Trials Of Statins In Patients Research Articles

Statin use and mortality of patients with prostate cancer: a meta-analysis.

ObjectiveThe aim of this meta-analysis was to investigate the effect of statin use on the mortality of patients with prostate cancer (PCa).MethodsAn electronic search of PubMed, Embase, and CENTRAL databases from inception to August 2015 was performed to find eligible studies. Articles investigating the association between statin use and mortality of PCa were identified. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models.ResultsIn total, 13 studies that enrolled 100,536 participants were included in this meta-analysis. Results showed that prediagnostic statin use had a significantly lower risk of both all-cause mortality (ACM; HR, 0.56; 95% CI, 0.38–0.83) and PCa-specific mortality (PCSM; HR, 0.53; 95% CI, 0.36–0.77). Similarly, postdiagnostic statin use was correlated with reductions in both ACM (HR, 0.77; 95% CI, 0.69–0.87) and PCSM (HR, 0.64; 95% CI, 0.52–0.79). When stratified by primary treatment, postdiagnostic use of statins had a 0.4-fold lower risk of ACM in patients with PCa who were treated with local therapy; both pre- and postdiagnostic use of statins was correlated with a significantly lower risk of PCSM in patients who were treated with androgen deprivation therapy.ConclusionBoth pre- and postdiagnostic use of statins is associated with better overall survival and PCa-specific survival. This suggests a need for randomized controlled trials of statins in patients with PCa.

The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Trial: Where to Now?

The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Trial: Where to Now?

Su1938 Statin Use Is Associated With Improved Survival in Patients With Oesophageal Cancer: A Survival Analysis Using the UK General Practice Research Database and National Cancer Registry

Introduction Patients with oesophageal cancer (OC) commonly present with an advanced stage of disease, and are often only amenable to palliative therapies. Of the minority suitable for potentially curative surgery, up to 50% develop recurrence at one year. Statins demonstrate several anticarcinogenic properties in oesophageal adenocarcinoma (OAC) cell lines including reducing cell proliferation, stimulating apoptosis and potentially limiting metastatic potential. We investigated for the first time the hypothesis that statin use after diagnosis or post-oesophagectomy was associated with improved survival in patients with OC. Methods Cases of OC diagnosed between 1st January 2000 and 31st December 2009 were identified from the UK General Practice Research Database (GPRD). The GPRD data was linked to the UK National Cancer Registry (NCR) to determine histological subtype. Cox proportional hazard regression analysis with time-dependent exposures, estimated the associations between statin use (versus non-users) from diagnosis and post-surgery on overall survival and disease-specific survival. Multivariate analyses were adjusted for age, gender, body mass index, diabetes mellitus, cardiovascular disease, oesophagectomy, chemotherapy, radiotherapy and ACE inhibitor use. Results In total 4445 cases of OC were identified, of which 606 were OAC and 344 were OSCC (histology data was available for 21.4% of patients). Overall 585 (13.2%) patients underwent oesophagectomy. In total 609 (13.7%) of patients were statin users following diagnosis and 109 (19.2%) following surgery. There were improved survival times following diagnosis for patients prescribed a statin with OC overall (HR = 0.71, 95% CI = 0.64–0.79, p Conclusion Statin use in patients with OC either after diagnosis or post-oesophagectomy is associated with improved survival. This data suggests a need for randomised controlled trials of statins in patients with OC. Disclosure of Interest None Declared

