Pharmaceutical Help to Control Cholesterol

Transcription

1 Pharmaceutical Help to Control Cholesterol Catherine E. Cooke, PharmD, BCPS, PAHM President, PosiHealth, Inc. Clinical Associate Professor, Univ. of Maryland This program has been brought to you by PharmCon PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

2 Pharmaceutical Help to Control Accreditation: Pharmacists L01-P_ Pharmacy Technicians L01-T Nurses L01-N Cholesterol CE Credits: 1.0 contact hour Target Audience: Pharmacists & Technicians Program Overview: This program focuses on methods for pharmacists to improve cardiovascular care, and manage medications for cholesterol and other related co-morbidities. The pharmacist must understand the potential of currently available treatment options (along with their probable results and possible side effects) and play an active role in educating patients on their strategies for cholesterol management. Objectives: Review the relationship between lipid values and cardiovascular risks to include goals for individual patients. Outline the importance of diet and exercise as the first treatment option for high cholesterol. Review the modes of action, efficacy, and advantages and disadvantages of currently available therapies. Describe the active role that pharmacists can play in collaboration with patients and physicians in setting aggressive patient goals, monitoring progress, and improving adherence to lipid management plans. This program has been brought to you by PharmCon

3 Pharmaceutical Help to Control Cholesterol Speaker: Catherine Cooke attained her Bachelor in Pharmacy from the University of Iowa and then went on to receive her Pharm.D. from the Medical University of South Carolina. Currently, she is the President, of PosiHealth, Inc. and a Clinical Associate Professor at the Univ. of Maryland Speaker Disclosure: Dr. Cooke has no actual or potential conflicts of interest in relation to this program This program has been brought to you by PharmCon PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity.

4 GC is a 47 yo man seen for follow-up appointment PMH: Hypertension, Dyslipidemia BP: 128/92mmHg Smokes 0.5-1ppd x 25 yrs Current medications: Lisinopril 20mg QD, Simvastatin 20mg QD Most recent lipid profile: TC = 192, TG = 140, LDL = 116, HDL = 48

5 MW is a 56 yo man with CAD? 56 yo AA man with CAD (had MI 3 months ago) TC = 155, TG = 125, LDL = 90, HDL = 40 What is your management plan?

6 Overview Recent Headlines Epidemiology of CHD Preventive Measures NCEP ATP III Guidelines (May 2001) NCEP Update (July 2004) Case Studies

7 Patients are hospitalized for CAD despite good lipid levels 231,986 hospitalizations from 541 hospitals with admission lipid levels documented in 136,905 (59.0%) Avg. LDL = / LDL <100 mg/dl in 49.6% LDL <70 mg/dl in 17.6% Avg. HDL / HDL <40 mg/dl in 54.6% Avg. Triglyceride 161 +/- 128 mg/dl Before admission, only 28,944 (21.1%) patients were receiving lipid-lowering medications. Sachdeva A, et al. Lipid levels in pts hospitalized w/ CAD. Am Heart J. 2009;157:111-7

8 ENHANCE trial Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression

9 ENHANCE trial Goal of trial was to compare the mean change in the intima-media thickness (IMT) measured at three sites in the carotid arteries in patients with heterozygous familial hypercholesterolemia (HeFH) Patient Population Age of years Diagnosis of FH Untreated LDL cholesterol 210 mg/dl Randomized to: ezetimibe/simvastatin 10/80 mg (n=357) simvastatin 80 mg alone (n=363) Groups were comparable for baseline low-density lipoprotein (LDL) cholesterol levels and baseline carotid IMT measurements

10 ENHANCE trial LDL levels at study end (24 months) Change from baseline to study endpoint for mean carotid IMT (mm)* New plaque formation (IMT) > 1.33 mm Ezetimibe/Simvastatin Simvastatin p-value mg/dl 56% reduction mg/dl 39% reduction / / p < 0.01 P= /322 (4.7%) 9/320 (2.8%) P=0.20 Cardiovascular endpoints (NB: underpowered to detect difference) Cardiovascular deaths 0.6% 0.3% P=NS Non-fatal MI 0.8% 0.6% P=NS Non-fatal stroke 0.3% 0.3% P=NS Need for revascularization 1.7% 1.4% P=NS

11 FDA Update of Safety Review The results from ENHANCE do not change FDA s position that an elevated LDL cholesterol is a risk factor for cardiovascular disease and that lowering LDL cholesterol reduces the risk for cardiovascular disease. Based on current available data, patients should not stop taking Vytorin or other cholesterol lowering medications and should talk to their doctor if they have any questions about Vytorin, Zetia, or the ENHANCE trial.

