Case Study: Applying Clinical Trial Data to Patient Management

Case:
The patient was a 62-year-old Caucasian woman when she was first seen at the Florida Lipid Institute in 2010. She had hypertension that was treated with losartan/HCTZ. She had no other significant past medical history. She had a family history of hypertension and diabetes and one brother who developed angina at the age of 48. Her review of systems was negative — specifically, she had no complaints of chest pain, transient ischemic episodes, or claudication. Her only medication was the losartan/HCTZ and she had no known drug allergies. She had never been on lipid-modifying therapy.

On physical exam, the patient’s height was 5-foot-4, her weight was 180 pounds, her waist circumference was 38 inches, and her blood pressure on treatment was 130/86. Her temperature, respiratory rate, and pulse were normal. Her cardiac, pulmonary, abdominal, neurological, dermatological, and vascular exams were all normal.

A fasting lipid panel obtained by her referring physician showed total cholesterol of 205 mg/dL, a low-density lipoprotein cholesterol (LDL-C) of 126 mg/dL, triglycerides of 156 mg/dL, and a high-density lipoprotein cholesterol (HDL- C) of 48 mg/dL — non-HDL was 157 mg/ dL. Her high-sensitivity C-reactive protein (hs-CRP) was elevated at 3.6 mg/L, and her fasting blood sugar was 112 mg/dL. All other values on her complete blood count (CBC), comprehensive metabolic panel, urine analysis (UA), and TSH were within normal limits.

She was specifically referred by her internist with the question, “Should this woman be on a statin?”

JUPITER Study:
The Justification for the Use of Statins in Primary Prevention (JUPITER) study was published in 2008.¹ The study enrolled 17,802 apparently healthy men over 50 years old and women over 60 years old who had an LDL less than 130 mg/Dl, and an hs-CRP >2.0 mg/L. They were randomized 1:1 to rosuvastatin 20 mg or placebo once daily. The study’s primary outcome was a reduction in an aggregate endpoint of myocardial infarction (MI), stroke, revascularization, hospitalization for unstable angina, and death from any cardiovascular cause. It was designed for a treatment duration of five years but was terminated at a median observation period of only 1.9 years by the data safety monitoring committee because of an overwhelming benefit seen in the rosuvastatin group. At termination, the active treatment group had a hazard ratio of 0.56 for the aggregate endpoint, 0.46 for MI, 0.52 for stroke, and 0.80 for death from any cause. When the study ended, the rosuvastatin arm had an average LDL-C reduction of 50 percent and an hs-CRP reduction of 37 percent.

The study received some criticism² following publication focused primarily on the early termination and the definition of “apparently healthy.” Critics pointed out that, in JUPITER’s “apparently healthy” population, 25 percent had hypertension (systolic BP>145), 50 percent were overweight, 25 percent were obese, 41 percent met the clinical criteria for the metabolic syndrome, and less than 17 percent were taking a daily aspirin.

In 2010, based on the results from JUPITER, the U.S. Food and Drug Administration (FDA) approved rosuvastatin for the “primary prevention of cardiovascular disease in individuals without clinically evident coronary heart disease but with an increased risk of cardiovascular disease based on age >50 years old in men and >60 years old in women, hsCRP> 2 mg/L and the presence of at least one additional cardiovascular risk factor.” (Crestor Package labeling)

Back to the Case:
After I first saw the patient, I repeated the lipid panel and hs-CRP. Her repeat labs showed TC = 203 mg/dL, LDL-C = 124 mg/dL, triglycerides 160 mg/dL, HDL-C = 47 mg/dL, non-HDLC 156 mg/dL, and an hs-CRP = 3.8.

According to ATP guidelines, her LDL goal was <130 and, based on that criteria, she clearly did not warrant statin therapy. But the patient could easily have been a “poster child” for the JUPITER study population, meeting all of the criteria identified in the FDA’s expanded indication for rosuvastatin. She also met all of the ATP criteria for the diagnosis of metabolic syndrome, a diagnosis found in a significant portion of the JUPITER study population.

In the spirit of the patient-centered approach emphasized by the new NLA Recommendations,³ I met with the patients and her husband to discuss treatment options. She decided, based in large part on the JUPITER study results, to start rosuvastatin 20 mg once daily. She also was referred to the clinic’s dietitian for weight and CVD risk reduction dietary interventions.

Case Follow-Up:
The patient most recently was seen at the Florida Lipid Institute in August. She remains free from cardiovascular disease. Her most recent lipid profile — on TLC plus rosuvastatin 20 mg once daily — showed TC = 136 mg/dL, LDL = 60 mg/ dL, triglycerides = 80 mg/dL, HDL = 60 mg/dL, and nonHDLC 76 mg/dL. Her hs-CRP is <1.0. After meeting with the dietitian a total of four times since her initial presentation, AT’s weight is down 20 pounds, her waist circumference is 34 inches, her fasting blood sugar is 88, and she no longer meets any of the criteria defining the metabolic syndrome.

Her care was patient-centered and I was delighted to work with an informed, compliant patient.

Disclosure statement: Dr. Ziajka received speaker honoraria from Kowa Pharmaceuticals, Abbott Laboratories, Merck and Co., Atherotech Inc., Hunter Heart Lab and AstraZeneca. He’s received a research grant from Genzyme and consulting fees from Hunter Heart Lab. 

References are listed on page 36 of the PDF.