[Non-ST-elevation acute coronary syndrome. Comparison of effects of atorvastatin and rosuvastatin on blood levels of lipids and markers of inflammation].

UNLABELLED: Data on rapid effects of statins in patients (pts) with acute coronary syndrome (ACS) are mostly from trials of atorvastatin (ATO). We hypothesized that due to high potency 10 mg of rosuvastatin (ROS) would produce same changes of lipids and inflammation markers as 40 mg ATO. METHODS: We openly randomized 53 pts (69.7+/-10.1 years, 58.5% - man) within 36 h of non ST elevation (NSTE) ACS (56.6% NSTE myocardial infarction) to ROS 10 (n=19), ATO 40 (n=19) mg/day or no statin (n=15). Pts with low density lipoprotein cholesterol (LDL-C) >6, triglycerides (TG) >4.5 mmol/l, C-reactive protein (CRP) >10 mg/l (non-fasting sample) were not included. LDL-C, high density lipoprotein (HDL)-C, TG, apolipoproteins A-1 (apoA), and B (apoB), high sensitivity CRP, tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6) were measured in fasting blood sampled at randomization and 2 weeks later. RESULTS: Both statins caused similar decreases of LDL-C (-44.0% ROS, -50% ATO; both p<0.00001 vs control [-4%]). TG significantly rose in ROS (p=0.042) and control (p=0.008) groups but not in ATO group (p=0.615). HDL-C decreased similarly in 3 groups. ApoA-1 did not differ between 3 groups at all time points. ApoB decreased more in ATO (-32.6%), than in ROS (-24%) group (p=0.049). CRP and IL-6 changes from baseline were insignificant. In ROS group CRP had tendency to decrease but same tendency took place in control. TNFalpha significantly increased in all groups. There were no significant differences between 3 groups in inflammation markers. CONCLUSION: In pts with NSTEACS effect on lipids of ROS 10 mg was somewhat inferior to ATO 40 mg/day. Unexpectedly ATO and ROS during first 14 days of NSTEACS produced no significant effect on inflammation markers possibly because of insufficient dose of both.

[Rosuvastatin and fenofibrate in patients with diabetes and low high density lipoprotein cholesterol: comparison of changes of lipid levels and some markers of inflammation].

PURPOSE: To compare lipid lowering profile and effects on markers of inflammation of rosuvastatin and fenofibrate in patients with type 2 diabetes with low high density lipoprotein (HDL) cholesterol (CH). METHODS: We enrolled into randomized open comparative study 30 pts (20 women) aged 62.5 +/- 7.2 (47-74) years with type 2 diabetes and low HDLCH level (below 1.0 mmol/l for men and 1.2 mmol/l for women). All patients had arterial hypertension, 25--coronary heart disease, 4--peripheral arterial disease. Baseline BMI was > 25 kg/m2 in all patients (above 30 kg/m2 in 70%). Median waist circumference was 105.5 cm. Patients were assigned to receive either rosuvastatin 10 mg/day (n=17) or fenobibrate 200 mg/day (n=13). Serum lipids, high sensitivity C reactive protein (CPR), interleukin 6 (IL-6) and fibrinogen levels were measured at baseline and after 3 months. RESULTS: Median fasting glucose and HbA1c were 9.14 mmol/l and 6.8%, 8.78 mmol/l and 7.0% at baseline and study end respectively, without significant differences between groups. Mean baseline levels of low density lipoprotein (LDL) CH, HDLCH and triglycerides (TG) were 3.9, 0.93, and 2.39 mmol/l, respectively. Median baseline CRP was relatively low (1.5, interquartile range 0.78-3.08 mg/l). Both rosuvastatin and fenofibrate decreased total CH, LDLCH and TG and increased HDLCH. Tendencies to more pronounced effect of rosuvastatin on total and LDL CH and fenofibrate on TG and HDLCH were not statistically significant. CPR, IL-6, and fibrinogen levels did not significantly change in either group. There were no associations between changes of lipid levels and those of CRP or IL-6 when all patients were taken together. CONCLUSION: In this relatively small group of overweight diabetics with low HDLCH rosuvastatin and fenofibrate exerted expected effects on lipid profile. However 3 months administration of both starting dose of rosuvastatin (10 mg) and standard dose of fenofibrate was similarly neutral relative to CPR, IL-6 and fibrinogen levels. This can reflect true absence of marked effect or be a consequence of low baseline values of these markers of inflammation.

