- Email: [email protected]
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Abstracts Methods: 10,001 patients with stable CHD randomized to atorvastatin 10mg or 80mg were followed for 4.9 years. We analyzed the occurrence of the primary endpoint of major cardiovascular events (CHD death, nonfatal non-procedurerelated MI, resuscitated cardiac arrest, or fatal or nonfatal stroke). To augment the number of events and to confirm the primary endpoint results we also analyzed any cardiovascular event. Cox proportional hazards modeling was carried out, and hazard ratios (HR) calculated at monthly intervals over the trial. Results: The reduction in major cardiovascular events in the atorvastatin 80mg group versus the 10mg group was apparent early and sustained for the duration of the study (HR ⬍1.0 at Month 1 and thereafter, Figure). Atorvastatin 80mg treatment was also associated with a reduction in any cardiovascular event from early after treatment initiation; again consistent throughout the study (HR ⬍1.0 at Month 1 and thereafter). Conclusions: The additional clinical benefit observed among stable CHD patients receiving atorvastatin 80mg in the TNT study was apparent early after treatment initiation and was maintained long-term.
210 Safety and Efficacy of Atorvastatin at Very Low LDL-C Levels: A Post-Hoc Analysis of the Treating to New Targets (TNT) Study John C. LaRosa, MD, Scott M. Grundy, John J.P. Kastelein, John B. Kostis, (Brooklyn, NY) Synopsis: In the Treating to New Targets (TNT) study, intensive lipid-lowering with atorvastatin 80 mg to an LDL-C of 2.0 mmol/l (77 mg/dl) provided additional clinical benefit in patients with stable coronary heart disease (CHD) perceived to be well controlled at LDL-C of approximately 2.6 mmol/l (100 mg/dl). Observational studies have raised concern about the safety of lowering LDL-C beyond levels recommended in current guidelines. Purpose: In this secondary analysis of the TNT study, we investigated whether attainment of very low LDL cholesterol levels was associated with a further reduction in major cardiovascular events compared with higher LDL cholesterol concentrations, and whether any incremental benefit was achieved without additional safety risk. Methods: 10,001 stable CHD patients with LDL-C ⬍3.4 mmol/l (130 mg/dl) were randomized to either atorvastatin 10 or 80 mg and followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event (fatal CHD, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or
159 fatal or nonfatal stroke). Patients were stratified by ontreatment LDL-C values into quintiles. Results: Baseline characteristics were similar across quintiles. A highly significant reduction in the primary end point was observed with lower levels of on-treatment LDL-C (P⬍0.0001). Death due to any cause and due to non-cardiovascular causes was lowest in the lowest LDL-C quintile (mean LDL-C 1.4 mmol/l [53.8 mg/dl]). Cardiovascular deaths were also reduced with lower levels of on-treatment LDL-C. There were no clinically important differences in adverse event rates across quintiles, with no increase in discontinuation due to treatment-related adverse events, muscle complaints, suicide, haemorrhagic stroke, or cancer deaths observed in the lowest quintile. Conclusions: These results confirm the safety and incremental clinical benefit of reducing LDL-C to very low levels (⬍1.7 mmol/l [64 mg/dl]) with atorvastatin in stable CHD patients.
