- Email: [email protected]
Comparison (of the quality of life and tolerability of lovastatin and pravastatin
158
Tuesday I I October 1994: Poster Abstracts Clinical trials
III, patients given fenofibrate +lO.S% vs -0.6%. Despite the difference in LDL-chol lowering, no difference was seen in apo B decrease, (P) -20.8% and (S) -26.5%. Improvement of the ratios of TCYHDL-Cand apo A-Uapo B was not different. Only fenofibrate, not simvastatin, lowered both fibrinogen (-10.3% vs +3.6%) and uric acid (-25% vs 0%). Safety parameters reflected drug-specific known side effects. We conclude that both drugs are efficient and safe in lowering lipid levels. Besides its advantages in type IIh hyperlipidemia, micronized fenofibrate also proved to be potent in lowering total and LDL-C as well as apo B-containing lipoproteins. Micronized fenofibrate is thus indicated not only in mixed forms of hyperlipidemia but also in primary hypercholesterolemia. 12601
Effect of lovastatin on early carotid atherosclerosis in women Hoen HM, Espeland MA, Applegate WB, Bendixen
wCD. BH, Bowman Gray Sch. of Med., Dept. of Public Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157-1063,
USA
Most primary and secondary prevention lipid-lowering trials focusing on atherosclerotic outcomes such as clinical events and mortality have enrolled male participants only, or have included an insufficient number of females from which to draw meaningful conclusions. The Asymptomatic Carotid Artery Plaque Study (ACAPS) enrolled 445 asymptomatic women (48% of the total cohort) with moderately elevated cholesterol to examine the effects of lovastatin on early-stage carotid atherosclerosis (primary outcome) and cardiovascular events (secondary outcome). ACAPS was a randomized clinical trial that tested, over an average 3-year period, the effects of lovastatin (20-40 mg/day) and/or warfarin (1 mg/day) on progression of early carotid atherosclerosis in men and women with LDL levels between the 60th and 90th percentile. Early carotid artery atherosclerosis was measured as intimal-medial wall thickening (IMT), as diagnosed by noninvasive B-mode ultrasonography. The IMT among women assigned to lovastatin regressed at a rate of 0.006 f 0.003 mm/year, while IMT among non-lovastatin women progressed by 0.007 f 0.003 mm/year (P = 0.0007). Women assigned to lovastatin also experienced fewer cardiovascular events than nonlovastatin women (1 versus 6 cardiovascular events, P = 0.07) and had significantly lower all-cause mortality (0 versus 5 deaths, P = 0.03). After adjusting for covariates such as age, clinical center, baseline IMT, post-menopausal status, hormone replacement therapy, blood pressure and smoking, the effect of lovastatin on IMT remained signiticant. These results reflect similar findings for the total male/female cohort. ACAPS is one of the first trials to suggest that lipid-lowering interventions imprut clinical benefit to women. Comparison (of the quality of life and tolerability of 12611 lovastatin and pravastatin Weir MB, Berger ML, McCaughtry ML, Liss CL, Santanello N,
either lovastatin 40 mg qd or pravastatin 40 mg qd for 12 weeks. Patients were scheduled to return for clinic visits following the baseline diet period, the placebo period and every 4 weeks during the active treatment period. At each visit, complete serum lipid profiles were obtained, adverse experiences were monitored and patients completed quality of life questionnaires. The analysis plan defined the primary endpoint as the change in quality of life as measured by the Nottingham Health Profile after 12 weeks of treatment. Three additional quality of life dimensions were also measured: perceived general health from The National Health and Nutrition Survey, sexual function from The Medical Outcomes Study and stress/life events from the NIH Post-CABG Study. Lipid-apheresis: an in vivo application of delipidation but apolipoprotein retention in plasma of calves by a continuous extracorporeal procedure Cham BE, Kostner KM, wDM, Dwivedy AK, Dept. of
12621
Cardiol., Wesley Hospital, 451 Coronation Drive, AuchenjTower Qld 4066, Australia
Lipid-apheresis (LA) is an effective procedure for acute reduction of plasma cholesterol concentrations. The delipidated plasma retains all apolipoproteins. Rapid regression of atherosclerosis can be obtained by this procedure. Six calves were used in this study. Two served as controls and four were made hypercholesterolemic by keeping them monogastric after birth and feeding them a high cholesterol, high saturated fat diet in their milk. LA consisted of plasma pheresis followed by plasma delipidation in a stationary chamber containing butanol and diisopropyl ether. The plasma was removed with a pump after phase separation. Organic solvents were subsequently removed by an ether wash and vacuum evaporation at 37°C. The delipidated plasma contained all its apolipoproteins and other constituents, only lipid being removed by this procedure. The delipidated plasma was remixed with red blood cells and m-infused into the animal. The procedure was continuous. There was a linear correlation