Endovenous laser ablation of varicose veins with the 1470 nm diode laser using a radial fiber - 1-year follow-up.

BACKGROUND: Endovenous laser ablation is one of the most accepted treatment options for insufficient great and small saphenous veins. The aim of this study was to investigate the long-term efficacy and safety of the radial fiber (ELVeS-radial kit™) for the 1470 nm diode laser in a 1-year follow-up. METHODS: A total of 308 lower limbs with primary insufficiency of great and small saphenous veins or insufficient tributaries were included in the prospective observational cohort study. The primary efficacy endpoint of the study was ultrasonographic proven elimination of venous reflux after at least 1 year. Secondary efficacy and further safety end points after 1 year were as follows: (1) sonographic exclusion of recanalization of the treated vein segments, (2) deep vein thrombosis, clinical pulmonary embolism or superficial vein thrombosis as defined by objective testing, (3) death from any cause, (4) persistent clinical complaints such as pain and paresthesia, (5) recurrent varicose veins. Patient satisfaction was assessed using a CIVIQ-2 questionnaire after 1 year. RESULTS: Follow-up could be completed in 91.2% of the patients. Excellent efficacy numbers with 99.6% occlusion of the treated varicose veins as elimination of reflux could be demonstrated. After 1 year, 96% of the treated veins disappeared completely sonographically; one recanalization was observed. No deep vein thrombosis or pulmonary embolism occurred, three superficial vein thrombosis were diagnosed in follow-up examinations. Four patients died, not related to pulmonary embolism. No persistent pain or paresthesia occurred in the follow-up. Recurrent varicose veins were diagnosed in 10 patients (2.81%). CONCLUSION: One-year follow-up showed that endovenous laser treatment of varicose veins with 1470 nm diode laser using the radial fiber is highly effective, also regarding in a 1-year follow-up.

[Cardiology quality assessment in Germany--pro and contra]. / Kardiologie--Qualitätssicherung in Deutschland. Pro und Contra.

The German National Institute for Quality in Healthcare has also developed a program of external quality assessment in the field of cardiology. Hospitals are committed to collect certain data of diagnostic coronary angiography, percutaneous coronary interventions and pacemaker implantations. If statistical abnormalities are observed a so called structured dialogue is implemented. The responsible physicians of the hospitals are asked to comment possible quality deficits. Appointed members of quality commissions examine the answers and can invite the responsible physicians for interviews or also visit the hospital. However the validity of the quality data is problematic, because audits or check-ups of quality assessment in place are lacking. Therefore the results should not be misused for a comparison or ranking of hospitals with each other. As long as the validity of the quality assessment has not been improved, the results should also not be accessible for other parties, such as health insurances.

[The importance of cholesterol-lowering in patients after coronary artery bypass surgery]. / Die Bedeutung der Cholesterinsenkung bei Patienten nach aortokoronarer Bypassoperation.

Patients with aortocoronary bypass surgery generally have a severe, advanced coronary atherosclerosis. An intensive risk-factor management should be of special importance in these patients. However, cholesterol treatment goals are the same for operated or non-operated patients with coronary artery disease. Effective cholesterol lowering does not only decrease the progression of atherosclerosis in native coronary vessels but also helps to prevent the development of atherosclerosis in venous bypass grafts. Clinical studies demonstrated that this leads to an improvement of clinical endpoints. Unfortunately we know from registries, that even in bypass patients recommended guidelines for cholesterol lowering are often not followed.

[Optimization of cholesterol reduction principles and clinical results of dual inhibition]. / Optimierte Cholesterinsenkung. Prinzip und klinische Resultate der dualen Hemmung.

Ezetimibe is a recently developed compound, which inhibits intestinal cholesterol absorption. Because there are hints for an increase of cholesterol absorption during statin therapy, the combination of Ezetimibe with a statin seems to be appropriate. This dual approach -- inhibition of intestinal cholesterol absorption and hepatic cholesterol synthesis -- offers a very potent reduction of cholesterol. The combination of statins with Ezetimibe leads to a further reduction of LDL-cholesterol up to 12-21%. The dual inhibition causes a more effective reduction of LDL-cholesterol than a statin monotherapy. LDL treatment goals can be reached more easily, and possible side effects of otherwise necessary high doses of statins can be avoided. Clinical endpoint studies with Ezetimibe are underway.

Rise of defibrillation energy requirement under carvedilol therapy.

