-
1.
Phase 2 trial comparing sorafenib, pravastatin, their combination or supportive care in HCC with Child-Pugh B cirrhosis.
Blanc, JF, Khemissa, F, Bronowicki, JP, Monterymard, C, Perarnau, JM, Bourgeois, V, Obled, S, Abdelghani, MB, Mabile-Archambeaud, I, Faroux, R, et al
Hepatology international. 2021;(1):93-104
Abstract
BACKGROUND AND AIMS There is limited data regarding the role for systemic treatment in patients with Hepatocellular Carcinoma with Child-Pugh B cirrhosis. METHODS PRODIGE 21 was a multicentric prospective non-comparative randomized trial. Patients were randomized to receive sorafenib (Arm A), pravastatin (Arm B), sorafenib-pravastatin (Arm C) combination, or best supportive care (Arm D). Primary endpoint was time to progression (TTP), secondary endpoints included safety and overall survival (OS). RESULTS 160 patients were randomized and 157 patients were included in the final analysis. 86% of patients were BCLC C and 55% had macrovascular invasion. The safety profiles of the drugs were as expected. Median TTP was 3.5, 2.8, 2.0 and 2.2 months in arms A, B, C and D, respectively, but analysis was limited by the number of patients deceased without radiological progression (59%). Median OS was similar between the four arms: 3.8 [95% CI: 2.4-6.5], 3.1 [95% CI: 1.9-4.3], 4.0 [95% CI: 3.2-5.5] and 3.5 months [95% CI: 2.2-5.4] in arms A, B, C and D, respectively. Median OS was 4.0 months [95% CI: 3.3-5.5] for patients treated with sorafenib, vs 2.9 months [95% CI: 2.2-3.9] for patients not treated with sorafenib. In patients with ALBI grade 1/2, median OS was 6.1 months [95% CI: 3.8-8.3] in patients treated with sorafenib vs 3.1 months [95% CI: 1.9-4.8] for patients not treated with sorafenib. CONCLUSION In the overall Child-Pugh B population, neither sorafenib nor pravastatin seemed to provide benefit. In the ALBI grade 1/2 sub-population, our trial suggests potential benefit of sorafenib. CLINICAL TRIAL REGISTRATION The study was referenced in clinicaltrials.gov (NCT01357486).
-
2.
Difference in statin effects on neointimal coverage after implantation of drug-eluting stents.
Yamamoto, H, Ikuta, S, Kobuke, K, Yasuda, M, Ikeda, T, Yamaji, K, Ueno, M, Iwanaga, Y, Miyazaki, S
Coronary artery disease. 2014;(4):290-5
Abstract
OBJECTIVE This study was carried out to examine the difference in effects between rosuvastatin and pravastatin on neointimal formation after the placement of a drug-eluting stent (DES). MATERIALS AND METHODS Forty patients who underwent placement of a DES in our hospital were prospectively randomized to receive rosuvastatin (n=20) or pravastatin (n=20), and analyzed by optical coherence tomography at the chronic stage. The main outcome measure was comparison of neointimal coverage analyzed at a strut level. RESULTS A significant reduction in total cholesterol, low-density lipoprotein, and white blood cell count was observed during the study in the rosuvastatin group (total cholesterol, from 4.82±0.90 to 4.43±0.77 mmol/l, P=0.038; low-density lipoprotein, from 2.85±0.76 to 2.34±0.57 mmol/l, P=0.006; white blood cell count, from 5810±1399 to 5355±1257/µl, P=0.048), but not in the pravastatin group. Although not statistically significant, C-reactive protein was lower in the rosuvastatin than in the pravastatin group at the chronic stage (1.14±1.21 vs. 7.67±13.67 mg/l, P=0.051). Malapposed and uncovered struts were significantly less frequent in the rosuvastatin group than in the pravastatin group (malapposed, 0.06 vs. 0.60%, P<0.001; uncovered, 6.49 vs. 11.29%, P<0.001). The difference in uncovered struts was maintained even when stent types were analyzed separately (everolimus-eluting stent, 4.81 vs. 6.21%, P=0.007; sirolimus-eluting stent, 14.40 vs. 20.86%, P<0.001). Comparison of neointimal thickness between the rosuvastatin and the pravastatin groups showed inconsistent results depending on the stent types analyzed. CONCLUSION Compared with pravastatin, the use of rosuvastatin resulted in lower frequency of uncovered and malapposed struts after the placement of a DES, which might be mediated through improved inflammatory and lipid profiles.
