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Effects of immunospecific LDL apheresis on lipoprotein (a) serum levels
Poster session abstracts / Atherosclerosis 115 (Suppl.) (1995) $45-S129 P12 Medical Treatment of Hyperlipidaemia
$93
P12 MEDICAL T R E A T M E N T OF HYPERLIPIDAEMIA 346
348
SUBSTANTIAL NON-COMPLIANCE TO DOSE AND TIME PRESCRIPTIONS FOR MEDICATIONS TREATING HYPERCHOLES TEROLEMIA W. Insull, A. Troendle, A. Silvers, C.W. Dunne Baylor College of Medicine, Houston, TX, USA.
THE KINETICS OF APOLIPOPROTEIN B METABOLISM IN BLOOD PLASMA OF PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA TREATED BY LDL APHERESIS Ye. B. Yarovaya, T.V. Rostapshova, N.A. Gavrilova, V.A. Metelskaya', V.V. Kukharchuk. Cardiology Research Centre; "National Research Centre for Preventive Medicine, Moscow, Russia
Although non-compliance commonly occurs and compromises the efficacy of most drugs, the non-compliance to inhibitors of HMGCoA reductase has been incompletely described. We estimated the patient compliance to fluvastatin using unobtrusive, continuous electronic monitoring of medication-taking events. In a controlled clinical trial of safety and efficacy of fluvastatin with 430 hypercholesterolemic patients (total cholesterol >6.7 mmol/L after diet therapy) at 12 American clinics, we compared fluvastatin 20 mg qhs, 20 mg bid and 40 mg qhs, and placebo bid. Random samples of patients were compliance monitored for both am and pm doses (n=64), am only (n=46), or pm only (n= 117) for an average of 80 days, range 27-108 days. Overall, mean compliance by the prescribed number of doses taken was 94%, range 54-110%. Mean compliance by the days the correct number of doses were taken was 81%, range 36-100%. Mean compliances to the prescribed am and pm schedules, ie within __+_ 6 hours were respectively 70.9% and 71.0%, range 23-100%. Correlation of the compliances of pm doses to am doses, measured by percentage of days prescribed dose taken, was significant, r = +0.79. Modest differences in compliance between drug and placebo appeared to occur. Conclusion: Noncompliance is a widespread and substantial clinical problem challenging the efficient and economical use of an effective and highly accepted reductase inhibitor.
LDL apheresis causing perturbations in plasma lipoprotein system with the loss of its steady state allows to develop a new approach for the estimation of apolipoprotein B (apo B) influx rate into circulation, the rate constants of transfer (T) and catabolism (Cvldl, Cldl) for two pools of apo B containing lipoproteins (LP) VLDL and LDL, basing on the dynamics of total apo B level after LDL apheresis. In a group of patients with familial hypercholesterolemia (FHC) (n= 10) treated by repeated LDL apheresis metabolic parameters were analysed and calculated using twocompartmental modelling as follows (mean+standart error): T = 0.34+0.16 (day i) (apo B V L D L ~ apo B LDL); Cvldl = 0.25:0.06 (dayt) Cldl= 0.12_+0.05 (dayt). The feasibility of the model for classification of behavioral types of apo B concentration after removal of apo B containing LP from blood plasma is shown. In patients with FCH stimulation action of LDL apheresis on the apo B influx rate into circulation are identified.