Statin Use and Reduced Cancer-Related Mortality

BackgroundA reduction in the availability of cholesterol may limit the cellular proliferation required for cancer growth and metastasis. We tested the hypothesis that statin use begun before a cancer diagnosis is associated with reduced cancer-related mortality.MethodsWe assessed mortality among patients from the entire Danish population who had received a diagnosis of cancer between 1995 and 2007, with follow-up until December 31, 2009. Among patients 40 years of age or older, 18,721 had used statins regularly before the cancer diagnosis and 277,204 had never used statins.ResultsMultivariable-adjusted hazard ratios for statin users, as compared with patients who had never used statins, were 0.85 (95% confidence interval [CI], 0.83 to 0.87) for death from any cause and 0.85 (95% CI, 0.82 to 0.87) for death from cancer. Adjusted hazard ratios for death from any cause according to the defined daily statin dose (the assumed average maintenance dose per day) were 0.82 (95% CI, 0.81 to 0.85) for a dose of 0.01 to 0.75 defined daily dose per day, 0.87 (95% CI, 0.83 to 0.89) for 0.76 to 1.50 defined daily dose per day, and 0.87 (95% CI, 0.81 to 0.91) for higher than 1.50 defined daily dose per day; the corresponding hazard ratios for death from cancer were 0.83 (95% CI, 0.81 to 0.86), 0.87 (95% CI, 0.83 to 0.91), and 0.87 (95% CI, 0.81 to 0.92). The reduced cancer-related mortality among statin users as compared with those who had never used statins was observed for each of 13 cancer types.ConclusionsStatin use in patients with cancer is associated with reduced cancer-related mortality. This suggests a need for trials of statins in patients with cancer.

Statins, inflammation and kidney disease

Inflammation is highly prevalent in patients with chronic kidney disease (CKD) and is consistently associated with cardiovascular morbidity and mortality. Clinical event rates increase with declining renal function and activation of the acute-phase response. Statins are potent anti-inflammatory drugs that reduce the incidence of cardiovascular events. Owing to the increased prevalence of inflammation in patients with CKD and the potent effect of statins in individuals with elevated levels of C-reactive protein, these drugs should be especially effective in patients with CKD. Whereas data indicate that pravastatin may prevent loss of kidney function to a greater extent in individuals with evidence of increased inflammation than in those who show no inflammation, two large, randomized statin trials in patients on hemodialysis found no benefit of statin therapy, neither in the whole study group nor after stratifying for inflammation. Irrespective of inflammation, guidelines recommend treatment of dyslipidemia in early stages of CKD, which is supported by results from recent meta-analyses, and the Study of Heart and Renal Protection (SHARP), a large, randomized, placebo-controlled trial.

Plasma Triglycerides and Cardiovascular Events in the Treating to New Targets and Incremental Decrease in End-Points Through Aggressive Lipid Lowering Trials of Statins in Patients With Coronary Artery Disease

Plasma Triglycerides and Cardiovascular Events in the Treating to New Targets and Incremental Decrease in End-Points Through Aggressive Lipid Lowering Trials of Statins in Patients With Coronary Artery Disease

Plasma Triglycerides and Cardiovascular Events in the Treating to New Targets and Incremental Decrease in End-Points Through Aggressive Lipid Lowering Trials of Statins in Patients With Coronary Artery Disease

We determined the ability of in-trial measurements of triglycerides (TGs) to predict new cardiovascular events (CVEs) using data from the Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) and Treating to New Targets (TNT) trials. The trials compared atorvastatin 80 mg/day with moderate-dose statin therapy (simvastatin 20 to 40 mg/day in IDEAL and atorvastatin 10 mg/day in TNT) in patients with clinically evident coronary heart disease or a history of myocardial infarction. The outcome measurement in the present research was CVE occurring after the first year of the trial. After adjusting for age, gender, and study, risk of CVEs increased with increasing TGs (p <0.001 for trend across quintiles of TGs). Patients in the highest quintile had a 63% higher rate of CVEs than patients in the lowest quintile (hazard ratio 1.63, 95% confidence interval 1.46 to 1.81) and the relation of TGs to risk was apparent even within the normal range of TGs. The ability of TG measurements to predict risk decreased when high-density lipoprotein cholesterol and apolipoprotein B:apolipoprotein A-1 were included in the statistical analysis, and it was abolished with inclusion of further variables (diabetes, body mass index, glucose, hypertension, and smoking; (p = 0.044 and 0.621, respectively, for trend across quintiles of TGs). Similar results were obtained in patients in whom low-density lipoprotein cholesterol had been lowered to guideline-recommended levels. In conclusion, even slightly increased TG levels are associated with higher risk of recurrence of CVEs in statin-treated patients and should be considered a useful marker of risk.