211 Severe Hypertriglyceridemia: Long-term Results Following Treatment in a Lipid Management Program Katherine S. Rhodes, RD, Martha S. Weintraub, Robert D. Brook, MD, Melvyn Rubenfire, MD, (Ann Arbor, MI) Synopsis: Severe hypertriglyceridemia is a risk factor for pancreatitis and may contribute to coronary disease risk, yet there is little information on the long-term efficacy of treatment. Purpose: To document the long-term results of lifestyle plus drug therapy of severe hypertriglyceridemia following initial treatment in a lipid management program. Methods: Consecutive consenting patients with triglycerides greater than or equal to 500 mg/dL were included unless on steroids, creatinine ⬎1.5mg/dL, or incomplete data. Comprehensive laboratory and nutrition assessments and initiation of a diet/exercise intervention occurred at Time 1 (T-1). T-2 (usually 4-8 weeks after T-1) included repeat lipids, nutrition follow-up, and a lipid specialist consult. T-3 represented the last visit in the clinic within one year. Questionnaires were mailed to assess progress at one year following the first clinic visit (T-4). Results: 66 patients (44 males; mean age 50.5 plus or minus 10.8 years; BMI 32.4 plus or minus 5.5 kg/m2), 17% with a history of pancreatitis; 35% with diabetes, 64% on lipidlowering medication (20% on statin only, 39% on fibrate only, 20% on statin/fibrate combination, 9% on fish oil). Initial lifestyle intervention resulted in median (IQR) triglyceride reduction from 937 (596-1768) mg/dL to 521(368-736) mg/dL (p⬍.001, log transformation). Improvement was independent of lipid-lowering medication. At T-3, 84% were on lipid-lowering medication (11% on statin only, 39% fibrate only, 29% on combination, 56% on fish oil). The incremental decrease in triglycerides at T-3
210 Safety and Efficacy of Atorvastatin at Very Low LDL-C Levels: A Post-Hoc Analysis of the Treating to New Targets (TNT) Study John C. LaRosa, MD, Scott M. Grundy, John J.P. Kastelein, John B. Kostis, (Brooklyn, NY) Synopsis: In the Treating to New Targets (TNT) study, intensive lipid-lowering with atorvastatin 80 mg to an LDL-C of 2.0 mmol/l (77 mg/dl) provided additional clinical benefit in patients with stable coronary heart disease (CHD) perceived to be well controlled at LDL-C of approximately 2.6 mmol/l (100 mg/dl). Observational studies have raised concern about the safety of lowering LDL-C beyond levels recommended in current guidelines. Purpose: In this secondary analysis of the TNT study, we investigated whether attainment of very low LDL cholesterol levels was associated with a further reduction in major cardiovascular events compared with higher LDL cholesterol concentrations, and whether any incremental benefit was achieved without additional safety risk. Methods: 10,001 stable CHD patients with LDL-C ⬍3.4 mmol/l (130 mg/dl) were randomized to either atorvastatin 10 or 80 mg and followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event (fatal CHD, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or
159 fatal or nonfatal stroke). Patients were stratified by ontreatment LDL-C values into quintiles. Results: Baseline characteristics were similar across quintiles. A highly significant reduction in the primary end point was observed with lower levels of on-treatment LDL-C (P⬍0.0001). Death due to any cause and due to non-cardiovascular causes was lowest in the lowest LDL-C quintile (mean LDL-C 1.4 mmol/l [53.8 mg/dl]). Cardiovascular deaths were also reduced with lower levels of on-treatment LDL-C. There were no clinically important differences in adverse event rates across quintiles, with no increase in discontinuation due to treatment-related adverse events, muscle complaints, suicide, haemorrhagic stroke, or cancer deaths observed in the lowest quintile. Conclusions: These results confirm the safety and incremental clinical benefit of reducing LDL-C to very low levels (⬍1.7 mmol/l [64 mg/dl]) with atorvastatin in stable CHD patients.
211 Severe Hypertriglyceridemia: Long-term Results Following Treatment in a Lipid Management Program Katherine S. Rhodes, RD, Martha S. Weintraub, Robert D. Brook, MD, Melvyn Rubenfire, MD, (Ann Arbor, MI) Synopsis: Severe hypertriglyceridemia is a risk factor for pancreatitis and may contribute to coronary disease risk, yet there is little information on the long-term efficacy of treatment. Purpose: To document the long-term results of lifestyle plus drug therapy of severe hypertriglyceridemia following initial treatment in a lipid management program. Methods: Consecutive consenting patients with triglycerides greater than or equal to 500 mg/dL were included unless on steroids, creatinine ⬎1.5mg/dL, or incomplete data. Comprehensive laboratory and nutrition assessments and initiation of a diet/exercise intervention occurred at Time 1 (T-1). T-2 (usually 4-8 weeks after T-1) included repeat lipids, nutrition follow-up, and a lipid specialist consult. T-3 represented the last visit in the clinic within one year. Questionnaires were mailed to assess progress at one year following the first clinic visit (T-4). Results: 66 patients (44 males; mean age 50.5 plus or minus 10.8 years; BMI 32.4 plus or minus 5.5 kg/m2), 17% with a history of pancreatitis; 35% with diabetes, 64% on lipidlowering medication (20% on statin only, 39% on fibrate only, 20% on statin/fibrate combination, 9% on fish oil). Initial lifestyle intervention resulted in median (IQR) triglyceride reduction from 937 (596-1768) mg/dL to 521(368-736) mg/dL (p⬍.001, log transformation). Improvement was independent of lipid-lowering medication. At T-3, 84% were on lipid-lowering medication (11% on statin only, 39% fibrate only, 29% on combination, 56% on fish oil). The incremental decrease in triglycerides at T-3