347
349
EFFECTS OF IMMUNOSPECIFIC LDL APHERESIS ON LIPOPROTEIN (a) SERUM LEVELS M. Jansen, K. Derfler. H. Hysek, J. Pidlich, W. Druml Internal Med III Dept Nephrology, Univ of Vienna, Austria
"AGGRESSIVE" LIPID LOWERING IS FOLLOWED BY POSITIVE CHANGES IN THE TIME COURSE OF CORONARY ARTERY DISEASE (CAD) V.O. Konstantinov, T.I. Makeeva, S.N. Sokolova, *K.Ya. Gurevich, "A.L. Kostuchenko, L.E. Vasilyeva, A.N. Klimov Institute for Experimental Medicine. "Clinic for Extracorporeal Haemocorrection. St.Petersburg, Russia
This study was performed to investigate the reduction of Lipoprotein(a) [Lp(a)] by immunospecific LDL apheresis [LDL aphl. Lp(a) consists of a low-density cholesterol [LDL-chol] part linked to the glycoprotein apolipoprotein(aL LDL apheresis is an extracorporal method which allows elimination of apolipoprotein B-100 lapo BI containing lipoproteins out of plasma by means of apo B antibody - containing columns (Therasorb, Baxter, Munich). For the necessary plasma separation we used an autopheresis C TPS machine (Fenwal/Baxter. USA). All treatments were performed using a peripheral veno-venous approach. Lipoproteins were determined before and following apheresis treatment (n=200; mean desorbed plasma volume: 5350_+755 ml) in 7 patients IP] with elevated Lp(a) semm levels: 2 p with homozygous. 4 p with heterozygous familial hypercholestrolemia and 1 p with selective elevation of Lp(a) levels: [ 1) mg/dl, "/p < 0.001] before LDL aph after LDL aph decrease % Lp(a):' 48+23 13+8" 72 LDL cholI~ 259_+91 78+43' 70 apo B~1 157_+38 49_+23" 69 [ 1) mg/dl, "p < 0.001 ] Mean Lp(a) levels before LDL aph was initiated were 84_+34 mg/dl. Pretreatment Lp(a) values decreased to 45-+29 mg/dl. In line with LDL chol, reduction in Lp(a) was depending on total plasma volume desorbed. Moreover Lp(a) was measured in the eluate during 31 treatments (mean Lp(a) desorbed: 1350-+455 mg). The increase of Lp(a) following LDL aph treatment was similar to that of LDL chol. lmmunospecific LDL aph has proven to be highly efficient to decrease elevated Lp(a) serum levels and might reduce the risk of coronary artery disease and bypass graft stenosis associated with elevated Lp(a) serum levels.
Sixty pts (49 males, 11 females, mean age 57 years) with unstable angina and primary hyperlipidemia received lipid lowering therapy for one year period. They made three groups, each consisting of 20 pts. Group (1) was given adequate doses of Iovastatin (L), group (2) underwent procedures of plasmoexchange of extracorporeal modified (by cryoprecipitation and addition of heparin) autoplasma (PEMA), group (3) had PEMA plus L therapy. A group of other 20 pts (control) received a standard antianginal therapy. A most significant decrease of total plasma cholesterol (-35%) and triglycerides (-52%) was found in (3). The patients of this group showed a permanent increase of physical exercise tolerance as revealed by bicycle ergometry, 85% had a stable improvement in their clinical state. In control group the clinical condition of 75% of pts remained without change. A combined L, and PEMA treatment reduces CAD complications and improves the quality of life of CAD pts.
$93
P12 MEDICAL T R E A T M E N T OF HYPERLIPIDAEMIA 346
348
SUBSTANTIAL NON-COMPLIANCE TO DOSE AND TIME PRESCRIPTIONS FOR MEDICATIONS TREATING HYPERCHOLES TEROLEMIA W. Insull, A. Troendle, A. Silvers, C.W. Dunne Baylor College of Medicine, Houston, TX, USA.
THE KINETICS OF APOLIPOPROTEIN B METABOLISM IN BLOOD PLASMA OF PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA TREATED BY LDL APHERESIS Ye. B. Yarovaya, T.V. Rostapshova, N.A. Gavrilova, V.A. Metelskaya', V.V. Kukharchuk. Cardiology Research Centre; "National Research Centre for Preventive Medicine, Moscow, Russia
Although non-compliance commonly occurs and compromises the efficacy of most drugs, the non-compliance to inhibitors of HMGCoA reductase has been incompletely described. We estimated the patient compliance to fluvastatin using unobtrusive, continuous electronic monitoring of medication-taking events. In a controlled clinical trial of safety and efficacy of fluvastatin with 430 hypercholesterolemic patients (total cholesterol >6.7 mmol/L after diet therapy) at 12 American clinics, we compared fluvastatin 20 mg qhs, 20 mg bid and 40 mg qhs, and placebo bid. Random samples of patients were compliance monitored for both am and pm doses (n=64), am only (n=46), or pm only (n= 117) for an average of 80 days, range 27-108 days. Overall, mean compliance by the prescribed number of doses taken was 94%, range 54-110%. Mean compliance by the days the correct number of doses were taken was 81%, range 36-100%. Mean compliances to the prescribed am and pm schedules, ie within __+_ 6 hours were respectively 70.9% and 71.0%, range 23-100%. Correlation of the compliances of pm doses to am doses, measured by percentage of days prescribed dose taken, was significant, r = +0.79. Modest differences in compliance between drug and placebo appeared to occur. Conclusion: Noncompliance is a widespread and substantial clinical problem challenging the efficient and economical use of an effective and highly accepted reductase inhibitor.
