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PubMed2005

Cancer risk among statin users: a population-based cohort study.

Hydroxymethylglutaryl-CoA reductase inhibitors (statins) have been linked with potential chemopreventive effects; however, the data are conflicting. We conducted a population-based cohort study using data from the Prescription Database of North Jutland County and the Danish Cancer Registry for the period 1989-2002. In a study population of 334,754 county residents, we compared overall and site-specific cancer incidence among 12,251 statin users (> or =2 prescriptions) with cancer incidence among nonusers and users of other lipid-lowering drugs (n = 1,257). Statistical analyses were based on age-standardization and Poisson regression analysis, adjusting for age, gender, calendar period and use of NSAIDs, hormone replacement therapy and cardiovascular drugs. We identified 398 cancer cases among statin users during a mean follow-up period of 3.3 years (range 0-14 years). The age- and gender-standardized incidence rates of cancer overall were 596 per 100,000 person-years among statin users, 645 per 100,000 person-years among nonusers and 795 per 100,000 person-years among users of other lipid-lowering drugs. Adjusted rate ratios for cancer overall among statin users were 0.86 (95% CI, 0.78-0.95) compared to nonusers and 0.73 (95% CI, 0.55-0.98) compared to users of other lipid-lowering drugs. No significantly increased or decreased rate ratios were observed for any of the studied site-specific cancers (liver, colorectum, lung, breast, prostate, female genital organs and lymphatic and haematopoietic tissue), but most estimates tended to be less than 1.0. Stratification by duration of follow-up or number of prescriptions revealed no clear trends. In summary, individuals prescribed statins experienced a slightly reduced cancer incidence compared to population controls of nonusers and users of other lipid-lowering drugs. Larger and longer-term studies are needed to determine the potentially protective effect of statin use on cancer development.

Adult↗
PubMed1989

Statin, a nonproliferation-specific protein, is associated with the nuclear envelope and is heterogeneously distributed in cells leaving quiescent state.

Statin, a protein of 57,000 daltons, is present primarily in the nuclei of nonproliferating cells of terminally differentiated tissues or of in vitro aged fibroblast cultures. In young growing cells, the protein can be induced to appear in the nuclei once the cell-cycle traverse is blocked by various tissue culture manipulations, such as serum starvation; this expression, however, can be rapidly removed by addition of serum. The disappearance of statin in cells leaving the quiescent state is not uniform along the periphery of the nucleus; it can be distributed in various patterns, such as caps, nodules, patches, or irregular granules. This unusual distribution seems to suggest that preferential sites exist at the region of the nuclear envelope where statin presence may residually remain. The concentration of statin at the nuclear envelope region in cells at G0-quiescent phase is confirmed by the intense staining of fluorescent antibody at the periphery of isolated rat liver nuclei. Further examination of the isolated nuclei reveals that the protein is associated with the lamina compartment of the nuclear envelope; this is evidenced by the results of immunoblotting experiments showing statin presence in the fraction enriched for lamins A-C. Immunogold labelling studies show that the protein is located in the general area of the nuclear envelope. These results suggest that statin in G0-quiescent cells is located predominantly at the nuclear envelope region and that in this vicinity there may exist geometrically sites of statin concentration as evidenced by the heterogeneous distribution in those cells experiencing the departure from the quiescent state.

Animals↗
PubMed2005

Statins in nephrotic syndrome: a new weapon against tissue injury.

The nephrotic syndrome is characterized by metabolic disorders leading to an increase in circulating lipoproteins levels. Hypertriglyceridemia and hypercholesterolemia in this case may depend on a reduction in triglyceride-rich lipoproteins catabolism and on an increase in hepatic synthesis of Apo B-containing lipoproteins. These alterations are the starting point of a self-maintaining mechanism, which can accelerate the progression of chronic renal failure. Indeed, hyperlipidemia can affect renal function, increase proteinuria and speed glomerulosclerosis, thus determining a higher risk of progression to dialysis. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is the rate-limiting enzyme in cholesterol synthesis from mevalonate and its inhibitors, or statins, can therefore interfere with the above-mentioned consequences of hyperlipidemia. Statins are already well known for their effectiveness on primary cardiovascular prevention, which cannot be explained only through their hypolipemic effect. As far as kidney diseases are concerned, statin therapy has been shown to prevent creatinine clearance decline and to slow renal function loss, particularly in case of proteinuria, and its favorable effect may depend only partially on the attenuation of hyperlipidemia. Statins may therefore confer tissue protection through lipid-independent mechanisms, which can be triggered by other mediators, such as angiotensin receptor blockers. Possible pathways for the protective action of statins, other than any hypocholesterolemic effect, are: cellular apoptosis/proliferation balance, inflammatory cytokines production, and signal transduction regulation. Statins also play a role in the regulation of the inflammatory and immune response, coagulation process, bone turnover, neovascularization, vascular tone, and arterial pressure. In this study, we would like to provide scientific evidences for the pleiotropic effects of statins, which could be the starting point for the development of new therapeutical strategies in different clinical areas.

