Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Statins”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2006

Preoperative statin therapy is associated with reduced cardiac mortality after coronary artery bypass graft surgery.

OBJECTIVE: Statin therapy in ambulatory populations is associated with a significant reduction in adverse cardiovascular events, including death and myocardial infarction. Much less is known about the beneficial effects of statins on acute perioperative cardiovascular events. The purpose of this study was to determine whether preoperative statin therapy is associated with a reduced risk of early cardiac death or nonfatal, in-hospital postoperative myocardial infarction after primary, elective coronary artery bypass graft surgery requiring cardiopulmonary bypass. METHODS: The Multicenter Study of Perioperative Ischemia (McSPI) Epidemiology II Study was a prospective, longitudinal study of 5436 patients undergoing coronary artery bypass graft surgery between November 1996 and June 2000 at 70 centers in 17 countries. The present study consisted of a pre-specified subset of these subjects divided into patients receiving (n = 1352) and not receiving (n = 1314) preoperative statin therapy. To control for potential bias related to use of statin therapy, the study estimated propensity scores by logistic regression to determine the predicted probability of inclusion in the "statin" group. Multivariate, stepwise logistic regression was then performed, controlling for patient demographics, medical history, operative characteristics, and propensity score to determine whether preoperative statin therapy was independently associated with a reduction in the risk of early (DOS-POD3) cardiac death and/or nonfatal, in-hospital postoperative myocardial infarction. RESULTS: Preoperative statin therapy was independently associated with a significant reduction (adjusted odds ratio [OR] 0.25; 95% confidence intervals [CI] 0.07-0.87) in the risk of early cardiac death after primary, elective coronary bypass surgery (0.3% vs 1.4%; P < .03), but was not associated with a reduced risk of postoperative nonfatal, in-hospital myocardial infarction (7.9% vs 6.2%; P = not significant). Discontinuation of statin therapy after surgery was independently associated with a significant increase in late (POD4-discharge) all-cause mortality (adjusted OR 2.64; 95% CI 1.32-5.26) compared with continuation of statin therapy (2.64% vs 0.60%; P < .01). This was true even when controlling for the postoperative discontinuation of aspirin, beta-blocker, or angiotensin-converting enzyme inhibitor therapy. Discontinuation of statin therapy after surgery was also independently associated with a significant increase in late cardiac mortality (adjusted OR 2.95; 95% CI 1.31-6.66) compared with continuation of statin therapy (1.91% vs 0.45%; P < 0.01). CONCLUSIONS: Preoperative statin use is associated with reduced cardiac mortality after primary, elective coronary artery bypass grafting. Postoperative statin discontinuation is associated with increased in-hospital mortality. Although further randomized trials are needed to confirm these findings, these data suggest the importance of perioperative statin administration.

Cardiopulmonary Bypass↗
PubMed2004

[Early initiation of statin therapy in patients with acute myocardial infarction after successful percutaneous coronary intervention].

OBJECTIVES: To evaluate the effect of statins on the prognosis of acute myocardial infarction after percutaneous coronary intervention (PCI). METHODS: We reviewed 280 patients with acute myocardial infarction who underwent PCI within 12 hr after the onset of symptoms. Statin therapy was initiated in 72 patients within 8.6 +/- 7.6 days after the onset (statin group) but not in the remaining 208 (no statin group). The time sequential changes of low-density lipoprotein cholesterol (LDL-C) and C-reactive protein (CRP) levels, and the angiographic findings at 6 months after PCI were compared. RESULTS: At onset, LDL-C levels in the statin group were significantly higher than those in the no statin group (140 +/- 35 vs 118 +/- 28 mg/dl, p < 0.01). However, at restudy, the values were similar between the two groups (113 +/- 19 vs 118 +/- 21 mg/dl, p = 0.19). CRP levels at restudy tended to be lower in the statin group than in the no statin group (0.11 +/- 0.12 vs 0.14 +/- 0.13 mg/dl, p = 0.07). Although the binary restenosis rates of the culprit lesion were almost equivalent (statin group 29% vs no statin group 23%, p = 0.30), new lesions in the non-culprit vessels tended to be found more frequently in the no statin group than in the statin group (13% vs 4%, p = 0.07). CRP levels at restudy were significantly higher in the patients with new lesions (n = 27) than in those without (n = 253; 0.25 +/- 0.17 vs 0.11 +/- 0.19 mg/dl, p < 0.01), whereas LDL-C levels were similar between the two groups (117 +/- 20 vs 113 +/- 27 mg/dl, p = 0.75). LDL-C, CRP at restudy and the rates of new lesions were similar in the patients receiving water-soluble statins (n = 42) and liposoluble statins (n = 30). CONCLUSIONS: Statin therapy initiated at the early phase of acute myocardial infarction might prevent the development of new lesions in non-culprit vessels without any influence on the restenosis rate of the culprit lesion.

