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Long-term safety of statin-fibrate combination treatment in the management of hypercholesterolaemia in patients with coronary artery disease
OBSERVATIONS
ON
LIPID-LOWERING
were calculated using meta-analytic techniques. Conclusions: There is no evidence from primary prevention trials that cholesterol lowering affects total mortality in healthy women, although the available data are limited. Limited evidence suggests that treatment of hypercholesterolemia in w o m e n with coronary disease may decrease CHD mortality. Future research should address the role of dietary and other n o n d r u g t r e a t m e n t of hypercholesterolemia in w o m e n at high risk for CHD.
THERAPIES
no other important differences between the two groups in the frequency of fatal or nonfatal events at six months. Conclusions: Treatment with high-dose lovastatin initiated before coronary angioplasty does not prevent or delay the process of restenosis in the first six months after the procedure.
Long-Term Safety of Statin-Fibrate Combination Treatment in the Management of Hypercholesterolaemia in Patients With Coronary Artery Disease M.D. Feher,J. Foxton,D. Banks,A.F.I.ant, R. Wray. Departmentof Clinkal Pharmacology/Therapeutics,ChafingCross/WestminsterMedicalSchool,London,Great Britain. Br Heart J 1995;74:14-7.
Lack of Effect of Lovastatin on Restenosis After Coronary Angioplasty W.S. Weintraub,S.J. Boccuzzi,J.L Klein, A.S. Kosinski,S.B. King III, R. Ivanhoe,J.C. Cedarholm,M.E. Stillabower,J.D. Talley, S.J. DeMaio,W.W. O'Neill,J.E. Frazier II, C.L Cohen-Bernstein,D.C. Robbins,C.L. Brown, III, kW. Alexander,Y.B. Mitchel,J.J. Hirsch, M.R. Melino, et al. Divisionof Cardiology,Emory UniversityHospital,Atlanta, GA. N Engt J Med 1994;331:1331-7.
Objective: To evaluate the long-term safety profile of treatment with a statin-fibrate combination in a cohort of patients with documented coronary artery, disease. Design: Retrospective cohort analytical study. Setting: District general hospital. Patients: 102 (81 male and 21 female) hypercholesterolaemic (total cholesterol concentration >6.5 mmol/l) patients with documented coronary artery disease and who had been treated with a statin-fibrate combination for over 1 year. Coronary artery disease was confirmed by angiography in 93 patients and by a positive (Bruce protocol) exercise test in the remainder. Fifty eight patients had a history of previous coronary bypass graft surgery. Interventions: Twice daily lipid lowering treatment was given, with the fibrate administered in the morning (either bezafibrate 400 mg (n = 101) or fenofibrate 200 mg (n = 1)) and the stain in the evening (either simvastatin 10 mg (n = 23), 20 mg (n = 72), or 40 mg (n = 2) or pravastatin 10 mg (n = 1) or 20 mg (n = 4)). Treatment continued for 1 (n = 9), 2 (n = 58), or 3 (n = 35) years. Main outcome measures: Selected laboratory variables (total cholesterol concentration and liver (aspartate transaminase (AST)) and muscle enzyme (creatine kinase (CK)) activities) and documented symptornatology. Results: A mean (SD) total cholesterol concentration of 5.2 (0.8) mmol/1 was achieved after combined treatment for 1 year which was maintained at annual follow up. Over a maxim u m 3 year follow up no patient reported myalgic symptoms and none had a measured CK activity > 10 times above normal. Four men on a simvastatin-bezafibrate combination had a CK activity rise to less than three times normal. Fourteen patients with a negative history of alcohol excess (consumption < 2 1 units/week) had borderline raised AST values. Conclusions: Statin-fibrate combination treatment for up to 3 years in a cohort of patients with coronary artery disease was not associated with serious disturbances in biochemical markers of muscle or liver function.
Background: Experimental and clinical observations suggest that lowering serum lipid levels may reduce the risk of restenosis after coronary angioplasty. We report the results of a prospective, randomized, double-blind trial evaluating whether lowering lipid levels with lovastatin can prevent or delay restenosis after angioplasty. Methods: Seven to 10 days before angioplasty, we randomly assigned eligible patients to receive lovastatin (40 mg orally twice daily) or placebo. Patients who underwent successful, complication-free, firsttime angioplasty of a native vessel (the index lesion) continued to receive therapy for six months, when a second coronary angiogram was obtained. The primary end point was the extent of restenosis of the index lesion, as assessed by quantitative coronary arteriography. Of 404 patients randomly assigned to study groups, 384 underwent angioplasty; 354 of the procedures were successful, and 321 patients underwent angiographic restudy at six months. Results: At baseline, the patients in the lovastatin group (n = 203) and the placebo group (n = 201) were similar with respect to demographic clinical, angiographic, and laboratory characteristics. At baseline the mean (-+SD) degree of stenosis, expressed as a percentage of the diameter of the vessel, was 64 + 11 percent in the lovastatin group, as compared with 63 -+ 11 percent in the placebo group (P = 0.22). Despite a 42 percent reduction in the serum level of low-density lipoprotein cholesterol in the lovastatin group, after six months of treatment the amount of stenosis seen in the second angiogram was 46 _+ 20 percent in the placebo group, as compared with 44 -+ 21 percent in the lovastatin group (P = 0.50). Similarly, there were no significant differences in minimal luminal diameter or other measures of restenosis. A trend was noted toward more myocardial infarctions in the lovastatin group, as a result of acute vessel closure or restenosis at the site of angioplasty, but there were
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51
ON
LIPID-LOWERING
were calculated using meta-analytic techniques. Conclusions: There is no evidence from primary prevention trials that cholesterol lowering affects total mortality in healthy women, although the available data are limited. Limited evidence suggests that treatment of hypercholesterolemia in w o m e n with coronary disease may decrease CHD mortality. Future research should address the role of dietary and other n o n d r u g t r e a t m e n t of hypercholesterolemia in w o m e n at high risk for CHD.