12 JUPITER trial Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin

13 JUPITER trial primary prevention 15,000 males aged 50 years and older and females aged 60 years and older No history of MI, stroke, or arterial revascularization LDL-cholesterol levels <130 mg/dl Patients were considered at risk for coronary heart disease on the basis on their elevated CRP levels (> 2mg/L). Randomized to rosuvastatin 20mg QD or placebo. The primary outcome was the rate of first major cardiovascular events, defined as the combined end point of cardiovascular death, stroke, myocardial infarction, hospitalization for unstable angina, or arterial revascularization.

14 JUPITER results The trial was stopped early median 2 yrs Rosuvastatin reduced LDL by 50% and hscrp by 37%. Primary end points were Rosuvastatin = 0.77 per 100 person-years of follow-up Placebo = 1.36 per 100 person-years of follow-up Hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<

15 Epidemiology of Coronary Heart Disease

16 Coronary Heart Disease (CHD) in the United States CHD is the single largest killer of men and women ~ 16 million have CHD Of the ~ 1.5 million who have MI 1/3 rd die (about half within 1 hr) 50% of men and 64% of women with sudden death from CHD have no previous symptoms of this disease AHA. Heart and Stroke Facts: 2007 Statistics Update

17 Plasma Total Cholesterol Events in Men and Women Aged 50 Effect of other Risk Factors (Framingham Study) 10 Year Risk of CHD Events (%) Plasma Total Cholesterol and 10 Year Risk of CHD Anderson. Circulation 1991;83: mmol/l mg/dl smoking SBP 160 mm Hg smoking SBP 160 mm Hg Men Women no other risk factors no other risk factors

18 Preventing Heart Attack & Death In Patients With CAD Smoking cessation Lipid management Physical activity Weight management Antiplatelet agents ACE inhibitors Beta-blockers Blood pressure control How many are achieving NCEP goals? Circulation 1995;92:2.

19 Non-Rx Therapies Plant Sterols Soy Fiber Red yeast rice Alcohol

20 Plant Sterols (sterol esters) Extracts of certain plants Inhibit the absorption of cholesterol in the small intestine Two plant sterols are now available in a spreadable form, as a substitute for margarine Sitosterol - extract of the soy plant (Take Control ) Sitostanol- extract of pine needles (Benechol ) FDA has authorized use of labeling health claims about the role of plant sterol or plant stanol esters in reducing the risk of CHD for foods containing these substances.

21 Soy Soy isoflavones estrogen-like substances found in various plants Soy protein Must ingest both isoflavones and soy protein to obtain benefit A diet containing 25 grams of soy protein and mg of soy isoflavones per day can reduce LDL cholesterol levels by about 10%.

22 Fiber Soluble fiber fiber that dissolve in water Common foods: oats, lentils, pinto beans, citrus, black beans, barley Psyllium (found in Metamucil)

23 Red yeast rice Red yeast rice (Cholestin ) used to contain lovastatin FDA made a determination that this dietary supplement was subject to regulation and removed it from shelves Now, it is illegal for red yeast rice to contain lovastatin Labels no longer state cholesterol-lowering properties

24 Alcohol Alcohol may increase HDL levels American Heart Association (2001) statement that doctors not recommend alcohol Amount ½ glass of wine for 3-4 days/week Type of alcohol (i.e., wine, beer, whiskey) doesn t appear to make a difference w/ regard to CHD reduction

25 Prescription Lipid-lowering therapies Guidelines on Lipid Management NCEP ATP III (2001) and Update (2004)

26 NHLBI: Clinical Practice Guidelines and Reports In Development Pediatric CV Risk Reduction CV Disease Risk Reduction, Adults Cholesterol Guidelines Update, ATP IV JNC-8 Hypertension Guidelines Update

27 Assess the patient s CHD Risk CHD/CHD Risk Equivalents Other Clinical Forms of Atherosclerotic Disease Peripheral arterial disease Abdominal aortic aneurysm Symptomatic carotid artery disease Diabetes Multiple risk factors (10-year risk for CHD >20% CHD)