-
3.
Pravastatin and cardiovascular outcomes stratified by baseline eGFR in the lipid- lowering component of ALLHAT.
Rahman, M, Baimbridge, C, Davis, BR, Barzilay, JI, Basile, JN, Henriquez, MA, Huml, A, Kopyt, N, Louis, GT, Pressel, SL, et al
Clinical nephrology. 2013;(4):235-48
-
-
Free full text
-
Abstract
BACKGROUND/AIMS: The role of statins in preventing cardiovascular outcomes in patients with chronic kidney disease (CKD) is unclear. This paper compares cardiovascular outcomes with pravastatin vs. usual care, stratified by baseline estimated glomerular filtration rate (eGFR). METHODS Post-hoc analyses of a prospective randomized open-label clinical trial; 10,151 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) were randomized to pravastatin 40 mg/day or usual care. Mean follow-up was 4.8 years. RESULTS Through Year 6, total cholesterol declined in pravastatin (-20.7%) and usualcare groups (-11.2%). Use of statin therapy in the pravastatin group was 89.8% (Year 2) and 87.0% (Year 6). Usual-care group statin use increased from 8.2% (Year 2) to 23.5% (Year 6). By primary intention-to-treat analyses, no significant differences were seen between groups for coronary heart disease (CHD), total mortality or combined cardiovascular disease; findings were consistent across eGFR strata. In exploratory "as-treated" analyses (patients actually using pravastatin vs. not using), pravastatin therapy was associated with lower mortality (HR = 0.76 (0.68 - 0.85), p<0.001) and lover CHD (HR=0.84 (0.73-0.97), p=0.01), but not combined cardiovascular disease (HR=0.95 (0.88-1.04), p=0.30). Total cholesterol reduction of 10 mg/dl from baseline to Year 2 was associated with 5% lower CHD risk. CONCLUSIONS In hypertensive patients with moderate dyslipidemia, pravastatin was not superior to usual care in preventing total mortality or CHD independent of baseline eGFR level. However, exploratory "as-treated" analyses suggest improved mortality and CHD risk in participants using pravastatin, and decreased CHD events associated with achieved reduction in total cholesterol. Potential benefit from statin therapy may depend on degree of reduction achieved in total and LDL-cholesterol and adherence to therapy.
-
4.
Risk reductions for cardiovascular disease with pravastatin treatment by dyslipidemia phenotype: a post hoc analysis of the MEGA Study.
Nishiwaki, M, Ikewaki, K, Ayaori, M, Mizuno, K, Ohashi, Y, Ohsuzu, F, Ishikawa, T, Nakamura, H, ,
Journal of cardiology. 2013;(3):196-200
Abstract
BACKGROUND The beneficial effect of statins for cardiovascular disease (CVD) prevention has been well established. However, the effectiveness among different phenotypes of dyslipidemia has not been confirmed. OBJECTIVE We evaluated the effect of pravastatin on the incidence of CVD in relation to the phenotype of dyslipidemia. METHODS The MEGA Study evaluated the effect of low-dose pravastatin on primary prevention of CVD in 7832 Japanese patients, who were randomized to diet alone or diet plus pravastatin and followed for more than 5 years. These patients were classified into phenotype IIa (n=5589) and IIb (n=2041) based on the electrophoretic pattern for this post hoc analysis. RESULTS In the diet group there was no significant difference in the incidence of coronary heart disease (CHD), stroke, CVD, and total mortality between the two phenotypes. Phenotype IIb patients, compared to phenotype IIa, had lower levels of high-density lipoprotein cholesterol (HDL-C) and a significantly higher incidence of CVD in relation to a low HDL-C level (<47.5mg/dL; p=0.02). Furthermore, pravastatin decreased the relative risk for each major endpoint in both type IIa and type IIb dyslipidemia. Significant risk reductions were observed for CHD by 38% (p=0.04) and CVD by 31% (p=0.02) in type IIa dyslipidemia but not in phenotype IIb. CONCLUSION Pravastatin therapy provided significant risk reductions for CHD and CVD in patients with phenotype IIa dyslipidemia, but not in those with phenotype IIb dyslipidemia.
