0
selected
-
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.
Autosomal dominant polycystic kidney disease in children.
Cadnapaphornchai, MA
Current opinion in pediatrics. 2015;(2):193-200
-
-
Free full text
-
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.
-
3.
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.
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.
-
5.
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
-
-
Free full text
-
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.
-
6.
Statins, fracture risk, and bone remodeling: What is true?
Rizzo, M, Rini, GB
The American journal of the medical sciences. 2006;(2):55-60
Abstract
Besides the action on plasma lipid levels, statins show a series of ancillary effects defined as all of their vascular and nonvascular effects independent from the cholesterol reduction. It has been recently hypothesized that one of these ancillary effects could be the improvement of bone health, due to the interference with bone metabolism. This may potentially represent the rationale for statins' use in the treatment of osteoporosis, the most common disease of the bone. Both experimental observations and clinical studies on this topic generated a number of conflicting results; however, the largest randomized clinical trials, the Scandinavian Simvastatin Survival Study (4S), Long Term Intervention with Pravastatin in Ischemic Disease (LIPID), and Heart Protection Study (HPS), indicate that statins do not prevent or reduce fracture risk.
-
7.
Are Canadian guidelines for cholesterol lowering in high-risk patients optimal?
Fitchett, DH, Leiter, LA, Tardif, JC, Goodman, S, Langer, A
The Canadian journal of cardiology. 2005;(1):85-90
Abstract
Recent Canadian lipid guidelines recommend that all high-risk patients receive medication to reduce low density lipoprotein cholesterol (LDL-C) below 2.5 mmol/L. The recently published Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) studies compared strategies of cholesterol lowering with atorvastatin 80 mg versus pravastatin 40 mg. Atorvastatin halted the progression of atherosclerosis (whereas atherosclerosis progressed in the patients receiving pravastatin), and resulted in a 16% reduction in the primary composite end point (all-cause death, myocardial infarction, unstable angina, revascularization and stroke) compared with the pravastatin-treated group. In the PROVE IT trial, LDL-C was reduced by atorvastatin to 1.6 mmol/L and by pravastatin to 2.46 mmol/L. Although lower LDL-C levels are one explanation for the improved outcomes with atorvastatin, pleiotropic differences of the two statins, such as their effects on inflammation and coagulation, cannot be excluded. Until trials are completed that compare outcomes from LDL-C lowering to different targets with the same statin, it is premature to recommend changes to the current Canadian guidelines. However, future recommendations may suggest much lower LDL-C targets than those currently recommended.
-
8.
ALLHAT-LLT: questions, questions, and more questions (and some answers).
Skerrett, PJ, Pasternak, RC
Current atherosclerosis reports. 2004;(5):375-80
Abstract
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial--Lipid Lowering Trial (ALLHAT-LLT) compared 40 mg/d of pravastatin with usual care among 10,355 men and women aged 55 years or older with stage 1 or 2 hypertension, at least one additional coronary heart disease risk factor, and low-density lipoprotein (LDL) cholesterol levels of 120 to 189 mg/dL. After a mean of 4.8 years of treatment and follow-up, the difference in total cholesterol between the two arms was 9.6%, whereas in a small, nonrandomized subsample, the LDL cholesterol differential was 16.7%. No differences were observed between the pravastatin and usual-care groups with respect to all-cause mortality, cardiovascular deaths, noncardiovascular deaths, and a composite endpoint of fatal coronary heart disease plus nonfatal myocardial infarction. Despite these null findings, the results of ALLHAT-LLT are not inconsistent with previous trials because of the very small lipid differences in the two arms. This indirectly supports the hypothesis that LDL cholesterol lowering is central to the cardiovascular benefits associated with statin therapy, with greater clinical impacts observed when there are greater differences between treatment and control arms. ALLHAT-LLT underscores the difficulty of conducting an open-label trial in an era of rapidly changing professional and public understanding of the possible benefits of lipid-lowering therapy and highlights the substantial gap between actual care in clinical practice and optimal care based on the best knowledge from randomized clinical trials.
-
9.
Lessons learned from the prospective pravastatin pooling project.
Byington, RP, Sacks, FM
Current atherosclerosis reports. 2004;(5):366-74
Abstract
The Prospective Pravastatin Pooling (PPP) Project was a prospectively defined collaboration of three randomized, placebo-controlled, long-term, monotherapy (40 mg/d) trials of the lipid-lowering agent pravastatin. A pooled database of 19,768 participants with a mean of 5.2 years of follow-up was created, providing the investigators with over 100,000 patient-years of experience to address questions on total and cause-specific mortality, coronary incidence, stroke, and safety. One trial (West of Scotland Coronary Prevention Study) was primary prevention and two (Cholesterol and Recurrent Events and Long-term Intervention with Pravastatin in Ischemic Disease) were secondary prevention. Pravastatin was shown to safely reduce all-cause mortality, fatal and nonfatal coronary events, and stroke events in patients with a broad range of patient characteristics.
-
10.
Conceptual foundations of the UCSD Statin Study: a randomized controlled trial assessing the impact of statins on cognition, behavior, and biochemistry.
Golomb, BA, Criqui, MH, White, H, Dimsdale, JE
Archives of internal medicine. 2004;(2):153-62
-
-
Free full text
-
Abstract
BACKGROUND Statin cholesterol-lowering drugs are among the most prescribed drugs in the United States. Their cardiac benefits are substantial and well supported. However, there has been persistent controversy regarding possible favorable or adverse effects of statins or of cholesterol reduction on cognition, mood, and behavior (including aggressive or violent behavior). METHODS The literature pertaining to the relationship of cholesterol or statins to several noncardiac domains was reviewed, including the link between statins (or cholesterol) and cognition, aggression, and serotonin. RESULTS There are reasons to think both favorable and adverse effects of statins and low cholesterol on cognition may pertain; the balance of these factors requires further elucidation. A substantial body of literature links low cholesterol level to aggressive behavior; statin randomized trials have not supported a connection, but they have not been designed to address this issue. A limited number of reports suggest a connection between reduced cholesterol level and reduced serotonin level, but more information is needed with serotonin measures that are practical for clinical use. Whether lipophilic and hydrophilic statins differ in their impact should be assessed. CONCLUSION There is a strong need for randomized controlled trial data to more clearly establish the impact of hydrophilic and lipophilic statins on cognition, aggression, and serotonin, as well as on other measures relevant to risks and quality-of-life impact in noncardiac domains.