Animals↗
PubMed2006

Elevated skeletal muscle phosphodiesters in adults using statin medications.

Elevated skeletal muscle phosphodiesters (PDE) have previously been reported with muscle-related disorders. Myalgia is a side effect of using statin cholesterol-lowering medications and, therefore, statin use may be associated with increased skeletal muscle PDE. The effect of cholesterol-lowering drugs on skeletal muscle phosphorus metabolites was determined with (31)P magnetic resonance spectroscopy. Resting (31)P metabolites of the anterior compartment muscles were measured in two groups (n = 20; age, 49 +/- 2 years); half were taking statins and the other half were not on these agents. Muscle PDE was 57% greater in the statin group than the control group. These data suggest that statin use increases muscle PDE. Our findings are particularly relevant due to the increasing use and higher dosing of statin medications. Further prospective studies should be performed to document a causal relationship between elevated PDE and statin use, in addition to quantifying correlates to muscle function.

Adult↗
PubMed1993

Expression of the nuclear membrane protein statin in cycling cells.

Statin is a 57 kD protein previously reported to be expressed by cells in G0. We have studied the detailed distribution of statin immunoreactivity in normal human and rat tissues, and correlated this with investigation of in vitro model systems. By laser confocal microscopy, statin immunoreactivity is localized to the nuclear membrane. In contrast to previous reports, using in vitro model systems we found that statin was also expressed by replicating cells as judged by both co-localization with [3H]thymidine-labelled and Ki67-labelled cells. Furthermore, in a nude mouse xenograft model the number of statin-labelled cells exceeded the number of quiescent cells as assessed by both fraction of labelled mitosis methods and labelling with [3H]thymidine and Ki67. We conclude that although there is an association between expression of the 57 kD nuclear membrane protein statin and growth arrest, this is not absolute and it is expressed in a sub-population of cycling cells. The properties of statin closely resemble those of nuclear lamins, members of the intermediate filament family.

Animals↗
PubMed2006

Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia.

Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable.

Adult↗
PubMed2007

Risk factors for statin-associated rhabdomyolysis.

PURPOSE: To identify and characterize risk factors for rhabdomyolysis in patients prescribed statin monotherapy or statin plus fibrate therapy. METHODS: A nested case-control study was conducted within a cohort of 252,460 new users of lipid-lowering medications across 11 geographically dispersed U.S. health plans. Twenty-one cases of rhabdomyolysis confirmed by medical record review were compared to 200 individually matched controls without rhabdomyolysis. A conditional logistic regression model was applied to evaluate the effects of age, gender, comorbidities, concurrent medication use, dosage, and duration of statin use on the development of rhabdomyolysis. RESULTS: Statin users 65 years of age and older have four times the risk of hospitalization for rhabdomyolysis than those under age 65 (odds ratio (OR) = 4.36, 95% confidence interval (CI): 1.5,14.1). We also observed a joint effect of high statin dosage and renal disease (p = 0.022). When these two variables were added to the model with age, we obtained an OR of 5.73 for dosage (95%CI: 0.63, 52.6) and 6.26 for renal disease (95%CI: 0.46, 63.38). Although not statistically significant, we did observe a greater than twofold increase in risk for rhabdomyolysis among females (OR = 2.53, 95%CI: 0.91, 7.32). CONCLUSIONS: Findings of this study indicate that older age is a risk factor for rhabdomyolysis among statin users. Although the evidence is not as strong, high statin dosage, renal disease, and female gender may be additional risk factors. Patients at higher risk of developing rhabdomyolysis should be closely monitored for signs and symptoms of the disease.