Aged↗
PubMed1994

Statin, a marker of cell cycle arrest, is overexpressed during the early phase of delayed NMDA toxicity in hippocampal cell cultures.

Statin is a 57-kDa protein exclusively expressed in nuclei of nonproliferating mammalian cells. Recent studies have suggested that statin may play a role in the maintenance of growth arrest. Several lines of evidence also support the notion that a variety of genes and gene products are modulated during cell proliferation and cell death. The present study examined the possibility that statin expression could be modulated during neuronal injury using N-methyl-Daspartate (NMDA)-induced toxicity to rat embryonic hippocampal cultures as a model. Immunocytochemical studies using a monoclonal antibody to statin revealed a prominent nuclear localization of statin in cultured hippocampal cells. Western blot analysis showed that this antibody recognizes a 57-kDa protein band, indicative of the presence of statin in this preparation. Brief exposure of hippocampal neurons to NMDA (500 microM) produced severe neuronal degeneration over the subsequent hours. NMDA-treated neurons markedly overexpressed statin. Both NMDA-induced neuronal toxicity and statin overexpression were prevented by the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohept-5,10-imine hydrogen maleate (MK-801). Interestingly, time course studies indicate that the increased expression of statin observed following NMDA exposure clearly preceded the appearance of the first signs of neuronal death as determined by vital staining. In addition, exposure of hippocampal neurons to the Ca2+ ionophore, A23187, produced a marked increase in statin immunodetection, indicating that statin expression is likely regulated in a Ca(2+)-dependent manner. Thus, these results show that statin, which is expressed at low levels in embryonic rat cultured hippocampal neurons, is rapidly overexpressed following a toxic insult produced by the activation of the NMDA receptor. The observation that statin overexpression occurs prior to neuronal death raises the possibility that the up-regulation of statin could be used as an early index of neuronal injury.

Animals↗
PubMed2006

Statin use in heart failure: a cause for concern?

BACKGROUND: Statins are effective in the prevention of coronary events and the treatment of acute coronary syndromes. However, their efficacy and safety in patients with heart failure (HF) are unknown. In this review, we discuss the evidence for the efficacy and safety of statin therapy in patients with HF. METHODS: We reviewed all original English-language, peer-reviewed journal articles published from 1985 to 2005 obtained from a search of the MEDLINE database. We focused on evidence for the efficacy and safety of statins based on data from patients with HF enrolled in major statin trials, analysis of the impact of statin use in patients with HF, and randomized clinical trials examining the effects of statins on cardiovascular outcomes in patients with HF. RESULTS: The major primary and secondary prevention statin trials largely excluded patients with HF. Statin use was also limited in randomized HF trials. Subgroup and retrospective analyses, and evidence from prospective cohort studies of statin use in patients with HF suggest statins improve cardiovascular prognosis in HF. The limited small randomized clinical trials also suggest statins improve symptoms, ejection fraction, and inflammatory biomarkers in patients with HF. CONCLUSIONS: A growing weight of evidence suggests that statins have beneficial effects in HF. At this time, there is little evidence to support withdrawing or withholding statins from patients with HF. Ongoing randomized controlled trials that examine the efficacy of statin therapy in patients with HF should clarify the role of these agents in the context of HF.

Animals↗
PubMed2005

Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality.

