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 145 records · Page 8Linked to original sources
PubMed2005

Progression of aortic valve sclerosis and aortic valve stenosis: what is the role of statin treatment?

BACKGROUND: It has recently been suggested that statins could slow the progression of aortic stenosis, but this hypothesis has not been validated in large series. Moreover, there is little information about the role of statin treatment in patients with aortic valve sclerosis. METHODS: From our database 1988--2002, we retrospectively identified 1136 consecutive patients with aortic valve sclerosis (peak aortic velocity [Vmax] > 1.5 and < 2 m/s), or mild to moderate aortic stenosis (Vmax 2.0-3.9 m/s) and with > or = 2 echocardiographic studies > or = 6 months apart; 121 (11 %) were treated with statins. As a control group we randomly selected 121 age-gender-matched patients not treated with statins, with similar initial Vmax. RESULTS: The mean follow-up duration was 54+/-34 months in the statin group, and 50+/-33 months in controls (p = 0.35). There were no differences between statin-treated patients and controls with respect to age, gender, and prevalence of hypertension. More patients in the statin group had documented hypercholesterolemia, diabetes, or had proven coronary artery disease. Overall, the rate of change of Vmax was not different between statin-treated patients and controls (0.13+/-0.24 vs 0.14+/-0.19 m/s/year, p = 0.72). However, in the subgroup of patients with aortic valve sclerosis (n = 52, 26 statin-treated, 26 controls), the rate of change of Vmax was significantly lower in statin-treated patients (0.04+/-0.04 vs 0.08+/-0.06 m/s/year, p = 0.007). CONCLUSIONS: The results of our retrospective study show that statins could be beneficial in retarding the progression of valvular aortic sclerosis to aortic stenosis. This suggests that statins retard the progression of aortic valve lesion in its early stage, a finding that may have important implications in the management of this very common disease.

Aged↗
PubMed2005

Modulation of the inflammatory process by statins.

Statins reduce cholesterol levels through competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme that regulates cholesterol synthesis. The cholesterol-lowering effect of statins is also due to an increase in the uptake of cholesterol by cells as a result of intracellular cholesterol depletion and enhanced expression of low-density lipoprotein (LDL) receptors. The use of statins as lipid-lowering agents has lead to remarkable changes in the treatment and prevention of ischemic heart disease. Results of large clinical trials of patients with ischemic heart disease have demonstrated that statins reduce inflammatory markers such as C-reactive protein, an independent risk factor in the disease. Statins exhibit properties that are beyond their lipid-lowering effects. These non-lipid-lowering properties involve the inhibition of the isoprenoid pathway through decreased synthesis of many nonsteroidal isoprenoid compounds. The focus on the immunomodulatory effect of statins is the result of the positive outcome of pravastatin treatment in cardiac transplantation patients, as well as angiographic regression studies showing insignificant changes in the degree of coronary stenosis despite a large reduction in cardiac events. Statin treatment reduces the risk of ischemic stroke despite the fact that LDL cholesterol is not directly associated with the risk of stroke. This observation lead to the investigation of the role of statins in inflammation and the immune system. Recent research data demonstrated that statins inhibit the induction of the major histocompatibility (MHC) class II expression by interferon-gamma (IFN-gamma), leading to repression of MHC II-mediated T-cell activation. Furthermore, statins inhibit the expression of specific cell surface receptors on monocytes, adhesion molecules and also integrin-dependent leucocyte adhesion. While statins may stimulate the secretion of caspase-1, IL-1beta and IL-18 in peripheral mononuclear cells in response to Mycobacterium tuberculosis, they exhibit additional effects on inflammation by decreasing IL-6 synthesis in human vascular smooth muscle cells (VSMC) in vitro. The focus of this monograph is to highlight the role of statins in the modulation of the immune system and inflammatory processes.

C-Reactive Protein↗
PubMed2026

Cardioprotective glucose-lowering drugs, statins, and secondary major adverse cardiovascular events: a nationwide cohort study of individuals with type 2 diabetes and cardiovascular disease.

