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Biomedical subjects

Evan A Stein

Publications and source records attributed to Evan A Stein.

8 recordsLinked to original sources
PubMed2002

Effects of simvastatin on C-reactive protein in mixed hyperlipidemic and hypertriglyceridemic patients.

This study examined the effects of simvastatin on C-reactive protein (CRP) and other inflammatory markers in study subjects with significant elevations in triglyceride (TG) blood levels. CRP, vascular cellular adhesion molecule (VCAM), serum amyloid A (SAA), and interleukin 6 (IL-6) were measured in archived plasma samples from 2 multicenter, randomized, double-blind, placebo-controlled studies designed to examine the lipid-altering efficacy of simvastatin in study subjects with elevated TGs. In the first study, 130 study subjects with mixed hyperlipidemia (low-density lipoprotein [LDL] cholesterol > or =130 mg/dl; TGs 300 to 700 mg/dl) received placebo or simvastatin 40 or 80 mg once daily for three 6-week periods in a complete-block crossover design. In the second study, 195 study subjects with hypertriglyceridemia (TGs 300 to 900 mg/dl) received daily doses of placebo or simvastatin 20, 40, or 80 mg for 6 weeks. Significant but weak correlations were observed between baseline CRP values and baseline levels of LDL cholesterol and high-density lipoprotein (HDL) cholesterol, but not with TGs. CRP was also correlated with body mass index and fasting levels of glucose and insulin. Treatment with simvastatin 20, 40, and 80 mg led to significant reductions in CRP plasma levels versus placebo (p <0.05). Although CRP change was weakly correlated with changes in LDL cholesterol, TGs, and HDL cholesterol, results of regression analyses showed that only baseline CRP and treatment allocation were significant predictors of CRP response after 6 weeks of study drug administration. Simvastatin had no effect on VCAM, SAA, or IL-6. In summary, simvastatin significantly reduced CRP in patients with mixed hyperlipidemia and hypertriglyceridemia.

Anticholesteremic Agents↗
PubMed2002

Identification and treatment of individuals at high risk of coronary heart disease.

Low-density lipoprotein (LDL) cholesterol reduction remains the cornerstone of coronary heart disease (CHD) prevention. The most dramatic and consistent reductions in LDL cholesterol and CHD risk are achieved with statin therapy. Identification of individuals at high CHD risk is important, not only for initiating appropriate treatment and minimizing morbidity and mortality but also for optimizing the cost-effectiveness of such treatment. A simple method for identifying high-risk individuals is to identify those with preexisting atherosclerotic disease, diabetes, or familial hypercholesterolemia (FH). Treatment options for achieving LDL cholesterol goals in high-risk patients include statins, bile acid sequestrants, niacin, and plant stanols. Statin therapy should be instituted at a dose likely to result in achievement of LDL cholesterol goals based on average response; it should then be aggressively titrated if the goals are not achieved. If LDL cholesterol goals are not achieved with maximal statin therapy, combination with a bile acid sequestrant, niacin, and/or stanols should be considered. Options likely to be available in the near future include more efficacious statins with greater potential for reducing LDL cholesterol in all patients but especially in high-risk patients, such as those with FH, enabling a greater proportion to achieve LDL cholesterol goals. Other options that may soon be available as additive agents to statins to achieve greater LDL cholesterol reductions include bile acid transport inhibitors and cholesterol absorption inhibitors.

Biomarkers↗
PubMed2002

Managing dyslipidemia in the high-risk patient.

Lipid-lowering agents have been shown to reduce morbidity and mortality associated with coronary artery disease (CAD) in all patients. However, these agents are more cost-effective in high-risk patients whose absolute risk of CAD is greater than that of low-risk patients. Furthermore, from preliminary data, it appears that there is greater risk reduction in those subjects achieving lower low-density lipoprotein cholesterol (LDL-C) levels (ie, lower is better). The identification and aggressive treatment of these patients should therefore be a high priority for clinicians. Guidelines from medical organizations, such as the Adult Treatment Panel (ATP) III of the US National Cholesterol Education Program (NCEP), emphasize that patients with CAD, diabetes, or global risk of CAD >20% over 10 years and LDL-C levels >130 mg/dL should receive drug therapy with a goal of reducing LDL-C levels to <100 mg/dL. The recent results of the United Kingdom's Heart Protection Study (HPS) strongly suggest that even those with CAD or who are at high risk and LDL-C levels >100 mg/dL would benefit from drug therapy. Although optimal LDL-C levels have been set at <100 mg/dL for high-risk patients, recent studies show only about 20% of such patients meet these goals. Thus, a large treatment gap remains that needs to be overcome if we are to continue to make significant inroads into preventing further morbidity and mortality in these high-risk subjects. Of therapeutic options available currently and for the near future, statins remain the most effective and well-tolerated form of lipid-lowering therapy. Other therapies include bile acid sequestrants, niacin, and plant stanols. However, none of these is, in general, sufficiently effective as an initial agent to achieve these more aggressive LDL-C goals in the high-risk patient. However, combination therapy with a statin and 1 of these other lipid-lowering agents is useful in patients who are unable to achieve lipid goals on monotherapy. A number of agents for reducing LDL-C levels currently in development may be available in the near future, including 2 new statins: pitavastatin and rosuvastatin. Rosuvastatin, which is in the later stages of the US Food and Drug Administration (FDA) approval process, has been shown to produce significantly greater reductions in LDL-C levels compared with atorvastatin, simvastatin, and pravastatin, and allows more patients to meet lipid goals. Ezetimibe, the first of an entirely new class of LDL-C-lowering agents that inhibit intestinal cholesterol absorption, also appears to offer significant therapeutic value. It is anticipated that these new options will allow clinicians to optimize the management of dyslipidemia in high-risk patients, thereby further reducing the morbidity and mortality of CAD.