We determined the effects of early statin treatment in acute myocardial infarction (AMI) on in-hospital morbidity and mortality. Experimental models of ischemia and reperfusion have shown that statins have early cardioprotective effects. However, the effect of statin use within the first 24 hours of admission on early morbidity and mortality in AMI has not been well studied. Data were collected on 300,823 patients who had AMI in the National Registry of Myocardial Infarction 4. In-hospital events were compared between patients who continued statin therapy received before the index AMI hospitalization (n = 17,118) or newly started statin therapy within the first 24 hours of hospitalization (n = 21,978) and patients who did not receive early statin treatment (n = 126,128) or whose statin therapy was discontinued (n = 9,411). New or continued treatment with a statin in the first 24 hours was associated with a decreased risk of mortality compared with no statin use (4.0% and 5.3% compared with 15.4% no statin). Discontinuation of statin treatment was associated with a slightly increased risk of mortality (16.5%). Early statin use was also associated with a lower incidence of cardiogenic shock, arrhythmias, cardiac arrest, rupture, but not recurrent myocardial infarction. Propensity analysis yielded mortality odds ratios of 0.46 for continued therapy, 0.42 for newly started therapy, and 1.25 for discontinued therapy for matched pairs versus no statin therapy (all p values <0.0001). In conclusion, the use of statin therapy within the first 24 hours of hospitalization for AMI is associated with a significantly lower rate of early complications and in-hospital mortality.

Aged↗
PubMed2004

Reduced creatine kinase release with statin use at the time of myocardial infarction.

BACKGROUND: Statin pre-treatment has been shown to reduce myocardial infarct size in animal models. We evaluated peak creatine kinase levels in humans based on concomitant or very early statin initiation following myocardial infarction. METHODS: We identified 66 consecutive patients who received a statin within 24 h of admission to our coronary care unit for myocardial infarction. Each statin patient was matched with three patients who had not received statin therapy (n=198). Statin patients were subgrouped into those receiving statin therapy at the time of infarction (n=44) and those initiated on statin therapy within 24 h of infarction (n=22). Peak total creatine kinase concentrations were compared between groups. A linear regression model was developed to test for differences in peak creatine kinase after adjusting for differences between groups. RESULTS: Patients receiving statin therapy within 24 h of admission had significantly smaller median peak creatine kinase concentrations compared to those not receiving a statin (416 IU/l [258, 992] vs. 699 IU/l [339, 1728]; p=0.020). Subgroup analysis revealed that the lower peak creatine kinase concentrations within the statin group were a result of lower creatine kinase concentrations in those patients on a statin at the time of myocardial infarction (399 IU/l [255, 869] vs. 678 IU/l [276, 1870]; p<0.05). This difference retained statistical significance after adjustment for differences between groups. CONCLUSION: Statin therapy at the time of myocardial infarction is associated with lower peak creatine kinase concentrations. This suggests that statins may exhibit protective effects in the setting of myocardial ischemia and/or infarction in humans.

Aged↗
PubMed2002

Withdrawal of statins increases event rates in patients with acute coronary syndromes.

BACKGROUND: HMG-CoA Reductase Inhibitors (statins) reduce cardiac event rates in patients with stable coronary heart disease. Withdrawal of chronic statin treatment during acute coronary syndromes may impair vascular function independent of lipid-lowering effects and thus increase cardiac event rate. METHODS AND RESULTS: We investigated the effects of statins on the cardiac event rate in 1616 patients of the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) study who had coronary artery disease and chest pain in the previous 24 hours. We recorded death and nonfatal myocardial infarction during the 30-day follow-up. Baseline clinical characteristics did not differ among 1249 patients without statin therapy, 379 patients with continued statin therapy, and 86 patients with discontinued statin therapy after hospitalization. Statin therapy was associated with a reduced event rate at 30-day follow-up compared with patients without statins (adjusted hazard ratio, 0.49 [95% CI, 0.21 to 0.86]; P=0.004). If the statin therapy was withdrawn after admission, cardiac risk increased compared with patients who continued to receive statins (2.93 [95% CI, 1.64 to 6.27]; P=0.005) and tended to be higher compared with patients who never received statins (1.69 [95% CI, 0.92 to 3.56]; P=0.15). This was related to an increased event rate during the first week after onset of symptoms and was independent of cholesterol levels. In a multivariate model, troponin T elevation (P=0.005), ST changes (P=0.02), and continuation of statin therapy (P=0.008) were the only independent predictors of patient outcome. CONCLUSIONS: Statin pretreatment in patients with acute coronary syndromes is associated with improved clinical outcome. However, discontinuation of statins after onset of symptoms completely abrogates this beneficial effect.