BACKGROUND: In type 2 diabetes, cardioprotective glucose-lowering drugs, including sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, and statins reduce the risk of secondary major adverse cardiovascular events. No trials examined the combination of these drugs as withholding statins in high-risk individuals would be unethical. We tested the hypothesis that cardioprotective glucose-lowering drug and statin combined is associated with lower risk of secondary major adverse cardiovascular events than either drug alone. METHODS: Individuals with type 2 diabetes and established cardiovascular disease from December 2012 through 2021 were identified via national Danish health registers. They were analyzed in an active comparator cohort including 15,404 individuals followed from treatment intensification with cardioprotective glucose-lowering drug or dipeptidyl peptidase-4 inhibitor and additionally in a time-varying cohort including 76,853 individuals with yearly updated treatment and covariate status. The treatment groups were: (i) no cardioprotective drug (no use of cardioprotective glucose-lowering drug or statin), (ii) cardioprotective glucose-lowering drug, (iii) statin, and (iv) cardioprotective glucose-lowering drug and statin. The primary outcome was a new major adverse cardiovascular event (myocardial infarction, stroke, or cardiovascular death). RESULTS: During mean 2.7 and 4.7&#xa0;years of follow-up, 1,843 and 23,051 had major adverse cardiovascular events in the active comparator and time-varying cohorts. In the active comparator cohort, when compared to nonusers of cardioprotective glucose-lowering drug or statin, multivariable adjusted hazard ratios of major adverse cardiovascular events were 0.82 (95% confidence interval: 0.67 to 1.02) for cardioprotective glucose-lowering drug, 0.85 (0.74 to 0.97) for statin, and 0.71 (0.60 to 0.84) for cardioprotective glucose-lowering drug and statin combined. Corresponding hazard ratios in the time-varying cohort were 0.77 (0.69 to 0.86), 0.73 (0.70 to 0.75), and 0.57 (0.54 to 0.60), respectively. When restricting the active comparator cohort to individuals entering observation between 2019 and 2021 with reduced statistical power, the corresponding hazard ratios were 0.86 (0.57 to 1.31), 0.89 (0.60 to 1.30), and 0.79 (0.54 to 1.14), respectively. In both cohorts p for interaction between cardioprotective glucose-lowering drug and statin was&#x2009;>&#x2009;0.05. CONCLUSIONS AND RELEVANCE: In individuals with type 2 diabetes and established cardiovascular disease, treatment with a cardioprotective glucose-lowering drug and statin in combination was associated with lower risk of secondary major adverse cardiovascular events than using either drug alone. This is important given the persistently suboptimal uptake of both drug classes in real-world practice. Some biases can never be completely excluded in real-world pharmacotherapy use studies such as this one, including confounding by indication, time-related or immortal time biases, and shifting standards of care, rendering causal interpretation unattainable; however, our results seemed consistent across numerous sensitivity analyses and designs.

Humans↗
PubMed2004

Early withdrawal of statin therapy in patients with non-ST-segment elevation myocardial infarction: national registry of myocardial infarction.

BACKGROUND: There is increasing interest in the non-lipid-lowering effects of statins and their effect on outcomes in patients with acute coronary syndrome. It has been suggested that withdrawal of statin therapy during an acute coronary syndrome may attenuate any benefits of pretreatment, thereby providing indirect evidence of the importance of their non-lipid-lowering effects. METHODS: This observational study compared the demographic and clinical characteristics and hospital outcomes in patients with non-ST-segment elevation myocardial infarction enrolled in the National Registry of Myocardial Infarction 4. Comparison groups consisted of patients previously receiving statins who also received statins within 24 hours of hospital admission (n = 9,001), patients previously using statins in whom therapy was discontinued (n = 4,870), and patients who did not receive statins at any time before or during hospitalization (n = 54,635). RESULTS: Of 13,871 patients receiving statins before hospital admission, 35.1% had treatment withdrawn during the first 24 hours of hospitalization. These patients had increased hospital morbidity and mortality rates relative to patients in whom therapy was continued, with higher rates of heart failure, ventricular arrhythmias, shock, and death. In multivariate analyses, these patients were at statistically significant increased risk of hospital death compared with those continuing statin therapy and at similar risk compared with those not receiving statins before or during hospitalization. CONCLUSIONS: Withdrawal of statin therapy in the first 24 hours of hospitalization for non-ST-segment elevation myocardial infarction is associated with worse hospital outcomes. In the absence of data from randomized clinical trials, our findings suggest that statin therapy should be continued during hospitalization for myocardial infarction unless strongly contraindicated.

Aged↗
PubMedDate not supplied

Early statin treatment following acute myocardial infarction and 1-year survival.

