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Journal of Cardiovascular Pharmacology... 2011Contrast-induced nephropathy (CIN) is associated with long-term morbidity, mortality, and increased health care costs. It has been suggested that statins have... (Review)
Review
Contrast-induced nephropathy (CIN) is associated with long-term morbidity, mortality, and increased health care costs. It has been suggested that statins have pleiotropic effects countering inflammatory and oxidative stress involved in CIN. Several studies support this theory; however, previously published studies have not evaluated the potential differences between statins in reducing the incidence of CIN. The purpose of this retrospective, single-center trial was to compare the incidence of CIN in patients receiving simvastatin or pravastatin therapy undergoing percutaneous coronary intervention (PCI). A total of 261 patients were included (145 received simvastatin and 116 received pravastatin) with the majority undergoing elective PCI. The population was predominantly male (65%), Hispanic (65%), and diabetic (62%), with a mean age of 59 years and a low-density lipoprotein (LDL) of 85 mg/dL. No significant differences were found between groups for risk factors or prophylactic strategies (eg, hydration). Contrast-induced nephropathy occurred in 26 patients (17.9%) in the simvastatin group versus 10 (8.6%) in the pravastatin group (P < .05). No patients required dialysis as a result of contrast administration. Acute kidney injury (AKI) occurred in 21 patients (14.5%) in the simvastatin group compared to 8 (6.9%) in the pravastatin group (P < .05). In multivariate analysis, the difference between statins remained an independent predictor for the development of CIN. In conclusion, patients on pravastatin had a significantly lower incidence of CIN compared to patients on simvastatin.
Topics: Contrast Media; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Male; Pravastatin; Simvastatin
PubMed: 21386035
DOI: 10.1177/1074248410394362 -
The Journal of Obstetrics and... Aug 2020Preeclampsia is characterized by the emergence of hypertension and proteinuria after 20 weeks of pregnancy, and it threatens both maternal and fetal lives if it...
Preeclampsia is characterized by the emergence of hypertension and proteinuria after 20 weeks of pregnancy, and it threatens both maternal and fetal lives if it proceeds unabated. Despite numerous studies, thus far the only fundamental therapy for preeclampsia is termination of pregnancy, leading to preterm birth. Furthermore, preeclamptic women are reported to be at risk for cardiovascular diseases for 10 years after delivery. Therefore, preventative and therapeutic strategies for preeclampsia are required. Recently, statins have been reported to improve the regeneration of vascular endothelium, and pravastatin has attracted attention as a potential preventative or therapeutic candidate for preeclampsia. Pravastatin has been demonstrated to have preventative effects in preeclampsia model mice, and a large volume of human data from pregnant women taking statins supports the safety of these drugs. Moreover, small clinical trials have reported that pravastatin has strong preventative or therapeutic effects on preeclampsia and it has the potential to improve the prognosis of pregnant women, fetuses and neonates affected by this condition.