Carvedilol, a nonselective beta 1-, beta 2-adrenoreceptor blocking agent with alpha 1-adrenoreceptor blocking activity, is often prescribed as an adjunctive pharmacological therapy in patients who received an ICD. Despite the new ICD technology, concomitant antiarrhythmic therapy still represents the most important concern in patients with an ICD. As illustrated by this case, carvedilol may also increase the energy requirement for internal defibrillation.

[Prophylaxis of bacterial endocarditis]. / Bakterielle Endokarditisprophylaxe.

An effective prophylaxis against bacterial endocarditis is necessary in patients at risk. In all medical specialities, a lack of information about the importance concerning an antibiotic prophylaxis of bacterial endocarditis remains. Among other institutions the American Heart Association has updated recommendations for the prevention of bacterial endocarditis in order to more clearly define when prophylaxis is or is not recommended, improve practitioner and patient compliance, and reduce cost as well as potential side effects.

[Risk of perioperative mortality and complications following biological aortic valve replacement in elderly patients: stented vs. unstented prostheses]. / Perioperatives Mortalitäts- und Komplikationsrisiko nach biologischem Aortenklappenersatz bei älteren Patienten: ungestentete vs. gestentete Bioprothesen.

Recently published studies suggest that the hemodynamic advantage of stentless bioprostheses in comparison to stented bioprostheses positively influence the long-term survival after aortic valve replacement. However, the more complex and time consuming implantation technique may increase the risk of operative death. Between April 1996 and September 2000, 201 patients with the mean age of 75 +/- 5 years underwent aortic valve replacement (AVR) with a stentless Medtronic Freestyle Bioprosthesis (FP) and 166 patients with a mean age of 77 +/- 5 years received a stented Medtronic Mosaic Bioprosthesis (MP). Patients requiring concomitant procedures other than coronary artery bypass grafting (CABG) were excluded. The operative mortality was 3.5% after AVR with the FP and 6% after AVR with the MP. Multiple logistic regression analysis considering the different patient populations revealed no increased risk of operative death after AVR with FB (p = 0.46). Previously heart operations (p = 0.046) and emergency operation (p = 0.022) were risk factors for operative death after AVR with the biological bioprostheses. The risk for postoperatively neurological impairment (p = 0.15) and other complications (p = 0.46) was furthermore not increased after implantation of a Freestyle stentless valve. The risk of delayed mobilization (p < 0.001) was 2.4-fold increased for patients after AVR with the Freestyle valve. A positive influence on survival due to the implantation of a stentless Freestyle valve could not be shown within the observed period. However, in spite of the more complex and time-consuming operation technique, the risk of operative death and postoperative complications is not increased after aortic valve replacement with the stentless FB.

[Prophylaxis of bacterial endocarditis]. / Bakterielle Endokarditisprophylaxe.

An effective prophylaxis against bacterial endocarditis is necessary in patients at risk. In all medical specialities, a lack of information about the importance concerning an antibiotic prophylaxis of bacterial endocarditis remains. Among other institutions the American Heart Association has updated recommendations for the prevention of bacterial endocarditis in order to more clearly define when prophylaxis is or is not recommended, improve practitioner and patient compliance, and reduce cost as well as potential side effects.

[Risk of perioperative mortality and complications following biological aortic valve replacement in elderly patients: stented vs unstented bioprotheses]. / Perioperatives Mortalitätsund Komplikationsrisiko nach biologischem Aortenklappenersatz bei älteren Patienten: ungestentete vs. gestentete Bioprothesen.

Recently published studies suggest that the hemodynamic advantage of stentless bioprostheses in comparison to stented bioprostheses positively influence the long-term survival after aortic valve replacement. However, the more complex and time consuming implantation technique may increase the risk of operative death. Between April 1996 and September 2000, 201 patients with the mean age of 75 ± 5 years underwent aortic valve replacement (AVR) with a stentless Medtronic Freestyle Bioprothesis (FP) and 166 patients with a mean age of 77 ± 5 years received a stented Medtronic Mosaic Biopros thesis (MP). Patients requiring concomitant procedures other than coronary artery bypass grafting (CABG) were excluded. The operative mortality was 3.5% after AVR with the FP and 6% after AVR with the MP. Multiple logistic regression analysis considering the different patient populations revealed no increased risk of operative death after AVR with FB (p = 0.46). Previously heart operations (p = 0.046) and emergency operation (p = 0.022) were risk factors for operative death after AVR with the biological bioprostheses. The risk for postoperatively neurological impairment (p = 0.15) and other complications (p = 0.46) was furthermore not increased after implantation of a Freestyle stentless valve. The risk of delayed mobilization (p < 0.001) was 2.4-fold increased for patients after AVR with the Freestyle valve. A positive influence on survival due to the implantation of a stentless Freestyle valve could not be shown within the observed period. However, in spite of the more complex and time-consuming operation technique, the risk of operative death and postoperative complications is not increased after aortic valve replacement with the stentless FB.

