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PubMed2005

Association between time of statin initiation after hospital discharge from acute myocardial infarction and risk of recurrence and mortality in patients > or =65 years of age.

Clinical studies have shown the benefit of statin use after acute myocardial infarction (AMI). However, it is uncertain how this benefit relates to the timing of statin initiation after AMI. We created a retrospective cohort (from 1996 to 2001) using health care databases in Quebec, Canada, to study patients (> or =65 years of age) who had AMI and differed in time of statin initiation within the first 90 days after discharge. Rates of recurrent AMI and mortality were compared between patients who initiated statins at discharge (early group) and those who initiated statins 1 month later and up to 90 days after discharge (delayed group). A multivariate Cox's regression model was used in the comparison. We used prescription time distribution matching to control for survival difference between groups. The early and delayed groups consisted of 3,075 and 1,187 patients, respectively. During the 1-year follow-up, there was no evidence to suggest a difference in outcome between groups. Adjusted hazard ratios for early versus delayed initiation were 1.03 (95% confidence interval 0.56 to 1.87) at 3 months and 1.24 (95% confidence interval 0.96 to 1.62) at 1 year. Analyses that were restricted to first-time statin users or excluded patients who had severe co-morbidity or were > or =85 years old did not change the results. Our findings were not affected by changing the definition of delayed use within the 90-day period. In conclusion, delay of statin initiation up to 30 to 90 days after discharge after AMI does not appear to lead to a difference in the rates of recurrent AMI and mortality compared with statin initiation at discharge.

Aged↗
PubMed2006

Effects of early statin treatment on symptomatic heart failure and ischemic events after acute myocardial infarction in Japanese.

Statins have been shown to prevent coronary artery disease and to preserve left ventricular function in dilated cardiomyopathy. We hypothesized that early use of statins would decrease cardiovascular events, including heart failure in patients with acute myocardial infarction (AMI). To examine the effect of statins in Japanese patients with AMI, a prospective, randomized, open-label trial was conducted in 486 patients with normal total cholesterol levels. Patients were randomly assigned to receive any available statin (n = 241) within 96 hours of AMI onset or no statin (n = 245) and were followed for up to 24 months. The primary end point was a composite of cardiovascular death, nonfatal AMI, recurrent symptomatic myocardial ischemia, congestive heart failure, and stroke. Event rate for the primary end point was lower in the statin group than in the nonstatin group (6.1% vs 11.4%, p = 0.0433). The statin group had a lower risk of congestive heart failure and symptomatic myocardial ischemia (p = 0.0154 and 0.0264, respectively). In conclusion, early lipid-lowering therapy with statins decreases recurrent cardiovascular events, in particular, congestive heart failure.

Aged↗
PubMed2006

Comparison of mortality rates in statin users versus nonstatin users in a United States veteran population.

Statins have been shown to be effective in reducing cardiovascular events and overall mortality in primary and secondary prevention trials. This study was designed to examine the effect of statin use on overall death. Cross-sectional data were obtained from the Department of Veterans Affairs Veterans Integrated Service Network 16 database for approximately 1.5 million veterans followed up in 10 hospitals in the southern United States. Statins were prescribed more often to elderly subjects with a history of coronary artery disease, hypertension, diabetes mellitus, current smoking, and using cardiovascular drugs (beta blockers, aspirin, angiotensin-converting enzyme inhibitors, and calcium channel blockers). The predictors of death were, as expected, cancer, diabetes mellitus, the use of cardiac drugs, and age. Importantly, using statins showed a highly significant negative association with death (odds ratio 0.54, 95% confidence interval 0.42 to 0.69, p <0.0001), even after adjustment for all other variables. Overall, the mean age at death among statin users was 2 years older than among nonstatin users, despite statin users being at a higher risk of death. In conclusion, the results of this study have shown that using statins is a potent life-saving strategy. The benefit observed in this study is unique because almost 1/2 the patients were >or=70 years of age when statin therapy was initiated.

Adrenergic beta-Antagonists↗
PubMed2006

Beyond lipid lowering: What have we learned about the benefits of statins from the acute coronary syndromes trials?