Topics: Animals; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Infant, Newborn; Mice; Pravastatin; Pre-Eclampsia; Pregnancy; Premature Birth; Proteinuria
PubMed: 32485787
DOI: 10.1111/jog.14295 -
Drugs Feb 1997Pravastatin is an HMG-CoA reductase inhibitor which lowers plasma cholesterol levels by inhibiting de novo cholesterol synthesis. Pravastatin produces consistent... (Review)
Review
Pravastatin is an HMG-CoA reductase inhibitor which lowers plasma cholesterol levels by inhibiting de novo cholesterol synthesis. Pravastatin produces consistent dose-dependent reductions in both total and low density lipoprotein (LDL)-cholesterol levels in patients with primary hypercholesterolaemia. Favourable changes in other parameters such as total triglyceride and high density lipoprotein (HDL)-cholesterol levels are generally modest. Combination therapy with other antihyperlipidaemic agents such as cholestyramine further enhances the efficacy of pravastatin in patients with severe dyslipidaemias. Available data suggest that pravastatin is effective in elderly patients and in patients with hypercholesterolaemia secondary to diabetes mellitus or renal disease. The benefit of cholesterol-lowering in terms of patient outcomes is currently an area of considerable interest. Recently completed regression studies (PLAC I, PLAC II, KAPS and REGRESS) show that pravastatin slows progression of atherosclerosis and lowers the incidence of coronary events in patients with mild to moderately severe hypercholesterolaemia and known coronary heart disease. Large scale primary (WOSCOPS) and secondary (CARE) prevention studies, moreover, demonstrate that pravastatin has beneficial effects on coronary morbidity and mortality. In WOSCOPS, all-cause mortality was reduced by 22%. Pravastatin is generally well tolerated by most patients (including the elderly), as evidenced by data from studies of up to 5 years in duration. As with other HMG-CoA reductase inhibitors, myopathy occurs rarely (< 0.1% of patients treated with pravastatin): approximately 1 to 2% of patients may present with raised serum levels of hepatic transaminases. Thus, with its favourable effects on cardiovascular morbidity/mortality and total mortality, pravastatin should be considered a first-line agent in patients with elevated cholesterol levels, multiple risk factors or coronary heart disease who are at high risk of cardiovascular morbidity.
Topics: Anticholesteremic Agents; Coronary Disease; Humans; Hypercholesterolemia; Pravastatin
PubMed: 9028747
DOI: 10.2165/00003495-199753020-00008 -
Pharmacogenomics Sep 2008In developed countries, cardiovascular disease is one of the leading causes of death. Among other statins, pravastatin is abundantly prescribed to reduce risk of... (Review)
Review
In developed countries, cardiovascular disease is one of the leading causes of death. Among other statins, pravastatin is abundantly prescribed to reduce risk of coronary artery disease by lowering cholesterol. Genetic factors are thought to be partly responsible for the interindividual variation in the response to pravastatin. This article reviews the most important studies conducted on the pharmacogenetics of pravastatin. Currently there is no evidence to advocate pharmacogenetic testing before initiating therapy.
Topics: Animals; Anticholesteremic Agents; Genetic Variation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Pharmacogenetics; Pravastatin
PubMed: 18781848
DOI: 10.2217/14622416.9.9.1207 -
Drugs & Aging 2003Pravastatin (Pravachol) is a competitive, reversible HMG-CoA reductase inhibitor that lowers serum cholesterol levels by inhibiting de novo cholesterol synthesis and has... (Review)
Review
UNLABELLED
Pravastatin (Pravachol) is a competitive, reversible HMG-CoA reductase inhibitor that lowers serum cholesterol levels by inhibiting de novo cholesterol synthesis and has antiatherogenic effects that appear to be partially independent of its lipid-lowering effects. Pravastatin 10-40 mg/day produced significant reductions (vs baseline or placebo) in serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in elderly patients (aged >or=60 or >or= 65 years) with hypercholesterolaemia or normal cholesterol levels. Serum triglyceride and high-density lipoprotein cholesterol levels also improved in some studies, but not in others. Coadministration of cholestyramine, another lipid-lowering agent, further enhanced the lipid-lowering effects of pravastatin in elderly patients. Data from the large, long-term (3-6 years) PROspective Study Of Pravastatin in the Elderly at Risk (PROSPER), Cholesterol And Recurrent Events trial (CARE) and Long term Intervention with Pravastatin in Ischaemic Disease (LIPID) trials demonstrated that pravastatin 40 mg/day reduces coronary events in elderly patients with hypercholesterolaemia or normal cholesterol levels, with or at high risk of developing coronary heart disease (CHD). In these trials, the incidence of death from CHD or the combined endpoint of death from CHD or nonfatal myocardial infarction was significantly lower in pravastatin than in placebo recipients. Pravastatin is well tolerated in the elderly, and adverse effects considered related to therapy are minimal. The most commonly occurring adverse events included gastrointestinal events, renal or genital system events, respiratory disorders, headaches and musculoskeletal pain.
