Cholesterol Medication Yields Dramatic Benefits

Use of AstraZeneca’s Crestor (rosuvastatin calcium) reduced the number of deaths, myocardial infarctions (MIs), and strokes as well as the need for bypass or angioplasty procedures by 45% in apparently healthy persons. Lead researcher Paul M. Ridker, MD, MPH, professor at Harvard Medical School, and director of the Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston, and colleagues presented results of the AstraZeneca-funded JUPITER (the Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) study at the 2008 Scientific Sessions of the American Heart Association held November 8 through 12 in New Orleans. Findings were published in the November 20 issue of the New England Journal of Medicine.

The researchers randomly assigned 17,802 persons to 20 mg/d of Crestor or placebo for an average of 1.9 years. Study participants had low-density lipoprotein (LDL) cholesterol levels of less than 130 mg/dL, but their levels of high-sensitivity C-reactive protein (hsCRP), an inflammatory marker associated with heart disease, were elevated (2 mg/L or higher). The study was stopped more than 2 years early because the benefit of taking the drug was so pronounced. “These benefits are approximately twice as large as what doctors expect when you use statins in patients with high cholesterol,” explained Ridker.

Crestor reduced the number of MIs and strokes by 54% and 48%, respectively, and the need for bypass surgery or angioplasty by 46% compared with placebo. There was a 20% reduction in all-cause mortality among participants taking Crestor compared with those who were given placebo. The Crestor group also had a 50% reduction in LDL cholesterol levels and a 37% reduction in hsCRP levels compared with the control group.

The team found that there was no difference between treatment groups for major adverse events, including cancer or myopathy. However, there was a higher incidence of physician-reported diabetes among participants who were given Crestor-a finding that is consistent with other statin studies, the researchers said.

“JUPITER should dramatically change prevention guidelines,” said another study author, James T. Willerson, MD, director of the Texas Heart Institute, Houston. “The bottom line here is simple: if your hsCRP is high, you should be on statin therapy regardless of your cholesterol level. This is an approach we can start using tomorrow.”

Combining PPIs and Plavix Increases Heart Risk

Persons who combine a proton pump inhibitor (PPI), such as Nexium (esomeprazole) or Prilosec (omeprazole), with Plavix (clopidogrel) have a 50% higher risk of having a cardiovascular event compared with those who take Plavix by itself. Robert S. Epstein, MD, MS, chief medical officer at Medco Health Solutions, led a team of researchers to examine why nearly 30% of persons who take Plavix do not process the drug effectively, as shown in earlier studies.

Epstein and colleagues tracked for 1 year 16,690 persons who had undergone a percutaneous coronary intervention, such as stent placement or balloon angioplasty, and were given Plavix as maintenance therapy. Of those, 9862 patients took Plavix alone and 6828 patients combined Plavix and a PPI.

Study results, which were presented at the 2008 Scientific Sessions of the American Heart Association, indicated that compared with patients who took only Plavix, those who took a PPI and Plavix concurrently had a 91% higher risk of unstable angina, a 74% higher risk of myocardial infarction, and a 17% higher risk of cardiac death.

While the mechanism remains unclear, the study authors suggest that PPIs interfere with a liver enzyme that converts Plavix to its active form.