The long-term benefits for prevention of primary and secondary cardiovascular events achieved by lowering serum cholesterol levels with statins are undisputed. However, results of early clinical trials and preclinical studies suggested the possibility that benefits of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may not be entirely due to their effects on low-density lipoprotein (LDL) cholesterol. Since then, large-scale clinical trials of statin treatment for acute coronary syndromes (ACS) have demonstrated early benefits that are associated with aggressive initiation of statin therapy. Support for pleiotropic effects of statins in these trials has been provided not only by these acute effects but also by apparent differences in efficacy between various statin regimens that seem unrelated to their effects on serum cholesterol levels. Analyses of biomarkers of inflammation, oxidation, and thrombosis in samples from patients in these studies have also suggested possible mechanisms underlying the benefits of statins in ACS. This article reviews some of the key statin trials in ACS and assesses the evidence for benefits of these drugs independent of their effects on LDL cholesterol.

Atorvastatin↗
PubMed2005

Differential associations of statin and fibrate treatment with carotid arterial remodeling.

BACKGROUND: The effects of statins on intima-media thickness (IMT) are well documented, whereas those of fibrates are unknown. Therefore we compared IMT under treatment with each class of drugs. METHODS: We studied a cohort of consecutive dyslipidemic subjects treated with statin (n = 291) or fibrate (n = 82) drugs. Fibrate-treated subjects were matched with the same number of statin-treated subjects to obtain two subgroups of similar demographic and risk factors including LDL cholesterol. Common carotid far wall IMT and lumen diameter were measured by ultrasonography. RESULTS: In the entire study population, IMT was greater in the fibrate group than in the statin group (P < .001), even after adjustment for LDL cholesterol and other covariates (P < .05). In the matched groups, IMT was greater in fibrate group than in the statin group (P < .01), even after adjustment for LDL cholesterol and other covariates including treatment duration (P < .01). The IMT correlated positively with treatment duration in the fibrate group (P < 0.05) but not in the statin group. In addition, IMT correlated positively with carotid lumen diameter in both the fibrate and statin groups (P < .05, P < .01) but with a lower slope in the former (P < .05). CONCLUSIONS: In this study fibrate treatment was associated with greater IMT, steeper IMT-time relationship, and lower compensatory carotid enlargement than was statin treatment. These differences were not explained by differences in LDL cholesterol.

Adult↗
PubMed2006

Statins: potential new indications in inflammatory conditions.

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are potent cholesterol-lowering drugs. In addition to their cholesterol-lowering properties, statins exert a number of so-called 'pleiotropic', vasculoprotective actions that include improvement of endothelial function, increased nitric oxide (NO) bioavailability, antioxidant properties, stabilisation of atherosclerotic plaques, regulation of progenitor cells, inhibition of inflammatory responses and immunomodulatory actions. Pleiotropic actions of statins may have potential clinical impact in vascular disease beyond cholesterol lowering. The ongoing Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), for example, tests the effects of statins in the primary prevention of cardiovascular disease among patients with low levels of low-density lipoprotein cholesterol (LDL-C) and elevated high-sensitivity C-reactive protein (hs-CRP). Additionally, previous studies have shown that although cholesterol is not an established stroke risk factor, statin therapy is associated with a reduction in the incidence of strokes. It is known that sudden withdrawal of statin treatment may acutely impair vascular function and increase morbidity and mortality in patients with vascular disease. Furthermore, the anti-inflammatory effects of statins may have clinical impact in a number of non-vascular conditions including multiple sclerosis and rheumatoid arthritis.

Animals↗
PubMed2006

Preoperative statin therapy and troponin T predict early complications of coronary artery surgery.

BACKGROUND: Pretreatment with statins reduces early ischemic events after percutaneous coronary interventions, primarily in patients with a high level of inflammation markers. We sought to examine the association between preoperative statin therapy, systemic inflammation, and myocardial ischemia with the occurrence of early cardiac complications after coronary artery bypass grafting surgery. METHODS: One hundred forty-one consecutive patients who underwent coronary artery bypass grafting surgery from two university tertiary hospitals were stratified according to their preoperative status of statin therapy (87 treated and 54 nontreated). Preoperative blood samples were collected for measurement of lipid parameters, C-reactive protein, interleukin-6, and troponin T. The evaluated primary endpoint was a composite of death and myocardial infarction at 30 days. RESULTS: Patients undergoing preoperative statin therapy showed a reduced incidence of death (2.3% versus 13.0%, p = 0.012), myocardial infarction (5.7% versus 18.5%, p = 0.017), and primary combined endpoint (8.0% versus 22.2%, p = 0.017). In the multivariate model, preoperative troponin T greater than 0.01 ng/mL (odds ratio 6.85, p = 0.001) and nonstatin therapy (odds ratio 4.2, p = 0.01) predicted a higher risk of primary endpoint. Statins showed a significant interaction with troponin T status and benefited primarily those patients with positive troponin T. Among 19 patients with troponin T greater than 0.01 ng/mL, the primary endpoint occurred in all 6 nonstatin-treated patients, but it occurred in only 1 of 13 statin-treated patients (p < 0.001). Neither C-reactive protein nor interleukin-6 predicted early complications, nor did they interact with statin therapy (p = not significant). CONCLUSIONS: Preoperative statin therapy reduces early complications and offers additional protection in patients with positive troponin T status, regardless of inflammatory markers.