CONCLUSION
Pravastatin effectively lowers serum TC and LDL-C levels and, as demonstrated in major clinical outcome trials, reduces coronary events in elderly patients with hypercholesterolaemia or normal cholesterol levels. Pravastatin is well tolerated and as such should be considered a first-line agents for primary or secondary prevention in older individuals with evident CHD or multiple risk factors for CHD.
Topics: Adult; Aged; Clinical Trials as Topic; Drug Interactions; Female; Geriatrics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Intestinal Absorption; Male; Middle Aged; Pravastatin; Tissue Distribution
PubMed: 14651445
DOI: 10.2165/00002512-200320140-00005 -
Bone Aug 2021Osteoarthritis (OA) is a disease associated with a disorder of cholesterol metabolism. Our previous studies showed that prenatal ethanol exposure (PEE) caused...
Osteoarthritis (OA) is a disease associated with a disorder of cholesterol metabolism. Our previous studies showed that prenatal ethanol exposure (PEE) caused cholesterol accumulation in articular cartilage and increased the susceptibility to OA in offspring. However, we did not determine whether pravastatin, a cholesterol-lowering agent, could rescue PEE-induced susceptibility to OA. Here, fetal rats were divided into a PEE group and a control group during pregnancy. At postnatal week (PW) 8, sixteen male offspring rats from both groups were injected papain through the articular cavity. Eight of them from each group were treated with pravastatin (20 mg/kg·d) by gavage for four weeks simultaneously. We found that pravastatin ameliorated papain-induced high expression of inflammatory factors [interleukin (IL)-1, IL-6], matrix degradation enzymes [matrix metalloproteinase (MMP)-3, MMP-13], and apoptosis factors (caspase-3 and caspase-8) in the cartilage of the PEE group. Also, pravastatin significantly reduced the content of TCH in the blood and cartilage of the PEE offspring and improved cholesterol efflux pathway. Our in vitro findings further confirmed that pravastatin partially reversed cholesterol-induced inflammation and apoptosis of chondrocytes. In conclusion, pravastatin effectively reduced inflammation and matrix degradation, and thus ameliorate OA susceptibility in articular cartilage by relieving cholesterol accumulation in chondrocyte.
Topics: Animals; Cartilage, Articular; Chondrocytes; Ethanol; Female; Male; Osteoarthritis; Pravastatin; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar
PubMed: 33915333
DOI: 10.1016/j.bone.2021.115976 -
The Journal of Maternal-fetal &... Dec 2022The Indonesian INOVASIA study is an ongoing multicentre randomized, open controlled trial of pravastatin for the prevention of preeclampsia in patients deemed to be high... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The Indonesian INOVASIA study is an ongoing multicentre randomized, open controlled trial of pravastatin for the prevention of preeclampsia in patients deemed to be high risk. Here we evaluate the effects of pravastatin on circulating inflammatory and endothelial markers, i.e. Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), Endothelin-1 (ET-1), and Nitric Oxide (NO).
METHODS
Pregnant women deemed to be at a high risk of developing preeclampsia women were recruited based on the Fetal Medicine Foundation preeclampsia screening test or a history of preterm preeclampsia, or clinical risk factors in combination with an abnormal uterine artery Doppler flow pattern at 11-20 week's gestation. This is a nested cohort study within the larger trial (INOVASIA); 38 patients were consecutively recruited and assigned to the pravastatin group and the control group. Participants in the pravastatin group received pravastatin (2 × 20 mg p.o) in addition to a standard regimen of aspirin (80 mg p.o) and calcium (1 g p.o), from 14 to 20 weeks until delivery. Blood samples to measure the various biomarkers were obtained in consecutive patients before starting the research medication and just before delivery (pre and post-test examination).
