Effects of Lopid-SR on plasma lipids, lipoproteins and apolipoproteins in patient with combined hyperlipidemia and hypertriglyceridemia

Tuesday II October 1994: Poster Abstracts Clinical trials

Further significant decreases were found in TC and LDL-C after 6 months in group 2. HDL-C did not change thereafter. These results indicate that CEE combined with pravastatin administration leads to marked decreases of TC and LDL-C, and pravastatin does not influence the HDL-C increase produced by CEE.

151

Results: group means are shown. GR

#

Age

PPl

PP2

CHOLl CHOL2

1

2 3 C

20 28 26 50

62 61 64 63

85* 86* 88* 60

87* 90* 60 60

280* 274* 281* 194

&&j& Wong L, Bethel Public Service Clinic, PO BOX 4921, Downey,

GR

AS1

AS2

TEE

TM

CA 90241, USA

1

17* 18* 17* 5

20* 19* 6 6

20* 28* 0 0

4* 5* 10 10

12341

Ultrasonic evidence of regression of aortic and coronary atherosclerosis in type II hyperlipidemia Zemplenyi T, Emont C, Evangelista A, McFadden J,

Serial digital ultrasonic measurements of the ascending aorta (AA) and coronary arteries (CA) demonstrate regression (REG) or progression (PROG) of grade 2 (Gr2) atherosclerosis (Athero) during intervention. Fifty Type II hyperlipidemic people were randomly selected and treated with lovastatin (20-40 mg/day). A second Type II group had basilar artery migraine (BAM). Serial measurements were made of: serum cholesterol (CHOL), BP, pulse pressure (PP), A stiffness (AS = PP/%AStr, %AStr = systolic change in A cross-sectional diameter/minimal A diameter X lOO%), serial ultrasonic measurements of AA wall and coronary density. All data were correlated by blind matrix. Results: group means are shown for groups with REG or PROG from before (1) and during (2) a mean of 3 years therapy. AA and CA change was determined by the change in Gr 2 Atbero volume (area x density change) calibrated by separate human postmortem studies. Gr 2 Athero has a characteristic range of density (D). Group means arc shown for the age matched groups (mean 66 years). Group

#

AS1

AS2

AD1

AD2

CAD1

CAD2

REG PROG BAM Cntl

30 20 30 40

11 10 7 6

4* 19* 7 6

158 160 42 40

100* 200* 42 40

1.50 155 30 30

90* 200* 30 30

Group

CHOLl CHOL2

SBPl

SBP2

PPl

PP2

REG PROG BAM Cntl

290 285 280 185

160 162 100 130

140* 164 100 130

82 80 40 50

60* 86 40 50

192* 290 190* 180

where: SBP, systolic BP; Cntl, control; *significant (sig) change from time 1 to 2 at P < 0.002 by t-test; CAD, D of anterior descending CA. Sig REG occurred in both the AA and CA in 30/30 patients. Type II BAM patients have low SBP and did not differ from the Cntl group at time 1 or 2. Functional aortic improvement occurred with lowering of SBP and PP in the REG group with sig decrease in AS and AD. Serial ultrasound permits objective evidence of regression in the AA and CA during intervention therapy. Prediction and prevention of cerebral thromboembolism by cholesterol reduction during serial ultrasonic observation of aortic wall change Bamdt R, Zemplenyi T, Mattson E, McFadden J, Cox T, Bethel

12351

Public Service Clinic, PO Box 4921, Downey, CA 90241, USA

High risk of cerebral thrombo-emholic events (CTEE) can be predicted by risk factor (RF) levels and ultrasonic visualization of grade 2-3 atherosclerosis (Athero) of ascending aorta (AA). Predictive parameters in group (Gr) I: RF levels, and aortic stiffness (AS) were used to identify patients at high risk (HR) from a randomly selected pool of 900 people (over 60 years). Intervention was prescribed in all HR cases, grouping blindly the ultrasonic response (Gr 2 = non-responders, Gr3 = responders) to therapy (clofibrate 2 g/day, type 11 American Heart Association Diet).

2 3 C

270* 280’ 196 190

where: #, the number of cases; 1, pre-therapy; 2, during therapy; CHOL, serum cholesterol; AS, aortic stiffness, PP/%A Strain; %A Strain, systolic change in A diameter (diam)/minimal diam x lOO%, PP, pulse pressure; *significantly (sig) higher than controls (GrC) by c-test, P < 0.001; TEE, # of cerebral TEE (by CT scan) in the time interval (TM, years). Patients with high CHOL, wide PP, and high AS had sig higher CTEE events. CR2 was predicted by pilot GRl. CHOL and PP had sig correlations with AS by multiple regression analysis, R = 0.98, P < 0.001. Regression of AA Athero in GR3 (shown by AS change) was associated with no TEE in 10 years. None of the 776 people with normal AS for age had cerebral TEE in 10 years. CTEE can be prevented by CHOL reduction with sig REG of AA Athero. Cholesterol ester storage disease: two new cases diagnosed in children Haeemenas Illingworth DR, Dept. of Med.-L465, Oregon 12361

