Family History (e.g. premature CAD) End-Organ Damage Ischaemic Heart Disease (AF, MI, CHF) Chronic Kidney Disease Stroke Peripheral Artery Disease Eyesight Failure

11 Secondary Causes of Hyperlipidemia Treat the underlying causes too! Causes Hormonal Liver Disease Nutritional Disorders Drug Induced Renal Dysfunction Conditions Pregnancy Diabetes Mellitus Hypothyroidism Primary Biliary Cirrhosis Extra Hepatic Biliary Obstruction Obesity Anorexia Nervosa Alcohol Abuse High Dose Thiazides Corticosteroids Sex Hormones Nephrotic Syndrome Chronic Renal Failure

12 OUTLINE Case Scenario What Is Hyperlipidemia And Long Term Sequelae Of Raised Levels? Major Risk Factors For Cardiovascular Disease Sobering Facts Of Hyperlipidemia Control In Singapore 2013 ACC/AHA Guideline: Cholesterol Treatment to Reduce ASCVD Risk In Adults Heavyweight Statins, Ezetimibe And PCSK9 Inhibitors Singapore CPG Lipid Guidelines 2016 Critical Role Of Diet And Exercise Answer To Case Scenario Quiz Questions

13 Sobering Facts Of Hyperlipidemia Control In Singapore Prevalence of hypercholesterolemia in Singapore is 48.3%. For every 10 Singaporeans, almost 5 of them have various levels of hypercholesterolemia!

14 Sobering Facts Of Hyperlipidemia Control In Singapore Prevalence and Control of Hypercholesterolemia as Defined by NCEP-ATPIII Guidelines and Predictors of LDL-C Goal Attainment in a Multi-Ethnic Asian Population Chin Meng Khoo, Tavintharan Subramaniam, E Shyong Tai, Jeannette Lee Statin-centric versus low-density lipoprotein-centric approach for atherosclerotic cardiovascular disease prevention: a Singapore perspective Peter Yan, Eng Kiat Kevin Tan, Jason Chon Jun Choo, Choon Fong Stanley Liew, Titus Lau, David D Waters

15 Sobering Facts Of Hyperlipidemia Control In Singapore Every day, 16 people die from cardiovascular disease (heart diseases and stroke) in Singapore. Cardiovascular disease accounted for 29.5% of all deaths in This means that nearly 1 out of 3 deaths in Singapore, is due to heart diseases or stroke.

16 Sobering Facts Of Hyperlipidemia Control In Singapore 17.3% of the participants are unaware they have this condition. Only 39.6% of the participants in the high risk category reported taking lipid lowering therapy. Even among those that received the lipid lowering therapy, less than 50% met the group specific LDL-C treatment goals. Compared to the Chinese ethnic group, both the Malay and Indian ethnic groups had higher probabilities of having LDL-C above the treatment goals, despite being aware of hypercholesterolemia.

17 Sobering Facts Of Hyperlipidemia Control In Singapore In the high CHD groups we do inadequate titration of statin therapy. Raising an awareness of hypercholesterolemia, appropriate lipid lowering therapy, weight management and smoking cessation may improve LDL-C goal attainment in this population. In Singapore, approximately 47% of patients used low-potency statins, the majority of which were prescribed by general practitioners; of these patients, 45% required up-titration. In particular, 40% 60% of diabetic patients required up-titration, but there was reluctance to up-titrate or switch to a higher dose or higher potency statin.

18 Sobering Facts Of Hyperlipidemia Control In Singapore Findings from a SingHealth Polyclinic study Medications NOT ethnicity control cholesterol levels Adherence to medication is critical in reaching the target values. Varies with ethnicity in Singapore. Race Adherence (%) Target Reached (%) Chinese Malay Indian However, ethnicity is but one of the other factors that influence lifestyle changes that are required to control blood cholesterol levels. Eg. Other Indians saw more results if they change their diets. Chinese saw more results if they were active. Source: The Strait Times, Tuesday 31 st May 2016 Dr Tan Ngiap Chuan, the Director of the Department of Research at SingHealth Polyclinics, observed that many patients with high cholesterol continue to be resistant to starting medication.

19 Sobering Facts Of Hyperlipidemia Control In Singapore Million Source: wwwtradingeconomics.com Statistics Singapore

20 Screening For Hyperlipidemia Should Begin Early For Screening is recommended for men and women aged 18 years and older in the presence of any of the following: Diabetes Mellitus. A family history of cardiovascular disease before age 50 years in male relatives or age 60 years in female relatives. A family history suggestive of familial hyperlipidemia. Multiple coronary artery disease risk factors (e.g. tobacco use, hypertension).