-
5.
Comparison of effects of pitavastatin versus pravastatin on serum proprotein convertase subtilisin/kexin type 9 levels in statin-naive patients with coronary artery disease.
Nozue, T, Hattori, H, Ishihara, M, Iwasaki, T, Hirano, T, Kawashiri, MA, Yamagishi, M, Michishita, I
The American journal of cardiology. 2013;(10):1415-9
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of serum low-density lipoprotein cholesterol levels. Although statins increase serum PCSK9 levels, the effects of different types of statins on the serum PCSK9 levels have not been examined in detail. The purpose of the present study was to compare the effects of pitavastatin versus pravastatin on the serum PCSK9 levels. A total of 164 patients with coronary artery disease who were not receiving lipid-lowering therapy were randomly assigned to receive either 4 mg/day of pitavastatin (intensive lipid-lowering therapy) or 20 mg/day of pravastatin (moderate lipid-lowering therapy). The serum PCSK9 levels were measured before statin treatment and 8 months after therapy. A significantly greater reduction in low-density lipoprotein cholesterol was observed in the pitavastatin group (-41% vs -28%, p = 0.0001). The serum levels of total PCSK9 and heterodimer PCSK9 significantly increased from 192 to 249 ng/ml (37%, p <0.0001) and 147 to 206 ng/ml (78%, p <0.0001) in the pitavastatin group and from 192 to 249 ng/ml (39%, p <0.0001) and 143 to 201 ng/ml (65%, p <0.0001) in the pravastatin group, respectively. The increase in total and heterodimer PSCK9 did not differ between the 2 groups. No significant correlations were found between the percentage of changes in heterodimer PCSK9 and changes in the various lipid parameters in either group. In conclusion, significant increases in the total and heterodimer PSCK9 levels were observed at 8 months after treatment with pitavastatin and pravastatin; however, these increases did not differ between the 2 statins.
-
6.
Comparative efficacy and safety of fenofibrate/pravastatin plus ezetimibe triple therapy and simvastatin/ezetimibe dual therapy in type 2 diabetic patients with mixed hyperlipidaemia and cardiovascular disease.
Farnier, M, Retterstøl, K, Steinmetz, A, Császár, A
Diabetes & vascular disease research. 2012;(3):205-15
Abstract
BACKGROUND This study was designed to compare the efficacy and safety of a fenofibrate/pravastatin 160/40 mg fixed-dose combination plus ezetimibe 10 mg triple therapy and simvastatin 20 mg plus ezetimibe 10 mg dual therapy in patients with type 2 diabetes, mixed hyperlipidaemia and cardiovascular disease. METHOD After a 6-week run-in period on simvastatin 20 mg, 273 patients with non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 100 mg/dl or low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dl were randomised to receive 12-week treatment with triple therapy or dual therapy, followed by a 12-week safety period during which all patients received the triple therapy. RESULTS At week 12, similar significant decreases in non-HDL-C were observed with both treatments. The triple therapy has induced a greater decrease in triglycerides (between-treatment difference: -14.6%, p = 0.007) and the dual therapy a greater decrease in LDL-C (between-treatment difference: +5.3%, p = 0.05). Both treatments were generally well tolerated. CONCLUSION The fenofibrate/pravastatin plus ezetimibe therapy improves the global atherogenic lipid profile in type 2 diabetic patients with mixed hyperlipidaemia.