THERAPIES
no other important differences between the two groups in the frequency of fatal or nonfatal events at six months. Conclusions: Treatment with high-dose lovastatin initiated before coronary angioplasty does not prevent or delay the process of restenosis in the first six months after the procedure.
Long-Term Safety of Statin-Fibrate Combination Treatment in the Management of Hypercholesterolaemia in Patients With Coronary Artery Disease M.D. Feher,J. Foxton,D. Banks,A.F.I.ant, R. Wray. Departmentof Clinkal Pharmacology/Therapeutics,ChafingCross/WestminsterMedicalSchool,London,Great Britain. Br Heart J 1995;74:14-7.
Lack of Effect of Lovastatin on Restenosis After Coronary Angioplasty W.S. Weintraub,S.J. Boccuzzi,J.L Klein, A.S. Kosinski,S.B. King III, R. Ivanhoe,J.C. Cedarholm,M.E. Stillabower,J.D. Talley, S.J. DeMaio,W.W. O'Neill,J.E. Frazier II, C.L Cohen-Bernstein,D.C. Robbins,C.L. Brown, III, kW. Alexander,Y.B. Mitchel,J.J. Hirsch, M.R. Melino, et al. Divisionof Cardiology,Emory UniversityHospital,Atlanta, GA. N Engt J Med 1994;331:1331-7.
Objective: To evaluate the long-term safety profile of treatment with a statin-fibrate combination in a cohort of patients with documented coronary artery, disease. Design: Retrospective cohort analytical study. Setting: District general hospital. Patients: 102 (81 male and 21 female) hypercholesterolaemic (total cholesterol concentration >6.5 mmol/l) patients with documented coronary artery disease and who had been treated with a statin-fibrate combination for over 1 year. Coronary artery disease was confirmed by angiography in 93 patients and by a positive (Bruce protocol) exercise test in the remainder. Fifty eight patients had a history of previous coronary bypass graft surgery. Interventions: Twice daily lipid lowering treatment was given, with the fibrate administered in the morning (either bezafibrate 400 mg (n = 101) or fenofibrate 200 mg (n = 1)) and the stain in the evening (either simvastatin 10 mg (n = 23), 20 mg (n = 72), or 40 mg (n = 2) or pravastatin 10 mg (n = 1) or 20 mg (n = 4)). Treatment continued for 1 (n = 9), 2 (n = 58), or 3 (n = 35) years. Main outcome measures: Selected laboratory variables (total cholesterol concentration and liver (aspartate transaminase (AST)) and muscle enzyme (creatine kinase (CK)) activities) and documented symptornatology. Results: A mean (SD) total cholesterol concentration of 5.2 (0.8) mmol/1 was achieved after combined treatment for 1 year which was maintained at annual follow up. Over a maxim u m 3 year follow up no patient reported myalgic symptoms and none had a measured CK activity > 10 times above normal. Four men on a simvastatin-bezafibrate combination had a CK activity rise to less than three times normal. Fourteen patients with a negative history of alcohol excess (consumption < 2 1 units/week) had borderline raised AST values. Conclusions: Statin-fibrate combination treatment for up to 3 years in a cohort of patients with coronary artery disease was not associated with serious disturbances in biochemical markers of muscle or liver function.
Background: Experimental and clinical observations suggest that lowering serum lipid levels may reduce the risk of restenosis after coronary angioplasty. We report the results of a prospective, randomized, double-blind trial evaluating whether lowering lipid levels with lovastatin can prevent or delay restenosis after angioplasty. Methods: Seven to 10 days before angioplasty, we randomly assigned eligible patients to receive lovastatin (40 mg orally twice daily) or placebo. Patients who underwent successful, complication-free, firsttime angioplasty of a native vessel (the index lesion) continued to receive therapy for six months, when a second coronary angiogram was obtained. The primary end point was the extent of restenosis of the index lesion, as assessed by quantitative coronary arteriography. Of 404 patients randomly assigned to study groups, 384 underwent angioplasty; 354 of the procedures were successful, and 321 patients underwent angiographic restudy at six months. Results: At baseline, the patients in the lovastatin group (n = 203) and the placebo group (n = 201) were similar with respect to demographic clinical, angiographic, and laboratory characteristics. At baseline the mean (-+SD) degree of stenosis, expressed as a percentage of the diameter of the vessel, was 64 + 11 percent in the lovastatin group, as compared with 63 -+ 11 percent in the placebo group (P = 0.22). Despite a 42 percent reduction in the serum level of low-density lipoprotein cholesterol in the lovastatin group, after six months of treatment the amount of stenosis seen in the second angiogram was 46 _+ 20 percent in the placebo group, as compared with 44 -+ 21 percent in the lovastatin group (P = 0.50). Similarly, there were no significant differences in minimal luminal diameter or other measures of restenosis. A trend was noted toward more myocardial infarctions in the lovastatin group, as a result of acute vessel closure or restenosis at the site of angioplasty, but there were
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