CONTEXT: Randomized trials have established statin treatment as secondary prevention in coronary artery disease, but it is unclear whether early treatment with statins following acute myocardial infarction (AMI) influences survival. OBJECTIVE: To evaluate the association between statin treatment initiated before or at the time of hospital discharge and 1-year mortality after AMI. DESIGN AND SETTING: Prospective cohort study using data from the Swedish Register of Cardiac Intensive Care on patients admitted to the coronary care units of 58 Swedish hospitals in 1995-1998. One-year mortality data were obtained from the Swedish National Cause of Death Register. PATIENTS: Patients with first registry-recorded AMI who were younger than 80 years and who were discharged alive from the hospital, including 5528 who received statins at or before discharge and 14 071 who did not. MAIN OUTCOME MEASURE: Relative risk of 1-year mortality according to statin treatment. RESULTS: At 1 year, unadjusted mortality was 9.3% (1307 deaths) in the no-statin group and 4.0% (219 deaths) in the statin treatment group. In regression analysis adjusting for confounding factors and propensity score for statin use, early statin treatment was associated with a reduction in 1-year mortality (relative risk, 0.75; 95% confidence interval, 0.63-0.89; P =.001) in hospital survivors of AMI. This reduction in mortality was similar among all subgroups based on age, sex, baseline characteristics, previous disease manifestations, and medications. CONCLUSIONS: Early initiation of statin treatment in patients with AMI is associated with reduced 1-year mortality. These results emphasize the importance of implementing the results of randomized statin trials in unselected AMI patients.

Aged↗
PubMedDate not supplied

Adherence with statin therapy in elderly patients with and without acute coronary syndromes.

CONTEXT: Landmark clinical trials have demonstrated the survival benefits of statins, with benefits usually starting after 1 to 2 years of treatment. Research prior to these trials of older lipid-lowering agents demonstrated low levels of 1-year adherence. OBJECTIVE: To compare 2-year adherence following statin initiation in 3 cohorts of patients: those with recent acute coronary syndrome (ACS), those with chronic coronary artery disease (CAD), and those without coronary disease (primary prevention). DESIGN AND SETTING: Cohort study using linked population-based administrative data from Ontario. PATIENTS: All patients aged 66 years or older who received at least 1 statin prescription between January 1994 and December 1998 and who did not have a statin prescription in the prior year were followed up for 2 years from their first statin prescription. There were 22,379 patients in the ACS, 36,106 in the chronic CAD, and 85,020 in the primary prevention cohorts. MAIN OUTCOME MEASURES: Adherence to statins, defined as a statin being dispensed at least every 120 days after the index prescription for 2 years. RESULTS: Two-year adherence rates in the cohorts were only 40.1% for ACS, 36.1% for chronic CAD, and 25.4% for primary prevention. Relative to the ACS cohort, nonadherence was more likely among patients receiving statins in the chronic CAD (relative risk [RR], 1.14; 95% CI, 1.11-1.16) and primary prevention cohorts (RR, 1.92; 95% CI, 1.87-1.96). CONCLUSIONS: Elderly patients with and without recent ACS have low rates of adherence to statins. This suggests that many patients initiating statin therapy may receive no or limited benefit from statins because of premature discontinuation.

Acute Disease↗
PubMed2006

Statins and cancer risk: a meta-analysis.

CONTEXT: Statins are cholesterol-lowering drugs that have been proven in randomized controlled trials to prevent cardiac events. Recent retrospective analyses have suggested that statins also prevent cancer. OBJECTIVES: To investigate the effect of statin therapy on cancer incidence and cancer death and to analyze the effect of statins on specific cancers and the effect of statin lipophilicity or derivation. DATA SOURCES: A systematic literature search of MEDLINE, EMBASE, CINAHL, Web of Science, CANCERLIT, and the Cochrane Systematic Review Database through July 2005 was conducted using specific search terms. A review of cardiology and cancer abstracts and manual review of references was also performed. STUDY SELECTION: Twenty-seven of the 8943 articles (n = 86,936 participants) initially identified met the inclusion criteria, reporting 26 randomized controlled trials of statins, with a mean duration of follow-up of at least 1 year, enrolling a minimum of 100 patients, and reporting data on either cancer incidence (n = 20 studies) or cancer death (n = 22 studies). DATA EXTRACTION: All data were independently extracted by 3 investigators using a standardized data abstraction tool. Weighted averages were reported as odds ratios (ORs) with 95% confidence intervals (CIs) using a random-effects model (DerSimonian and Laird methods). Statistical heterogeneity scores were assessed with the Q statistic. DATA SYNTHESIS: In meta-analyses including 6662 incident cancers and 2407 cancer deaths, statins did not reduce the incidence of cancer (OR, 1.02; 95% CI, 0.97-1.07) or cancer deaths (OR, 1.01; 95% CI, 0.93-1.09). No reductions were noted for any individual cancer type. This null effect on cancer incidence persisted when only hydrophilic, lipophilic, naturally derived, or synthetically derived statins were evaluated. CONCLUSIONS: Statins have a neutral effect on cancer and cancer death risk in randomized controlled trials. We found that no type of cancer was affected by statin use and no subtype of statin affected the risk of cancer.