21 Measurement Conversions LDL-C > 190 mg/dl is equivalent to > 4.92 mmol/l. LDL-C mg/dl is equivalent to mmol/l. Triglycerides above 1.7 mmol/l is not good.

22 OUTLINE Case Scenario What Is Hyperlipidemia And Long Term Sequelae Of Raised Levels? Major Risk Factors For Cardiovascular Disease Sobering Facts Of Hyperlipidemia Control In Singapore 2013 ACC/AHA Guideline: Cholesterol Treatment to Reduce ASCVD Risk In Adults Heavyweight Statins, Ezetimibe And PCSK9 Inhibitors Singapore CPG Lipid Guidelines 2016 Critical Role Of Diet And Exercise Answer To Case Scenario Quiz Questions

23 2013 ACC/AHA Guideline: Cholesterol Treatment To Reduce ASCVD Risk In Adults

24 2013 ACC/AHA Guideline: Cholesterol Treatment To Reduce ASCVD Risk In Adults ASCVD Calculator calculated risk risk with optimal risk factors** calculated risk risk with optimal risk factors Gender Age Race HDL - Cholesterol (mg/dl) Total Cholesterol (mg/dl) Diabetes Systolic Blood Pressure Treatment for Hypertension Smoker * Intended for use if there is not ASCVD and the LDL-cholesterol is <190mg/dL. ** Optimal risk factors include: Total cholesterol of 170mg/dL, HDL-cholesterol of 50mg/dL, Systolic BP of 110mm Hg. Not taking medications for hypertension, Not a diabetic, Not a smoker.

25 2013 ACC/AHA Guideline: Cholesterol Treatment To Reduce ASCVD Risk In Adults

26 2013 ACC/AHA Guideline: Cholesterol Treatment To Reduce ASCVD Risk In Adults

27 2013 ACC/AHA Guideline: Cholesterol Treatment To Reduce ASCVD Risk In Adults

28 2013 ACC/AHA Guideline: Cholesterol Treatment To Reduce ASCVD Risk In Adults

29 2013 ACC/AHA Guideline: Cholesterol Treatment To Reduce ASCVD Risk In Adults

30 2013 ACC/AHA Guideline: Cholesterol Treatment To Reduce ASCVD Risk In Adults

31 OUTLINE Case Scenario What Is Hyperlipidemia And Long Term Sequelae Of Raised Levels? Major Risk Factors For Cardiovascular Disease Sobering Facts Of Hyperlipidemia Control In Singapore 2013 ACC/AHA Guideline: Cholesterol Treatment to Reduce ASCVD Risk In Adults Heavyweight Statins, Ezetimibe And PCSK9 Inhibitors Singapore CPG Lipid Guidelines 2016 Critical Role Of Diet And Exercise Answer To Case Scenario Quiz Questions

32 The Heavyweight Statins Have Gone Generic! Rosuvastatin Calcium 20 mg tab Lipirex (Atorvastatin) 20 mg tab Rosuvastatina 10 mg tab Mylan-Rosuvastatin 40 mg tab

33 Ezetimibe Purpose Of Ezetimibe: It lowers plasma cholesterol levels. It acts by decreasing cholesterol absorption in the small intestine.

34 Ezetimibe How To Use Ezetimibe: As an add-on drug in association with statins when the therapeutic target is not achieved at the maximum tolerated statin dose, OR As an alternative to statins in patients who are intolerant of statins or with contraindications to statins. It may be used alone (marketed as Zetia or Ezetrol), when other cholesterol-lowering medications are not tolerated, OR Together with statins (e.g., Ezetimibe / Simvastatin marketed as Vytorin or Inegy) when statins alone do not control cholesterol

35 Introducing: PCSK9 Inhibitors Now even more exciting the introduction of the PCSK9 Inhibitors: Currently two drugs are available: i. Alirocumab (Praluent) and ii. Evolocumab (Repatha). The recommended starting dose of Praluent is 75 mg administered subcutaneously every 2 weeks or alternatively 300 mg every 4 weeks (monthly) for patients who prefer less frequent dosing. The recommended subcutaneous dosage of Repatha is either 140 mg every 2 weeks or 420 mg once monthly. These two drugs are indicated for patient with hereditary hypercholesterolemia and patients with atherosclerosis who require additional lowering of LDL cholesterol when diet and statin treatment has not worked.

36 Mode of Action of PCSK9 Inhibitors

37 Mode of Action of PCSK9 Inhibitors By blocking PCSK9 (Proprotein Convertase Subtilisin / Kexin Type-9), a liver-derived protease enzyme. This enzyme controls the number of low-density lipoprotein receptors, which help to regulate blood cholesterol levels. Any mutation in PCSK9 reduces LDL receptor levels in the liver, leading to high levels of LDL cholesterol. Since lowering LDL cholesterol reduces the incidence of cardiovascular disease, therefore, by blocking PCSK9's ability to work, Repatha and Praluent make more receptors available to get rid of LDL cholesterol from the blood and, as a result, lower LDL cholesterol levels.