Acute Disease↗
PubMed2003

Determination of lipid profiles and use of statins in patients with ischemic stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Statins reduce the risk of myocardial infarction and stroke in patients with vascular disease. Inappropriate serum lipid determination and underuse of statins have been documented in patients with coronary artery disease. Evaluation of hyperlipidemia and treatment with statins in patients with recent ischemic cerebrovascular events have not yet been investigated. METHODS: We determined the frequency of total cholesterol (TC) and low-density lipoprotein cholesterol measurements and the use of statins in a multicenter prospective cohort study of 1743 patients with acute ischemic stroke or transient ischemic attack (TIA). Using multivariate logistic regression analysis, we determined the influence of several clinical variables on lipid measurements and the prescription of statins at hospital discharge. RESULTS: TC was measured in 90% and low-density lipoprotein cholesterol was measured in 48% of the patients. Differences between the centers accounted for most of the observed variability in a multivariate model. Statin prescription also varied widely between the centers. The prescription of a statin at discharge was most strongly associated with statin intake before the event and with increasing TC levels; elderly patients received statins less often. Coronary artery disease, peripheral artery disease, and other manifestations of atherosclerosis were not independently associated with the use of statins; 68% of the patients with manifest atherosclerosis and TC levels >200 mg/dL were discharged without a statin. CONCLUSIONS: The determination of serum lipid profiles varies widely between different centers. Statins are highly underused in patients with recent ischemic stroke or TIA, particularly in those in whom statins are indicated according to existing recommendations (eg, patients with additional coronary artery disease and hypercholesterolemia). Currently, international guidelines concerning the use of statins are not adequately implemented in clinical practice in patients with stroke or TIA.

Aged↗
PubMed2006

How many "Me-Too" drugs are enough? The case of physician preferences for specific statins.

BACKGROUND: The increasing availability of "Me-Too" drugs has provided considerable treatment options for clinicians. However, the number of such drugs within a class that are actually used by clinicians has not been well studied. OBJECTIVE: To determine the number of different statins that individual physicians use in practice. METHODS: The Ontario Drug Benefit database was used to identify physicians who issued at least 10 incident statin prescriptions between October 2001 and May 2003 for patients aged 66 years and older. A preferred statin was defined for each physician, and the proportion of each physician's incident prescriptions written for that agent was determined. We then determined the number of different statins required to fill each physician's incident prescribing needs. RESULTS: A total of 3426 physicians wrote 73,571 incident statin prescriptions. The mean percentage of prescriptions written for each physician's preferred statin formulation was 73.7%. Repeat analysis to examine the proportion of prescriptions filled using each physician's top 2 statin formulations found that the average physician wrote the vast majority of his or her incident prescriptions (94.9%) for only 1 or 2 statins. Half of all physicians used, at most, 2 different statins for all incident prescribing, while 91.3% of physicians used, at most, 3 different statins for all of their incident prescribing. CONCLUSIONS: A high proportion of Ontario physicians issued the majority of their incident statin prescriptions for the same statin formulation. Most physicians required, at most, 3 different statins for all incident statin prescribing.

Adult↗
PubMed2006

Drug and medical cost effects of a drug formulary change with therapeutic interchange for statin drugs in a multistate managed Medicaid organization.