Health

Sciences' Univ., Portland, OR 97201 USA

Cholesterol ester storage disease (CESD) is a rare disorder characterized by a hereditary deficiency of acid cholesteryl ester hydrolase activity. This autosomal recessive disorder is associated with hypercholesterolemia and accumulation in the lysosome of cholesterol esters. We report two new cases diagnosed with CESD, two siblings, a sister and brother, ages 6 and 8 respectively. The diagnosis was confirmed in cultured fibroblasts from each child that demonstrated a deficiency in lysosomal acid cholesteryl ester hydrolase activity (ACEH). Fibroblasts were also obtained from each parent. The ACEH in the sister and brother were 2.2 and 1.3% of control tibroblasts, respectively. The parents of these siblings also showed a low ACEH activity; the father and the mother were 27.1 and 23.5% of control tibroblasts. In addition, to determine the possible efficacy of treating the children with lovastatin, the cultured fibroblasts from each was used to determine: (1) the binding, internalization and degradation of LDL by the LDL receptor, (2) rates of cholesterol synthesis and (3) the levels of free and esterified cholesterol in the presence and absence of lovastatin. These results were compared with the activity and levels found in the children’s parents and in normal tibroblasts. The siblings with CESD had si nificantly lower ability to bind, internalize and degrade the I2BI-labeled LDL. In contrast, the parents showed normal high-affinity LDL receptor activity. The presence of lovastatin in the medium of CESD fibroblasts caused endogenous lipid levels to decrease dramatically and this decrease was due to a 50% decrease in esterified cholesterol. These in vitro data indicate that the children treatment with lovastatin.

with CESD

may benefit

from

Effects of Lopid-SR on plasma lipids, lipoproteins and apolipoproteins in patient with combined hyperlipidemia and hypertriglyceridemia Yane CY, Gu ZW, Xie YH, Valentinova NV, Yang M, Yeshurun D, Quion JA, Gotto Jr AM, Dept. of Med., Baylor College of Med.

1237]

Atherosclerosis X, Montreal, October 1994

152

Tuesday 11 October 1994: Poster Abstracts Clinical trials

and the Methodist Hospital, 6535 Fannin, MS/A601, Houston, TX? USA

12391 Quality

Eleven patients (5 with type IIB and 6 with type. V) were randomized for 8 weeks to either Lopid-SR (sustained release) 2 x 600 mg/day or placebo treatment which were represented as with drug or without dmg, respectively. After drug therapy, triglyceride decreased an average of 68% and HDL-C increased an average of 17%. Furthermore, apo E, C-I, C-III, and VLDL all showed significant decreases; the mean were by 46, 24, 17 and 77%, respectively. By contrast, there were minimal changes in the concentrations of total cholesterol and apo B. VLDL subfractions were separated and classified on the basis of heparin binding (VLDLR) or non-binding (VLDLHR.1 and VLDLm_2) which reflected the presence or absence of apo E. All subfractions showed remarkable decreases and the apo E to apo B molar ratio in VLDL declined by 46% after drug therapy. C apolipoprotein composition in VLDL revealed a significantly higher content of apo C-II (19%) and a lower content of apo C-III (9%) after Lopid-SR treatment. VLDL and its subfractions were reduced to a greater extent in the type V versus the IIB patients. After LopidSR treatment, the mean total of plasma level of apo E, C-I, and C-III declined by 43, 19 and 9% in type IIB and 46, 23 and 18% in type V, respectively. Apo C-I and C-III concentrations were reduced much less than apo E. This resulted in an increase in the ratio of apo C-III to apo E. In conclusion, Lopid-SR is a potent lipid regulating drug that affects plasma triglycerides and VLDL. The proportionate reduction in concentrations of VLDL and its subfractions by Lopid-SR is greater in type V than in II-B.

West Point, PA 19486 and Massachusetts Boston, MA 02114, USA

12381 a,

Nicotinic acid @IA) treatment of older persons with hypercholesterolemia (IX): subanalysis of the Coronary Drug Project (CDP) data Ripsin C, McCaffrey D, Dept. of Family Practice,