[New strategies in the treatment of restenosis]. / Neue Strategien zur Behandlung der Restenose.

Twenty-three years after introduction of coronary angioplasty (PTCA), the inhibition of restenosis formation continues to be the major challenge for the interventional cardiologist. About 35-50% of all patients undergoing PTCA develop a renarrowing of the intravascular lumen within the following six months. The use of specific systemic drug therapy as well as different angioplastic methods (rotablation, atherectomy, laser angioplasty) all failed to significantly reduce restenosis. Local drug delivery and local gene therapy have only shown to be effective in animal experiments. Restenosis can be reduced by the use of stents; however restenosis can also develop within the stents. The treatment of choice for severe in-stent restenosis may become radiotherapy, which seems to be a promising tool also for other forms of restenosis.

[New strategies to treat restenosis]. / Neue Strategien zur Behandlung der Restenose.

Twenty-three years after introduction of coronary angioplasty (PTCA), the inhibition of restenosis formation continues to be the major challenge for the interventional cardiologist. About 35-50% of all patients undergoing PTCA develop a renarrowing of the intravascular lumen within the following six months. The use of specific systemic drug therapy as well as different angioplastic methods (rotablation, atherectomy, laser angioplasty) all failed to significantly reduce restenosis. Local drug delivery and local gene therapy have only shown to be effective in animal experiments. Restenosis can be reduced by the use of stents; however restenosis can also develop within the stents. The treatment of choice for severe in-stent restenosis may become radiotherapy, which seems to be a promising tool also for other forms of restenosis.

Attenuated progression of coronary artery disease after 6 years of multifactorial risk intervention: role of physical exercise.

BACKGROUND: It was the aim of this study to assess the long-term effects of physical exercise and low-fat diet on the progression of coronary artery disease. At the beginning of the study, 113 male patients with coronary artery disease were randomized to an intervention group (n=56) or a control group (n=57); 90 patients (80%) could be reevaluated after 6 years. METHODS AND RESULTS: Patients in the intervention group (n=40) showed a reduction in total serum cholesterol (6.03+/-1.03 versus 5.67+/-1.01 mmol/L; P<.03) and triglyceride levels (1.94+/-0.8 versus 1.6+/-0.89 mmol/L; P<.005) and maintained their initial body mass index (26+/-2 versus 27+/-2 kg/m2; P=NS), but results were not statistically different from the control group (n=50) (total serum cholesterol, 6.05+/-1.02 versus 5.79+/-0.88 mmol/L; triglycerides, 2.25+/-1.28 versus 1.85+/-0.96 mmol/L [both P=NS]; body mass index, 26+/-2 versus 28+/-3 kg/m2 [P<.0001]). In the intervention group, there was a significant 28% increase in physical work capacity (166+/-59 versus 212+/-89 W; P<.001), whereas values remained essentially unchanged in the control group (165+/-51 versus 170+/-60 W; P=NS; between groups, P<.05). In the intervention group, coronary stenoses progressed at a significantly slower rate than in the control group (P<.0001). Energy expenditure during exercise was assessed in a subgroup; patients with regression of coronary stenoses spent an average of 1784+/-384 kcal/wk (approximately 4 hours of moderate aerobic exercise per week). Multivariate regression analysis identified only physical work capacity as independently contributing to angiographic changes. CONCLUSIONS: After 6 years of multifactorial risk intervention, there is significant and persistent improvement in lipoprotein levels and physical work capacity, which results in a significant retardation of disease progression. These beneficial effects appear to be largely due to chronic physical exercise.

LDL stimulates chemotaxis of human monocytes through a cyclooxygenase-dependent pathway.