Humans↗
PubMed2004

HMG CoA reductase inhibitors (statins) for dialysis patients.

BACKGROUND: Cardiovascular disease accounts for more than half the number of deaths among dialysis patients. The role of HMG CoA reductase inhibitors (statins) in the treatment of hyperlipidemia in dialysis patients is unclear and their safety has not been established. OBJECTIVES: To assess the benefits and harms of statins in peritoneal dialysis (PD) and hemodialysis patients (HD). SEARCH STRATEGY: We searched MEDLINE (1966-July 2003), EMBASE (1980-July 2003), the Cochrane Central Register of Controlled trials (CENTRAL, in The Cochrane Library - issue 2, 2004), the Cochrane Renal Group's specialized register (April 2004) and handsearched reference lists of textbooks, articles and scientific proceedings. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs comparing statins with placebo, no treatment or other statins in dialysis patients. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model after testing for heterogeneity. The results were expressed as weighted mean difference (WMD) for continuous outcomes and relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). MAIN RESULTS: Six studies involving 357 participants were identified - three studies had both continuous ambulatory peritoneal dialysis (CAPD) and HD participants, two included only HD participants and one study only included CAPD participants. Studies were all of short duration and morbidity and mortality were not assessed. Average total cholesterol decreased significantly with statins compared to placebo in all dialysis patients (WMD -53.70 mg/dL (1.40 mmol/L), 95% CI -66.95 to -40.54). Similarly, average LDL cholesterol decreased significantly with statins in comparison to placebo in all patients (WMD -55.40 mg/dL (1.44 mmol/L), 95% CI -69.90 to -40.90) as did average triglycerides (-33.72 mg/dL (0.37 mmol/L), 95% CI -54.16 to -13.28). There was a significant increase in average HDL cholesterol levels (WMD 4.84 mg/dL (0.13 mmol/L), 95% CI 0.28 to 9.40) with statins compared to placebo in HD but not in CAPD patients. One trial compared statins to the hypolidemic agent probucol and found no significant differences between the two treatment groups. REVIEWERS' CONCLUSIONS: Statins used for 12 weeks decreased cholesterol levels in dialysis patients similar to the general population. Included studies were of short duration and therefore the efficacy of statins in decreasing the cardiovascular, cerebrovascular events and mortality rates is still unclear. The safety of statins needs to be addressed in the current ongoing clinical trials.

Cholesterol↗
PubMed1990

The relationship of expression of statin, the nuclear protein of nonproliferating cells, to the differentiation and cell cycle of astroglia in cultures and in situ.

Cells in the quiescent, nonproliferative state express a protein, statin, in their nuclei. When the cells reenter the cell cycle, statin disappears and another protein, cyclin, appears. We have examined mouse astroglia at various stages of differentiation in cultures and astroglia in adult mouse brains for the presence of statin. In cultures initiated from the neopallium of newborn mice, the glial fibrillary acidic protein (GFAP)+ stellate astrocytes were statin-negative (statin-) but cyclin-positive (cyclin+). In the same cultures, large flat cells (senescent cells) were statin+ but cyclin-. In frozen sections of the brains of adult mice and in brain smears, GFAP+ astrocytes were statin-. Neither stellate astrocytes grown in cultures for 30 or more days nor astrocytes in adult mouse brain were labeled when pulsed with bromodeoxyuridine (BudR). When astroglia were treated with dibutyrl cyclic adenosine monophosphate (dBcAMP), large stellate cells that closely resemble reactive astrocytes in situ formed. These cells were all statin+ from 11-62 days in vitro; however, reactive astrocytes in mouse neopallium, 4-50 days after a stab wound, were statin-. In colony cultures, senescent cells became statin+, whereas stellate astrocytes and their precursor cells remained statin-. These observations indicate that normal astrocytes both in cultures and in situ retain the potential to divide and probably progress through the cell cycle at a very slow rate.