Aged↗
PubMed2006

Statins decrease TNF-alpha-induced osteoprotegerin production by endothelial cells and smooth muscle cells in vitro.

Recent reports have implicated osteoprotegerin (OPG) in cardiovascular disease processes. Endothelial and smooth muscle cells produce OPG and its expression in these cells is upregulated by inflammatory mediators. Statins, which besides their lipid lowering properties have various vasculoprotective effects, have been shown to regulate OPG expression in osteoblasts. We investigated whether statins affect the expression of OPG in human endothelial and smooth muscle cells. Using an ELISA we could demonstrate that statins reduce tumor necrosis factor-alpha (TNF-alpha)-induced OPG production in cultured human endothelial cells and smooth muscle cells. Atorvastatin also downregulated interleukin-1alpha (IL-1alpha)-induced OPG production in endothelial cells. A significant reduction of TNF-alpha-induced OPG was seen when statins were used in the nanomolar range. These results were confirmed at the level of specific mRNA expression by real-time-PCR. Using LDH leakage as a marker of cell damage we show that cell viability was not affected by statins at concentrations used in our study. The effect of statins on TNF-alpha-induced OPG production was reversed by mevalonate and geranyl-geranyl pyrophosphate at the level of protein production and at the level of mRNA expression, suggesting that it was brought about by inhibition of the mevalonic acid pathway and protein prenylation. Through our results we have added OPG to the list of molecules whose TNF-alpha-induced upregulation is counteracted by statins. If such an effect is also operative in the in vivo setting, one could postulate a role for statins in the modulation of cardiovascular disease processes possibly regulated by OPG.

Base Sequence↗
PubMed2006

Statin-related adverse events: a meta-analysis.

BACKGROUND: The absolute frequencies of adverse events (AEs) between statins and placebo are very low in clinical trials, making clinical interpretation and application difficult. OBJECTIVES: This meta-analysis was intended to synthesize the collective AE data observed in prospective randomized clinical trials to facilitate clinical interpretation. METHODS: Using the search terms atorvastatin, simvastatin,pravastatin, rosuvastatin, fluvastatin, lovastatin, prospective trial, and randomized trial, the MEDLINE/EMBASE and the Cochrane Collaboration databases were reviewed for prospective randomized primary and secondary prevention trials of statin monotherapy. Nonrandomized uncontrolled studies and those missing AE data were excluded. The Mantel-Haenszel test for fixed and random effects was used to calculate odds ratios (ORs) and log ORs. RESULTS: Eighteen trials including 71,108 persons, and 301,374 person-years of follow-up were represented in this analysis. There were 36,062 persons receiving a statin and 35,046 receiving a placebo. Statin therapy increased the risk of any AE by 39% (OR = 1.4; 95% CI, 1.09-1.80; P = 0.008; NNH [number needed to harm] = 197) compared with placebo. Statins were associated with a 26% reduction in the risk of a clinical cardiovascular event (OR = 0.74; 95% CI, 0.69-0.80; P < 0.001; number needed to treat = 27). Treating 1000 patients with a statin would prevent 37 cardiovascular events, and 5 AEs would be observed. Serious events (creatine phosphokinase >10 times the upper limit of normal or rhabdomyolysis) are infrequent (NNH = 3400) and rhabdomyolysis, although serious, is rare (NNH = 7428). Atorvastatin was associated with the greatest risk of AEs and fluvastatin with the least risk. Simvastatin, pravastatin, and lovastatin had similar odds of AEs. Nonurgent AEs such as myalgia and liver function elevations were responsible for approximately two thirds of AEs reported in trials. CONCLUSIONS: Statin therapy was associated with greater odds of AEs compared with placebo but with substantial clinical benefit. Similar rates of serious AEs were observed between statin and placebo.

Humans↗
PubMed2004

Effects of statins and farnesyltransferase inhibitors on the development and progression of cancer.

Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors - HMG-CoA reductase inhibitors) have been approved for the treatment of lipid disorders. Recently, in vivo studies with experimental animals and in vitro studies indicated a possible role for statins in the treatment of malignancies. Inhibition of the enzyme HMG-CoA reductase results in decreased farnesylation and geranylgeranylation of several proteins essential for cellular proliferation and survival. Inhibition of Ras farnesylation was originally thought to be the mechanism that mediates statin-induced effects in cancer. Consequently, specific inhibitors of the enzyme farnesyltransferase (FTIs) were developed. Currently, the mechanisms that mediate statin- and FTI-induced antitumour effects are questioned. It remains unclear which proteins and signal transduction cascades are involved. This review focuses on the effects and possible therapeutic application of statins and FTIs. Antitumour properties such as induction of growth arrest and apoptosis, inhibition of metastasis and inhibition of angiogenesis are discussed. Furthermore, the mechanisms of statin- and farnesyltransferase inhibitor-induced effects and the involvement of a number of cellular components (such as farnesylated and geranylgeranylated proteins, the mitogen-activated protein kinase signalling pathway, the phosphoinositide 3'-kinase signalling pathway, and cell cycle regulatory proteins) are reviewed. In addition, clinical and epidemiological data with respect to statins and farnesyltransferase inhibitors are summarised. We propose that inhibitors of the mevalonate pathway are particularly effective when administered in combination with other drugs. Therefore, the mechanisms and effects of combined therapy of statins or farnesyltransferase inhibitors with chemotherapeutics, biphosphonates, non-steroidal anti-inflammatory drugs, specific inhibitors of geranylgeranyltransferase and inhibitors of tyrosine kinase activity are discussed.

Alkyl and Aryl Transferases↗
PubMed2005

A comparison of six statins on the development of intimal hyperplasia in a human vein culture model.

OBJECTIVE: Intimal hyperplasia (IH) threatens the patency of up to 35% of saphenous vein (SV) bypass grafts. In addition to reducing cholesterol levels, statins may modulate smooth muscle cell proliferation and migration. Statins inhibit matrix metalloproteinase (MMP) activity. We therefore investigated the effect of six statins on neointimal formation and MMP activity in human SV organ culture. STUDY DESIGN: Human SV specimens were cultured for 14 days in the presence of six different statins and subsequently processed for measurement of neointimal thickness and MMP activity. The drug concentrations chosen corresponded to the manufacturers' Cmax. RESULTS: The six statins all significantly reduced IH development (P = 0.004) in association with reduced expression of proMMP-2 and 9 (P = 0.03) and reduced activity of activated MMP-2 and 9 (P = 0.03). CONCLUSION: This study suggests that the potential benefit of statins in reducing IH is a class effect and not confined to specific statins. The reduction of IH produced by statins may in part be due to their inhibition of MMPs.

Collagenases↗
PubMed2005

The benefit of fibrates in the treatment of 'bad HDL-C responders to statins'.

BACKGROUND: Lowering high levels of low-density lipoprotein cholesterol (LDL-C) is the primary aim in the prevention of cardiac events. However, low levels of high-density lipoprotein cholesterol (HDL-C) are also associated with an increased risk of ischemic heart disease. Some patients have lower HDL-C during statin treatment than before the treatment. These patients were first described in 2002 as 'bad HDL-C responders to statins'. The aim of this study was to describe the benefit of fibrates in monotherapy for these patients. METHODS: A cross-sectional survey of lipid levels, cardiovascular disease and risk factors in outpatients treated for dyslipidemia. For this study we analyzed the lipid levels, drug treatment and medical history for 14 patients with low HDL-C (<40 mg/dl) during statin treatment and ever treated with fibrates. RESULTS: Total cholesterol (TC) and LDL-C were respectively 8% and 6% higher with fibrates compared to statins. Mean HDL-C was 49% higher during fibrate treatment and TC to HDL-C and LDL-C to HDL-C were respectively 26% and 27% lower with fibrates. CONCLUSIONS: Patients with low levels of HDL-C during statin treatment had far better levels for HDL-C, TC to HDL-C and LDL-C to HDL-C with fibrates in monotherapy. For bad HDL-C responders to statins with low or normal LDL-C treatment with fibrates instead of statins should be considered. For those with high LDL-C fibrates should be added to statins. A randomized double-blind crossover trial with simvastatin and fenofibrate has been initiated to corroborate these findings.

