1.
Long-Term Effectiveness and Safety of Pravastatin in Patients With Coronary Heart Disease: Sixteen Years of Follow-Up of the LIPID Study.
Hague, WE, Simes, J, Kirby, A, Keech, AC, White, HD, Hunt, D, Nestel, PJ, Colquhoun, DM, Pater, H, Stewart, RA, et al
Circulation. 2016;(19):1851-60
Abstract
BACKGROUND We aimed to assess the long-term effects of treatment with statin therapy on all-cause mortality, cause-specific mortality, and cancer incidence from extended follow-up of the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) trial. METHODS AND RESULTS LIPID initially compared pravastatin and placebo over 6 years in 9014 patients with previous coronary heart disease. After the double-blind period, all patients were offered open-label statin therapy. Data were obtained over a further 10 years from 7721 patients, by direct contact for 2 years, by questionnaires thereafter, and from mortality and cancer registries. During extended follow-up, 85% assigned pravastatin and 84% assigned placebo took statin therapy. Patients assigned pravastatin maintained a significantly lower risk of death from coronary heart disease (relative risk [RR] 0.89; 95% confidence interval [CI], 0.81-0.97; P=0.009), from cardiovascular disease (RR, 0.88; 95% CI, 0.81-0.95; P=0.002), and from any cause (RR, 0.91; 95% CI, 0.85-0.97; absolute risk reduction, 2.6%; P=0.003).Cancer incidence was similar by original treatment group during the double-blind period (RR, 0.94; 95% CI, 0.82-1.08; P=0.41), later follow-up (RR, 1.02; 95% CI, 0.91-1.14; P=0.74), and overall (RR, 0.99; 95% CI, 0.91-1.08; P=0.83). There were no significant differences in cancer mortality, or in the incidence of organ-specific cancers. Cancer findings were confirmed in a meta-analysis with other large statin trials with extended follow-up. CONCLUSIONS In LIPID, the absolute survival benefit from 6 years of pravastatin treatment appeared to be maintained for the next 10 years, with a similar risk of death among survivors in both groups after the initial period. Treatment with statins does not influence cancer or death from noncardiovascular causes during long-term follow-up.
2.
Early initiation of statin treatment in children with familial hypercholesterolaemia.
Braamskamp, MJ, Hutten, BA, Wiegman, A
Current opinion in lipidology. 2015;(3):236-9
Abstract
PURPOSE OF REVIEW This article provides recent insights on the early onset of atherosclerosis in heterozygous familial hypercholesterolemia and reports on novel treatment options as well as on the consequences of long-term statin use in childhood. RECENT FINDINGS Children with familial hypercholesterolemia have greater mean carotid intima-media thickness (cIMT) than their unaffected siblings even before the age of 8 years, which is several years earlier than previously reported. In those children, 2 years of rosuvastatin treatment resulted in slowing of the cIMT progression. In addition, in a 10-year follow-up study after a pravastatin intervention trial, long-term statin therapy in young adult familial hypercholesterolemia patients was associated with normalization of cIMT progression and appeared effective in prevention of very premature cardiovascular events. These effects were observed without untoward safety concerns. However, a majority of these young adults did not reach cholesterol goals according to general guidelines, indicating the need for improvement of treatment in this patient group. SUMMARY The importance, efficacy and safety of early initiation statin therapy in familial hypercholesterolemia children were further confirmed by recent findings. Nevertheless, to reach current treatment goals, the use of more potent statins is required and has been proven well tolerated and effective in young children.
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Therapies for polycystic kidney disease.
Bissler, JJ
Current opinion in pediatrics. 2015;(2):227-32
Abstract
PURPOSE OF REVIEW All polycystic diseases of the kidney exhibit tubular or saccular cysts. The cysts can either be open to the tubule or isolated sacs that have lost their connections. Polycystic kidney diseases derived from different genetic mutations share basic mechanisms of cytogenesis, formation, and progressive enlargement, involving a cellular organelle called the primary cilium. Given the mechanistic commonalities, this review will focus on the therapeutic approaches currently available or under development that likely apply to all inherited renal cystic diseases. RECENT FINDINGS Recent advances in clinical trials and preclinical experiments have illuminated common signaling pathway involvement. SUMMARY Avoidance of nephrotoxic drugs or radio-contrast and maintaining normal BMI are routine preventive measures. Limiting the intake of calories, salt, and protein, together with increased intake of fruits, vegetables, and water are dietary treatments that should be started early in the course of the disease. Potential pharmacological treatments targeting cyst initiation and progression are on the horizon.
4.
Autosomal dominant polycystic kidney disease in children.
Cadnapaphornchai, MA
Current opinion in pediatrics. 2015;(2):193-200
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Abstract
PURPOSE OF REVIEW Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, affecting one in 500 individuals. The cardinal manifestation of ADPKD is progressive cystic dilatation of renal tubules with kidney enlargement and progression to end-stage renal disease in approximately half of cases by 60 years of age. Although previously considered a condition of adults, it is clear that children and young adults are subject to the complications of ADPKD. RECENT FINDINGS It has been increasingly recognized that interventions early in life are necessary in order to confer the best long-term outcome in this common condition. Therefore, it is imperative for pediatricians to recognize the manifestations and complications of this disease. Until recently ADPKD management focused on general principles of chronic kidney disease. However, several recent clinical trials in children and adults with ADPKD have focused on disease-specific therapies. SUMMARY This review will highlight the clinical manifestations, diagnosis, and appropriate management of ADPKD in childhood and will review recent relevant clinical trials in children and adults with this condition.
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Challenges of studying drugs in pregnancy for off-label indications: pravastatin for preeclampsia prevention.
Cleary, KL, Roney, K, Costantine, M
Seminars in perinatology. 2014;(8):523-7
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Abstract
Statins (3-hydroxy-3 methyl-glutaryl coenzyme-A reductase inhibitors) are the most commonly prescribed cholesterol-lowering medications due to their efficacy in reducing cardiovascular mortality and morbidities, tolerability, and safety profiles. Based on pathophysiologic similarities between cardiovascular disease and preeclampsia, a common and dangerous complication of pregnancy, there is an increasing interest in studying this class of medications during pregnancy to prevent and/or treat preeclampsia. Undergoing such a study, which entails the use of a pregnancy class X medication for an off-label indication in pregnancy, requires intensive multidisciplinary involvement of a group of experts in basic and clinical pharmacology, research methods, pregnancy physiology and maternal-fetal medicine, as well as U.S. Food and Drug Administration (FDA) regulatory guidelines and practice. Issues of potential fetal risk, altered maternal-fetal pharmacokinetics and pharmacodynamics, and regulatory challenges are real, and must be carefully considered in the process of research in this arena.