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British Journal of Clinical Pharmacology Aug 2023Rhabdomyolysis is a serious adverse drug reaction of statins. There are few studies comparing the risk of rhabdomyolysis between the different statins. Using the WHO...
Rhabdomyolysis is a serious adverse drug reaction of statins. There are few studies comparing the risk of rhabdomyolysis between the different statins. Using the WHO pharmacovigilance database, VigiBase®, we compared the risk of rhabdomyolysis reporting of seven statins (atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin, with cerivastatin excluded). All reports of rhabdomyolysis in VigiBase® in adults with statins until 31 December 2022 were included. Results are expressed as reporting odds ratio (ROR, 95% CI). Among 10 657 reports with rhabdomyolysis with statins, simvastatin was the highest risk statin in comparison with others: ROR = 2.20 (2.11-2.29). The risk was higher in men, older than 74 years and in cases of drug interactions.
Topics: Male; Adult; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmacovigilance; Simvastatin; Atorvastatin; Rhabdomyolysis
PubMed: 37186323
DOI: 10.1111/bcp.15757 -
Journal of Clinical Medicine Sep 2023Throughout the history of medicine, preeclampsia has remained an enigmatic field of obstetrics. In 2023, despite its prevalence and impact, preeclampsia's exact cause... (Review)
Review
Throughout the history of medicine, preeclampsia has remained an enigmatic field of obstetrics. In 2023, despite its prevalence and impact, preeclampsia's exact cause and effective treatment remain elusive; the current options are limited to delivery. The purpose of this review is to summarize the knowledge of the possible novel prophylactic therapies and screening methods for preeclampsia, thereby providing valuable insights for healthcare professionals and researchers. Aspirin and LMWH have already been widely used; meanwhile, calcium, vitamin D, and pravastatin show promise, and endothelin receptor antagonists are being explored. Stress reduction, dietary changes, and lifestyle modifications are also being investigated. Another interesting and fast-growing area is AI- and software-based screening methods. It is also key to find novel biomarkers, which, in some cases, are not only able to predict the development of the disease, but some of them hold promise to be a potential therapeutic target. We conclude that, while a definitive cure for preeclampsia may not be eligible in the near future, it is likely that the assessment and enhancement of preventive methods will lead to the prevention of many cases. However, it is also important to highlight that more additional research is needed in the future to clarify the exact pathophysiology of preeclampsia and to thus identify potential therapeutic targets for more improved treatment methods.
PubMed: 37762960
DOI: 10.3390/jcm12186020 -
Current Hypertension Reports Feb 2020To review the rationale and biological plausibility and discuss the current research on novel interventions for the prevention of preeclampsia. (Review)
Review
PURPOSE OF REVIEW
To review the rationale and biological plausibility and discuss the current research on novel interventions for the prevention of preeclampsia.
RECENT FINDINGS
Preeclampsia affects up to 8% of pregnancies worldwide and remains a major cause of maternal and neonatal morbidity and mortality. Multiple medications have been investigated or repurposed as potential effective interventions for preeclampsia prevention. Aspirin is currently the only drug for which there is some evidence of benefit for preeclampsia prevention, and its use is recommended by professional societies for pregnancies at risk. Statins have shown promise for prevention of preeclampsia in animal models and human pilot studies, without any trend or concerns for safety signals or teratogenicity. The use of metformin has also gained popularity in experimental studies, but observations from randomized clinical trials were not consistent on its utility as a possible intervention for preeclampsia prevention. While initial studies evaluating esomeprazole were promising, randomized trials failed to show benefit. Contemporary research shows exciting new opportunities for prophylactic treatment for preeclampsia, to prevent this debilitating and life-threatening disease.
Topics: Animals; Aspirin; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Pre-Eclampsia; Pregnancy
PubMed: 32052203
DOI: 10.1007/s11906-020-1026-8 -
Saudi Pharmaceutical Journal : SPJ :... May 2023Statins have been reported to have potential anti-proliferative effects through an unknown mechanism. This study aims to investigate the anti-proliferative activities of...
