Case Studies

Session: Case studies on the treatment of dyslipidemia and cardiovascular disease risk

During this lively symposium, chaired by Dr S Scheidt (New York, USA), the speakers highlighted the difficulties that physicians encounter in clinical practice, using patient case histories.

Why use case studies to highlight therapeutic problems?
Dr S Scheidt, New York, USA

Dr Scheidt opened this session by considering the necessity of examining case studies when discussing therapeutic problems.

Despite the efforts of clinicians, many patients remain under-treated for primary and secondary prevention of coronary heart disease (CHD).^1,2 In addition, statins are not used effectively in women, the elderly, and patients with diabetic dyslipidemia.

He then went on to discuss the main features of the newly updated National Cholesterol Education Program third Adult Treatment Panel (NCEP ATP III) guidelines. These guidelines consider diabetes mellitus as a CHD equivalent, and identify an LDL-C of 100 mg/dL as optimal and a HDL-C <40 mg/dL as a CHD risk factor. New recommendations for the screening and detection of lipid abnormalities and the addition of therapeutic lifestyle changes (TLC) are further additions to the new guidelines.

Dr Scheidt concluded by posing the questions he hoped would be answered throughout the course of the session, including:

• Is there a threshold LDL-C value in the primary prevention of CHD?
• What is the cost:benefit ratio of widespread primary prevention?
• Does combination therapy have benefits in certain patient populations?
• Are statins useful for the primary prevention of stroke and small vessel disease?

Case 1: Primary prevention for the multiple risk factor patient
Dr O Etingin, New York, USA

The use of hormone replacement therapy (HRT) for the treatment of elevated LDL-C is controversial. Although the Nurses Health Study has shown an association between HRT and reduced risk of future CHD, subsequent randomized studies have produced conflicting data.

The Heart and Estrogen Progestin Replacement Study (HERS) showed that HRT has no beneficial effect on cardiovascular events in female patients with established CHD. Indeed, during the first two years of the study there was an increase in the number of cardiovascular events in patients receiving HRT. Similarly, the Estrogen and Atherosclerosis Trial (ERA) examined 309 women with heart disease, and found that there was no cardiovascular benefit gained from estrogen or estrogen/progestin therapy.

The controversial use of HRT was highlighted by the case history of a 49-year-old peri-menopausal women. The patient was diagnosed with hyperlipidemia 5 years previously, and she had been prescribed a combination of atorvastatin and an estrogen/progesterone agent. The patient voluntarily discontinued the atorvastatin therapy following some generalized muscle pain.

On initial consultation, she exhibited a normal cardiac examination, blood pressure and pulse. Lipid profiling showed the patient had a total cholesterol of 258 mg/dL, an LDL-C of 186 mg/dL and a normal HDL-C of 54 mg/dL. Dr Etingin went on to discuss the following points:

• What (if any) benefit the patient was getting from the HRT therapy?
• What effect HRT has on lipid levels?
• Should HRT continue in this patient?

A straw poll showed that all the delegates would recommend the patient restart statin therapy, however, only a small number believed that HRT should be continued for the treatment of lipid abnormalities in this patient. One delegate noted that using HRT to modify lipid abnormalities was not warranted, as the data in favor of such treatment was insubstantial.

It was noted that the patient should not have terminated her statin therapy, as generalized muscle pain is not indicative of myalgia.

To conclude, Dr Etingin told delegates that while she continued to prescribe HRT to this patient, she had encouraged her to restart the atorvastatin therapy. As a result her LDL-C level had been reduced to 140 mg/dL - 10 mg/dL higher than the desired primary prevention target.

Case 2: Treatment of severe dyslipidemia
Dr B Gordon, New York, USA

Patients with familial hypercholesterolemia (FH) are at a very high risk of developing premature CHD. Current lipid-lowering therapies often fail to adequately modify lipid levels in these patients, and therefore other treatment options should be considered.

These options include triple drug therapy, with a statin/resin/niacin combination being the most widely recommended. Other alternatives include LDL apheresis and surgical therapies such as intestinal bypass and liver transplantation. While gene therapy may offer benefit to patients with FH in the future, the introduction of new drugs such as the superstatins and MTP inhibitors may provide promising alternatives to current treatments.