Adult↗
PubMed2002

Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia.

This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol > or =4.14 mmol/L (160 mg/dl) and < 6.47 mmol/L (250 mg/dl) and triglycerides < or =4.52 mmol/L (400 mg/dl) were randomized to 12 weeks of once-daily placebo (n = 132), rosuvastatin 5 mg (n = 128), rosuvastatin 10 mg (n = 129), or atorvastatin 10 mg (n = 127). The primary efficacy end point was percent change in LDL cholesterol. Secondary efficacy variables were achievement of National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II), ATP III, and European Atherosclerosis Society LDL cholesterol goals and percent change from baseline in high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, non-HDL cholesterol, apolipoprotein B, and apolipoprotein A-I. Rosuvastatin 5 and 10 mg compared with atorvastatin 10 mg were associated with greater LDL cholesterol reductions (-40% and -43% vs 35%; p <0.01 and p <0.001, respectively) and HDL cholesterol increases (13% and 12% vs 8%, p <0.01 and p <0.05, respectively). Total cholesterol and apolipoprotein B reductions and apolipoprotein A-I increases were also greater with rosuvastatin; triglyceride reductions were similar. Rosuvastatin 5 and 10 mg were associated with improved achievement in ATP II (84% in both rosuvastatin groups vs 73%) and ATP III (84% and 82% vs 72%) LDL cholesterol goals, and rosuvastatin 10 mg was more effective than atorvastatin in achieving European Atherosclerosis Society LDL cholesterol goals. Both treatments were well tolerated.

Anticholesteremic Agents↗
PubMed2002

Lipoprotein changes with statins.

The effects of statins and other lipid drugs are assessed by their ability to affect specific lipid fractions. Although there has been a great deal written abut the statins, most recent papers have focused on the comparative effects of the statins on triglycerides and high-density lipoprotein cholesterol, or have been concerned with the nonlipid effects of these drugs. In addition, some recent papers have focused on new parameters that may mediate cardiovascular risk, such as high-sensitivity C-reactive protein.

Cholesterol, HDL↗
PubMed2002

Management of dyslipidemia in the high-risk patient.

Lipid-lowering agents have been shown to reduce morbidity and mortality associated with coronary heart disease (CHD), particularly in high-risk patients. The identification and treatment of these patients should therefore be a high priority for clinicians. Guidelines from medical organizations, such as the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) and the American Diabetes Association (ADA), suggest that patients with low-density lipoprotein cholesterol (LDL-C) levels > or =130 mg/dL, and perhaps even those with levels > or =100 mg/dL, should receive drug therapy. Optimal LDL-C levels have been set at <100 mg/dL and <115 mg/dL for high-risk patients by US and European guidelines, respectively. However, a recent survey shows that only about 20% of high-risk patients currently meet these goals. In order to achieve therapeutic targets for LDL-C, the statins are the foundation of treatment, as they are the most effective and best-tolerated form of lipid-lowering therapy. Other therapeutic options include bile acid sequestrants, niacin, and plant stanols, although seldom as monotherapy. Combination therapy with a statin and one of these other lipid-lowering agents can be useful in patients who are unable to achieve target lipid levels through monotherapy. There remains, however, a need for additional agents. Some of the new options for reducing LDL-C levels that may be available in the near future include 2 new statins, pitavastatin and rosuvastatin. In patients with heterozygous familial hypercholesterolemia, rosuvastatin, which is currently under review by the Food and Drug Administration (FDA), has been shown to produce significantly greater reductions in LDL-C than atorvastatin over its full dose range. In comparative clinical trials, it has also enabled more patients with primary hypercholesterolemia to meet lipid goals than atorvastatin, simvastatin, and pravastatin. Inhibitors of bile acid transport or cholesterol absorption may also have therapeutic value. The first cholesterol absorption inhibitor, ezetimibe, which has just been approved by the FDA, appears to be most effective when combined with a statin. It is anticipated that such new options will allow clinicians to optimize the management of dyslipidemia in high-risk patients, thereby reducing the morbidity and mortality of CHD.

Anticholesteremic Agents↗
PubMed2002

An investigative look: selective cholesterol absorption inhibitors--embarking on a new standard of care.

Phase 2 and 3 clinical trials evaluating the selective cholesterol absorption inhibitor ezetimibe have demonstrated that the drug is safe and effective, both as monotherapy and in combination with several statins. Placebo-controlled phase 2 studies of 8 and 12 weeks' duration established that ezetimibe monotherapy achieved maximum cholesterol lowering at doses between 10 and 20 mg daily. Additional dose-scheduling studies demonstrated that evening dosing was only slightly more effective than morning dosing, and that the drug could be taken with or without food without any impairment in efficacy. These studies also showed that ezetimibe was well tolerated, with side effects no different from those seen with placebo. Short-term, early phase 2 studies evaluating the coadministration of ezetimibe and a number of different statins found that coadministration was safe, that ezetimibe did not alter the pharmacokinetics of the statins or vice versa, and that the reductions in low-density lipoprotein cholesterol were complementary, with the degree of cholesterol lowering seen with ezetimibe monotherapy maintained when it was given in combination with a statin. These studies indicate that combination therapy with ezetimibe and a starting dose of a statin produces a reduction in cholesterol levels equivalent to that seen with an 8-fold higher statin dose. Larger, long-term phase 3 trials confirmed the efficacy and safety of the 10-mg dose and also demonstrated that ezetimibe monotherapy is an excellent alternative for patients who cannot tolerate statins.

Anticholesteremic Agents↗