Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 60-year-old man with type 2 diabetes mellitus and hypertension visits the office to establish medical care. He reports monitoring his blood pressure and blood glucose measurements at home with good results. He had a cholesterol panel checked approximately 5 years ago, at which time he was instructed by his prior physician to exercise, lose weight, and reduce his intake of dietary cholesterol. He has made some lifestyle changes, which he believes have helped his blood pressure and glucose control. His hypertension has been treated for 15 years and his diabetes for 5 years. His daily medications include lisinopril, amlodipine, metformin, and aspirin.

On physical examination, blood pressure is 128/65 mm Hg and pulse is 76/min. BMI is 26. The remainder of the physical examination is normal.

Laboratory studies:

Total cholesterol	215 mg/dL (5.6 mmol/L)
Triglycerides	185 mg/dL (2.1 mmol/L)
HDL cholesterol	39 mg/dL (1.0 mmol/L)
LDL cholesterol	145 mg/dL (3.8 mmol/L)
Hemoglobin A1c	6.5%

Which of the following medications is the best choice for reducing this patient’s risk of cardiovascular disease?

A) Colestipol
B) Ezetimibe
C) Niacin
D) Simvastatin

MKSAP Answer and Critique

The correct answer is D) Simvastatin. This item is available to MKSAP 15 subscribers as item 10 in the Pulmonary and Critical Care Medicine section. More information about MKSAP 15 is available online.

This patient has multiple risk factors for coronary artery disease (CAD), including diabetes mellitus, hypertension, and hypercholesterolemia. Given his age and risk factors, he is at high risk (20%) of having a CAD event within the next 10 years. The goal LDL cholesterol level for a patient with two or more risk factors for CAD is dependent on the 10-year risk for a CAD event based upon the Framingham risk equation. In patients with two or more risk factors and with an intermediate (10%-20%) 10-year risk, the goal LDL cholesterol level is below 130 mg/dL (3.4 mmol/L). However, in patients with two or more risk factors and a high risk (>20%) of a CAD event, the goal LDL cholesterol level is below 100 mg/dL (2.6 mmol/L). A statin is the first-line treatment for cholesterol reduction. In June 2011, the FDA issued new guidelines indicating that simvastatin dosing in patients taking amlodipine should not exceed 20 mg daily due to a drug-drug interaction and an increased risk of rhabdomyolysis. If simvastatin is selected in this case, it should be limited to 20 mg daily or less with appropriate monitoring of clinical and laboratory parameters. Other statins are not known to have a clear interaction with amlodipine and would be reasonable alternatives in this patient.

Colestipol interrupts bile acid reabsorption and reduces LDL cholesterol levels by 10% to 15%. It is often used as a second-line drug with statins because it acts synergistically to induce LDL receptors. However, it can interfere with the absorption of this patient’s other medications, and for these reasons, is not the best initial management of his hyperlipidemia.

Although ezetimibe reduces LDL cholesterol levels by reducing cholesterol absorption from the intestine, there are presently no clinical trial results showing that this medication reduces cardiovascular disease events, in contrast to statins, such as simvastatin. Therefore, ezetimibe should be reserved as an adjunct to other cholesterol-lowering medications if goal level is not achieved or for patients intolerant or allergic to other proven medications.

Niacin is an effective medication for lowering LDL cholesterol and increasing HDL levels but is often not tolerated because of its side effects (nausea and flushing), particularly at the dosage needed to achieve adequate reduction of LDL cholesterol. Niacin would be a poor choice for this patient because it can cause glucose intolerance, potentially worsening his glucose control.

Key Point

• The indication to initiate cholesterol-lowering medication as well as the goal level for treatment are dependent on the absolute level of LDL cholesterol and the estimated 10-year risk for a coronary artery disease event.

Learn more about ACP’s MKSAP 15.

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