Dr Gordon continued his discussion of FH treatment by presenting the case history of a 49-year-old man who had undergone coronary artery bypass graft (CABG) surgery in 1998. He had a family history for CHD, but was not diabetic and did not have hypertension. Previous lipid profile data indicated that the patient had heterozygous familial hypercholesterolemia (HeFH), as his total cholesterol was >400 mg/dL and his LDL-C was around 350 mg/dL.

He was receiving atorvastatin 80 mg/day, but due to gastrointestinal tolerability problems niacin and resins had not been prescribed. Upon examination by Dr Gordon, the patient had a fasting total cholesterol of 319 mg/dL, an LDL-C of 227 mg/dL and HDL-C of 37 mg/dL.

During the delegate discussion, Dr Gordon stated that he had adjusted the patient’s diet to reduce his intake of simple carbohydrates, increased his level of physical activity and prescribed colesevelam 2.5 g/day in addition to the atorvastatin 80 mg/day. The patient did not have tolerability problems with the newer resin therapy. Following these changes to treatment, the lipid profile of the patient was moderately improved: LDL-C around 200 mg/dL, HDL-C 40 mg/dL and triglycerides 100 mg/dL. Furthermore, LDL apheresis was added to the management program, reducing the LDL-C to around 130 mg/dL.

Case 3: Are the roles of surgical and medical intervention complementary?
Dr. CJ Vaughan, New York, USA

Dr Vaughan presented two case histories, which emphasized very different treatment issues. The first case was that of a 34-year-old man who had presented with lateral wall myocardial infarction (MI).

The patient had poorly controlled diabetes mellitus, hypertension and had a body mass index (BMI) of 13.7 kg/m². Several members of his family had CHD and premature coronary death. Lipid screening showed that the patient had mixed hyperlipidemia: LDL-C 180 mg/dL, HDL-C 22 mg/dL and triglycerides 723 mg/dL.

Dr Vaughan stated that reducing the LDL-C level was his priority, and therefore the dose of atorvastatin therapy was increased from 20 to 80 mg/day. This reduced the patient’s LDL-C level to 92 mg/dL and his high density lipoprotein (HDL)-C increased to 31 mg/dL. Fenofibrate and an ACE inhibitor were later added to the treatment regimen.

Although the patient’s liver function tests were slightly abnormal following the change in atorvastatin dose, Dr Vaughan stated that he decided to continue therapy.

Dr Scheidt agreed that continuation of this therapy was warranted, stating that clinicians should only be concerned when AST and ALT levels double or triple.

Dr Vaughan continued his presentation with the case history of a 22-year-old woman who had been referred to him following a routine physical examination by the patient’s employers. The examination showed that the patient was hypercholesterolemic, with a total cholesterol of 323 mg/dL and LDL-C of 208 mg/dL.

Her HDL-C level was high at 84 mg/dL, she had no previous history of heart disease, was not overweight, exercised regularly, had a normal physical examination, and was not taking any medications. However, she had a positive family history as her father had an MI when he was 51 years old.

It was noted that although the patient’s lipid profile and family history made her a candidate for statin therapy, these agents are not recommended for use in women of childbearing age. Also, the patient was reluctant to commit to lifelong drug treatment at such a young age. Dr Vaughan asked the panel and assembled audience what management strategy would be best suited to this patient.

The lively discussion that followed concluded that this patient should receive statin therapy and effective birth control. The statin therapy could be discontinued some months prior to conception if the patient decided to start a family. Dr Etingin from the panel stated that this strategy had worked for one of her patients; where the individual had discontinued atorvastatin therapy twice to have children and during the period without statin treatment her LDL-C had remained stable at 110 mg/dL.

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References:
1. Sidney C, Smith Jr MD. Bridging the Treatment Gap. Am J Cardiol 2000; 85(12): 3-7.
2. Sueta CA, Chowdhury M, Boccuzzi SJ, et al. Analysis of the degree of undertreatment of hyperlipidemia and congestive heart failure secondary to coronary artery disease. Am J Cardiol 1999; 84(9): 1143.

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