Animals↗
PubMed2006

Results from a rosuvastatin historical cohort study in more than 45,000 Dutch statin users, a PHARMO study.

PURPOSE: Clinical benefits of statin therapy are accepted, but their safety profiles have been under scrutiny, particularly for the recently introduced statin, rosuvastatin, relating to serious adverse events involving muscle, kidney and liver. Therefore, a historical cohort study was performed to evaluate the association between rosuvastatin versus other statin use and the incidence of rhabdomyolysis, myopathy, acute renal failure and hepatic impairment. METHODS: Incident users of rosuvastatin or other statins in 2003-2004 and a cohort of patients not prescribed statins were included from the PHARMO database of >2 million Dutch residents. Cases of hospitalisations for myopathy, rhabdomyolysis, acute renal failure or hepatic impairment were identified for these cohorts. Potential cases were validated through a multi-step process using data obtained from hospital records. Additionally, cases of all cause deaths were identified from certification alone. RESULTS: In 2003 and 2004, 10,147 incident rosuvastatin users, 37,396 incident other statin users and 99,935 patients without statin prescriptions were included. There were 26 validated outcome events in the three cohorts including one case each of myopathy (other statin group) and rhabdomyolysis (non-treated group). There were no significant differences in the incidence of outcome events between rosuvastatin and other statin users. CONCLUSION: This study indicated that the number of outcome events is less than 1 per 3000 person years. This study in more than 45,000 Dutch statin users suggests that rosuvastatin does not lead to an increased incidence of rhabdomyolysis, myopathy, acute renal failure or hepatic impairment compared to other statins.

Acute Kidney Injury↗
PubMed2006

Association of statin therapy and increased survival in patients with multiple organ dysfunction syndrome.

OBJECTIVE: The multiple organ dysfunction syndrome (MODS) is the sequential failure of several organ systems after a trigger event, such as sepsis, pneumonia or cardiogenic shock. Even today, mortality is high. Statin therapy is associated with reduction of inflammation and subsequent rates of severe sepsis and ICU admission of patients admitted to hospital with presumed or documented acute bacterial infection. Our study aimed to characterize a potential survival benefit by statin therapy in MODS patients. DESIGN: Retrospective cohort study. SETTING: Twelve-bed medical intensive care unit in a university center. PATIENTS: Forty score-defined MODS patients under statin treatment and 80 age- and sex-matched score-defined MODS patients without statin treatment. Inclusion criterion was an APACHE II score > or = 20 at admission to ICU. INTERVENTIONS: Assessment of statin treatment and calculation of disease severity by scoring. The patients were followed up for 28-day mortality as well as for hospital mortality. MEASUREMENTS AND RESULTS: The MODS severity was equally pronounced in both groups. There were 42/80 deaths in the group without statin treatment and 13/40 deaths in the statin group (28-day mortality 53% vs. 33%, p = 0.03). Cox proportional hazard analysis revealed a hazard ratio of 0.53 (95% CI 0.29-0.99, p = 0.04). Hospital mortality was calculated at 72% (non-statin group) vs. 35% (statin group; chi-square = 15.6, p < 0.0001). The overall hospital mortality was 60%. CONCLUSIONS: Patients under statin treatment developing MODS might have a better outcome than patients without statin therapy, probably by reduction of inflammatory responses and increase of vagal activity in MODS.

Atorvastatin↗
PubMed2004

Level of awareness of on-treatment patients about prescribed statins.