Statins have been reported to have potential anti-proliferative effects through an unknown mechanism. This study aims to investigate the anti-proliferative activities of five statins, including simvastatin, rosuvastatin, fluvastatin, atorvastatin, and pravastatin, against five different cancer cell lines; cervical epithelial carcinoma DoTc2 4510, malignant melanoma A-375, muscle Ewing's sarcoma A-673, hepatocellular carcinoma HUH-7, as well as breast cancer cells MCF-7. At 100 µM, simvastatin and atorvastatin significantly inhibited 70% of cellular proliferation. At the same concentration, rosuvastatin and fluvastatin showed about 50% of inhibition only in A-375 and A-673 cancer cells in a time- and dose-dependent manner. Of all the statin drugs used, pravastatin had the least inhibitory effect on all the cancer cell lines. Western Blot analysis showed a decrease in mTOR level, and the expression of p53 tumour suppression and BCL-2 proteins was relatively elevated compared to the untreated cells. Simvastatin and atorvastatin may inhibit cellular proliferation via BCL-2/p53, Bax/Bak, and PI3K/Akt/mTOR signalling pathways. This is the first research to evaluate the anti-cancer effects of simvastatin, rosuvastatin, fluvastatin, atorvastatin, and pravastatin against five different cell lines from distinct origins and provided a relevant comparison of their efficacies for their anti-proliferative activity.
PubMed: 37181137
DOI: 10.1016/j.jsps.2023.03.013 -
Pravastatin and placental insufficiency associated disorders: A systematic review and meta-analysis.Frontiers in Pharmacology 2022Uteroplacental insufficiency associated disorders, such as preeclampsia, fetal growth restriction and obstetrical antiphospholipid syndrome, share pathophysiology and...
Uteroplacental insufficiency associated disorders, such as preeclampsia, fetal growth restriction and obstetrical antiphospholipid syndrome, share pathophysiology and risk factors with cardiovascular diseases treated with statins. To evaluate pregnancy outcomes among women with uteroplacental insufficiency disorders who were treated with statins. Electronic databases were searched from inception to January 2022 Cohort studies and randomized controlled trials. Pooled odds ratios were calculated using a random-effects model; meta-regression was utilized when applicable. The analysis included ten studies describing 1,391 women with uteroplacental insufficiency disorders: 703 treated with pravastatin and 688 not treated with statins. Women treated with pravastatin demonstrated significant prolongation of pregnancy (mean difference 0.44 weeks, 95%CI:0.01-0.87, = 0.04, I = 96%) and less neonatal intensive care unit admissions (OR = 0.42, 95%CI: 0.23-0.75, = 0.004, I = 25%). In subgroup analysis, prolongation of pregnancy from study entry to delivery was statistically significant in cohort studies (mean difference 8.93 weeks, 95%CI:4.22-13.95, = 0.00) but not in randomized control studies. Trends were observed toward a decrease in preeclampsia diagnoses (OR = 0.54, 95%CI:0.27-1.09, = 0.09, I = 44%), perinatal death (OR = 0.32, 95%CI:0.09-1.13, = 0.08, I = 54%) and an increase in birth weight (mean difference = 102 g, 95%CI: -14-212, = 0.08, I = 96%). A meta-regression analysis demonstrated an association between earlier gestational age at initiation of treatment and a lower risk of preeclampsia development (R = 1). Pravastatin treatment prolonged pregnancy duration and improved associated obstetrical outcomes in pregnancies complicated with uteroplacental insufficiency disorders in cohort studies. https://www.crd.york.ac.uk/prospero/ identifier CRD42020165804 17/2/2020.
PubMed: 36438820
DOI: 10.3389/fphar.2022.1021548 -
Frontiers in Medicine 2022To review of the efficacy and safety of pravastatin use for prophylaxis and treatment of preeclampsia.
OBJECTIVE
To review of the efficacy and safety of pravastatin use for prophylaxis and treatment of preeclampsia.
DESIGN
Systematic review and meta-analysis of clinical studies evaluating pravastatin for treatment and/or prophylaxis of preeclampsia.
DATA COLLECTION
Two independent reviewers systematically searched data from PubMed, Scopus, Web of Science, Cochrane, Embase, and clinicaltrials.gov databases, for studies evaluating pravastatin for prevention of pre-eclampsia.