Use of lipid-modulating drugs in complicated course of coronary heart disease.

We present the results of the study of lipid-modulating drugs (pravastatin, atorvastatin, simvastatin, and fibrate gemfibrozil) in complicated coronary heart disease (acute coronary syndrome without ST elevation, chronic heart failure. In acute coronary syndrome statins produced a positive effect on some studied parameters, while in heart failure only the safety of short-term therapy with statins was demonstrated.

[Early use of gemfibrozil in patients with non ST Elevation acute coronary syndrome. Changes of markers of inflammation and von Willebrand factor].

UNLABELLED: It is not known whether PPAR-alpha agonist gemfibrozil is able to exert rapidly its lipid modulating, potential antiinflammatory and antithrombotic effects in patients with non-ST elevation acute coronary syndrome (NSTEACS), as some other lipid lowering drugs e.g. statins do. METHODS: We randomized 44 patients with NSTEACS to open gemfibrozil (n=22, 600 mg b.i.d for 90 days) or no gemfibrozil (controls, n=22) within 24 hours after pain onset. Semiquantitative C-reactive protein (CRP) latex test was used at baseline for exclusion of patients with overt inflammation. All patients received dalteparin or enoxaparin for >48 hours and oral aspirin (125 mg/day) and were treated noninvasively. Lipids, high sensitive CRP, soluble CD40 ligand (CD40L) and von Willebrand factor (vWF) activity were assessed on days 1 (baseline), 4, 7, 14, 30 and (except CD40L) 90. RESULTS: Gemfibrozil use was associated with significant lowering of triglycerides by day 30, however it did not prevent acute significant decline of high density lipoprotein cholesterol (HDL-C), which was similar in both groups. CD40L level significantly increased while CRP levels decreased by day 30 in both groups. Moreover, selection of a subgroup with baseline HDL-C <1.0 mmol/l did not reveal any difference in changes of CRP or CD40L between gemfibrosil treated and control patients. vWF activity did not change in controls and significantly increased in gemfibrozil group by days 7, 14, but from lower baseline level. CONCLUSION: In patients with NSTEACS early administration of gemfibrozil was not associated with positive changes of CRP and CD40L levels or vWF activity compared with control group.

[Short term simvastatin use in patients with heart failure of ischemic origin. Changes of blood lipids, markers of inflammation and left ventricular function].

AIM: To study changes of left ventricular function and some markers of inflammation during use of simvastatin in patients with ischemic systolic heart failure. METHODS: Statin naive patients (n=70) with coronary heart disease (CHD), NYHA class II-IV HF and LV ejection fraction (EF) 35% or less after 1 month of stabilization were randomized to simvastatin 40 mg/day (n=36) or no statin (n=34). Lipids, tumor necrosis factor alpha (TNF), and C-reactive protein (CRP) were measured and echocardiography carried out at baseline and in 4 months. In patients with sinus rhythm (n=48) left ventricular diastolic function was assessed by Doppler echo. Seven patients were not restudied and analysis included data from 32 (statin) and 31 (control) patients. RESULTS: Groups were similar except baseline CRP which was significantly higher in controls. In statin treated patients reduction of low density lipoprotein (LDL) cholesterol (CH) was 42%, triglyceride levels also significantly decreased. High density lipoprotein CH rose by 14.4 and 12.9% in statin and control groups, respectively. Despite lower initial level decrease of CRP was significant only in statin group. No significant changes of TNF occurred in either group. Left ventricular EF rose equally in statin treated (+5.7+/-4.7%) and untreated (+4.1+/-4.6%) patients (p=ns). Significant increase of peak atrial filling velocity (A) and decrease of E/A in statin group were difficult to interpret in the presence of systolic dysfunction. CONCLUSION: Short term simvastatin use in patients with systolic heart failure due to CHD caused lowering of LDLCH and CRP however this was not associated with changes of left ventricular EF different from those in control group.

[Short Term Simvastatin Use in Patients With Systolic Heart Failure of Ischemic Origin Did Not Preclude Elevation of N-Terminal pro-Brain Natriuretic Peptide Level.].