Univ. qf Minnesota, 825 Washington Ave. SE, Minneapolis, MN 55414, USA

LongitudinaI studies (Framingham, Baltimore Longitudinal Study on Aging) have demonstrated that HC continues to be a risk factor for cardiovascular disease into the 8th decade, yet HC treatment in the elderly remains controversial. We analyzed a subgroup of older NA-treated subjects, 60-64 years of age (N= 231), from the CDP, a 6-year study of HC intervention in high-risk males with previous history of myocardial infarction. The older subject group was 60-64 years at study entry, 66-70 years at study end, and 7579 years at final post-study followup. Comparisons were made with younger NA-treated subjects (30-50 years, N = 411) with respect to HC reduction and blood chemistries, and with older controls (60-64 years, N = 542) with respect to long-term mortality. For the entire study sample, NA-treated subjects (N= 1119) were compared with control subjects (N= 2787) with respect to short-term morbidity. Compared to younger NA-treated subjects, older treated subjects had greater HC reduction after 5 years (-12% vs -7%, P < 0.03) and greater increase in liver enzymes (SGOT = +34% vs +16%, P < 0.001; Alk Phos = +22% vs +14%, P < 0.04). but showed no difference in blood glucose and bilirubin. Compared to older control subjects, the older NA-treated subjects had greater survival at 15-year followup (60% vs 52%, P < 0.01). For the entire study group, NA-treated subjects had fewer non-fatal myocardial infarctions during the 6-year treatment period than did control subjects (10.4% vs 14.78, P < 0.001). The CDP data suggest that NA treatment of HC in individuals (at least males) into the 8th decade may be beneficial, but that liver function tests should perhaps be monitored closely in this group.

of life in a 6-week study of simvastatin vs pravastatin L Belle P, Pastemak R, Liss C, Santanello N, Merck & Co., Inc., General Hospital,

We compared the effects of 6 weeks of simvastatin or pravastatin therapy at the usual starting doses on quality of life as measured by the 6 domains of the Nottingham Health Profile (NHP): energy, pain, emotional reactions, sleep, social isolation, and physical mobility. After a 6-week placebo baseline period, 473 patients with LDL-C 2190 mg/dl (4.9 mrnol/l) on the NCEP Step I diet were randomized to 6 weeks of simvastatin (S) 10 mg qpm or pravastatin (P) 20 mg qhs, or to S 5 mg or P 10 mg if 65 years of age or older. The mean percent reductions in LDLC were 26% for S and 23% for P, P < 0.001, for the 462 patients completing the study and there were no significant between-group differences in side-effect profiles. For each domain of the NHP, the mean changes in scores (raw and adjusted by weight items) for each treatment group were compared as were the changes for each patient categorized as improved, no change or worse. Standard non-parametric methods were used. Of the 421 patients who completed the NHP at baseline, 92% completed the end-oftreatment NHP. Them were no between-group differences in any domain of the NHP for mean changes in scores. For each domain, between 75 and 90% of patients had no change in their scores. For all six domains for P and four of the six domains for S, the remaining patients were equally divided between those who improved and worsened. For the other two domains for S, mom than twice as many patients improved as worsened compared to baseline: sleep (17% vs 8% P < 0.05) and physical mobility (13% vs 5%, P=NS) domains. We conclude that, using usual starting doses, simvastatin is more effective than pravastatin at reducing LDL cholesterol and that there is no evidence in this short-term study that either drug adversely affects quality of life. Simvastatin in the secondary prevention of coronary atherosclerosis vUFE, Bestehom HP, Petersen J, Samek L, Peters K, Betz P, Braunagel K, Spinder M, Roskamm H, Hen-Zentrum D-79188 Bad Krozingen, Germany; Benesch L, Schemehat K, Fachklin. Rhein-Ruhr, Essen; Bltimchen G, Claus J, Klin. Roderbirken, Leichlingen; Mathes P, Klin. Hirhenried; Kappenberger L, CHVV Lausanne; Wieland H, Becker JF, Univ. Freiburg (central lab.); Neiss A, T. Univ. Munich (statistics), Germany and Switzerland

12401

The objective of the multicenter, randomized, double-blind, placebo-controlled Coronary Intervention Study (CIS) is to assess the effects of simvastatin on progression in 254 men with documented coronary artery disease (CAD) and hypercholesterolemia. Entry criteria were the presence of at least 3 coronary segments with a reduction in lumen diameter of 2 25% and a mean serum cholesterol of 2 207 mgldl after diet. Treatment with (20 to) 40 mg simvastatin or placebo o.d. included diet in both treatment groups and, as a reserve medication, cholestyramine, and was pursued for about 2.5 years. The two treatment groups were comparable with respect to baseline variables such as average age (49.3 years), height (175.1 cm), weight (80.4 kg), blood pressure (123.3fl9.4 mm), risk factors, ventricular score (index 1.03-0.91) and coronary score (1.99-2.14 vessel-disease), and lipid values (baseline serum LDL-C 165.7 mg/dl). Primary end points of the study are the angiographic progression of CAD measured both by a computer-aided quantitative measure (mean minimum stenosis diameter per patient), and by a semiquantitative visual coronary analysis, namely the global change score. Secondary end points include the clinical events, i.e. fatal and non-fatal cardiovascular and non-cardiovascular

Atherosclerosis X, Montreal, October 1994