Adult↗
PubMed2006

Case selection for statins was similar in two Canadian provinces: BC and Ontario.

OBJECTIVES: Though statins are fully reimbursed by the public drug programs for seniors in British Columbia (BC) and Ontario, Canada, population-based rates of statin prescription are markedly higher in Ontario. We aimed to assess whether new statin users in BC and Ontario differ in terms of their risk for future coronary heart disease (CHD) events. STUDY DESIGN AND SETTING: We collected information for 1998-2001 on demographics, outpatient prescriptions, physician visits, hospital admissions, and vital status from administrative databases to compare the proportions of new statin users aged 66 years and older who had evidence of an acute coronary syndrome (ACS), chronic CHD, neither ACS nor CHD but diabetes, or none of the above. RESULTS: Approximately 15% and 20% of BC and Ontario seniors, respectively, had filled a statin prescription by 2001. Among new statin users in the two provinces, virtually identical proportions had evidence of ACS (8%), chronic CHD (25%), and diabetes (14%), for an overall proportion of roughly 50% at high risk for CHD events. CONCLUSION: New statin users in BC and Ontario were at similar risk for future CHD events. Poorer case selection is unlikely to explain the relatively higher rates of statin prescription in Ontario.

Aged↗
PubMed2005

Histologic and ultrastructural study on statin graft in rabbit skulls.

PURPOSE: To study the early healing pattern of statin-induced osteogenesis, we examined the early histologic and ultrastructural pictures of bone defect healing with and without statin. MATERIALS AND METHODS: Twenty-eight bone defects were created in the parietal bone of 14 New Zealand White rabbits. In the Statin Group of 7 rabbits, the defects were grafted with collagen matrix carriers mixed with statin solution. In the Collagen Matrix Group of 7 rabbits, the defects were grafted with collagen matrix carriers mixed with water for injection. The Statin Group and the Collagen Matrix Group were killed on day 1, 2, 3, 4, 5, 6, or 14 after surgery. Bone defects with surrounding tissues were prepared for histologic assessment. Bone defects of day 14 were also prepared for ultrastructural assessment. RESULTS: New bone was formed on day 5 in the defects grafted with statin. No cartilage intermediate stage was detected. This occurred 1 day earlier than for those grafted with the carrier alone. The bone defects of day 14 showed that an abundance of bone was formed in the Statin Group and osteocytes were identified ultrastructurally. CONCLUSIONS: This study supported statin-induced and accelerated bone formation locally.

Animals↗
PubMed2005

Potential utility of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in diabetic retinopathy.

Diabetic retinopathy is a common and potentially devastating microvascular complication in diabetes and is a leading cause of acquired blindness among the people of occupational age. However, therapeutic options for the treatment of proliferative diabetic retinopathy, photocoagulation and vitrectomy, are limited by considerable side effects. Therefore, to develop novel therapeutic strategies that specifically target diabetic retinopathy is desired for patients with diabetes. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress. There is a growing body of evidence to show that AGEs-their receptor (RAGE) interactions are involved in the development and progression of diabetic retinopathy. Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, have been recently shown to reduce the risk for cardiovascular events in diabetic patients with or without coronary artery disease. However, the efficacy of statin therapy for diabetic retinopathy is not fully investigated. We have recently found that protein prenylation is crucial for the AGE-RAGE signaling in microvascular endothelial cells. By blocking the protein prenylation, cerivastatin completely prevented the AGE-RAGE-elicited angiogenesis via suppression of vascular endothelial growth factor (VEGF). These observations let us to speculate that statins might be a promising remedy for treating patients with diabetic retinopathy by acting as a potential inhibitor of the AGE-RAGE signaling pathway in microvascular endothelial cells. In this paper, we would like to propose the possible ways of testing our hypotheses. (1) Does treatment with statins decrease the risk for the development and progression of diabetic retinopathy in patients with normocholesterolemia? (2) If the answer is yes, is this beneficial effect of statins superior to that of other cholesterol-lowering agents with equihypolipidemic properties? (3) Does statin treatment suppress retinal VEGF expression in diabetic patients? (4) Does treatment with pyridoxamine, a post-Amadori inhibitor of AGE formation, attenuate the beneficial effects of statins on diabetic retinopathy? These clinical studies could clarify whether the use of statins is of benefit in patients with AGE-RAGE-related disorders such as diabetic retinopathy, even in the absence of hypercholesterolemia.

Acyl Coenzyme A↗
PubMed2004

Metaanalysis of statins and survival in de novo cardiac transplantation.