OBJECTIVE: Therapeutic interchange (TI) interventions are commonly used to manage pharmacy benefit costs. While several studies have considered the effect that TI interventions have on drug costs, most have not considered the effect they have on medical management costs. The purpose of the present study was to assess drug cost and drug therapy management costs of a TI intervention following a change in the drug formulary for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) drugs, including the conversion of atorvastatin from formulary to nonformulary status. METHODS: A retrospective, quasi-experimental within-subjects design was used in this study. Administrative claims data were obtained from a select northeastern segment of a multistate Medicaid managed care organization (MCO). To be included in the study, patients had to meet the following criteria: (1) they must have had a minimum of 3 atorvastatin prescriptions during a 6-month enrollment phase, (2) they must have been continuously enrolled throughout the 900-day study period, and (3) they must have switched from atorvastatin to another statin between April 1, 2003, and July 31, 2003. The day of the switch from atorvastatin marked for each patient the end of the 12-month pre-TI period and the beginning of the 12-month post-TI period. Two separate dependent variables were developed: (1) statin drug costs (statin cost + dispensing fee) and (2) the costs paid by the MCO for the medical management of statin therapy, including office visit costs and the medical laboratory costs of measuring lipids and creatine kinase, and of checking liver functions. To estimate expenditures over 24 months, a panel analytic technique was used that allows each patient to serve as his or her own control. Multivariate models were used to assess the effects of the TI policy while controlling for age, gender, adjunctive dyslipidemia therapy, comorbidity, presence of a prior coronary artery event, statin compliance, cardiologist management, and disease severity. RESULTS: Of the 3,636 patients who met the study inclusion criteria and were converted from atorvastatin to an alternate statin drug, 129 patients (3.5%) switched back to atorvastatin following the TI. The average statin cost per claim in the 12-month post-TI period was Dollars 70.93, 9.5% less than the average cost in the 12-month pre-TI period (Dollars 78.40). The average cost per patient per year (PPPY) for statin laboratory tests (lipid panels, creatine kinase tests, and liver function tests) increased by 31.5% to Dollars 16.15 in the post-TI period compared with Dollars 12.28 PPPY in the pre-TI period, and medical office visit costs increased by 44.9% to Dollars 20.70 PPPY in the post-TI period compared with Dollars 14.29 PPPY in the preperiod. These increased costs related to the medical management of statin therapy were overwhelmed by an 11.7% reduction in statin drug costs, from Dollars 793.69 PPPY in the pre-TI period to Dollars 701.01 PPPY in the post-TI period, resulting in a net 10.0% reduction for combined statin costs and related medical costs, from Dollars 820.27 PPPY in the pre-TI period to Dollars 737.87 in the post-TI period. After limiting the analysis to patients who did not convert from atorvastatin to pravastatin (which cost more than atorvastatin before the rebate) and controlling for the influence of potential confounders, statin expenditure decreased by 33% (P < 0.001). Multivariate models indicated no statistically significant differences in the costs related to the medical management of statin therapy after the TI compared with before the TI.

Acyl Coenzyme A↗
PubMed1990

Expression of statin, a non-proliferation-dependent nuclear protein, in the postnatal rat brain: evidence for substantial retention of neuroglial proliferative capacity with aging.

Statin is a 57 kDa protein expressed in nuclei of reversibly and irreversibly growth-arrested (Go-phase) cells. In this report, immunohistochemical localization of statin in the developing and aging rat brain was achieved using the monoclonal antibody, S-44. On postnatal day 2, post-migratory neurons in the developing cerebral cortex were statin-positive. Many statin-negative cells were observed in the lateral subependymal zone of the lateral ventricle. By postnatal day 10, most neuronal nuclei were statin-positive although small numbers of statin-negative neurons were still encountered in the lateral subependymal zone and hippocampal dentate gyrus. At 3, 18 and 33 months, all neuronal nuclei surveyed were statin-positive. These results support the contention that, save for the postnatal persistence of 'germinal zones' such as the subependymal region and dentate gyrus, neuronal proliferation in the rat is largely completed by the time of birth. In striking contrast to neuronal statin expression, a significant fraction of neuroglia in both grey and white matter remains statin-negative at all ages examined. In the corpus callosum, 33.2%, 34.0% and 34.7% of glial nuclei were statin-negative at 3, 18 and 33 months, respectively. These findings indicate that: (i) even in senescent brain, the cycling (statin-negative) glial pool is substantially larger than previously surmised from S-phase labeling experiments; and (ii) during aging, the ratio of noncycling-to-cycling neuroglia remains very tightly regulated. Examination of other non-neuronal cell types revealed that most, if not all, ependymal and choroid plexus epithelial cells were statin-positive in the neonatal and adult brains in keeping with the predominantly prenatal proliferation of these tissues. Our results indicate that statin immunolabeling using the S-44 antibody is a powerful technique for the in situ identification of non-proliferating cells in the developing and aging nervous system.