RESULTS
Fourteen studies were identified, including 1,570 pregnant women who received either pravastatin or placebo, published between 2003 and 2022. From these studies, 5 studies were identified for inclusion in the meta-analysis to evaluate the role of pravastatin use prior to 20 weeks of gestation, to prevent pre-eclampsia, Pravastatin treatment reduced the incidence of preeclampsia by 61% and premature birth by 45%. Among the newborns, there was a 45% reduction in intrauterine growth retardation (IUGR) in the treated group, as well as a 77% reduction in those receiving neonatal intensive care unit (NICU) admissions.
CONCLUSION
Prophylactic treatment with pravastatin appears to reduce risk of developing pre-eclampsia as well as potentially lowering risk of IUGR, preterm birth, and NICU admission in neonates.
PubMed: 36714131
DOI: 10.3389/fmed.2022.1076372 -
Therapeutics and Clinical Risk... 2019Autosomal dominant polycystic kidney disease (ADPKD) is an inherited multisystem disorder, characterized by renal and extra-renal fluid-filled cyst formation and... (Review)
Review
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited multisystem disorder, characterized by renal and extra-renal fluid-filled cyst formation and increased kidney volume that eventually leads to end-stage renal disease. ADPKD is considered the fourth leading cause of end-stage renal disease in the United States and globally. Care of patients with ADPKD was, for a long time, limited to supportive lifestyle measures, due to the lack of therapeutic strategies targeting the main pathways involved in the pathophysiology of ADPKD. As the first FDA approved treatment of ADPKD, Vasopressin (V) receptor blocking agent, tolvaptan, is an urgently awaited advance for ADPKD patients. In our review, we also shed some lights on what is beyond Tolvaptan as there are other medications in the pipeline and many medications have been or are currently being studied in clinical trials such as Tesevatinib, Metformin and Pravastatin, with the goal of slowing the rate of progression of ADPKD by reducing the increase in total kidney volume or maintaining eGFR. Here, we review updates in the perspectives and management of ADPKD.
PubMed: 31692482
DOI: 10.2147/TCRM.S196244 -
Current Hypertension Reports Feb 2024To review recent data describing the challenges and innovations in therapeutic research focused on the prevention and treatment of preeclampsia. (Review)
Review
PURPOSE OF REVIEW
To review recent data describing the challenges and innovations in therapeutic research focused on the prevention and treatment of preeclampsia.
RECENT FINDINGS
Pregnant individuals have traditionally been excluded from therapeutic research, resulting in a paucity of innovation in therapeutics for pregnancy-specific medical conditions, especially preeclampsia. With the increased awareness of maternal morbidity and mortality, there is significant interest among researchers to expand therapeutic research in pregnancy. Several medications, including aspirin, pravastatin, metformin, and esomeprazole, which are commonly used in non-pregnant populations, are now being investigated for preeclampsia prevention. However, given the historic precedent of exclusion, along with the regulatory, ethical, and feasibility concerns that accompany this population, the study of these and novel medications has been complicated by numerous challenges. While complex, and laden with challenges, there is great ongoing need for therapeutic research to address preeclampsia. Aspirin, pravastatin, metformin, and esomeprazole have all shown promise as potential therapeutic agents; however, their use remains to be optimized, and innovative therapeutics need to be developed.
Topics: Female; Humans; Pregnancy; Aspirin; Esomeprazole; Hypertension; Metformin; Pravastatin; Pre-Eclampsia; Pregnancy Complications; Clinical Trials as Topic
PubMed: 37971596
DOI: 10.1007/s11906-023-01276-y -
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 -
Obstetrics and Gynecology Clinics of... Mar 2023Preeclampsia is a hypertensive disorder of pregnancy affecting up to 8% of pregnancies. It is associated with significant neonatal and maternal morbidities and... (Review)
Review
Preeclampsia is a hypertensive disorder of pregnancy affecting up to 8% of pregnancies. It is associated with significant neonatal and maternal morbidities and mortality. Although its pathogenesis is not completely understood, abnormal placentation resulting in imbalance in angiogenic factors, increased inflammation, and endothelial dysfunction are thought to be key pathways in the development of the disease. Administration of low-dose aspirin is recommended by professional societies for the prevention of preeclampsia in high-risk individuals. In this review, we summarize the evidence behind the use of low-dose aspirin and pravastatin in pregnant individuals at high risk of preeclampsia.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Aspirin; Pre-Eclampsia; Pravastatin; Pregnancy, High-Risk; Hypertension
PubMed: 36822711
DOI: 10.1016/j.ogc.2022.10.005