28 Risk Factors Cigarette smoking Hypertension (blood pressure >140/90mmHg or on antihypertensive medication) Low HDL cholesterol (<40 mg/dl) Family history of premature CHD (CHD in male first-degree relative <55 years; CHD in female first-degree relative <65 years) Age (men >45 years; women >55 years) HDL cholesterol >60 mg/dl counts as a negative risk factor

29 2004 PPS ATP III: Updated LDL-C Goals, Treatment Cutpoints Risk Category LDL-C Goal Initiate TLC Consider Drug Therapy High risk: CHD or CHD risk equivalents * (10-year risk >20%) <100 mg/dl (optional: <70 mg/dl) 100 mg/dl 100 mg/dl (<100 mg/dl: consider drug options) Moderately high risk: 2 risk factors (10-year risk 10% 20%) <130 mg/dl (optional: <100 mg/dl) 130 mg/dl 130 mg/dl ( mg/dl: consider drug options) * CHD risk equivalents: clinical manifestations of noncoronary forms of atherosclerotic disease (transient ischemic attacks or stroke of carotid origin >50% obstruction of a carotid artery), diabetes, and 2 risk factors with 10-year risk >20% for hard CHD. The optional LDL-C goal of <70 mg/dl is favored in those at very high risk (eg, people with diabetes, smokers) as well as those with metabolic syndrome, acute coronary syndrome, high TG, and/or non HDL-C <100 mg/dl. Any person at high or moderately high risk with lifestyle-related risk factors is a candidate for TLC to modify these risk factors regardless of LDL-C level. Grundy SM et al. Circulation. 2004;110:

30 2004 PPS ATP III: Updated LDL-C Goals, Treatment Cutpoints (cont d) Risk Category LDL-C Goal Initiate TLC Moderate risk: 2 risk factors (10-year risk <10%) Lower risk: 0 1 risk factor Not modified in update Consider Drug Therapy <130 mg/dl 130 mg/dl 160 mg/dl <160 mg/dl 160 mg/dl 190 mg/dl ( mg/dl: LDL-C lowering drug optional) Grundy SM et al. Circulation. 2004;110:

31 Treatment of LDL-C High LDL-C Visit 1 Therapeutic lifestyle change Initiate statin therapy Drug therapy Alternative: BAR or niacin Visit 2/follow-up If not at LDL-C goal Escalate statin dose OR add a BAR or niacin Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:

32 Statin Atorvastatin (Lipitor ) Fluvastatin (Lescol ) Lovastatin (Mevacor ) Pravastatin (Pravachol ) Rosuvastatin (Crestor ) Simvastatin (Zocor ) Primary prevention of cardiovascular disease To reduce the risk of MI, stroke or revascularization procedures and angina in adult patients without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as age, smoking, hypertension, low HDL-C, or a family history of early CHD and to reduce the risk of MI or stroke in patients with type 2 diabetes, and without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as retinopathy, albuminuria, smoking, or hypertension To reduce the risk of MI, unstable angina and coronary revascularization procedures in individuals without symptomatic cardiovascular disease, average to moderately elevated total-c and LDL-C, and below average HDL-C To reduce the risk of MI, revascularization procedures and cardiovascular mortality in hypercholesterolemic patients without clinically evident CHD To slow the progression of atherosclerosis in adult patients as part of a treatment strategy to lower total-c and LDL-C to target levels Labeled Indications Secondary prevention of cardiovascular disease To reduce the risk of non-fatal myocardial infarction and fatal and non-fatal stroke in patients with clinically evident coronary heart disease To slow the progression of coronary atherosclerosis in patients with CHD and to reduce the risk of undergoing coronary revascularization procedures in patients with CHD To slow the progression of coronary atherosclerosis in patients with CHD To reduce the risk of total mortality by reducing coronary death, MI, revascularization procedures, stroke and stroke/transient ischemic attack (TIA) in patients with clinically evident CHD and to slow the progression of coronary atherosclerosis in patients with clinically evident CHD Reduce risk of CHD mortality and cardiovascular events (non-fatal MI and stroke, coronary and non-coronary revascularization procedures) in patients with existing CHD, diabetes, peripheral vessel disease, history of stroke, or other cerebrovascular disease