Adult↗
PubMedDate not supplied

The potential for drug interactions with statin therapy in Ireland.

BACKGROUND: Seven percent of acute hospital admissions result from adverse drug reactions, of which 25% are due to drug interactions. Adverse effects of statin drugs occur in 3% of patients, mainly due to co-prescribing with other lipid-lowering agents or agents that alter their metabolism. AIM: The aim of this study was to investigate co-prescribing of the frequently-used statin medications with interacting drugs. METHODS: Data from the General Medical Services (GMS) scheme of the Eastern Health Board from January to December 1998 were used in this study. Using the coding index for statins, co-prescribing was identified when concomitant medications were administered under the same GMS claim number. RESULTS: Of 7,602 patients prescribed statins, co-prescribing of simvastatin, atorvastatin and fluvastatin with competing substrates or inhibitors of their metabolism occurred in 32, 26 and 13.4% of prescriptions issued. Thirty-four per cent of patients on simvastatin, 28% on atorvastatin and 16% on fluvastatin were prescribed medications with drug interaction potential. CONCLUSION: Co-prescribing of statins with competing substrates or inhibitors of their metabolism occurred in up to one-third of prescriptions issued. When statins are co-prescribed with recognised inhibitors of drug metabolism, pravastatin, which does not undergo significant hepatic metabolism, is the statin of choice.

Aryl Hydrocarbon Hydroxylases↗
PubMed2003

Beyond lipid-lowering: effects of statins on endothelial nitric oxide.

Endothelial dysfunction is now recognised as an important process in the pathogenesis of atherosclerosis. Nitric oxide (NO) release by the endothelium regulates blood flow, inflammation and platelet aggregation, and consequently its disruption during endothelial dysfunction can decrease plaque stability and encourage the formation of atherosclerotic lesions and thrombi. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) are often utilised in the prevention of coronary heart disease due to their efficacy at lowering lipid levels. However, statins may also prevent atherosclerotic disease by non-lipid or pleiotropic effects, for example, improving endothelial function by promoting the production of NO. There are various mechanisms whereby statins may alter NO release, such as inhibiting the production of mevalonate and important isoprenoid intermediates, thereby preventing the isoprenylation of the small GTPase Rho, which negatively regulates the expression of endothelial nitric oxide synthase (eNOS). Furthermore, statins may also increase eNOS activity via post-translational activation of the phosphatidylinositol 3-kinase/protein kinase Akt (PI3 K/Akt) pathway and/or through an interaction with the molecular chaperone heat-shock protein 90 (HSP90). Data suggest that statins may vary in their efficacy for enhancing the release of NO, and the mechanisms dictating these differences are not yet clear. By increasing NO production, statins may interfere with atherosclerotic lesion development, stabilise plaque, inhibit platelet aggregation, improve blood flow and protect against ischaemia. Therefore, the ability of statins to improve endothelial function through the release of NO may partially account for their beneficial effects at reducing the incidence of cardiovascular events.

Arteriosclerosis↗
PubMed2005

Understanding adherence to official guidelines on statin prescribing in primary health care--a multi-level methodological approach.

OBJECTIVE: The aim was to investigate the role that municipalities and out-patient health care centres (HCCs) have in understanding adherence to official guidelines on statin prescribing. Our hypothesis was that after guideline publication, adherence to recommended statin prescription would increase and variance among HCCs and municipalities would decrease. Since multi-level regression analysis (MLRA) is a relatively new methodology in pharmacoepidemiology, we also aimed to explore the application of MLRA in our investigation. METHODS: We obtained data from the Swedish Corporation of Pharmacies record of sales regarding all initial prescriptions of statins issued between April and December 2003. We applied multi-level analysis on 34,514 individual prescriptions (level 1) nested within 226 HCCs (level 2), which in turn were nested within 33 municipalities (level 3). Temporal trends and gender differences were investigated by means of random slope analysis. Variance was expressed using median odds ratio (MOR) and interval odds ratio. RESULTS: HCCs appeared to be more relevant than municipalities for understanding the physicians' propensity to prescribe a recommended statin (MOR(HCC) = 1.96 and MOR(Municipality) = 1.41). Overall prevalence of adherence was very low (about 20%). After publication of the guidelines, prescription of recommended statins increased, and variance among HCCs decreased but only during the first 4 months of the observation period. CONCLUSION: The publication of official guidelines in the county of Scania exerted a positive influence on statin prescription but, at the end of the observation period, adherence was still low and practice variation high. These facts may reflect inefficient therapeutic traditions and suggest that more intensive interventions may be necessary to promote rational statin prescription.