between percent plasma treated and percent change in plasma cholesterol concentration in both the hypercholesterolemic and normocholesterolemic groups. After LA it took approximately 48 h for the plasma cholesterol concentration to return to its initial value, suggesting rapid mobilization of cholesterol to the plasma pool. The total blood volume could be treated in one session. On some occasions the procedure was repeated daily. Biochemical, hematological and post mortem analysis of organs indicated that the procedure was safe. The animals tolerated the procedure well. Based on this and other studies, approval has been obtained to start human clinical studies in 1994. Lipid-apheresis: an in vivo application of delipidation hut apolipoprotein retention in plasma of pigs by a continuous extracorporeal procedure Cham BE, Kostner KM, Q&&un DM, Dwivedy AK, Dept. of
1263(
Univ. of Maryland Hosp, Div. of Nephrology, N3W143, 22 S. Greene St., Baltimore, MD 21201, USA
Cardiol., Wesley Hospital, 451 Coronation Ave., Auchenjlower Qld 4066, Australia
This multicenter US study compared the effects of 12 weeks of treatment with lovastatin (40 mg) or pravastatin (40 mg) on quality of life. Male patients, 20-65 years old, with primary hypercholesterolemia (Types IIa and IIb) were eligible for enrollment if baseline LDL-C met NCEP ATPl guidelines: 2190 mg/dl for patients without CHD or <2 risk factors; 2 160 mg/dl for patients with CHD or 22 risk factors. Eligible patients were enrolled into a 6-week diet (NCEP Step 1 or AHA Phase I) baseline period followed by a 6-week diet + placebo period. At 27 sites, approximately 420 patients whose LDL-C still met NCEP guidelines for drug therapy after the 3 months of dietary intervention were randomized into the double-blind active treatment period to receive
It was previously shown that lipid-apheresis (LA) was an effective procedure for rapid regression of induced atherosclerosis in an avian model. The object of this study was to determine whether a continuous extracorporeal LA procedure could be applied effectively and safely to a large animal model with and without atherosclerosis. Eleven pigs were used in this study. Six served as controls and five were made hypercholesterolemic by feeding them with a high cholesterol high saturated fat diet. LA consisted of plasma pheresis followed by plasma delipidation in a stationary chamber containing butanol and diisopropyl ether. The plasma was removed with a pump after phase separation. Organic solvents were subsequently removed by an ether wash and vacuum
Atherosclerosis X, Montreal, October 1994
Tuesday I I October 1994: Poster Abstracts Clinical trials
III, patients given fenofibrate +lO.S% vs -0.6%. Despite the difference in LDL-chol lowering, no difference was seen in apo B decrease, (P) -20.8% and (S) -26.5%. Improvement of the ratios of TCYHDL-Cand apo A-Uapo B was not different. Only fenofibrate, not simvastatin, lowered both fibrinogen (-10.3% vs +3.6%) and uric acid (-25% vs 0%). Safety parameters reflected drug-specific known side effects. We conclude that both drugs are efficient and safe in lowering lipid levels. Besides its advantages in type IIh hyperlipidemia, micronized fenofibrate also proved to be potent in lowering total and LDL-C as well as apo B-containing lipoproteins. Micronized fenofibrate is thus indicated not only in mixed forms of hyperlipidemia but also in primary hypercholesterolemia. 12601
Effect of lovastatin on early carotid atherosclerosis in women Hoen HM, Espeland MA, Applegate WB, Bendixen
wCD. BH, Bowman Gray Sch. of Med., Dept. of Public Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157-1063,
USA
Most primary and secondary prevention lipid-lowering trials focusing on atherosclerotic outcomes such as clinical events and mortality have enrolled male participants only, or have included an insufficient number of females from which to draw meaningful conclusions. The Asymptomatic Carotid Artery Plaque Study (ACAPS) enrolled 445 asymptomatic women (48% of the total cohort) with moderately elevated cholesterol to examine the effects of lovastatin on early-stage carotid atherosclerosis (primary outcome) and cardiovascular events (secondary outcome). ACAPS was a randomized clinical trial that tested, over an average 3-year period, the effects of lovastatin (20-40 mg/day) and/or warfarin (1 mg/day) on progression of early carotid atherosclerosis in men and women with LDL levels between the 60th and 90th percentile. Early carotid artery atherosclerosis was measured as intimal-medial wall thickening (IMT), as diagnosed by noninvasive B-mode ultrasonography. The IMT among women assigned to lovastatin regressed at a rate of 0.006 f 0.003 mm/year, while IMT among non-lovastatin women progressed by 0.007 f 0.003 mm/year (P = 0.0007). Women assigned to lovastatin also experienced fewer cardiovascular events than nonlovastatin women (1 versus 6 cardiovascular events, P = 0.07) and had significantly lower all-cause mortality (0 versus 5 deaths, P = 0.03). After adjusting for covariates such as age, clinical center, baseline IMT, post-menopausal status, hormone replacement therapy, blood pressure and smoking, the effect of lovastatin on IMT remained signiticant. These results reflect similar findings for the total male/female cohort. ACAPS is one of the first trials to suggest that lipid-lowering interventions imprut clinical benefit to women. Comparison (of the quality of life and tolerability of 12611 lovastatin and pravastatin Weir MB, Berger ML, McCaughtry ML, Liss CL, Santanello N,