Cardiovascular risk reduction: What do recent trials with rosuvastatin tell us?

Abundant evidence from large-scale clinical trials supports the importance of lowering low-density lipoprotein cholesterol (LDL-C) to decrease the risk of cardiovascular disease (CVD) events. The LDL-C targets in various guidelines remain important treatment goals but, even in trials where statin therapy achieves substantial reduction of LDL-C, a significant number of CVD events still occur and the residual risk remains high. These findings suggest that lipid parameters other than LDL-C, such as high-density lipoprotein cholesterol (HDL-C), triglycerides, and LDL particle size, can influence the risk of CVD. On this basis, other strategies that can alter the lipid profile, in particular raising HDL.C, may provide additional benefits. Other factors such as HDL-C functionality and susceptibility to oxidation and inflammatory factors can also influence cardiovascular risk. In addition to the modifications of the lipid profile, statins have cholesterol-independent beneficial pleiotropic effects. The contribution of these effects to event reduction is not yet fully understood. Recently, the body of evidence has expanded to support the use of intensive statin therapy in broader patient populations. The JUPITER trial has shown the benefit of intensive statin treatment in low-risk subjects with high levels of high-sensitivity C-reactive protein and average levels of LDL-C. Unlike the setting of primary and secondary prevention, the results of statin trials in patients with heart failure have shown no clear benefit in terms of survival. The recently published AURORA trial was carried out to investigate the effect of rosuvastatin in patients with end-stage renal disease undergoing chronic hemodialysis. In this trial no benefit on cardiovascular events was shown with statin therapy. In conclusion, large outcomes trials have clearly shown that statin treatments have a favorable benefit/risk profile in a large range of patients at different levels of risk, with the exception of patients with heart failure and those with renal disease undergoing dialysis. Further evidence is needed on the role of therapeutic strategies on the so-called residual risk.

Assessing the benefits and harms of statin treatment in patients with chronic kidney disease

This Practice Point commentary discusses a meta-analysis by Strippoli et al. that included 50 randomized and quasi-randomized trials of statins in patients with different stages of kidney disease (predialysis, dialysis and transplantation; n = 30,144). The authors found that statins safely reduced lipid concentrations and the risk of cardiovascular events and cardiovascular mortality, but that the agents had no effect on all-cause mortality overall and had uncertain renoprotective effects. The analysis was comprehensive and well executed. A decreased risk of all-cause mortality with statins was found in studies of predialysis patients but not in studies of renal transplant recipients or patients on chronic dialysis. Statin doses used in the trials were well tolerated and safe in all subgroups of patients with chronic kidney disease; therefore, we feel that statin use to maintain LDL cholesterol below 100 mg/dl (2.6 mmol/l) should be initiated to potentially decrease cardiovascular risk in such patients. The benefits of statin therapy on all-cause mortality and the clinically significant benefits of this treatment on progression of kidney disease are still unclear, and additional trial evidence in patients with chronic kidney disease is needed.

The Role of Statins in the Prevention of Heart Failure After Acute Coronary Syndrome

Patients who have acute coronary syndrome complicated by heart failure have increased short- and long-term morbidity and mortality. Besides the proven action in reducing cardiovascular events and mortality, statins also reduce the risk of developing heart failure after acute coronary syndrome. The pathways responsible for this benefit are likely a result of the "pleiotropic" actions of statins. The ongoing trials of statins in patients who have heart failure will help to further characterize this benefit.