Drug Prescriptions↗
PubMed2001

Metabolism and drug interactions of 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors (statins).

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors (statins) are mainly considered for long-term use and often constitute part of a multiple-drug regime. Besides common adverse drug effects, such as nausea, abdominal discomfort and headaches, all statins harbour the risk of myopathy and fatal rhabdomyolysis. Usually, the frequency of myopathy is low but the incidence increases during concomitant drug therapy. Statins do not differ in their pharmacodynamic property. Therefore, the differences in their pharmacokinetic profiles, i.e. affinity for metabolising enzymes, constitute the rationale for choosing a specific statin especially for combination therapy. In order to point out harmful combinations of therapeutics, this review summarises the pharmacokinetic data of six clinically used statins (atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin and simvastatin) with special regard to metabolism and drug interactions. In summary, statins that lack a significant hepatic metabolism, i.e. pravastatin, or that are metabolised by more than one cytochrome P450 isoenzyme, i.e. fluvastatin, or whose metabolism is taken over by other cytochrome P450 isoenzymes in case of blockage of the main metabolising enzyme, i.e. cerivastatin, are the least prone to drug interactions. Nevertheless, in case of a specific concomitant drug therapy known to be associated with a higher risk of adverse events, i.e. cyclosporin A and statin, clinical symptoms of myopathy and biochemical data, such as increasing serum creatine phosphokinase, should be monitored carefully.

Atorvastatin↗
PubMed2005

Beyond the statins: new therapeutic perspectives in cardiovascular disease prevention.

Reduction of low-density lipoprotein cholesterol (LDL-C) with statin therapy is currently identified in treatment guidelines as the primary focus for patients with or at risk of coronary heart disease (CHD). Yet despite effective statin therapy there is still an unacceptably high residual coronary risk. A substantial proportion of patients with CHD have mixed dyslipidemia, including low levels of high-density lipoprotein cholesterol (HDL-C), an independent and predictive risk factor for CHD. Although effective in reducing LDL-C, statin therapy has only modest effects in raising HDL-C. Fibrate therapy is an alternative lipid-modifying strategy, and is effective in reducing CHD mortality and morbidity, with the magnitude of clinical benefit similar to statin therapy. Multi-drug therapy with complementary mechanisms of action has been proposed as a means of improving lipid-modifying efficacy. Nicotinic acid is the most potent agent for increasing HDL-C and also substantially reduces LDL-C and triglycerides. Addition of nicotinic acid to statin therapy would be a logical management approach, given the potential for complementary therapeutic benefit. The clinical benefits of this combination are supported by the results of the HDL Atherosclerosis Treatment Study, which showed reduction of 60-90% in the incidence of major coronary events when both agents were administered. In addition, combination treatment led to angiographic regression of stenosis, compared with placebo, rather than slowed progression as previously reported with statin monotherapy. Given that the prevalence of low HDL-C, particularly amongst individuals with CHD, is higher than previously anticipated, combining nicotinic acid and a statin represents an innovative approach to further reducing CHD risk.

Cardiovascular Diseases↗
PubMed2006

Cholesterol, C-reactive protein, and cerebrovascular events following intensive and moderate statin therapy.