Aging↗
PubMed2006

Statin safety: an overview and assessment of the data--2005.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statin drugs, have been studied in numerous controlled human research trials involving hundreds of thousands of study participants. Statins have been prescribed for millions of patients. Based on this vast research and clinical experience, statins have been shown to improve lipid blood levels and reduce atherosclerotic coronary artery disease (CAD) risk, resulting in reduced CAD morbidity and mortality, and in several studies, reduced overall ("all-cause") mortality. From a safety perspective, both research trial evidence and clinical practice experience have demonstrated that statins are generally well tolerated. However, as with all pharmaceuticals, safety considerations exist with both monotherapy and combination statin therapy, mainly involving potential adverse effects on muscle, liver, kidney, and the nervous system. The evidence supporting statin-related potential adverse experiences on these organ systems is sometimes strong and based on clear clinical trial evidence (such as the increased risk of muscle enzyme elevation with higher statin doses). The evidence is at other times more speculative, being based on case reports and inconclusive clinical trial data (such as possible favorable or unfavorable effects of statins on cognition). Because the use of statins is so widespread, it is useful for the clinician to understand statin safety issues and the level of available evidence supporting the contention that various adverse effects are caused by statins. This review presents an assessment of statin safety based on an overview of the current statin safety data and their clinical implications.

Chemical and Drug Induced Liver Injury↗
PubMed2005

Safety of statins when response is carefully monitored: a study of 336 heart recipients.

BACKGROUND: Statins are used as first-line drugs against hypercholesterolemia after heart transplantation. Randomized clinical trials have shown that they reduce cholesterol levels, and the incidence of rejection and coronary vasculopathy. Adverse effects have been related to the use of certain statins, high statin dosages, comorbidities, and coadministration with cyclosporine. However, estimation of the risk of adverse effects for a given patient is difficult. The aims of this study were to determine the incidence of various kinds of adverse effect of statins; to evaluate certain potential risk factors; and to assess the efficacy of early response to signs of adverse effects. METHODS: Between April 1991 and December 2003, we retrospectively evaluated 336 heart transplant patients (including 55 women) with regard to the occurrence of possible adverse effects of statins (rhabdomyolysis, myalgia, hepatotoxicity, high CK without muscle symptoms, and others). Resolution on reduction of dosage or discontinuance and/or change of statin were deemed to constitute confirmation of cause. Relations were sought between adverse effects and age, sex, immunosuppressive therapy, kidney failure, body mass index (BMI), arterial hypertension, and diabetes mellitus. RESULTS: Possible adverse events of statins were suffered by 60 patients, all of them men. The causal role of statins was confirmed in 41 (12.2% of all 336): hepatotoxicity was suffered by 13, high CK without muscle ache or weakness by 18, rhabdomyolysis by 5, myalgia by 3, and other effects by 2. The incidence of confirmed statin-related complications was higher among patients with BMI >29 kg/m(2) than among those with lower BMI (P = .055). None of the patients with confirmed statin-related complications needed dialysis, none died, and permanent suspension of statin treatment was only necessary in 13 cases (3.9% of the 336). CONCLUSIONS: Some 10% to 20% of HT patients appear to suffer adverse side effects of initial statin therapy. However, early detection of such effects through diligent clinical and analytical monitoring allows the therapy to be modified in time to minimize the appearance of severe complications. In only a minority of cases permanent suspension of statin therapy is necessary.

Adolescent↗
PubMed2002

Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia.

Ezetimibe is a lipid-lowering drug that inhibits the intestinal absorption of dietary and biliary cholesterol by blocking passage across the intestinal wall. The efficacy and safety of adding ezetimibe to ongoing statin therapy in patients with primary hypercholesterolemia was evaluated in a randomized, double-blind, placebo-controlled study. The study group included 769 adults (aged > or =18 years) with primary hypercholesterolemia who had not achieved National Cholesterol Education Program (NCEP) Adult Treatment Panel II goals with dietary alteration and statin monotherapy. Patients receiving a stable dose of a statin for > or =6 weeks were randomized to receive concurrent treatment with placebo (n = 390) or ezetimibe (n = 379), 10 mg/day, in addition to continuing their open-label statin for 8 weeks. The primary efficacy variable was the percent change in low-density lipoprotein (LDL) cholesterol from baseline with statin monotherapy to end point after intervention (secondary variables: high-density lipoprotein [HDL] cholesterol and triglycerides). Ongoing statin therapy plus ezetimibe led to changes of -25.1% for LDL cholesterol (HDL cholesterol +2.7%; triglycerides -14.0%) compared with LDL cholesterol -3.7% (p <0.001), HDL cholesterol +1.0% (p <0.05), and triglycerides -2.9% (p <0.001) for placebo added to ongoing statin therapy. Among patients not at LDL cholesterol goal at on-statin baseline, 71.5% receiving statin plus ezetimibe versus 18.9% receiving statin plus placebo reached goal at end point (odds ratio 23.7; p <0.001). The co-administration of statin and ezetimibe was generally well tolerated. Adding ezetimibe to ongoing statin therapy led to substantial additional reduction in LDL cholesterol levels, facilitating attainment of NCEP goals. Ezetimibe offers a new therapeutic option for patients receiving statins who require further reduction in LDL cholesterol.