BACKGROUND: Statins are frequently prescribed drugs for patients with coronary heart disease according to evidence-based medicine. However, compliance with these agents has still been far from ideal, since they require long term, probably life long therapy. We conducted a survey on patients who were already on statin treatment and evaluated their level of awareness of prescribed statins. METHODS: 236 participants (117 male, 119 female), who had been on treatment with statins for at least three months, were enrolled in our study after giving informed consent. Patients were asked close-ended survey questions. RESULTS: Only 5.5% of participants were on statin treatment for primary prevention, and 16.1% of them had a CHD equivalent, defined as those with clinical manifestations of noncoronary forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, carotid artery disease) and diabetes mellitus. Most participants (70%) stated that they had been using statins to decrease cholesterol, whereas 16.5% stated that they had no idea. More than half of the participants (58%) stated that they did not know how long they would have to keep using their statins, whereas 21% replied that they would use them continuously. One fifth of participants had some idea about side effects. Participants in whom statin therapy was started during hospitalisation for coronary angiography and/or PCI more frequently answered that statins should be used continuously (49% vs. 12% not hospitalised, p < 0.01). Also, therapy adjustment by the physician led to a better understanding of the need for continuous use (55% vs. 31% without medication change, p < 0.001), as was the case for patients with < 2 co-medications (36% vs. 17% with > 2 co-medications, p 0.002). Presence of other risk factors did not have any impact on level of awareness. CONCLUSION: Comprehensive information at initial prescription, initiation of statins during hospitalization, dose adjustment during follow up, and as little co-medication as possible seem to increase the level of awareness of the benefits of long-term statin treatment. This might result in better compliance rates.

Adult↗
PubMed2006

Incidence of statin hepatotoxicity in patients with hepatitis C.

BACKGROUND AND AIMS: Statins are considered contraindicated in patients with chronic liver disease. Our objective was to determine the risk of developing hepatotoxicity from statin therapy in hyperlipidemic patients with hepatitis C. METHODS: Changes in liver biochemistry values within 12 months compared with baseline were determined in 3 cohorts matched for age, sex, and body mass index: (I) 166 anti-hepatitis C virus (HCV)-positive hyperlipidemic veterans who were initiated on statin therapy; (II) 332 anti-HCV-positive veterans who had not received statin therapy; and (III) 332 anti-HCV-negative hyperlipidemic veterans who were initiated on statin therapy. An increase in liver biochemistry values was defined as mild-moderate or severe as proposed in a previous study on statin hepatotoxicity in a non-hepatitis C population. RESULTS: In patients with hepatitis C, statin therapy (cohort I) was associated with a higher incidence of mild-moderate liver biochemistry value increases compared with those not on statin therapy (cohort II) (22.9% vs 13.3%, respectively, P = .009), but a lower incidence of severe increases (1.2% vs 6.6%, respectively, P = .015). Among patients started on statin therapy (cohorts I and III), the incidence of mild-moderate liver biochemistry value increases (22.9% vs 16.3%, respectively, P = .094), severe increases (1.2% vs 1%, respectively, P = .874), or discontinuation of statin therapy as a result of hepatotoxicity (21.6% vs 9.2%, respectively, P = .147) were similar in hepatitis C-positive and hepatitis C-negative patients. CONCLUSIONS: Statin therapy was not associated with a higher risk of severe hepatotoxicity in patients with chronic hepatitis C and appeared safe.

Alanine Transaminase↗
PubMed2006

Effects of receipt of chronic statin therapy before the onset of acute myocardial infarction: a retrospective study in patients undergoing primary percutaneous coronary intervention.