BACKGROUND: While statins have been shown to reduce cerebrovascular events (CVE), the relationship between cholesterol, C-reactive protein (CRP), and CVE in patients treated with different statin strategies is still being explored. METHODS: PROVE IT-TIMI 22 was a randomized trial of intensive (atorvastatin 80 mg/day) and moderate (pravastatin 40 mg/day) statin therapy in 4,162 patients with acute coronary syndromes followed for an average of 24 months; serial biomarkers allowed for an assessment of the lipid and non-lipid effects of statins as they relate to CVE. RESULTS: In this study, 45 patients on intensive statin therapy and 40 patients on moderate statin therapy had a CVE during the study period (2.1% v. 1.9%, P = 0.62). While the lipid profiles of patients with and without CVE were similar, those with CVE had higher CRP levels at 30 days and 4 months (2.7 v. 1.9, 2.4 v. 1.7 mg/L; P = 0.012, P = 0.005). Day 30 CRP remained an independent predictor of CVE after adjusting for age, development of atrial fibrillation, diabetes, and prior CVE. Patients with low density lipoprotein (LDL) levels < 70 mg/dL and > or = 70 mg/dL had similar rates of CVE, while patients with CRP < 2 mg/L tended to have lower event rates when compared to those with higher levels. The lowest rates of CVE were seen in patients who had LDL < 70 mg/dL and CRP < 2 mg/L. CONCLUSION: In PROVE IT--TIMI 22, achieved LDL levels did not appear to independently impact the rate of CVE. In contrast, patients with elevated CRP levels were at higher risk of stroke or transient ischemic attack, reinforcing the link between inflammation and CVE. The goal of this PROVE IT-TIMI 22 sub-study was to examine the relationship between cholesterol, CRP, and CVE in patients on intensive and moderate statin therapy. The achieved lipid levels were similar in patients with and without a CVE; however, the achieved levels of CRP were higher in patients who subsequently developed a stroke or TIA. These findings further support the relationship between inflammation and CVE.

Aged↗
PubMed2003

Statins and myotoxicity.

The significant age-adjusted decline in cardiovascular mortality that has occurred over the past three decades is multifactorial. However, the advent of statin therapy has markedly facilitated the optimization of dyslipidemia in patients at risk for coronary events. Statin therapy has proven to be effective in reducing morbidity and mortality in large-scale primary and secondary prevention trials. As with all therapies, the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co A) reductase inhibitors is not without clinical risks. Myopathy, albeit uncommon, was one of the earliest clinical problems associated with statin therapy. Recent data from the large-scale statin mega-trials have clarified the quantitative clinical risk-benefit relationship of reductase inhibitors relative to the induction of muscle toxicity. Histopathologic studies have clarified the potential role of statins in the syndrome of myalgias and normal creatine kinase levels. However, the precise mechanism of statin-associated muscle toxicity remains unclear and is potentially related to genetically mediated muscle enzyme defects, drug interactions, intracellular depletion of metabolic intermediates, and intrinsic properties of the statins per se.

Clinical Trials as Topic↗
PubMed2005

Nonlipid-lowering effects of statins.

Statins have been shown to effectively reduce cardiovascular events in patients with hypercholesterolemia, diabetes, and coronary disease, and after an acute coronary syndrome in several large-scale clinical trials. Interestingly, numerous studies have suggested that statins exert potentially important effects independent of lipid lowering (ie, improve endothelial function, reduce oxidant stress), and have direct anti-inflammatory, antithrombotic, and plaque-stabilizing effects. These beneficial effects may contribute to cardiovascular protection by statin therapy beyond low-density lipoprotein (LDL) cholesterol lowering. Therefore, it remains unclear at present to what extent the beneficial cardiovascular effects of statin treatment are dependent on LDL cholesterol lowering (ie, whether the same effect would be achieved by other modes of lipid lowering). Consequently, statins should be used as a first-line therapy for lipid lowering. Importantly, the observation of LDL cholesterol-independent effects of statins has stimulated clinical studies testing a wider use of statin treatment for diseases that are not thought to be related to increased LDL cholesterol levels, such as in patients with chronic heart failure (in particular dilated cardiomyopathy) and even in inflammatory diseases such as rheumatoid arthritis and multiple sclerosis.

Journal Article↗
PubMedDate not supplied

Statin therapy for Alzheimer's disease: will it work?

