How would you manage Ms. Gold - PDF Free Download

How would you manage Ms. Gold 32 yo Asian woman with dyslipidemia Current medications: Simvastatin 20mg QD Most recent lipid profile: TC = 246, TG = 100, LDL = 176, HDL = 50

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

Learning Objectives 1. REVIEW epidemiology of high cholesterol to include cardiovascular risks and goals for individual patients 2. DESCRIBE the lifestyle changes and pharmaceutical choices available to reduce cholesterol levels 3. EXPLAIN the modes of action, efficacy, and advantages and disadvantages of currently available pharmacological therapies. 4. DESCRIBE the active role that pharmacists can play in collaboration with patients and physicians in setting patient goals, monitoring progress, and improving adherence to lipid management plans.

Overview Recent Headlines in the News Epidemiology of CHD NCEP ATP III Guidelines (May 2001) NCEP Update (July 2004) Managing Patients with Dyslipidemia

ENHANCE trial Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression

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 30-75 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

ENHANCE trial Ezetimibe/Simvastatin Simvastatin p-value 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 141.3 mg/dl 56% reduction 192.7 mg/dl 39% reduction 0.0111 +/- 0.0038 0.0058 +/- 0.0037 p < 0.01 P=0.29 15/322 (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

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

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.

Epidemiology

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

Coronary Heart Disease (CHD) in Women in the United States 1 out of 2 American women die of CHD 1 out of 25 American women die of breast CA While strides have been made in reducing CHD, the absolute number of deaths due to CHD is increasing Castelli WP, Anderson K. Am J Med. 1986;8 (suppl 2A):23-32. AHA. Heart and Stroke Facts: 2007 Statistics Update

Annual Incidence of MI in Women and Men in the U.S. Estimated Number of Persons (1000s) 450 400 350 300 250 200 150 100 50 0 29-44y 45-64y >65y Men Women Age

Plasma Total Cholesterol and 10 Year Risk of CHD Events in Men and Women Aged 50 Effect of other Risk Factors (Framingham Study) 10 Year Risk of CHD Events (%) Plasma Total Cholesterol 35 30 25 20 15 10 5 0 Anderson. Circulation 1991;83:356. 5 6 7 8 mmol/l 200 250 300 mg/dl smoking SBP 160 mm Hg smoking SBP 160 mm Hg Men Women no other risk factors no other risk factors

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 Regarding Cholesterol, how many are achieving NCEP goals? Circulation 1995;92:2.

Clinical Data Summary Several statins shown to be effective in reducing coronary risk in both primary and secondary prevention settings How do we use this evidence to manage patients with dyslipidemia?

NCEP Guidelines ATP III May 2001 National Cholesterol Education Program Adult Treatment Panel

Assess the patient s 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)

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

Treatment Decisions Based on LDL Cholesterol: Dietary Therapy PATIENT INITIATION LEVEL LDL GOAL Without CHD* and with fewer than 2 risk factors 160 mg/dl <160 mg/dl Without CHD* and with 2 or more risk factors 130 mg/dl <130 mg/dl With CHD* >100 mg/dl 100 mg/dl *CHD/CHD Risk Equivalents

Goals for Drug Therapy Based on NCEP Guidelines FOR INDIVIDUALS WITH ADD DRUG THERAPY IF LDL IS LDL GOALS No CHD* and with <2 other 190 mg/dl <160 mg/dl risk factors No CHD* but with >2 other 160 mg/dl for 10-year risk <10% <130 mg/dl CHD risk factors 130 mg/dl for 10-year risk 10-20% Definite CHD or CHD Risk 130 mg/dl 100 mg/dl Equivalents *CHD/CHD Risk Equivalents

2004 PPS Update to ATP III Guidelines: Rationale Since ATP III completion in 2001, 5 large clinical outcome trials of statin therapy have been published Heart Protection Study (HPS) Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Lipid-Lowering Trial (ALLHAT-LLT) Anglo-Scandinavian Cardiac Outcomes Trial Lipid-Lowering Arm (ASCOT-LLA) Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) trial ATP III update incorporates information from these trials Grundy SM et al. Circulation. 2004;110:227-239.

2004 PPS Update to ATP III Guidelines: Rationale (cont d) Results of 5 trials Confirm the benefit of cholesterol-lowering therapy in moderately high and high-risk patients Support the ATP III LDL-C goal of <100 mg/dl Support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDLlowering therapy in these patients Confirm that older persons benefit from therapeutic lowering of LDL-C Provide new information on efficacy of risk reduction in high-risk patients with relatively low LDL-C levels Grundy SM et al. Circulation. 2004;110:227-239.

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 (100 129 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;110:227-239.

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 (160 189 mg/dl: LDL-C lowering drug optional) Grundy SM et al. Circulation. 2004;110:227-239.

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;285:2486-2497.

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.

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 http://www.consumersunion.org/campaigns/statinsupdate-2pager-july06.pdf

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

How would you manage Ms. Gold 32 yo Asian woman with dyslipidemia Current medications: Simvastatin 20mg QD Most recent lipid profile: TC = 246, TG = 100, LDL = 176, HDL = 50

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

Conclusion Manage patients according to their cardiac risk using drug therapies with proven reductions in cardiovascular morbidity and mortality.