Statin Use and Hospitalization for Sepsis in Patients With Chronic Kidney Disease

Patients with chronic kidney disease are at high risk for sepsis and sepsis-related mortality. To assess whether statin use is associated with a reduction in sepsis events [corrected] in dialysis patients. National prospective cohort study that enrolled 1041 incident dialysis patients at 81 US not-for-profit outpatient dialysis clinics from October 1995 to June 1998, with follow-up to January 2005. Statin use was determined by medical record review. Rates of sepsis events [corrected] between statin users and control patients were compared using multivariate regression models, with adjustment for potential confounders in the overall cohort and in a subcohort in which control patients were matched to statin users according to their likelihood (propensity) to have been prescribed a statin. Sepsis events [corrected] were determined through hospital records from the United States Renal Data System (mean follow-up, 3.4 years). There were 303 sepsis events [corrected] Rates of sepsis events [corrected] were significantly lower in patients receiving statins (crude incidence rate, 41/1000 patient-years) than in those not receiving statins (crude incidence rate, 110/1000 patient-years) (P<.001). With adjustment for demographics and dialysis modality, statin users were substantially less likely to be subsequently hospitalized for sepsis (incidence rate ratio, 0.41; 95% confidence interval [CI], 0.25-0.68). Further adjustment for comorbidities and laboratory values continued to show this protective association (incidence rate ratio, 0.38; 95% CI, 0.21-0.67). In the propensity-matched subcohort, statin use was even more protective (incidence rate ratio, 0.24; 95% CI, 0.11-0.49). Use of statins was strongly and independently associated with a reduction in the risk of sepsis events [corrected] in patients who had chronic kidney disease and were receiving dialysis. Randomized trials of statins in patients with chronic kidney disease should examine the prevention of sepsis as a potentially important benefit.

Statin therapy for coronary heart disease and its effect on stroke

Coronary heart disease (CHD) and stroke share common risk factors and are the leading causes of death and disability in the United States. Although the impact of elevated cholesterol on stroke risk has been disputed, numerous trials using 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (ie, statins) in patients with CHD have demonstrated a significant reduction in stroke incidence as a secondary endpoint. It is likely that statins are pleiotropic in stroke prevention, providing benefits through both cholesterol reduction and cholesterol-independent mechanisms. In this article, we review the relationship between cholesterol and stroke, randomized trials of statins in patients with CHD and high risk for CHD that have assessed stroke risk, and the putative mechanisms of stroke prevention by statins.

Coronary Artery Disease Prognosis and C-Reactive Protein Levels Improve in Proportion to Percent Lowering of Low-Density Lipoprotein

This editorial outlines the data supporting aggressive lipid goals and options for treating low-density lipoprotein (LDL) cholesterol to a range of approximately 30 to 70 mg/dl. The physiologically normal cholesterol range is approximately 30 to 70 mg/dl for native hunter-gatherers, healthy human neonates, free-living primates, and virtually all wild mammals. Randomized statin trials in patients with recent acute coronary syndromes and stable coronary artery disease have demonstrated that cardiovascular events are reduced and cardiovascular survival optimized when LDL cholesterol is reduced to <70 mg/dl. Secondary prevention trials have shown a decrease in all-cause mortality in proportion to the magnitude of LDL cholesterol reduction. An original analysis of available data shows that the ability of a lipid-lowering therapy to reduce the C-reactive protein level is closely correlated with its efficacy in LDL cholesterol reduction. Randomized trial data have shown no relation between either percentage LDL cholesterol decrease or final LDL cholesterol level achieved and the risk for myopathy or hepatic transaminase elevations associated with statins. Therefore, intensive LDL cholesterol reduction to levels of 30 to 70 mg/dl should be pursued in subjects with or at high risk for coronary artery disease.

Statin therapy in the treatment of Alzheimer disease: what is the rationale?

Alzheimer disease (AD) is a chronic neurodegenerative disorder that is manifested by cognitive decline, neuropsychiatric symptoms, and diffuse structural abnormalities in the brain. Its prevalence is predicted to rise 4-fold in the next 50 years. AD is characterized pathologically by deposition of extracellular beta-amyloid and accumulation of neurofibrillary tangles. Neuronal death and specific neurotransmitter deficits also are part of the pathologic picture. Strategies to delay symptom progression have focused on addressing the neurotransmitter deficits. Strategies to delay the onset or biologic progression of AD largely have targeted the plaques formed by the deposition of beta-amyloid. AD and cardiovascular disease share common risk factors, notably hypercholesterolemia, and occur together more often than expected by chance. Therapy with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) is the first-line treatment option for hypercholesterolemia, and observational studies have suggested that the risk of AD is reduced in patients who receive statin therapy in midlife. This reduction in risk of AD observed with statin therapy may be due to statins reducing beta-amyloid formation and deposition or to their known anti-inflammatory effects. Two randomized double-blind statin trials in patients with AD to assess the potential for statins to slow disease progression are currently under way. If successful, statin AD primary prevention trials may be developed.