Effect of statins on N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with heart failure has not been well elucidated. Purpose. To assess changes of NT-proBNP during short term use of simvastatin in patients with coronary heart disease (CHD) and chronic systolic heart failure. Patients and methods. Statin naive patients (n=70) with coronary heart disease (CHD), NYHA class II-IV hart failure and LV ejection fraction (EF) 35% or less after correction of treatment and 1 month of stabilization on standard therapy were randomized to open simvastatin 40 mg/day (n=36) or no statin (n=34). In 65.1% of pts (65.6 and 64.5% in statin and control groups, respectively) beta-blockers were either initiated or their dose was corrected during <> phase of the study. Blood plasma lipids, NT-proBNP were measured and echocardiography carried out at randomization and in 4 months. Seven patients were not restudied and analysis included data from 32 (statin) and 31 (control) patients. Results. Baseline characteristics of groups were similar. Addition of statin to standard therapy was associated with lowering of low density lipoprotein cholesterol (-42%) and triglycerides (-14%). Changes of other parameters were similar in both groups including equal increases of NT-proBNP (from 540.9 to 1082.2 fmol/ml, p<0.0001, and from 639.6 to 1119.72 fmol/ml, p<0.0001, in control and simvastatin group, respectively). Baseline NT-proBNP correlated negatively with ejection fraction and positively with left ventricular dimensions, heart failure class and blood serum creatinine. The patients were followed for 1 year. Baseline NT-proBNP level was related to hospitalizations because of heart failure exacerbation during this year. Conclusion. In a group of patients with systolic heart failure due to CHD and trivial relationships between baseline NT-proBNP level and characteristics of heart failure severity short term simvastatin use caused expected LDLCH lowering but was associated with NT-proBNP increase equal to that observed in control group. Rise of NT-proBNP in both groups was probably related to activation of beta-blocker therapy.

[Relationship Between Lipid Lowering and Changes of Hemostasis and Inflammation During Use of Statins in Non-ST Elevation Acute Coronary Syndrome]. / Sviaz' izmenenii urovnei lipidov i markerov vospaleniia i gemostaza, proizoshedshikh vo vremia priema statinov, u bol'nykh s ostrym koronarnym sindromom bez pod"ema segmenta ST na EKG.

AIM: To analyze relationship between changes of lipid levels and parameters of hemostasis and inflammation in a previously reported comparative study of some biological effects of pravastatin and atorvastatin in patients with non ST elevation acute coronary syndrome (NSTEACS). METHODS: Ninety aspirin and heparin treated patients with NSTEACS were randomized to open pravastatin 40 mg/day (n=31) and atorvastatin 10 (n=30) or 40 mg/day (n=29). At baseline, on days 7 and 14 we measured levels of thrombin-antithrombin complex (TAT), prothrombin fragments 1+2 (F1+2), D-dimer, von Willebrand factor (vWF) and C-reactive protein (CRP) and assessed platelet aggregation. Spearman correlation coefficients were calculated for mean deltas of all parameters {[(baseline - day 7) + (baseline - day 14)]/2} for all patients. The patients were divided into quartiles according to absolute LDL CH lowering by day 14. RESULTS: Levels of LDL and total CH significantly decreased in all groups (atorvastatin 40 mg/day >> atorvastatin 10 mg/day > pravastatin). Contrary to pravastatin the use of atorvastatin was associated with increases of F 1+2, TAT, and decrease of vWF. Platelet aggregation decreased only in atorvastatin 40 mg/day group (p<0.05) and CRP decreased in combined atorvastatin group (p<0.05). Most pronounced relationship existed between changes of lipid levels and vWF. Lowering of total and LDL CH correlated positively with decreases of vWF (r=0.25, p=0.018, and r=0.23, p=0.032, respectively) and quartile analysis showed that vWF decreased only in patients with marked LDL CH lowering (quartiles 3, 4). Negative correlation was found between changes of total CH and those of TAT (r=-0.22, p=0.039), and between changes of CRP and HDL CH (r=-0.24, p=0.03). TAT and F 1+2 levels significantly increased in those patients in whom LDL CH level <2.5 mmol/l was achieved by day 14 and tended to decrease in other patients. No relationship was found between changes of lipids and platelet aggregation. CONCLUSION: Rapid (in 14 days) changes of some parameters of hemostasis occurring during treatment of patients with NSTEACS with various statins were related to degree of lipid lowering possibly irrespective of a statin used. Most evident was relationship between changes of lipids and von Willebrand factor.