either lovastatin 40 mg qd or pravastatin 40 mg qd for 12 weeks. Patients were scheduled to return for clinic visits following the baseline diet period, the placebo period and every 4 weeks during the active treatment period. At each visit, complete serum lipid profiles were obtained, adverse experiences were monitored and patients completed quality of life questionnaires. The analysis plan defined the primary endpoint as the change in quality of life as measured by the Nottingham Health Profile after 12 weeks of treatment. Three additional quality of life dimensions were also measured: perceived general health from The National Health and Nutrition Survey, sexual function from The Medical Outcomes Study and stress/life events from the NIH Post-CABG Study. Lipid-apheresis: an in vivo application of delipidation but apolipoprotein retention in plasma of calves by a continuous extracorporeal procedure Cham BE, Kostner KM, wDM, Dwivedy AK, Dept. of
12621
Cardiol., Wesley Hospital, 451 Coronation Drive, AuchenjTower Qld 4066, Australia
Lipid-apheresis (LA) is an effective procedure for acute reduction of plasma cholesterol concentrations. The delipidated plasma retains all apolipoproteins. Rapid regression of atherosclerosis can be obtained by this procedure. Six calves were used in this study. Two served as controls and four were made hypercholesterolemic by keeping them monogastric after birth and feeding them a high cholesterol, high saturated fat diet in their milk. LA consisted of plasma pheresis followed by plasma delipidation in a stationary chamber containing butanol and diisopropyl ether. The plasma was removed with a pump after phase separation. Organic solvents were subsequently removed by an ether wash and vacuum evaporation at 37°C. The delipidated plasma contained all its apolipoproteins and other constituents, only lipid being removed by this procedure. The delipidated plasma was remixed with red blood cells and m-infused into the animal. The procedure was continuous. There was a linear correlation between percent plasma treated and percent change in plasma cholesterol concentration in both the hypercholesterolemic and normocholesterolemic groups. After LA it took approximately 48 h for the plasma cholesterol concentration to return to its initial value, suggesting rapid mobilization of cholesterol to the plasma pool. The total blood volume could be treated in one session. On some occasions the procedure was repeated daily. Biochemical, hematological and post mortem analysis of organs indicated that the procedure was safe. The animals tolerated the procedure well. Based on this and other studies, approval has been obtained to start human clinical studies in 1994. Lipid-apheresis: an in vivo application of delipidation hut apolipoprotein retention in plasma of pigs by a continuous extracorporeal procedure Cham BE, Kostner KM, Q&&un DM, Dwivedy AK, Dept. of
1263(
Univ. of Maryland Hosp, Div. of Nephrology, N3W143, 22 S. Greene St., Baltimore, MD 21201, USA
Cardiol., Wesley Hospital, 451 Coronation Ave., Auchenjlower Qld 4066, Australia
This multicenter US study compared the effects of 12 weeks of treatment with lovastatin (40 mg) or pravastatin (40 mg) on quality of life. Male patients, 20-65 years old, with primary hypercholesterolemia (Types IIa and IIb) were eligible for enrollment if baseline LDL-C met NCEP ATPl guidelines: 2190 mg/dl for patients without CHD or <2 risk factors; 2 160 mg/dl for patients with CHD or 22 risk factors. Eligible patients were enrolled into a 6-week diet (NCEP Step 1 or AHA Phase I) baseline period followed by a 6-week diet + placebo period. At 27 sites, approximately 420 patients whose LDL-C still met NCEP guidelines for drug therapy after the 3 months of dietary intervention were randomized into the double-blind active treatment period to receive
It was previously shown that lipid-apheresis (LA) was an effective procedure for rapid regression of induced atherosclerosis in an avian model. The object of this study was to determine whether a continuous extracorporeal LA procedure could be applied effectively and safely to a large animal model with and without atherosclerosis. Eleven pigs were used in this study. Six served as controls and five were made hypercholesterolemic by feeding them with a high cholesterol high saturated fat diet. LA consisted of plasma pheresis followed by plasma delipidation in a stationary chamber containing butanol and diisopropyl ether. The plasma was removed with a pump after phase separation. Organic solvents were subsequently removed by an ether wash and vacuum
Atherosclerosis X, Montreal, October 1994