Disease-modifying therapies are being developed for Alzheimer's disease (AD). These are expected to slow the clinical progression of the disease or delay its onset. Cerebral accumulation of amyloid beta (A beta) peptides is an early and perhaps necessary event for establishing AD pathology. Consequently therapies aimed at attenuating brain amyloidosis are expected to be disease modifying. Based on the epidemiological evidence pointing to a link between cholesterol metabolism and AD and the numerous laboratory studies implicating cholesterol in the process of A beta production and accumulation, it is now believed that cholesterol-lowering therapies will be of value as disease modifying agents. Several epidemiological studies revealed that statin use for the treatment of coronary arterial disease is associated with a decreased prevalence or a decreased risk of developing AD. These observations require both preclinical and clinical validation. The former involves testing statins in one or more animal models of AD in order to establish which disease features are affected by statin treatment, the relative efficacy with which different statins modify these features and the mechanism(s) by which statins affect AD phenotypes. The latter requires prospective, randomized, placebo controlled trials to evaluate the effect of statin treatment on cognitive and AD biomarker outcomes. We have initiated a study aimed at determining the effects of atorvastatin (Lipitor), a statin with the largest US market share, on brain A beta deposition in the PSAPP transgenic mouse model of Alzheimer's amyloidosis. Our results indicate that Lipitor treatment markedly attenuates A beta deposition in this animal model.

Alzheimer Disease↗
PubMed2006

Are statins created equal? Evidence from randomized trials of pravastatin, simvastatin, and atorvastatin for cardiovascular disease prevention.

BACKGROUND: The relative efficacy of different statins for long-term cardiovascular prevention remains largely undetermined. METHODS: Using adjusted indirect comparison, we compared 3 statins (pravastatin, simvastatin, and atorvastatin) based on published randomized placebo-controlled trials for long-term cardiovascular prevention. A systematic literature search between 1980 and 2004 was conducted. Randomized placebo-controlled trials of the 3 statins, which studied cardiovascular diseases or death as the outcome, enrolled > or = 1000 participants, and had > or = 1-year follow-up, were included. Trials were grouped according to the statin under study. A pooled relative risk (RR) was derived from each set of trials using a random-effects model. Adjusted indirect comparisons using pooled RRs were made between statins with regard to prespecified clinical outcomes. RESULTS: Eight placebo-controlled trials met the inclusion criteria, including 4 pravastatin trials (n = 25,572), 2 simvastatin trials (n = 24,980), and 2 atorvastatin trials (n = 13,143). All trials had a similar degree of lipid reduction. Graphical and statistical assessments showed minimal heterogeneity in the trials' effect sizes. Adjusted indirect comparisons did not reveal a statistically significant difference between statins in reducing fatal coronary heart disease and nonfatal myocardial infarctions (simvastatin vs pravastatin: RR 0.93 [95% CI 0.84-1.03]; atorvastatin vs simvastatin: RR 0.84 [95% CI 0.66-1.08]; atorvastatin vs pravastatin: RR 0.79 [95% CI 0.61-1.02]). We were unable to detect differences either in outcomes for fatal and nonfatal strokes, all cardiovascular deaths, and all-cause mortality. CONCLUSION: Evidence from published statin randomized placebo-controlled trials suggests that pravastatin, simvastatin, and atorvastatin, when used at their standard dosages, show no statistically significant difference in their effect on long-term cardiovascular prevention.

Atorvastatin↗
PubMed2006

Benefit versus risk in statin treatment.

The Statin Safety Assessment Conference of the National Lipid Association (NLA), reported in this supplement to The American Journal of Cardiology, provides a comprehensive evaluation of old and new experience on adverse events associated with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins. To place these in context, one can express both the risk of side effects and the benefits for cardiovascular disease in terms of events per person-year of statin treatment. The mortality risk from fatal rhabdomyolysis is approximately 0.3 per 100,000 person-years, and the risks of nonfatal rhabdomyolysis and of putative statin-attributable peripheral neuropathy are approximately 3 and 12 events, respectively, per 100,000 person-years. Reports of acute liver failure and acute or chronic kidney disease give lower rate estimates that, even when corrected for underreporting, are approximately equal to the background rates of these conditions in the general population, lending scant support for statin-attributable etiology. In contrast, the benefit of statin use is to avert several hundred deaths and several hundred cases each of heart and brain infarction per 100,000 person-years in appropriately treated high-risk patients. Although population estimates such as these are useful, they must be translated repeatedly to individual patient-provider encounters, where clinical skill and art must combine with scientific evidence. The continued publication of individual case reports and small randomized trials among groups of patients with potential side effects should be encouraged. Statins should not be used in situations where minimal benefit is expected, as safety data and risk-benefit analysis must be meshed with guidelines that help the clinician decide whom to treat and how aggressively to treat.

Coronary Artery Disease↗