Adult↗
PubMed2002

Statin therapy is associated with reduced mortality across all age groups of individuals with significant coronary disease, including very elderly patients.

OBJECTIVES: This study evaluated the effect of statin therapy on mortality in individuals with significant coronary artery disease (CAD) stratified by age. BACKGROUND: Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) significantly reduce morbidity and mortality in individuals with CAD. Unfortunately, the large statin trials excluded individuals over 80 years old, and it is therefore unknown whether very elderly individuals benefit from statins as do younger individuals. METHODS: A cohort of 7,220 individuals with angiographically defined significant CAD (> or =70%) was included. Statin prescription was determined at hospital discharge. Patients were followed up for 3.3 +/- 1.8 years (maximum 6.8). Patients were grouped by age (<65, 65 to 79, and > or =80 years) to determine whether statin therapy reduced mortality in an age-dependent manner. RESULTS: Average age was 65 +/- 12 years; 74% were male; and 31% had a postmyocardial infarction status. Overall mortality was 16%. Elderly patients were significantly less likely to receive statins than younger patients (> or =80 years: 19.8%; 65 to 79 years: 21.1%; <65 years: 28.0%; p < 0.001). Mortality was decreased among statin recipients in all age groups: > or =80 years: 29.5% among patients not taking a statin versus 8.5% of those taking a statin (adjusted hazard ratio [HR] 0.50, p = 0.036); 65 to 79 years: 18.7% vs. 6.0% (HR 0.56, p < 0.001); and <65 years: 8.9% vs. 3.1% (HR 0.70, p = 0.097). CONCLUSIONS: Statin therapy is associated with reduced mortality in all age groups of individuals with significant CAD, including very elderly individuals. Although older patients were less likely to receive statin therapy, they received a greater absolute risk reduction than younger individuals. More aggressive statin use after CAD diagnosis may be indicated, even in older patients.

Adult↗
PubMed2004

Prescription of statins to dyslipidemic patients affected by liver diseases: a subtle balance between risks and benefits.

AIM: Statins reduce cardiovascular morbidity and mortality in the general population with an excellent risk-benefit profile. The most frequent adverse events are myopathy and increase in hepatic aminotransferases. In this review, we consider the role of liver in metabolism of statins, their potential hepatic toxicity and the guidelines for their prescription in patients affected by different liver diseases. DATA SYNTHESIS: Statin-induced hepatic toxicity: i) occurs in 1-3% of patients; ii) is characterized by increased aminotransferase levels; iii) is dose-related; iv) is frequently asymptomatic; v) usually reverts after dosage reduction or treatment withdrawal. Finally, after recovery, a rechallenge with the same or other statins may not result in increased aminotranferases. CONCLUSIONS: Caution is needed when prescribing statins to patients with liver disease, and liver toxicity should always be monitored during statin treatment. In particular, i) the potential hepatic toxicity requires frequent control of biochemical parameters related to hepatic cytolysis and cholestasis in all patients on statins; ii) administration of statins is counterindicated in patients with advanced or end-stage parenchymal liver disease due to the relevant impairment of their metabolism; iii) cholestatic disorders with secondary dyslipidemia do not require statin treatment even if relevant alterations of the lipid pattern are detected; iv) patients with acute liver disease of viral or alcoholic etiology should not receive statins until normalization of cytolysis enzymes; v) chronic hepatitis patients may be treated by statins if their cardiovascular risk is elevated and provided that careful follow-up is carried out to rapidly recognize the onset of further liver damage; vi) liver transplantation recipients affected by dyslipidemia induced by immunosuppressive therapy can be treated with statins under careful clinical control; vii) the benefits of statins should likely overcome the risks in the large majority of dyslipidemic patients affected by non-alcoholic hepatosteatosis, a disease frequently diagnosed in insulin-resistant subjects.

