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 low-
density 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, AND TREATMENT OF HIGH CHOLESTEROL
RECOMMENDATIONS

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. Smoking Cessation – raises LDL and lowers HDL cholesterol,

increasing the risk for
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: intense flushing (face, neck, ears), itching, and GI tract
(gastric upset, nausea,
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