BACKGROUND: The use of HMG CoA reductase inhibitors (statins) after cardiac transplantation has been suggested to decrease the incidence of severe rejection and improve survival. Individual investigations that have led to this suggestion are randomized (but not placebo-controlled) studies, including small patient numbers that have (and thus underpowered) and enrolling heterogeneous subjects (including retransplant recipients). The purpose of this pooled analysis was to quantify the benefit of statins on survival in de novo cardiac transplant recipients. METHODS: Medline (1966 to 2003) was queried using the keywords statin, HMG CoA reductase inhibitors, cardiac transplantation, transplant, cholesterol, atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin. In addition, we searched the cited literature and previously published systematic reviews. Of 36 articles retrieved, 3 randomized controlled studies met our population inclusion criteria; namely age >18 years, de novo heart transplant recipients, statin therapy within 3 months, and > or = 1-year follow-up. Pooled data were metaanalyzed by Mantel-Haenszel tests using a random effects model that included tests for heterogeneity. RESULTS: The three pooled studies included 246 patients (statin, n = 129; no statin, n = 117) and 27 events (11%). The pooled analysis demonstrated a significant reduction in mortality with statin use (RR 0.31; 95% CI 0.13 to 0.7; P = .006) without significant heterogeneity (P = .7) among the studies. Two of the three studies reported allograft rejection with hemodynamic compromise. The pooled analysis demonstrated a significant benefit on this endpoint (RR 0.22, 95% CI 0.08 to 0.63; P = .004). CONCLUSION: This meta-analysis demonstrates that statin therapy decreases rejection episodes with hemodynamic consequences and improves 1-year heart transplant survival.

Graft Rejection↗
PubMed2006

Long-term safety and effectiveness of statins for heart transplant recipients in routine clinical practice.

BACKGROUND: Whereas the efficacy of statins after heart transplantation (HT) in controlled study settings has been clearly demonstrated, more extensive data are required on the safety and effectiveness of long-term treatment in routine clinical practice. METHODS: We analyzed the risks and benefits in clinical practice of treatment with statins in all patients who survived HT for at least a month from December 1985 through 2001. RESULTS: During a mean follow-up of 4.8+/-3.8 years, 186 patients were treated with statins (for a median duration [25th to 75th percentile] of 29 [12 to 54] months), while 48 received dietary therapy alone. Patients treated with statins (pravastatin, 48%; atorvastatin, 37%; simvastatin, 14%) presented linearized rates of rhabdomyolisis, myositis, and significant transaminase elevation of 0.37%, 0.74%, and 0.37% per year of treatment, respectively (no fatal event occurred). Low-density lipoprotein decreased after statins by 19% (P<.001). At multivariate analysis, treatment with statins was independently associated with reduced risk of cardiac allograft vasculopathy and overall mortality (P<.001). CONCLUSIONS: Our data provide necessary confirmation of the safety and effectiveness in routine clinical practice of appropriately monitored long-term administration of statins (particularly atorvastatin, pravastatin, and simvastatin) in the chronic post-HT phase. Strict follow-up is needed for HT recipients receiving high doses of statins with/without other medications potentially exacerbating the risk of adverse effects.

Adult↗
PubMed2005

Statin mediated protection of the ischemic myocardium.

Hypercholesterolemia is a major risk factor in the development of cardiovascular disease and HMG-CoA reductase inhibitors (i.e. statins) were originally designed to reduce serum cholesterol levels and thus reduce this risk factor. However, it has become increasingly apparent that the effects of statins extend well beyond their lipid lowering actions, and these pleiotropic effects have a major role in protecting the myocardium against ischemic injury. There have been a large number of clinical studies demonstrating the safety and efficacy of statins in reducing total mortality as well as many other secondary endpoint markers in patients with cardiovascular disease. In addition, statins appear to benefit patients with a variety of clinical conditions such as acute coronary syndromes and severe heart failure. Recent experimental studies demonstrated that stains can rapidly (i.e. within hours) upregulate endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production. These landmark studies of statins and eNOS function set the foundation for the investigation of the protective effects of statins. Many experimental studies investigating the effects of statins on eNOS and cardiac injury in the setting of ischemia and reperfusion have been performed in an attempt to determine the extent of the protection as well as the mechanism of the protection. This review article will focus on our current understanding of statin-mediated protection of the myocardium against ischemia-reperfusion injury and infarction.

Cardiotonic Agents↗