Monocyte migration into the vessel wall is an early step in atherogenesis. Even though a number of chemotactic factors have been identified, the regulation of the chemotactic response is not clearly understood. As the release of arachidonic acid has been implicated in monocyte chemotaxis, we studied the influence of LDL, which can supply this fatty acid to cells, on the chemotactic mobility of monocytes. Migration of human monocytic U937 cells was abolished by a 30-hour incubation in medium containing lipoprotein-depleted 10% fetal calf serum. Thereafter, human VLDL, LDL, acetyl LDL, methyl LDL, HDL, free cholesterol, linoleic acid, oleic acid, or arachidonic acid was added. At the end of varying incubation periods (0.5 to 8 hours), chemotaxis, viability, and cellular cholesterol content were measured. In the same experimental setting we also studied the effects of the pharmacological agents chloroquine, indomethacin, and acetylsalicylic acid on LDL-mediated chemotaxis. Chemotaxis was restored by LDL in a dose- and time-dependent manner starting at concentrations as low as 5 micrograms/mL and at incubations as brief as 30 minutes. The other lipoproteins tested (VLDL, HDL, acetyl LDL, and methyl LDL) as well as free cholesterol had no comparable effect on chemotaxis. Viability and total cholesterol content did not differ among the groups. Simultaneous incubation of cells with chloroquine, indomethacin, and acetylsalicylic acid reduced restitution of chemotaxis by LDL by 71%, 82%, and 68%, respectively. In contrast, the agents had only slight inhibitory effects on the chemotactic mobility of serum-fed control cells. Incubation with linoleic acid showed a 60% restoration of chemotaxis, whereas arachidonic acid stimulated chemotaxis by 140% compared with the positive control. Preincubation of LDL with the monoclonal antibody MB47 directed against LDL resulted in a significantly reduced migratory response. The data suggest a novel cyclooxygenase-dependent regulatory mechanism of chemotaxis by LDL.

Predictive value of lipid profile for salutary coronary angiographic changes in patients on a low-fat diet and physical exercise program.

In this study, 113 patients with modestly elevated levels of low-density lipoprotein cholesterol (<210 mg/dl) and coronary artery disease were randomized to an intervention group (n=56) or a control group (n=57). The intervention program consisted of daily exercise and a low-fat diet according to the American Heart Association's recommendation phase III; patients in the control group received "usual care" rendered by their private physician. After 1 year, complete data were available for all 92 patients (intervention: n=40; control: n=52) who underwent repeat coronary angiography. During the study course, patients in the intervention group showed an increase in apolipoprotein A-I(123 +/- 18 vs 129 +/- 20 mg/dl; p < 0.02) and apolipoprotein A-I/B (1.3 +/- 0.4 vs 1.5 +/- 0.4; p <0.01) and a decrease in apolipoprotein B (99 +/- 20 vs 89 +/- 18 mg/dl; p < 0.01), while apolipoprotein A-II remained unchanged (38 +/- 6 vs 38 +/- 6 mg/dl; p=NS). In the control group, there were no significant changes (apolipoprotein A-I, 124 +/- 17 vs 128 +/- 13 mg/dl; apolipoprotein A-II, 38 +/- 6 vs 39 +/- 6 mg/dl; apolipoprotein B, 100 +/- 21 vs 99 +/- 16 mg/dl; apolipoprotein A-I/B, 1.3 +/- 0.3 vs 1.4 +/- 0.5; all p=NS). As previously reported, there was a significant retardation of progression in patients in the intervention group (progression 23%, no change 45%, regression 32%) compared with the control group (progression 48%, no change 35%, regression 17%) (p < 0.05). Although retardation of progression was significantly associated with an increase in apolipoprotein A-I/B and a decrease in apolipoprotein B (p < 0.05), these gave way in multivariate analysis to changes in total cholesterol/high-density lipoprotein cholesterol, absolute levels of low-density lipoprotein cholesterol, and, in a subgroup of patients, to leisure-time physical activity (all p < 0.05). These data demonstrate that an intervention based on a low-fat diet and intensive physical exercise is capable of improving apolipoprotein levels, associated with retardation of progression of coronary artery disease. However, total cholesterol/high-density lipoprotein cholesterol and low-density lipoprotein cholesterol appear superior to apolipoproteins as metabolic markers for effective treatment in patients with coronary artery disease.

Fibrinogen promotes monocyte adhesion via a protein kinase C dependent mechanism.