-
7.
Effects of rosuvastatin versus pravastatin on low-density lipoprotein diameter in HIV-1-infected patients receiving ritonavir-boosted protease inhibitor.
Bittar, R, Giral, P, Aslangul, E, Assoumou, L, Valantin, MA, Kalmykova, O, Federspiel, MC, Cherfils, C, Costagliola, D, Bonnefont-Rousselot, D, et al
AIDS (London, England). 2012;(14):1801-5
Abstract
OBJECTIVE HIV infection is associated with an atherogenic lipoprotein profile, and ritonavir-boosted protease inhibitors exacerbate this phenotype. We evaluated the effect of 45 days of rosuvastatin versus pravastatin on the low-density lipoprotein (LDL) size and the distribution of LDL subfractions in HIV-1 patients receiving boosted protease inhibitors with elevated LDL levels. DESIGN Substudy of the randomized double-blind multicentre ANRS 126 VIHstatine trial. SETTING Twenty clinical centres in France. PATIENTS HIV-infected patients receiving boosted protease inhibitors with dyslipidaemia (LDL cholesterol > 4.1 mmol/l and triglycerides < 8.8 mmol/l). INTERVENTION Rosuvastatin 10 mg/day (n = 39) or pravastatin 40 mg/day (n = 37) for 45 days. MAIN OUTCOME MEASURE(S): LDL size and distribution of LDL subfractions blindly assessed by gradient gel electrophoresis at baseline and at day 45. RESULTS Rosuvastatin was more effective than pravastatin in increasing the diameter of the LDL peak. The LDL diameter change was 0.33 ± 0.59 nm in the rosuvastatin group versus -0.01 ± 0.52 nm in the pravastatin group (P = 0.021). Rosuvastatin was also more effective in increasing significantly the percentage of large LDL (LDL1, P = 0.038; LDL2, P = 0.031) and in decreasing the percentage of small LDL (LDL3, P = 0.009). CONCLUSION Rosuvastatin was more effective than pravastatin in normalizing LDL size and LDL subfraction distributions, leading to a less atherogenic phenotype.
-
8.
Effect of dalcetrapib plus pravastatin on lipoprotein metabolism and high-density lipoprotein composition and function in dyslipidemic patients: results of a phase IIb dose-ranging study.
Ballantyne, CM, Miller, M, Niesor, EJ, Burgess, T, Kallend, D, Stein, EA
American heart journal. 2012;(3):515-21, 521.e1-3
Abstract
BACKGROUND Cholesteryl ester transfer protein (CETP) is involved in high-density lipoprotein (HDL) remodeling and transfer of lipids between HDL particles and other lipoproteins. Epidemiologic studies show that both elevated HDL-cholesterol (HDL-C) and reduced CETP activity attenuate cardiovascular risk, making inhibition or modulation of CETP a potential therapeutic target. This study analyzed the effect of dalcetrapib on lipoprotein profile, CETP activity, and cellular cholesterol efflux when co-administered with pravastatin in patients with low or average HDL-C. METHODS Patients were randomized in a double-blind fashion to receive placebo or dalcetrapib 300, 600, or 900 mg once daily for 12 weeks. All patients were concomitantly treated to their low-density lipoprotein cholesterol target with pravastatin. Lipoprotein profile was analyzed by nuclear magnetic resonance spectroscopy and polyacrylamide gradient gel electrophoresis. Composition of the HDL fraction was assessed after polyethylene glycol precipitation. Contribution of this fraction to cholesterol efflux was assessed using radiolabeled donor cells. RESULTS Co-administration of dalcetrapib with pravastatin increased HDL-C, apolipoproteins (apo) A-I and A-II, and CETP mass, and decreased CETP activity. A relative increase in large HDL and low-density lipoprotein subparticle fractions was observed. High-density lipoprotein composition showed increased association of esterified cholesterol, free cholesterol, phospholipids, apo A-I, and apo E. Adenosine 5'-triphosphate-binding cassette A1- and scavenger receptor type BI-mediated cholesterol efflux increased. CONCLUSIONS Dalcetrapib up to 600 mg, combined with pravastatin, increased HDL-C and altered lipoprotein profile, HDL composition, and HDL function, with little further change at a 900-mg dose. The impact on cardiovascular events in dyslipidemic patients is being evaluated.