Statins for stroke prevention: disappointment and hope.

The occurrence of stroke increases with age, particularly affecting the older elderly, a population also at higher risk for coronary heart disease (CHD). Epidemiological and observational studies have not shown a clear association between cholesterol levels and all causes of stroke. Nonetheless, large, long-term statin trials in patients with established CHD or at high risk for CHD have shown that statins decrease stroke incidence in these populations. Combined data from 9 trials including 70,070 patients indicated relative and absolute risk reductions for stroke of 21% and 0.9%, respectively, with statins. The number of strokes prevented per 1000 patients treated for 5 years in patients with CHD is 9 for statins, compared with 17.3 for antiplatelet agents. Statins have not yet been shown to reduce stroke risk in the typical general population without known CHD, nor have they been shown to prevent recurrent stroke in patients with prior stroke. Potential reasons for the effects of statins on stroke and the non-cholesterol-lowering mechanisms that may be involved are discussed. Treatment strategies based on global cardiovascular risk may be most effective. Additional studies in patients representative of the typical stroke population are needed.

スタチン療法の意義：Ｊ‐ＳＴＡＲＳを中心に

Beneficial effects of long-term HMG-CoA reductase inhibitor (statin) treatment for primary and secondary prevention of coronary heart disease (CHD) have been shown in several clinical trials and some of these statin trials in patients with established or high risk for CHD have shown that statins decrease stroke incidence. However, beneficial effects of statin for patients with chronic ischemic stroke and no histry of CHD remains to be clalified. The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Study is a prospectivee randomised, open, blinded endpoint study designed to evaluate the effects of pravastatin 10mg/day in patients who preveously experienced an ischemic stroke other than cardioembolic infarction, but who do not have any CHD requiring statin treatment. We planed to enroll a total of 3, 000 patients, aged 45-80 years whc have serum cholesterol level of 180-240mg/dl. The primary endpoint is fatal and non-fatal stroke recurrence during the follow-up period of 5 year and the data collection phase of the study is expected to be completed by April 2010. Effects of statin on hs-CRP and carotid intima-media thickness will also be investigated as substudies of J-STARS. The detailed process for J-STARS protocol establishment have been presented in this symposium.

Blood pressure lowering and ACE inhibition for the avoidance of cardiac and cerebral events

See doi:10.1016/S1095-668X(02)00804-7for the article to which this editorial refers. It is now well established that the level of blood pressure, whether systolic or diastolic, is an important determinant of the risks of both stroke and heart attack—not only among those with high blood pressure but also among those with average or below average blood pressure levels.1 However, while numerous clinical trials have demonstrated that blood pressure lowering treatments reduce the risks of stroke and of heart attack in hypertensives,2,3 until recently there has been little evidence about the effects of such therapy in non-hypertensives. Since many individuals at very high risk of stroke or heart attack do not have hypertension, there is a considerable interest in determining whether there are benefits of blood pressure lowering agents for high-risk individuals with average or below average blood pressure levels. This question mirrors another posed a decade ago about the effects of blood cholesterol lowering in high-risk patients with average or below average cholesterol levels—a question answered decisively by trials of statins in patients with coronary heart disease.4–6 Over the past 2 years, two major trials have been completed that have demonstrated important benefits of ACE inhibitor-based regimens for patients at high risk of coronary events or stroke, whether hypertensive or non-hypertensive. The Heart Outcomes Protection Evaluation (HOPE) study was designed to determine the effects of treatment with ramipril …