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1.
J Am Coll Cardiol ; 32(3): 665-72, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9741509

ABSTRACT

OBJECTIVES: This study compared the efficacy and safety of atorvastatin, fluvastatin, lovastatin, and simvastatin in patients with documented atherosclerosis treated to U.S. National Cholesterol Education Program (NCEP) recommended low-density-lipoprotein (LDL) cholesterol concentration (< or = 100 mg/dl [2.59 mmol/liter]). BACKGROUND: For patients with advanced atherosclerosis, NCEP recommends lipid-lowering drug therapy if LDL cholesterol remains > or = 130 mg/dl (3.36 mmol/liter). METHODS: A total of 318 men or women with documented atherosclerosis and LDL cholesterol > or = 130 mg/dl (3.36 mmol/liter) and < or = 250 mg/dl (6.5 mmol/liter), and triglycerides < or = 400 mg/dl (4.5 mmol/liter) participated in this 54-week, multicenter, open-label, randomized, parallel-group, active-controlled, treat-to-target study. Patients were titrated at 12-week intervals until the LDL cholesterol goal was reached. Number of patients reaching target LDL cholesterol levels and dose to reach target were evaluated. RESULTS: At the starting doses, atorvastatin 10 mg produced significantly greater decreases (p < 0.05) in plasma LDL cholesterol than the other treatments. Subsequently, the percentage of patients reaching goal at the starting dose was 32% for atorvastatin, 1% for fluvastatin, 10% for lovastatin and 22% for simvastatin. Atorvastatin-treated patients required a lower median dose than other treatments. Median doses at week 54 with the last available visit carried forward were atorvastatin 20 mg/day, fluvastatin 40 mg/day + colestipol 20 g/day, lovastatin 80 mg/day, simvastatin 40 mg/day. CONCLUSIONS: A significantly greater number (p < 0.05) of patients with confirmed atherosclerosis treated with atorvastatin reached the target LDL cholesterol concentration at the starting dose than patients treated with fluvastatin or lovastatin, and significantly fewer (p < 0.05) patients treated with atorvastatin required combination therapy with colestipol to achieve target LDL cholesterol concentrations than all other statins tested.


Subject(s)
Anticholesteremic Agents/therapeutic use , Arteriosclerosis/blood , Arteriosclerosis/drug therapy , Cholesterol, LDL/blood , Fatty Acids, Monounsaturated/therapeutic use , Heptanoic Acids/therapeutic use , Indoles/therapeutic use , Lovastatin/therapeutic use , Pyrroles/therapeutic use , Simvastatin/therapeutic use , Anticholesteremic Agents/adverse effects , Atorvastatin , Colestipol/adverse effects , Colestipol/therapeutic use , Combined Modality Therapy , Diet, Fat-Restricted , Dose-Response Relationship, Drug , Drug Therapy, Combination , Fatty Acids, Monounsaturated/adverse effects , Female , Fluvastatin , Heptanoic Acids/adverse effects , Humans , Indoles/adverse effects , Lovastatin/adverse effects , Male , Pyrroles/adverse effects , Simvastatin/adverse effects , Treatment Outcome
2.
Pharmacoeconomics ; 14(1): 59-70, 1998 Jul.
Article in English | MEDLINE | ID: mdl-10182195

ABSTRACT

OBJECTIVE: Recognising the importance of treating hyperlipidaemia, the National Cholesterol Education Program (NCEP) has established widely accepted treatment goals for low density lipoprotein cholesterol (LDL-C). Medications used most commonly to achieve these LDL-C goals are HMG-CoA reductase inhibitors. The relative resource utilisation and cost associated with the use of reductase inhibitors of different LDL-C lowering efficacy are unknown, but are major health and economic concerns. The objective of this study was to determine the mean total cost of care to reach NCEP goals with various reductase inhibitors. DESIGN: In a randomised, 54-week, 30-centre controlled trial we compared resources used and costs associated with treating patients to achieve NCEP goals using 4 reductase inhibitors: atorvastatin, simvastatin, lovastatin and fluvastatin. PATIENTS AND PARTICIPANTS: The trial studied 662 patients; 318 had known atherosclerotic disease. INTERVENTIONS: Reductase inhibitor therapy was initiated at recommended starting doses and increased according to NCEP guidelines and package insert information. For patients who did not reach the goal at the highest recommended dose of each reductase inhibitor, the resin colestipol was added. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with atorvastatin, compared-with other reductase inhibitors, were more likely to reach NCEP goals during treatment (p < 0.05), required fewer office visits (p < 0.001) and less adjuvant colestipol therapy (p = 0.001). Consequently, the mean total cost of care (1996 values) to reach NCEP goals was lower with atorvastatin [$US1064; 95% confidence interval (CI): $US953 to $US1176] compared with simvastatin ($US1471, 95% CI: $US1304 to $US1648), lovastatin ($US1972; 95% CI: $US1758 to $US2186) and fluvastatin ($US1542; 95% CI: $US1384 to $US1710). Results were similar for patients with or without known atherosclerotic disease. CONCLUSIONS: In patients requiring drug therapy for hypercholesterolaemia, NCEP LDL-C goals are achieved significantly more often using fewer resources with atorvastatin compared with simvastatin, lovastatin or fluvastatin.


Subject(s)
Anticholesteremic Agents/economics , Fatty Acids, Monounsaturated/economics , Health Policy/economics , Heptanoic Acids/economics , Hypercholesterolemia/economics , Indoles/economics , Lovastatin/economics , Pyrroles/economics , Simvastatin/economics , Aged , Anticholesteremic Agents/therapeutic use , Atorvastatin , Cost-Benefit Analysis , Fatty Acids, Monounsaturated/therapeutic use , Female , Fluvastatin , Heptanoic Acids/therapeutic use , Humans , Hypercholesterolemia/drug therapy , Indoles/therapeutic use , Lovastatin/therapeutic use , Male , Middle Aged , Pyrroles/therapeutic use , Simvastatin/therapeutic use , United States
3.
Ciba Found Symp ; 202: 61-76; discussion 76-82, 1996.
Article in English | MEDLINE | ID: mdl-9243010

ABSTRACT

The diversity of terrestrial hot spring systems, resulting from the large scale coupled transfer of heat and mass in the Earth's crust, maximizes opportunities for evolving ecosystems by the continuous supply of nutrients (P, N, C, S) together with the metals (e.g. K, Mg, Mo, Zn) essential to biogenesis. Cyclic, evaporative micro-environments are common, and potentially catalytic mineral surfaces are also continually created through rock alteration and mineral deposition in and around hot springs. These dynamical systems constitute highly interactive, open, chemical environments capable of establishing complex biochemical microreactors. Volcanic collapse settings on oceanic islands, provide a highly dynamic scenario for the initiation of life and development of diverse ecosystems at the earliest stages of development of the Earth's crust.


Subject(s)
Earth, Planet , Ecosystem , Hot Temperature , Origin of Life , Volcanic Eruptions , Archaea/physiology , Chemical Phenomena , Chemistry, Physical , Fossils , Geography , Geologic Sediments , Membranes , Metals/chemistry , Minerals/chemistry , Oceans and Seas , Phosphates/chemistry , Sulfur/chemistry , Templates, Genetic , Water/chemistry
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