RESULT
The number of samples on the 2 time points for the various biomarkers was: VEGF: 38, IL-6: 30, ET-1: 38, and NO: 35. IL-6 levels decreased significantly in the pravastatin group (mean ± SD): (191.87 ± 82.99 vs. 151.85 + 48.46, = .013), while levels in the control group did not change significantly (median (interquartile range)) (144.17 (53.91) vs. 140.82 (16.18), = .177). ET-1 levels decreased significantly in the pravastatin group (3.64 ± 0.85 vs. 3.01 ± 0.74, = .006) while the control group had more or less stable levels (3.57 ± 1.12 vs. 3.78 ± 0.73 = .594). NO was the only serum marker that showed significant changes in both groups. NO levels increased in pravastatin group (11.30 (17.43) vs. 41.90 (53.18), = .044) and decreased in control group (38.70 (34.80) vs. 10.03 (26.96), = .002). VEGF levels appeared to follow opposite trends in the 2 groups (NS) (Pravastatin: 3.22 (0.62) vs. 3.28 (0.75), = .402. Control: 3.38 (0.83) vs. 3.06 (0.74), = .287).
CONCLUSION
Administration of 40 mg pravastatin resulted in an improvement in NO levels, and a decrease in IL-6 and endothelin (ET-1) levels. The direction of the effect of pravastatin on these biomarkers appears to underpin the potential for a beneficial effect of pravastatin in the prevention of preeclampsia.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Biomarkers; Cohort Studies; Cytokines; Interleukin-6; Pravastatin; Pre-Eclampsia; Vascular Endothelial Growth Factor A
PubMed: 33522342
DOI: 10.1080/14767058.2021.1879785 -
Circulation Research Oct 2021[Figure: see text].
[Figure: see text].
Topics: Animals; Antineoplastic Agents; Autophagy; Autophagy-Related Protein 7; Cardiotoxicity; Doxorubicin; Myocarditis; Pravastatin; Spironolactone; Zebrafish; Zebrafish Proteins
PubMed: 34384247
DOI: 10.1161/CIRCRESAHA.121.319104 -
American Journal of Obstetrics and... Dec 2021Preeclampsia remains a major cause of maternal and neonatal morbidity and mortality. Biologic plausibility, compelling preliminary data, and a pilot clinical trial... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Preeclampsia remains a major cause of maternal and neonatal morbidity and mortality. Biologic plausibility, compelling preliminary data, and a pilot clinical trial support the safety and utility of pravastatin for the prevention of preeclampsia.
OBJECTIVE
We previously reported the results of a phase I clinical trial using a low dose (10 mg) of pravastatin in high-risk pregnant women. Here, we report a follow-up, randomized trial of 20 mg pravastatin versus placebo among pregnant women with previous preeclampsia who required delivery before 34+6 weeks' gestation with the objective of evaluating the safety and pharmacokinetic parameters of pravastatin.
STUDY DESIGN
This was a pilot, multicenter, blinded, placebo-controlled, randomized trial of women with singleton, nonanomalous pregnancies at high risk for preeclampsia. Women between 12+0 and 16+6 weeks of gestation were assigned to receive a daily pravastatin dose of 20 mg or placebo orally until delivery. In addition, steady-state pravastatin pharmacokinetic studies were conducted in the second and third trimesters of pregnancy and at 4 to 6 months postpartum. Primary outcomes included maternal-fetal safety and pharmacokinetic parameters of pravastatin during pregnancy. Secondary outcomes included maternal and umbilical cord blood chemistries and maternal and neonatal outcomes, including rates of preeclampsia and preterm delivery, gestational age at delivery, and birthweight.
RESULTS
Of note, 10 women assigned to receive pravastatin and 10 assigned to receive the placebo completed the trial. No significant differences were observed between the 2 groups in the rates of adverse or serious adverse events, congenital anomalies, or maternal and umbilical cord blood chemistries. Headache followed by heartburn and musculoskeletal pain were the most common side effects. We report the pravastatin pharmacokinetic parameters including pravastatin area under the curve (total drug exposure over a dosing interval), apparent oral clearance, half-life, and others during pregnancy and compare it with those values measured during the postpartum period. In the majority of the umbilical cord and maternal samples at the time of delivery, pravastatin concentrations were below the limit of quantification of the assay. The pregnancy and neonatal outcomes were more favorable in the pravastatin group. All newborns passed their brainstem auditory evoked response potential or similar hearing screening tests. The average maximum concentration and area under the curve values were more than 2-fold higher following a daily 20 mg dose compared with a 10 mg daily pravastatin dose, but the apparent oral clearance, half-life, and time to reach maximum concentration were similar, which is consistent with the previously reported linear, dose-independent pharmacokinetics of pravastatin in nonpregnant subjects.