Alanine Transaminase↗
PubMed2006

The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study.

BACKGROUND: Statins improve cardiovascular outcome, but less is known on the renal outcome. We, therefore, studied the relationship between the use of statins and urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in two settings: a randomized controlled trial (RCT) and an observational cohort study, in which patients were included to study the impact of an elevated UAE on renal and cardiovascular prognosis. METHODS: We used data from the Prevention of REnal and Vascular ENd-stage Disease Intervention trial (PREVEND-IT) and the PREVEND cohort study. The PREVEND-IT subjects (788 with a UAE 15-300 mg/day) received pravastatin 40 mg/day vs placebo and/or fosinopril 20 mg/day vs placebo in a 2x2 factorial-RCT design. Of the 3440 cohort subjects, 469 used statins during the 4-year follow-up period. Multivariate-regression adjusted for confounding factors and the propensity score was used to estimate the relation between statin use and UAE and GFR. RESULTS: In the RCT, pravastatin did not change UAE or GFR, neither in fosinopril yes/no subgroups. In the observational cohort, statin use was associated with a rise in UAE (+12.1%), compared with statin non-use (+3.6%, P<0.001). This rise was most pronounced in those on statins prior to the first screening [+24.8% (95% CI: 11.9-39.2)], those using statins>3 years [+18.5% (7.3-30.8)] and those with >1 or >2 defined daily doses (+15.7 and +17.3%, respectively). These differences remained significant after adjustment for relevant variables and propensity score. The rise in UAE could not be attributed to a higher dose or a specific statin. GFR fell in 4 years in both statin users and non-users (4.6+/-13.5 and 2.4+/-11.2, respectively). The fall in GFR between groups was not different after adjustment (P=0.11). CONCLUSIONS: We conclude from the RCT data that statins do not lower UAE in subjects selected because of an elevated UAE instead of hyperlipidaemia. In the observational cohort study, the use of statins similarly was not associated with a fall in UAE; UAE instead increased. Statin treatment was not associated with a significant change in GFR in these subjects with only modestly impaired GFR.

Adult↗
PubMed2003

Withdrawal of statin treatment abrogates stroke protection in mice.

BACKGROUND AND PURPOSE: Statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors) reduce stroke damage independent of lipid lowering by upregulation of endothelial nitric oxide synthase (eNOS). Acute withdrawal of statin treatment may suppress endothelial NO production and impair vascular function. METHODS: To test this hypothesis, we treated 129/SV mice with atorvastatin (10 mg/kg) for 14 days and then withdrew treatment. RESULTS: Treatment with atorvastatin conferred stroke protection by 40% after filamentous occlusion of the middle cerebral artery followed by reperfusion. Withdrawal of statin treatment, however, resulted in the loss of stroke protection after 2 and 4 days. In mouse aortas and brain vasculature, statins upregulated eNOS message 2.3- and 1.7-fold, respectively, as measured by reverse transcription-polymerase chain reaction. Withdrawal of statins resulted in 5- and 2.7-fold downregulation of eNOS in aorta and brain, respectively, after 2 days. Statin treatment decreased RhoA GTPase membrane expression to 48%, while withdrawal of statins resulted in 4-fold increase of RhoA in the membrane. Moreover, platelet factor 4 and beta-thromboglobulin in plasma were significantly downregulated by statin treatment, but withdrawal of statins resulted in a 2.9- and 3.1-fold upregulation after 2 days, respectively. Thrombus formation induced by ligature of the inferior vena cava was significantly reduced by statin treatment. When statin treatment was withdrawn, however, protection was lost between 2 and 4 days. CONCLUSIONS: Acute termination of statin treatment results in a rapid loss of protection in mouse models of cerebral ischemia and thrombus formation independent of lipid lowering. In patients with acute or impending stroke, withdrawal of statins may impair outcome.

Animals↗