-
9.
Comparative study of bezafibrate and pravastatin in patients with coronary artery disease and high levels of remnant lipoprotein.
Sano, K, Nakamura, T, Hirano, M, Kitta, Y, Kobayashi, T, Fujioka, D, Saito, Y, Yano, T, Watanabe, K, Watanabe, Y, et al
Circulation journal : official journal of the Japanese Circulation Society. 2010;(8):1644-50
Abstract
BACKGROUND Remnant lipoproteinemia is a strong risk factor for cardiovascular (CV) diseases. This study examined which of 2 common lipid-lowering drugs (fibrates and statins) is more effective in patients with remnant lipoproteinemia and if lowering remnant lipoprotein levels can reduce CV risk. METHODS AND RESULTS Remnant lipoprotein levels were measured by an immunoseparation method (remnant-like lipoprotein particles cholesterol: RLP-C) in 274 patients with coronary artery disease and high RLP-C levels (>or=5.0 mg/dl). They were randomly assigned to receive bezafibrate (200-400 mg/day) or pravastatin (10-20 mg/day), and were prospectively followed-up for 1 year or until the occurrence of CV events. Complete follow-up data were obtained in 180 patients. RLP-C levels at 1 year of treatment were reduced more by bezafibrate than pravastatin (37% and 25% from baseline, respectively). During follow-up, bezafibrate-treated patients had 3 CV events, compared with 12 events in pravastatin-treated patients (P<0.01). In multivariate logistic regression analysis, a decrease in RLP-C level was significantly associated with a reduction in CV events after adjustment for treatment group and changes in levels of other lipids. CONCLUSIONS Bezafibrate therapy decreased RLP-C levels to a greater extent than pravastatin and a decrease in RLP-C level may be associated with a reduction in CV events in patients with high RLP-C levels.
-
10.
Can intensive lipid-lowering therapy with statins ameliorate atherosclerosis in Japanese patients? Rationale and design of the JART study.
Kurabayashi, M, Sakuma, I, Kawamori, R, Daida, H, Yamazaki, T, Yoshida, M, Hata, M, Masuda, I, Kaku, K, Yokoi, H, et al
Journal of atherosclerosis and thrombosis. 2010;(4):416-22
Abstract
AIM: In Japan, heart disease and cerebral ischemic disease are major causes of death. A decrease in the level of low-density lipoprotein cholesterol (LDL-C) through intensive treatment with statins positively correlates with a reduction in the volume of plaques in patients with cardiovascular disease. The METEOR trial, evaluating the effect of rosuvastatin on carotid intima-media thickness (IMT), was conducted only in Europe and the US. Here we planned another trial, the Justification for Atherosclerosis Regression Treatment (JART) study, to clarify the efficacy of intensive lipid-lowering therapy with rosuvastatin in Japanese with atherosclerosis. METHODS AND RESULTS Four hundred patients with hypercholesterolemia (LDL-C >or=140 mg/dL) and a maximum IMT of >or=1.1 mm will be treated for 24 months either with intensive lipid-lowering therapy with rosuvastatin (target LDL-C levels: 80 mg/dL for primary prevention, and 70 mg/dL for secondary prevention) or conventional lipid-lowering therapy with pravastatin (target LDL-C level: complying with JASGL2007). The primary endpoint will be the percent change of mean-IMT and the objectives of the study are to compare the two protocols. CONCLUSION The JART trial is a prospective, randomized, open-label, blinded end-point evaluation, multi-center, parallel-group, comparative study to examine the regressive effect of intensive lipid-lowering therapy with statins on atherosclerosis by evaluating IMT in the Japanese population.