Chapter 48 - Prophylaxis Of Coronary Heart Disease

CHAPTER 48 PROPHYLAXIS OF CORONARY HEART: DRUGS THAT LOWER LDL CHOLESTEROL LEVELS atherosclerosis – also known as coronary heart disease (CHD) - thickening of the coronary arteries - moderate CHD manifests as anginal pain - severe CHD sets the stage for MI - begins with development of a fatty streak in the arterial wall - as atherosclerotic plaque grows, it impedes coronary blood flow, causing anginal pain - risk of developing CHD is directly related to increased levels of blood cholesterol in the form of lowdensity lipoproteins (LDLs) - preferred method for lowering LDLs is modification of diet

I.

PLASMA LIPOPROTEINS

A.

VERY LOW DENSITY LIPOPROTEINS - contains triglycerides (and some cholesterol) as their core lipids - physiologic role is delivery of triglycerides from the liver to adipose tissue and muscle - studies suggest a link between elevated levels of VLDLs and development of atherosclerosis - elevation of triglycerides (>500 mg/dl) increases the risk of pancreatitis B.

LOW-DENSITY LIPOPROTEINS - contains cholesterol as primary core lipids - physiologic role is delivery of cholesterol to nonhepatic tissues - of all lipoproteins, LDLs make the greatest contribution to coronary atherosclerosis C.

HIGH-DENSITY LIPOPROTEINS - contains cholesterol as primary core lipids - carry cholesterol from peripheral tissue back to the liver - promote cholesterol removal - elevation of HDLs reduces the risk of CHD (actively promote against CHD)

Major Risk Factors (Other than high LDL cholesterol) that Modify LDL Treatment Goals Positive Risk Factors • Age Men ≥ 45 yr Women ≥ 55 yr •

Family history of premature CHD in a first-degree relative: Male first-degree relative < 55 yr old or Female first-degree relative < 65 yr old

•

Hypertension: blood pressure ≥ 140/90 or taking antihypertensive medication

•

Current cigarette smoking (smoked at least 1 in the last month)

• Low HDL cholesterol (< 40 mg/dl) Negative Risk Factor • High HDL cholesterol (≥ 60 mg/dl)

II. DETECTION, EVALUATION, RECOMMENDATIONS

AND

TREATMENT

OF

HIGH CHOLESTEROL

A.

TREATMENT OF HIGH LDL CHOLESTEROL 1. Therapeutic Lifestyle Changes a. TLC Diet – objectives are to reduce LDL cholesterol and establish / maintain a healthy weight - central feature of the diet is reduced intake of cholesterol and saturated fats - intake trans fat should be minimized - increased intake of soluble fiber - increased intake of plant stanols and sterols b.

Weight Control – major risk factor for CHD

c. Exercise – can reduce blood pressure, decrease insulin resistance, and improve overall cardiovascular performance d. increasing the risk for

Smoking Cessation – raises LDL and lowers HDL cholesterol, CHD

2.

Drug Therapy - drugs are not the first-line therapy for lowering LDL cholesterol - drugs should be employed only if TLCs fail to reduce LDL to an acceptable level - - and then only if the combination of elevated LDL cholesterol and the patient’s CHD risk category justify drug use - most effective agents are the HMG-CoA reductase inhibitors (lovastatin), also known as statins - treatment is initiated with a single drug, almost always a statin - if ineffective, a bile-acid sequestrant or nicotinic acid can be added to the regimen

- because LDL cholesterol returns to pretreatment values if drugs are withdrawn, treatment must continue lifelong - benefit of drug therapy is primary prevention

III.

DRUGS

AND

OTHER PRODUCTS USED

TO

ALTER PLASMA LIPIDS

A.

HMG-COA REDUCTASE INHIBITORS (STATINS) - atorvastatin (lipitor) and simvastatin (zocor) - classified in FDA Risk Category X: risks to the fetus outweigh any potential benefits of treatments - no compelling reason to continue lipid-lowering drugs during pregnancy Adverse Affects: generally well tolerated headache, rash or GI disturbances (dyspepsia, cramps, flatulence, constipation, abdominal pain) hepatotoxicity (liver injury) and myopathy (muscle tissue injury) - rarely Drug Interactions: Fibrates = can cause myopathy = combined with statin, the risk is greater than with the agents separately B.

NICOTINIC ACID (NIACIN) - reduces LDL and TG levels, reducing the risk of major coronary events and may reduce total mortality - increases HDL levels better than any other drug - administered orally (tablets, capsules, elixir) with or after meals Adverse Effects: (gastric upset, nausea,

intense flushing (face, neck, ears), itching, and GI tract

vomiting, diarrhea) hepatotoxic raises blood levels of homocysteine, increasing CHD risk hyperglycemia and gouty arthritis C.

FIBRIC ACID DERIVATIVES (FIBRATES) - lopid, tricor - most effective drugs available for lowering triglyceride levels - can raise HDL cholesterol - have little or no effect on LDL cholesterol - can increase the risk of bleeding in patients taking warfarin (an anticoagulant) and the risk of rhabdomyolysis in patients taking statins

1.

Gemfibrozil – lopid - decreases triglyceride (VLDL) levels and raises HDL

cholesterol levels - does not reduce LDL cholesterol - principal indication is hypertriglyceridemia - treatment is limited to patients who have not responded adequately to weight loss and diet modification Adverse Effects: generally well tolerated rashes and GI disturbances (nausea, abdominal pain, diarrhea) increased biliary cholesterol saturation, increasing risk of gallstones myopathy (muscle injury, tenderness, weakness, or unusual muscle pain) hepatotoxic (disrupted liver function, possibly liver cancer) Drug Interactions: displaces warfarin from plasma albumin, increasing anticoagulant effects increases risk of statin-induced myopathy