CONCLUSION
This study confirmed the overall safety and favorable pregnancy outcomes for pravastatin in women at high risk for preeclampsia. This favorable risk-benefit analysis justifies a larger clinical trial to evaluate the efficacy of pravastatin for the prevention of preeclampsia. Until then, pravastatin use during pregnancy remains investigational.
Topics: Adult; Double-Blind Method; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pilot Projects; Pravastatin; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Second; Prenatal Care; Treatment Outcome; Young Adult
PubMed: 34033812
DOI: 10.1016/j.ajog.2021.05.018 -
PharmacoEconomics Aug 1998Coronary heart disease (CHD) is a major cause of death and illness in industrialised countries. Like other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase... (Review)
Review
UNLABELLED
Coronary heart disease (CHD) is a major cause of death and illness in industrialised countries. Like other hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin reduces total and low density lipoprotein (LDL)-cholesterol levels and increases high density lipoprotein (HDL)-cholesterol levels. Cholesterol modification with pravastatin in middle-aged hypercholesterolaemic men without CHD (i.e. primary prevention) was shown in the West of Scotland Coronary Prevention Study (WOSCOPS) to reduce the incidence of fatal and nonfatal coronary events. In several other large studies, pravastatin reduced the incidence of CHD events in patients with prior CHD (secondary prevention). Large, long term studies of the relationship between cholesterol modification and CHD event rate have been conducted for some, but not all, other HMG-CoA reductase inhibitors. A UK pharmacoeconomic analysis of the WOSCOPS data indicated that primary prevention with pravastatin was associated with a cost of 20,375 Pounds per year of life gained (YLG) [discounted]. Treatment of men at high risk for CHD resulted in a lower cost estimate (13,995 Pounds/YLG). A US economic analysis based on secondary prevention with pravastatin in large plaque regression studies suggested a net cost of drug therapy of $US7124 to $US12,665 per YLG. A number of projected-risk models have attempted to calculate the cost effectiveness of primary or secondary prevention with pravastatin compared with other lipid-modifying interventions. These comparisons indicated that pravastatin was economically superior to intensive lifestyle counselling without drug therapy. Pravastatin generally appeared to be less cost effective than other HMG-CoA reductase inhibitors, although the relative effectiveness of the various drugs depended on the model considered. Risk-projection economic models are subject to methodological limitations, principally the necessity of estimating clinical effectiveness from epidemiological data (often derived from the Framingham Heart Study). An increased absolute risk of CHD improves the cost effectiveness of lipid-lowering therapy. Thus, the cost per YLG of pravastatin in secondary prevention is, in general, lower than that of primary prevention, reflecting the higher absolute risk of second versus first CHD events. However, it is important to note that individual absolute risk rates may overlap between patients receiving primary and secondary prevention. Similarly, treatment of selected individual patients at high risk for CHD events is associated with a lower cost per YLG than unselected treatment.
CONCLUSION
In large clinical studies, pravastatin effectively reduced the risk of primary and secondary CHD events. These benefits come at a substantial economic cost, but one that is in line with accepted costs for other medical interventions. Selective treatment of patients or populations at high risk of CHD events improves the cost effectiveness of pravastatin therapy.
Topics: Anticholesteremic Agents; Coronary Disease; Cost of Illness; Cost-Benefit Analysis; Humans; Lipids; Pravastatin
PubMed: 10186462
DOI: 10.2165/00019053-199814020-00010