Pharmacy & Therapeutics - January 2009 - (Page 32) MEETING HIGHLIGHTS: AHA and United European Gastroenterology Week reductions of 47% were found for rosuvastatin in combined MI/stroke/cardiovascular death and for arterial revascularization or hospitalization for unstable angina (P < 0.00001 for both groups). A subgroup analysis showed consistent benefits for age, smoking status, race, and region (U.S., Canada, and the rest of the world), or hsCRP above the subgroups receiving 2 mg/L only. Rates of serious adverse events were similar: 15.2% with rosuvastatin and 15.5% with placebo. All-cause mortality, the secondary endpoint, was reduced by 20% in the rosuvastatin group (247 of 8,901 placebo patients, 198 of 8,901 rosuvastatin patients; P = 0.02). Dr. Ridker concluded, “Despite evaluating a population with lipid levels widely considered to be ‘optimal’ in almost all current prevention algorithms, the relative benefit observed in JUPITER was greater than in almost all prior statin trials.” • Marvin Lipman, MD, Chief Medical Adviser for Consumer Reports, and Professor Emeritus of Clinical Medicine, New York Medical College, Valhalla, N.Y. Among infrequent, less than enthusiastic responses to the JUPITER conclusions, Dr. Lipman commented in an interview: “You have to look at the minutiae. About half the population had significant risk factors. About 15% were smokers, and about 41% had metabolic syndrome. So this is not exactly a low risk population that he [Dr. Ridker] was studying—as was implied by the low LDL levels.” Dr. Lipman also pointed out that the calculation of an NNT of 25 was based on extrapolations to five years. At 1.9 years, when the study was stopped, the NNT was 125. He added, “I don’t think this study will change my way of using a CRP in the treatment of patients. I find it handy where the LDL-C is borderline—between 125 and 140 mg/dL— where you hem and haw about putting someone on a statin for the rest of his or her life.” received placebo or one of two doses of colesevelam (1.875 g/ day or 3.75 g/day) for eight weeks. During a subsequent openlabel period, all patients received colesevelam 3.75 g/day with or without a statin for 16 weeks. LDL-C reductions were greatest with the higher dose of 3.75 mg/day, with the percent change in LDL-C from baseline (the primary endpoint) at –10.0 after eight weeks and –14.0 at 26 weeks (P ≤ 0.0001). Triglyceride levels increased significantly (P ≤ 0.0001) but not in a dose-dependent manner, and the increase was not significantly greater than with placebo. Gastrointestinal (GI) disorders, the most common adverse events likely to be drug-related, were similar in all groups. Similarly, compliance was approximately 85% in all groups. In an interview, Dr. Stein described his own recent unpublished longitudinal study, which compared heart attacks in 1,200 children with heFH before 1977 and after 1983 when treatment with statins became widespread. That study showed almost a 50% reduction in heart attacks and an extension of time between cardiovascular events from about five years to 8.5 and nine years. He concluded, “The use of colesevelam may improve the management of LDL-C abnormalities in pediatric patients with heFH.” References 1. Ridker PM, Rifai N, Clearfield M, et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001;344:1959–1965. 2. Ridker P, Danielson, E, Fonseca F, et al., the JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195– 2207. 3. Insull W Jr, Toth P, Mullican W, et al. Effectiveness of colesevelam hydrochloride in decreasing LDL cholesterol in patients with primary hypercholesterolemia: A 24-week randomized controlled trial. Mayo Clin Proc 2001;76(10):971–982. 4. Hunninghake D. Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively. Atherosclerosis 2001;158(2):407–416. Familial Hypercholesterolemia and Colesevelam (Welchol) • Evan Stein, MD, PhD, Professor of Pathology and Laboratory Medicine, University of Cincinnati, Ohio Colesevelam (Welchol, Daiichi Sankyo) safely and effectively lowered LDL-C levels in children with heterozygous familial hypercholesterolemia (heFH), according to preliminary data on treatment with the bile acid sequestrant in this population. Investigator Stein said that untreated individuals with heFH die of cardiovascular disease (CVD), on average, between 40 and 50 years of age. In an interview, he said that children with FH at age 13 have carotid intimal thickening equivalent to that of a middle-aged man. Earlier research in adults had shown that colesevelam alone reduced LDL-C levels by up to 15%3 and in combination with statins, it reduced LDL-C levels by up to 48%.4 Dr. Stein’s 32-week, randomized, double-blind, parallel-group study (in 41 sites and 12 countries) enrolled 194 children with heFH between 10 and 17 years of age. LDL-C levels in these children were above 160 mg/dL or above130 mg/dL if they were using statins. After a stabilization period, the children United European Gastroenterology Week The meeting in Vienna hosted a record total number of almost 12,000 participants from October 18 to 22, 2008. Decade-Long Trend Shows Increasing NSAID-Related Lower GI Complication Rates • Angel Lanas, MD, Professor of Medicine, University Hospital, Zaragoza, Spain • Ingvar Bjarnason, MD, Professor of Digestive Diseases; Guy’s, King’s, and St. Thomas’ School of Medicine; London, U.K. The puzzle pieces coming together to suggest increasing rates of lower GI risk may also point to effective therapeutic strategies. But more clinical study pieces need to be assemcontinued on page 35 32 P&T® • January 2009 • Vol. 34 No. 1
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