33 Comparative reductions in LDL-C per 10mg of statin Statin Average expected LDL-C reduction Atorvastatin (Lipitor ) 34-38% Fluvastatin (Lescol ) 22%* Lovastatin (Mevacor ) 21% Pravastatin (Pravachol ) 18-25% Rosuvastatin (Crestor ) 43-50% Simvastatin (Zocor ) 26-33% *Based on 20mg fluvastatin Adapted from

34 When LDL lowering medications are used, obtain at least a 30-40% reduction in LDL-C levels. Lipid Management Pharmacotherapy Therapy TC LDL HDL TG Patient tolerability Statins* 19-37% 25-50% 4-12% 14-29% Good Ezetimibe 13% 18% 1% 9% Good Bile acid sequestrants 7-10% 10-18% 3% Neutral or Poor Nicotinic acid 10-20% 10-20% 14-35% 30-70% Reasonable to Poor Fibrates 19% 4-21% 11-13% 30% Good HDL-C=High-density lipoprotein cholesterol, LDL-C=Low-density lipoprotein cholesterol, TC=Total cholesterol, TG=Triglycerides *Daily dose of 40mg of each drug, excluding rosuvastatin.

35 Medication Adherence Adherence often varies over time Types of non-adherence Over and under use Administration errors wrong time, wrong route, delayed or omitted dose, etc. Reasons for non-adherence I just forgot Too expensive

36 Adherence Curves for Statins in 1 3 Cohorts (n = 143,505 elderly Canadian patients) ~ 70% at 6 months Acute Coronary Syndrome Coronary Artery Disease Primary Prevention ~55% at 6 months month JAMA 2002;288:462

37 Solutions Self-Management (e.g., blood pressure monitoring, glucose monitoring) Refill reminders (e.g., telephone, electronic, mail etc.) Adherence aids (e.g., pill boxes, calendars) Simplify dosing regimen (e.g., QD drugs, packaging) Education on disease and drug (e.g., written and oral information)

38 GC is a 47 yo man seen for follow-up appointment PHM: Hypertension, Dyslipidemia BP: 128/92mmHg Smokes 0.5-1ppd x 25 yrs Current medications: Lisinopril 20mg QD, Simvastatin 20mg QD Most recent lipid profile: TC = 192, TG = 140, LDL = 116, HDL = 48

39 2004 PPS ATP III: Updated LDL-C Goals, Treatment Cutpoints (cont d) Risk Category LDL-C Goal Initiate TLC Moderate risk: 2 risk factors (10-year risk <10%) Lower risk: 0 1 risk factor Not modified in update Consider Drug Therapy <130 mg/dl 130 mg/dl 160 mg/dl <160 mg/dl 160 mg/dl 190 mg/dl ( mg/dl: LDL-C lowering drug optional) Grundy SM et al. Circulation. 2004;110:

40 MW is a 56 yo man with CAD? 56 yo AA man with CAD (had MI 3 months ago) TC = 155, TG = 125, LDL = 90, HDL = 40 What is your management plan?

41 2004 PPS ATP III: Updated LDL-C Goals, Treatment Cutpoints Risk Category LDL-C Goal Initiate TLC Consider Drug Therapy High risk: CHD or CHD risk equivalents * (10-year risk >20%) <100 mg/dl (optional: <70 mg/dl) 100 mg/dl 100 mg/dl (<100 mg/dl: consider drug options) Moderately high risk: 2 risk factors (10-year risk 10% 20%) <130 mg/dl (optional: <100 mg/dl) 130 mg/dl 130 mg/dl ( mg/dl: consider drug options) * CHD risk equivalents: clinical manifestations of noncoronary forms of atherosclerotic disease (transient ischemic attacks or stroke of carotid origin >50% obstruction of a carotid artery), diabetes, and 2 risk factors with 10-year risk >20% for hard CHD. The optional LDL-C goal of <70 mg/dl is favored in those at very high risk (eg, people with diabetes, smokers) as well as those with metabolic syndrome, acute coronary syndrome, high TG, and/or non HDL-C <100 mg/dl. Any person at high or moderately high risk with lifestyle-related risk factors is a candidate for TLC to modify these risk factors regardless of LDL-C level. Grundy SM et al. Circulation. 2004;110:

42 Conclusion Treatment decisions must be based not only on the level of risk before the initiation of treatment, but also on the anticipated reduction of that risk with a specific therapy