LDL apheresis causing perturbations in plasma lipoprotein system with the loss of its steady state allows to develop a new approach for the estimation of apolipoprotein B (apo B) influx rate into circulation, the rate constants of transfer (T) and catabolism (Cvldl, Cldl) for two pools of apo B containing lipoproteins (LP) VLDL and LDL, basing on the dynamics of total apo B level after LDL apheresis. In a group of patients with familial hypercholesterolemia (FHC) (n= 10) treated by repeated LDL apheresis metabolic parameters were analysed and calculated using twocompartmental modelling as follows (mean+standart error): T = 0.34+0.16 (day i) (apo B V L D L ~ apo B LDL); Cvldl = 0.25:0.06 (dayt) Cldl= 0.12_+0.05 (dayt). The feasibility of the model for classification of behavioral types of apo B concentration after removal of apo B containing LP from blood plasma is shown. In patients with FCH stimulation action of LDL apheresis on the apo B influx rate into circulation are identified.
347
349
EFFECTS OF IMMUNOSPECIFIC LDL APHERESIS ON LIPOPROTEIN (a) SERUM LEVELS M. Jansen, K. Derfler. H. Hysek, J. Pidlich, W. Druml Internal Med III Dept Nephrology, Univ of Vienna, Austria
"AGGRESSIVE" LIPID LOWERING IS FOLLOWED BY POSITIVE CHANGES IN THE TIME COURSE OF CORONARY ARTERY DISEASE (CAD) V.O. Konstantinov, T.I. Makeeva, S.N. Sokolova, *K.Ya. Gurevich, "A.L. Kostuchenko, L.E. Vasilyeva, A.N. Klimov Institute for Experimental Medicine. "Clinic for Extracorporeal Haemocorrection. St.Petersburg, Russia
This study was performed to investigate the reduction of Lipoprotein(a) [Lp(a)] by immunospecific LDL apheresis [LDL aphl. Lp(a) consists of a low-density cholesterol [LDL-chol] part linked to the glycoprotein apolipoprotein(aL LDL apheresis is an extracorporal method which allows elimination of apolipoprotein B-100 lapo BI containing lipoproteins out of plasma by means of apo B antibody - containing columns (Therasorb, Baxter, Munich). For the necessary plasma separation we used an autopheresis C TPS machine (Fenwal/Baxter. USA). All treatments were performed using a peripheral veno-venous approach. Lipoproteins were determined before and following apheresis treatment (n=200; mean desorbed plasma volume: 5350_+755 ml) in 7 patients IP] with elevated Lp(a) semm levels: 2 p with homozygous. 4 p with heterozygous familial hypercholestrolemia and 1 p with selective elevation of Lp(a) levels: [ 1) mg/dl, "/p < 0.001] before LDL aph after LDL aph decrease % Lp(a):' 48+23 13+8" 72 LDL cholI~ 259_+91 78+43' 70 apo B~1 157_+38 49_+23" 69 [ 1) mg/dl, "p < 0.001 ] Mean Lp(a) levels before LDL aph was initiated were 84_+34 mg/dl. Pretreatment Lp(a) values decreased to 45-+29 mg/dl. In line with LDL chol, reduction in Lp(a) was depending on total plasma volume desorbed. Moreover Lp(a) was measured in the eluate during 31 treatments (mean Lp(a) desorbed: 1350-+455 mg). The increase of Lp(a) following LDL aph treatment was similar to that of LDL chol. lmmunospecific LDL aph has proven to be highly efficient to decrease elevated Lp(a) serum levels and might reduce the risk of coronary artery disease and bypass graft stenosis associated with elevated Lp(a) serum levels.
Sixty pts (49 males, 11 females, mean age 57 years) with unstable angina and primary hyperlipidemia received lipid lowering therapy for one year period. They made three groups, each consisting of 20 pts. Group (1) was given adequate doses of Iovastatin (L), group (2) underwent procedures of plasmoexchange of extracorporeal modified (by cryoprecipitation and addition of heparin) autoplasma (PEMA), group (3) had PEMA plus L therapy. A group of other 20 pts (control) received a standard antianginal therapy. A most significant decrease of total plasma cholesterol (-35%) and triglycerides (-52%) was found in (3). The patients of this group showed a permanent increase of physical exercise tolerance as revealed by bicycle ergometry, 85% had a stable improvement in their clinical state. In control group the clinical condition of 75% of pts remained without change. A combined L, and PEMA treatment reduces CAD complications and improves the quality of life of CAD pts.