[Markers of inflammation and platelet aggregation in patients with non ST elevation acute coronary syndrome treated with atorvastatin or pravastatin]. / Ostryi koronarnyi sindrom bez pod"emov segmenta ST na EKG: agregatsiia trombotsitov i markery vospaleniia pri rannem primenenii atorvastatina i pravastatina.

AIM: To find out whether early use of atorvastatin and pravastatin in patients with non-ST elevation acute coronary syndrome is associated with rapid changes of platelet aggregation and plasma levels of markers of inflammation. MATERIAL AND METHODS: Ninety patients (<24h from pain onset, age 64+/-10 years) treated with aspirin and heparin were randomized to open atorvastatin 10 mg/day (n=30), atorvastatin 40 mg/day (n=29) or pravastatin 40 mg/day (n=31). Spontaneous and ADP induced platelet aggregation (light transmission), plasma levels of interleukin 6 (IL-6) and C-reactive protein (CRP) (immunoassay) were assessed at baseline, on days 7 and 14. RESULTS: Baseline clinical characteristics, platelet aggregation parameters, CRP and IL-6 levels were similar in all groups. In all groups levels of total and low-density lipoprotein (LDL) cholesterol (CH) were lowered by days 7 (p<0.01) and 14 (p<0.01 vs. baseline and for both atorvastatin groups vs. day 7). Spontaneous platelet aggregation decreased by 15% from baseline, p<0.01, on day 14 in patients receiving atorvastatin 40 and was unchanged in other groups. Changes of ADP induced platelet aggregation, IL-6 and CRP levels were not significant in all groups. However combination of 2 atorvastatin groups (n=59) revealed decrease of CRP by 18% from baseline on day 14 (from 6.94+/-0.97 to 4.76+/-0.76 mg/l, p=0.028). No correlations were found between changes of LDL CH and those of other parameters. CONCLUSION: In otherwise conventionally treated patients with non-ST elevation acute coronary syndrome early use of atorvastatin was associated with rapid (in 14 days) decrease of CRP level. Higher dose of atorvastatin (40 mg/day) induced favorable changes of spontaneous platelet aggregation. There were no significant changes of parameters studied in pravastatin treated patients.

[Non ST elevation acute coronary syndrome: early use of pravastatin or atorvastatin is associated with divergent changes of parameters of hemostasis]. / Ostryi koronarnyi sindrom bez pod"emov segmenta ST na EKG: raznonapravlennye izmeneniia pokazatelei gemostaza pri rannem primenenii atorvastatina i pravastatina.

PURPOSE: To find out whether pravastatin and atorvastatin rapidly (in 1-2 weeks) and similarly affect hemostasis in patients with non-ST elevation acute coronary syndrome (NSTEACS). METHODS: Ninety aspirin and heparin treated patients with NSTEACS were randomized <24 hours from pain onset to open pravastatin 40 mg/day (n=31), atorvastatin 10 mg/day (n=30) or atorvastatin 40 mg/day (n=29). At baseline, on days 7, 14 plasma thrombin-antithrombin complex (TAT), prothrombin fragments 1+2 (F1+2), D-dimer, von Willebrand factor (vWF) were measured by ELISA. Results were compared with data from controls (n=18) of another randomized study on similarly treated patients. RESULTS: In all treatment groups levels of low-density lipoprotein cholesterol (LDLCH) were lowered by days 7 (p<0,01) and 14 (p<0,01 vs. baseline and for both atorvastatin groups vs. day 7). In pravastatin group levels of TAT and F1+2 decreased, while vWF level increased. In atorvastatin groups levels of TAT and F 1+2 increased while level of vWF decreased. Contrary to pravastatin group changes in atorvastatin treated patients more resembled those in controls not receiving lipid lowering drugs. Changes of both LDLCH and TCH directly correlated only with changes of vWF (r=0.23, p=0.03 and r=0.25, p=0.02, respectively). No consistent changes of D-dimer occurred. CONCLUSION: Early use of atorvastatin and pravastatin in patients with NSTEACS was associated with rapid divergent changes of some hemostatic parameters. Except lowering of von Willebrand factor changes in atorvastatin treated patients more resembled those in controls not receiving lipid lowering drugs. Von Willebrand factor was the only parameter which changes weakly but significantly correlated with changes of CH and LDL CH levels.