The accumulation of blood monocytes at sites of predilection of the vessel wall is an early cellular event of atherogenesis. Proteins of the vessel wall may facilitate monocyte adhesion and thus promote their recruitment. It has been shown that the relative content of extracellular fibrinogen increases during lesion development, and this study investigated the contribution of immobilized fibrinogen to monocyte adhesion and the underlying mechanism. Freshly isolated human blood monocytes were cultivated in serum-free RPMI 1640 in tissue culture wells precoated with albumin, fibrinogen, or fibrin. After 16 h the plates were washed and adherent cells enumerated. Immobilized fibrinogen enhanced monocyte adhesion more than 1.9-fold compared to immobilized albumin or fibrin (P < 0.05). Concomitant addition of the protein kinase C (PKC) inhibitors staurosporine or H7 suppressed monocyte adherence to immobilized fibrinogen but exerted no significant effect upon adhesion to any other surface tested. Stimulation of monocytes using phorbol myristate acetate resulted in increased binding of monocytes on fibrinogen but not on bovine serum albumin. When PKC activity was reduced through prolonged incubation with PMA for 16 h, a significant reduction of monocyte adhesion on fibrinogen was observed. Peptides containing RGD sequences, which have been demonstrated to be ligands for certain integrins, did not inhibit monocyte adhesion. The data suggest that fibrinogen promotes monocyte adhesion in vitro by a PKC-dependent mechanism. PKC appears to be important not only for the initial cell adhesion but also for sustained binding of monocytes to fibrinogen.

Impact of intensive physical exercise and low-fat diet on collateral vessel formation in stable angina pectoris and angiographically confirmed coronary artery disease.

This randomized study was performed to assess the effects of > 3 hours of physical exercise per week and low-fat diet on collateral formation in nonselected patients with coronary artery disease (intervention group, n = 56). Results were compared with those of patients in a control group (n = 57), who received usual care by their private physicians. Coronary lesions were assessed by quantitative coronary angiography at the beginning and after 1 year of study (n = 92). As previously reported, after 1 year there was a significant retardation of progression of coronary artery disease in the intervention group as compared with the control group. In this study, evaluation of collateral formation revealed no significant difference between both groups, and changes in hemodynamic and metabolic variables or leisure time physical activity were not related to changes in collateral formation. Although progression of the disease was significantly related to an increase in collateral formation, regression was significantly related to a decrease in collateral formation (p < 0.00001). Because patients in the intervention group exercised for > 3 hours/week, and patients with regression of coronary artery disease even dedicated 5 to 6 hours to leisure time physical activity per week, these findings question whether an exercise program within the safety tolerance of patients will be able to induce coronary collateralization in the presence of regression of coronary artery disease.

Low-dose radioactive endovascular stents prevent smooth muscle cell proliferation and neointimal hyperplasia in rabbits.

BACKGROUND: Restenosis induced by smooth muscle cell (SMC) migration and proliferation and neointimal thickening limits the clinical success of balloon angioplasty and stent implantation. In this study, the long-term effect of endovascular irradiation via low-dose radioactive stents on neointima formation was compared with conventional stent implantation in a rabbit model. METHODS AND RESULTS: Palmaz-Schatz stents were made radioactive in a cyclotron. The stents had a very low activity (maximum, 35 microCi), and thus, manipulation did not require extensive radiation protection. One, 4, 12, and 52 weeks after the implantation of nonradioactive stents and radioactive stents in rabbit iliac arteries, neointimal thickening was analyzed by quantitative histomorphometry. Immunostaining for endothelial cell von Willebrand factor, macrophages, SMC alpha-actin, collagen type I, and proliferating cell nuclear antigen (PCNA) was performed to determine radiation-induced changes in the arterial wall. SMC proliferation was quantified by computer-assisted cell counting of PCNA-immunoreactive cells. Neointima formation was markedly suppressed by the implantation of radioactive stents in a dose-dependent fashion at all observed time points. At peak proliferative activity of SMCs 1 week after nonradioactive stent implantation, 30 +/- 2% of SMCs in the neointima were proliferating, compared with 0.5 +/- 0.1% of SMCs after implantation of stents with an initial activity of 35 microCi (P < .001). The neointima covering radioactive stents was characterized by decreased smooth muscle cellularity and increased extracellular matrix formation. Further, we observed a delayed endothelialization depending on the radiation dose. No difference in vascular thrombosis was found after nonradioactive and radioactive stent implantation. CONCLUSIONS: The results of this study clearly indicate that low-dose radioactive endovascular stents potently inhibit SMC proliferation and neointimal hyperplasia in rabbits.

Fibrin-targeted recombinant hirudin inhibits fibrin deposition on experimental clots more efficiently than recombinant hirudin.