BACKGROUND: Studies have reported an association between receipt of statin therapy and a reduction in complications after elective percutaneous coronary intervention (PCI). However, there are limited data on the effects of chronic statin therapy before the occurrence of an acute myocardial infarction (AMI). OBJECTIVE: This study investigated whether administration of chronic statin therapy before AMI was associated with a reduction in reperfusion injury in AMI patients undergoing PCI. METHODS: This was a retrospective study of consecutive patients with a first AMI who underwent successful reperfusion therapy with PCI within 24 hours after the onset of AMI between April 1998 and October 2003. Patients were stratified according to whether they had or had not been receiving chronic statin therapy for > or = 1 month before the onset of AMI. The following end points were compared after PCI: electrocardiographic resolution of ST segment elevation, defined as a reduction of > or = 50% from the initial value; achievement of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow; corrected TIMI frame count (cTFC); maximum serum creatine kinase (CK) level; and the type and frequency of ventricular arrhythmias. RESULTS: The study enrolled 386 patients, 40 of whom had been receiving statin therapy before the onset of AMI. The clinical characteristics of the 2 groups were similar at baseline, with the exceptions of a significantly higher rate of hyperlipidemia in the statin group compared with the nonstatin group (P < 0.001), significantly greater chronic use of aspirin therapy (P < 0.001), and significantly greater chronic use of antihypertensive medications (beta-blockers: P = 0.004; angiotensin-converting enzyme inhibitors/angiotensin II-receptor blockers: P = 0.007; calcium channel blockers: P = 0.006). Electrocardiographic ST segment resolution after PCI was observed in 87.5% and 69.9% of the statin and nonstatin groups, respectively (hazard ratio [HR]: 3.01; 95% CI, 1.15-7.90; P = 0.025). Achievement of TIMI grade 3 flow after PCI was seen in 95.0% of the statin group and 83.5% of the nonstatin group (HR: 3.75; 95% CI, 0.88-16.0; P = NS). Patients treated with a statin had a significantly lower mean (SD) maximum CK level compared with the nonstatin group (2300 [1449] vs 3538 [3170] IU/mL, respectively; P = 0.015) and a lower cTFC after PCI (18.8 [4.0] vs 24.2 [14.2]; P = 0.017). The difference in reperfusion arrhythmias between groups was not statistically significant. After adjustment for baseline covariates, pretreatment with a statin was found to be an independent predictor of ST segment resolution after PCI (HR: 2.95; 95% CI, 1.08-8.09; P = 0.035) and prevention of impaired coronary flow (HR: 3.00; 95% CI, 1.63-5.55; P < 0.001). CONCLUSION: In this study, receipt of chronic statin therapy before the onset of AMI was associated with improvement in epicardial perfusion and a reduction in myocardial necrosis after PCI.

Adrenergic beta-Antagonists↗
PubMed2006

Effects of statin therapy on arrhythmic events and survival in patients with nonischemic dilated cardiomyopathy.

OBJECTIVES: We sought to evaluate whether statins were associated with a survival benefit and significant attenuation in life-threatening arrhythmias in patients with nonischemic dilated cardiomyopathy. BACKGROUND: Statins are associated with a reduction in appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with coronary artery disease and improved clinical status in nonischemic dilated cardiomyopathy. METHODS: The effect of statin use on time to death or resuscitated cardiac arrest and time to arrhythmic sudden death was evaluated in 458 patients enrolled in the DEFINITE (DEFIbrillators in Non-Ischemic cardiomyopathy Treatment Evaluation) study. The effect of statin use on time to first appropriate shock was analyzed only in the 229 patients who were randomized to ICD therapy. RESULTS: The unadjusted hazard ratio (HR) for death among patients on versus those not on statin therapy was 0.22 (95% confidence interval [CI] 0.09 to 0.55; p = 0.001). When controlled for statin effects, ICD therapy was associated with improved survival (HR 0.61; 95% CI 0.38 to 0.99; p = 0.04). There was one arrhythmic sudden death in the 110 patients receiving statin therapy (0.9%) versus 18 of 348 patients not receiving statins (5.2%; p = 0.04). The unadjusted HR for arrhythmic sudden death among patients on versus those not on statin therapy was 0.16 (95% CI 0.022 to 1.21; p = 0.08). The HR for appropriate shocks among patients on versus those not on statin therapy was 0.78 (95% CI 0.34 to 1.82) after adjustment for baseline differences in the two groups. CONCLUSIONS: Statin use in the DEFINITE study was associated with a 78% reduction in mortality. This reduction was caused, in part, by a reduction in arrhythmic sudden death. These findings should be confirmed in a prospective, randomized clinical trial.

Aged↗
PubMed2001

Usefulness of in-hospital prescription of statin agents after angiographic diagnosis of coronary artery disease in improving continued compliance and reduced mortality.

Despite well-documented clinical benefit of the use of statins in patients with coronary artery disease (CAD) and even mild lipid elevations, studies have documented the presence of a significant "treatment gap" between those patients in whom treatment is indicated and those patients who actually receive it. It has been proposed that a prescription for statin therapy given to indicated patients at the time of initial angiographic diagnosis of CAD has the potential to improve long-term medication compliance, but this requires further evaluation. We prospectively followed 600 patients with angiographically demonstrated CAD (diameter stenosis > or = 70%) who met the National Cholesterol Education Project (NCEP) guidelines for statin therapy for an average of 3.0 years (range 2.0 to 4.6). Patients were an average of 65 years of age, 78% were men, 77% presented initially with acute ischemic syndrome, and 64 (10.7%) died during follow-up. Overall, 105 patients (18%) were discharged from the initial hospitalization with a statin prescription. At long-term follow-up, the number of patients taking statins had increased to 47%. However, long-term statin compliance was significantly higher among patients initially discharged with a statin prescription than those who were not (77% vs 40%; p < 0.0001). Additionally, those patients discharged with a statin prescription had significantly reduced mortality rate at long-term follow-up (5.7% vs 11.7%; p = 0.05). Cox hazard regression analysis, controlling for all known clinical baseline variables, confirmed the absence of a prehospital discharge statin prescription to be an independent predictor of increased mortality (hazard ratio 2.4) with a statistical trend (p = 0.06). Thus, this study demonstrates that after angiographic diagnosis of CAD, prescription of appropriate statin therapy at the time of hospital discharge improves long-term statin compliance and may significantly enhance survival.