38 Results On The Clinical Efficacy of PCSK9 Clinical Trial On PRALUENT Treatment with alirocumab reduced cardiovascular outcomes and allcause deaths by 15 percent in patients with acute coronary syndrome (ACS) and higher-than-ideal atherogenic lipoprotein levels despite intensive or maximally tolerated statin therapy, according to results of the ODYSSEY Outcomes trial. After a median follow-up of 2.8 years, LDL-C levels were 53.3 mg/dl in the alirocumab group compared with mg/dl in the placebo group, for an absolute reduction of 54.7 percent. The primary endpoint of major adverse cardiovascular events (MACE) the time to first occurrence of coronary heart disease (CHD) death, nonfatal myocardial infarction (MI), unstable angina requiring hospitalization or ischemic stroke was significantly lower in the alirocumab group versus the placebo group (9.5 vs percent).

39 Evolocumab (Repatha): The FOURIER trial showed that evolocumab was superior to placebo at reducing adverse cardiovascular event The primary outcome, incidence of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization, occurred in 12.6% of the evolocumab group versus 14.6% of the placebo group (p < ). This finding was consistent among all tested subgroups. Benefit was enhanced among higher-risk subgroups (those with recent MI, multiple prior MIs, and residual multivessel coronary artery disease) compared to those without such characteristics. Secondary outcomes: Absolute reduction in LDL-C was 56 mg/dl with evolocumab versus placebo (median LDL-C = 30 mg/dl) Any serious adverse event: 24.8% with evolocumab versus 24.7% with placebo 5/21/2018

40 OUTLINE Case Scenario What Is Hyperlipidemia And Long Term Sequelae Of Raised Levels? Major Risk Factors For Cardiovascular Disease Sobering Facts Of Hyperlipidemia Control In Singapore 2013 ACC/AHA Guideline: Cholesterol Treatment to Reduce ASCVD Risk In Adults Heavyweight Statins, Ezetimibe And PCSK9 Inhibitors Singapore CPG Lipid Guidelines 2016 Critical Role Of Diet And Exercise Answer To Case Scenario Quiz Questions

41 Singapore CPG Lipid Guidelines 2016 Framingham Point Score Modified for Singapore Population The risk scores were retained in these guidelines because these risk functions have been re-calibrated based on epidemiological data derived within each of the three ethnic groups in Singapore. The modification was carried out as part of collaboration between investigators at: Singapore Ministry of Health (MOH), Singapore General Hospital (SGH), National University of Singapore (NUH), and Prof. Ralph B D Agostino from the Framingham Heart Study, USA.

42 Singapore CPG Lipid Guidelines 2016 Framingham Point Score Modified for Singapore Population 5/21/2018

43 Singapore CPG Lipid Guidelines 2016 What does our 2016 Singapore CPG guidelines emphasise? It recognizes that patients with diabetes mellitus may not necessarily experience the same risk as patients with established CAD. As such, patients with diabetes can be stratified into 2 Levels Of Risk: OR Very High Risk, High Risk based on the presence or absence of chronic kidney disease. Retain treat to target levels of low density lipoprotein (LDL) cholesterol based on the risk of CAD in individual patients. However, there is also the option for physicians to increase the dose of statins to those used in randomised controlled trials, even when the LDL cholesterol targets have been achieved. Similar to the 2013 ACC/AHA ASCVD Guidelines.

44 Singapore CPG Lipid Guidelines 2016 Risk Stratification

45 Singapore CPG Lipid Guidelines 2016 Is Xstatin 10 mg good enough? Very High Risk patients, must push the LDL goals to less than 2.1 mmol/l (80 mg/dl). LDL reduction 50 % of the baseline if tolerated. Stretched goal. High Risk patients, must push the LDL goals to less Than 2.6 mmol/l (100 mg /dl). LDL reduction of < 30 to <50% of the baseline if tolerated. Stretched goal.