BACKGROUND: Although the indirect thrombin inhibitor heparin and the more potent direct inhibitor hirudin are useful in preventing thrombosis, a substantial opportunity remains for improving the thrombus selectivity of thrombin inhibitors. METHODS AND RESULTS: To explore the effect of targeting an antithrombin to the surface of a clot, we covalently linked recombinant hirudin to the Fab' (or IgG) of a monoclonal antibody (59D8) that selectively binds to an epitope on fibrin that becomes exposed only after thrombin cleaves fibrinopeptide B. Antibody-coupled hirudin bound to an immobilized peptide of the fibrin beta-chain amino-terminal sequence and inhibited the peptidolytic activity of thrombin more efficiently than free hirudin. Thrombin inhibition dependent on binding to immobilized fibrin monomer was enhanced 1100-fold (P < .0001). Hirudin-59D8 Fab' was 10 times more effective than hirudin in inhibiting fibrin deposition on experimental clot surfaces in fibrinogen solution (P < .0001) and human plasma (P < .0001). The more effective inhibition of thrombin by the conjugate was supported by significantly diminished concentrations of fibrinopeptide A in the plasma supernatant of the clot (P = .0001). Inhibition of clotting by an uncoupled mixture of hirudin and 59D8 Fab' was indistinguishable from that by hirudin alone, indicating that the conjugate's greater inhibitory activity was due to the covalent linkage between antibody and hirudin. CONCLUSIONS: Fibrin-targeted hirudin (in comparison with unmodified hirudin) significantly reduces fibrin deposition on the surface of experimental clots.

Increased messenger RNA levels for low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat liver after long-term ethanol ingestion.

Because long-term alcohol intake leads to severe alterations of cholesterol metabolism resulting in both elevated serum cholesterol levels and increased hepatic concentrations of cholesterol esters, we investigated the effect of long-term ethanol consumption on the hepatic messenger RNA (mRNA) content of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and low-density lipoprotein receptor, two major regulatory factors in cholesterol metabolism, and of apoprotein E. Twenty-four male Sprague-Dawley rats were pair-fed nutritionally adequate liquid diets containing 36% of total calories as either ethanol or isocaloric carbohydrates for 3 wk. In addition, the lipid content of the diets was varied, resulting in 35%, 17.5%, and 8.8% of total calories corresponding to a daily intake of cholesterol of between 1.2 and 6.3 mg/kg body wt. Although increasing dietary cholesterol intake resulted in a significant decrease of hepatic mRNA for low-density lipoprotein receptor and HMG-CoA reductase (p < 0.05), long-term ethanol consumption led to a significant increase of the mRNA for both proteins (p < 0.01), and this increase was predominantly obvious in animals fed a low-cholesterol diet. In contrast, mRNA content of apoprotein E was found to be significantly lower in livers from rats fed ethanol for a prolonged period of time as compared with controls (p < 0.01), and this effect was found to be still present, although less pronounced, after low cholesterol intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of primary hypercholesterolemia: fluvastatin versus bezafibrate.

The effects of fluvastatin and bezafibrate on lipids, lipoproteins, and apoproteins (apo) were investigated in a multicenter randomized, double-blind, parallel-group study. After 8 weeks of strictly controlled (computer-based assessment) dietary stabilization, patients with primary hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] > or = 160 mg/dL; triglycerides < or = 300 mg/dL) were enrolled into a 6-week placebo phase. Altogether, 131 patients were randomized to receive either fluvastatin at 40 mg once daily (n = 64; mean age 53 years) or bezafibrate at 400 mg once daily (n = 67; mean age 52 years) for 12 weeks. Compliance with the diet was monitored (3-day food records) after 6 and 12 weeks. Fluvastatin led to significant reductions in LDL-C (-23%), total cholesterol (-17%), LDL-C/high-density lipoprotein cholesterol (HDL-C) (-24%) and apo B (-19%). Fluvastatin significantly increased LpA-I (+8%) and apo E (+20%). Bezafibrate produced significant reductions in LDL-C (-17%), total cholesterol (-13%), LDL-C/HDL-C (-24%), triglycerides (-28%), apo B (-15%), and LpA-I (-10%) and significantly increased HDL-C (+12%), apo A-I (+9%), apo A-II (+30%), apo E (+14%), and Lp(a) (+3%). No clinically notable increases in levels of liver enzymes or creatine phosphokinase were observed with either treatment. Both treatments were well tolerated. There was a low incidence of adverse events that tended to be mild and included headache, muscular pain, angina, and dyspepsia. The frequency of adverse events was similar in both treatment groups, and no significant differences in dietary behavior were observed. In conclusion, fluvastatin is a well tolerated 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia. Effects of fluvastatin on LpA-I occur irrespective of changes in HDL-C.