Aged↗
PubMed2002

Patient survival after renal transplantation III: the effects of statins.

BACKGROUND: Kidney transplant recipients have high cardiovascular risk and an unfavorable cardiovascular risk profile, which frequently includes hyperlipidemia. Although the use of HMG-CoA reductase inhibitors (statins) is associated with improved survival in the general population, the effects of these drugs on the survival of kidney transplant recipients have not been established. METHODS: In this study, we determined which factors were associated with the use of statins in a population of 1,574 adult, kidney allograft recipients, transplanted in one institution. A risk factor analysis of patient survival was done with a primary focus on the possible relationship between statin use and survival. RESULTS: The percent of patients treated with statins increased progressively from 1982 to 1996. Statins were used significantly more often in whites (30%) than in blacks (20%, P = 0.001) and in older individuals. These differences in statin use were not due to differences in lipid levels among the patient groups. As expected, the group of patients treated with statins had significantly higher serum lipid levels than untreated patients. Patient survival was significantly better in patients treated with statins than in untreated patients. That relationship became apparent, however, only after controlling for three additional factors: recipient age, transplant year, and serum cholesterol levels. In a multivariable Cox survival model, patient survival was associated significantly with statin use (hazard ratio [HR] = 0.76; confidence interval [CI], 0.6 to 0.96; P = 0.02), recipient age (HR = 1.05; CI, 1.04 to 1.06; P < 0.0001), and transplant year (HR = 1.05; CI, 1.01 to 1.08; P = 0.001). The serum cholesterol level was not associated significantly with patient survival in this model, but cholesterol significantly modified the relationship between statin use and patient survival. CONCLUSIONS: Renal transplant recipients treated with statins have a 24% better survival than patients who do not receive these drugs.

Adult↗
PubMed2004

Statin induction of liver fatty acid-binding protein (L-FABP) gene expression is peroxisome proliferator-activated receptor-alpha-dependent.

Statins are drugs widely used in humans to treat hypercholesterolemia. Statins act by inhibiting cholesterol synthesis resulting in the activation of the transcription factor sterol-responsive element-binding protein-2 that controls the expression of genes involved in cholesterol homeostasis. Statin therapy also decreases plasma triglyceride and non-esterified fatty acid levels, but the mechanism behind this effect remains more elusive. Liver fatty acid-binding protein (L-FABP) plays a role in the influx of long-chain fatty acids into hepatocytes. Here we show that L-FABP is a target for statins. In rat hepatocytes, simvastatin treatment induced L-FABP mRNA levels in a dose-dependent manner. Moreover, L-FABP promoter activity was induced by statin treatment. Progressive 5'-deletion analysis revealed that the peroxisome proliferator-activated receptor (PPAR)-responsive element located at position -67/-55 was responsible for the statin-mediated transactivation of the rat L-FABP promoter. Moreover, treatment with simvastatin and the PPARalpha agonist Wy14,649 resulted in a synergistic induction of L-FABP expression (mRNA and protein) in rat Fao hepatoma cells. This effect was also observed in vivo in wild-type mice but not in PPARalpha-null animals demonstrating the direct implication of PPARalpha in L-FABP regulation by statin treatment. Statin treatment resulted in a rise in PPARalpha mRNA levels both in vitro and in vivo and activated the mouse PPARalpha promoter in a reporter assay. Altogether, these data demonstrate that L-FABP expression is up-regulated by statins through a mechanism involving PPARalpha. Moreover, PPARalpha might be a statin target gene. These effects might contribute to the triglyceride/non-esterified fatty acid-lowering properties of statins.

Animals↗