46 Singapore CPG Lipid Guidelines 2016 Is Xstatin 10 mg good enough? Intermediate Risk Group: Target LDL is 3.4 mmol/l (130 mg/dl) with LDL target of 2.6 mmol/l being an option. Low Risk Group: Target LDL is <4.1 mmol/l with LDL target of 3.4 mmol/l being an option. High TG and low HDL Patient with high TG of 4.5 mmol/l (400 mg/dl). Treat first with Fibrates, Niacin, Omega 3 oils etc. Fenofibrates can be considered as an add on therapy to statins in very high risk or high risk patients when TG is between 2.3 mmol/l (200 mg/dl) and 4.5 mmol/l (400 mg /dl), in the presence of low HDL (<1.0 mmol/l or 40 mg/dl in males, <1.3 mmol/l or 50 mg/dl in females)

47 Use of Ezetimibe and PCSK9 Inhibitor Key Recommendations For The Treatment Of Blood Cholesterol To Reduce And Prevent Atherosclerotic Cardiovascular Disease (ASCVD) Risk In Adults 5/21/2018 Source: Dr Peter Yan et al Singapore Med J 2016; 57(7): doi: /smedj

48 Singapore CPG Lipid Guidelines 2016 Caution when using Statins, as with any drug

49 OUTLINE Case Scenario What Is Hyperlipidemia And Long Term Sequelae Of Raised Levels? Major Risk Factors For Cardiovascular Disease Sobering Facts Of Hyperlipidemia Control In Singapore 2013 ACC/AHA Guideline: Cholesterol Treatment to Reduce ASCVD Risk In Adults Heavyweight Statins, Ezetimibe And PCSK9 Inhibitors Singapore CPG Lipid Guidelines 2016 Critical Role Of Diet And Exercise Answer To Case Scenario Quiz Questions

50 Critical Role Of Diet & Exercise Exercise is Critical!

51 Critical Role Of Diet & Exercise

52 Critical Role Of Diet & Exercise Recommended Diet & Lifestyle Changes

53 Critical Role Of Diet & Exercise Food for Thought What fits your busy schedule better, exercising one hour a day or being dead 24 hours a day? We found a bunch of these clogging your arteries. They re cholesterol pills.

54 OUTLINE Case Scenario What Is Hyperlipidemia And Long Term Sequelae Of Raised Levels? Major Risk Factors For Cardiovascular Disease Sobering Facts Of Hyperlipidemia Control In Singapore 2013 ACC/AHA Guideline: Cholesterol Treatment to Reduce ASCVD Risk In Adults Heavyweight Statins, Ezetimibe And PCSK9 Inhibitors Singapore CPG Lipid Guidelines 2016 Critical Role Of Diet And Exercise Answer To Case Scenario Quiz Questions

55 Answer to the Quiz.

56 Case Scenario: What Are You Going To Do? You see an elderly 72 year old Malay gentleman with Diabetes, Hyperlipidemia, and Ischaemic Heart Disease with PCI done referred from a RH for follow up of his chronic medical issues. Latest lipids LDL 2.2 mmol/l, HDL 1.1 mmol/l,tg 1.0 mmol/l, HbA1C 6.8 %,LFT, CK normal, BP 120/80 mmhg. Excellent diet control and exercise. Compliant with medication. No drug allergy. Currently on: Metformin 500 mg bd Losartan 50 mg om Lovastatin 10 mg on Aspirin 100 mg om Famotidine 40 mg om Answer: Atorvastatin 40 mg on What are you going to do with regards to the statins dose? Are you going to: a. Keep it to Lovastatin 10mg on? b. Reduce the dose to Lovastatin 5mg on? c. Change to Simvastatin 40mg on? d. Change to Atorvastatin 40mg on?

57 OUTLINE Case Scenario What Is Hyperlipidemia And Long Term Sequelae Of Raised Levels? Major Risk Factors For Cardiovascular Disease Sobering Facts Of Hyperlipidemia Control In Singapore 2013 ACC/AHA Guideline: Cholesterol Treatment to Reduce ASCVD Risk In Adults Heavyweight Statins, Ezetimibe And PCSK9 Inhibitors Singapore CPG Lipid Guidelines 2016 Critical Role Of Diet And Exercise Answer To Case Scenario Quiz Questions

58 Quiz: Question 1 A 78 year old Indian Lady with: Hypertension, Hyperlipidaemia, Diabetes with triple vessel disease, and With PCI done. What is the dose of Statin? Answer: High dose of statin. a. Low Dose b. Medium Dose c. High Dose

59 Quiz: Question 2 A 21 year old with Familial Hypercholesterolaemia LDL > 4.92 mmol/l. What is the dose of Statin? Answer: High dose of statin. a. Low Dose b. Medium Dose c. High Dose

60 Quiz: Question 3 A 80 year old patient with diabetes with no end organ damage, LDL =4.50 mmol/l. What is the dose of Statin? Answer: Controversial?? Moderate strength?? a. Low Dose b. Medium Dose c. High Dose

61 Quiz: Question 4 A 100 year old patient, ADL and IADL independent with mild kidney disease, and LDL >4.92 mmol/l. What is the dose of Statin? a. Low Dose b. Medium Dose c. High Dose Answer: Medium dose of statins if tolerated.

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