Statins
Drugs

Another Study Ties Statins to T2D: Should Practice Change? 2023

Sunday Express: EXCLUSIVE: Statins linked to 20,000 side effects and 227 deaths 2018

See also Red Yeast Rice: Chinese Secret for Lower Cholesterol

Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia.1991

Myopathy, defined as muscle symptoms with a creatine kinase elevation greater than 10 times the upper limit of normal, was found in only one patient (0.1%) receiving 40 mg once daily and four patients (0.2%) receiving 80 mg/d of lovastatin.

Roberto S. Accolla & Giovanna Tosi,
Dipartimento di Medicina Sperimentale Universita' dell’Insubria, terranno
un seminario dal titolo: “Intrinsic and adaptive immunity: the dual
function CIITA as viral restriction factor and as inducer of specific
immunity against tumors"

Differential inhibitory effects of lovastatin on protein isoprenylation and sterol synthesis. 1990

• It has been reported that when 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors are utilized for treatment of hypercholesterolemia, as much as 50% inhibition of whole body cholesterol biosynthesis is observed. As general inhibitors of isoprenoid biosynthesis, these compounds can also inhibit the synthesis of the substituents of isoprenylated proteins. For two mammalian proteins (p21ras and lamin A), it has been demonstrated that such inhibition of biosynthesis of the isoprenoid substituent blocks proteolytic maturation of these proteins. It has been argued that advantage may be taken of this phenomenon to block the synthesis of p21ras in malignancies. It is also possible that treatment of hypercholesterolemia with lovastatin might produce problematic inhibition of protein processing dependent upon isoprenylation. In this report, we compare the concentration dependence of inhibition of isoprenylation dependent protein processing and sterol biosynthesis. Effects of partial inhibition of isoprenylated protein processing on whole cells can be sensitively assessed by visualization of lamina structure through indirect immunofluorescence. Our results indicate that the degree of inhibition of p21ras and prelamin A maturation by lovastatin is identical. Thus, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors are unlikely to be useful as anti-malignancy drugs. However, the conditions of lovastatin treatment which produce 50% inhibition of sterol biosynthesis analogous to pharmacological conditions, produce no observable effects on isoprenylated protein maturation.

Molecular clues into the pathogenesis of statin-mediated muscle toxicity. 2005

• The pathophysiology of statin-mediated muscle dysfunction is poorly defined. Reductions in skeletal muscle membrane cholesterol were initially thought to account for the range of myopathic reactions, e.g., myalgia, elevated serum creatine kinase, or rhabdomyolysis. This assumption however, does not consider a potential role of the isoprenoids in the pathophysiology of statin myopathy. The observation that derangements in mevalonate kinase (MK), but not more distal enzymes of cholesterologenesis, are associated with a skeletal myopathy suggests a critical role for the isoprenoids in the maintenance of muscle. Statins also deplete the isoprenoid pool by inhibiting the enzyme, beta-hydroxy-beta-methylglutaryl coenzyme A reductase, which is upstream of MK. Identifying candidate proteins that are both dependent on isoprenoid-mediated modification and associated with muscle disease, when genetically mutated, offers further insight into potential mechanisms of statin myopathy. For example, lamin A/C, selenoprotein N, alpha- and beta-dystroglycan, and cytoskeletal G-proteins all require isoprenylation for optimal function. Understanding the pleiotropic effects of protein prenylation, and the potential consequences of a generalized insufficiency of this form of protein modification, may help clarify the molecular pathogenesis of statin myopathy.

Coenzyme Q and diabetes

Statin induced diabetes

CoQ administration improves diabetes?

Statins effects on Candida mt

The statins, simvastatin and atorvastatin are the most widely prescribed drugs. Statins lower cholesterol levels through their action on HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase, an essential enzyme for the biosynthesis of cholesterol. Fungal HMG-CoA reductases are also inhibited by statins, resulting in reduced levels of ergosterol (the fungal equivalent of cholesterol) and concomitant growth inhibition. This effect occurs in a range of fungal species and possibly affects fungal colonization of people on statin therapy. Furthermore, it may suggest that statins could have a role in new antifungal therapies. Possibly associated with the reduction in ergosterol levels, statins also inhibit respiratory growth. In the yeast, Candida glabrata, passage with statins dramatically increased the frequencies of petite mutants that were devoid of mitochondrial DNA, suggesting that statins caused a defect in the maintenance of mitochondrial DNA. These observations in C. glabrata may provide further insights into side effects of statins in humans undergoing treatment for hypercholesterolaemia. In addition, C. glabrata may be highly useful for the preliminary screening of agents to reduce statin side effects.

Possibili effetti avversi da statine
Il paziente in terapia con statine dovrebbe essere monitorato in modo proattivo; questi farmaci, infatti, possono dare vari effetti avversi inattesi, con un rischio massimo nel corso del primo anno di trattamento. È quanto dimostra uno studio di coorte basato sulla popolazione effettuato da Julia Hippisley-Cox e Carol Coupland della Divisione di Cure primarie all'University Park di Nottingham (UK). È stato utilizzato un archivio informatico con i dati di 368 ambulatori di medicina generale dell'Inghilterra e del Galles relativi a 2.004.692 pazienti di età compresa tra 30 e 84 anni ai quali era prescitto un inibitore dell'HmCoA reduttasi: simvastatina (70,7%), atorvastatina (22,3%), pravastatina (3,6%), rosuvastatina (1,9%) e fluvastatina (1,4%). Nel complesso non è emersa per alcuna molecola l'associazione con il rischio aumentato di patologie oncologiche, neurologiche, reumatologiche o ematologiche. Si è anzi notata in generale una ridotta probabilità di cancro esofageo. È però cresciuto il rischio di disfunzione epatica di grado moderato o grave (più evidente con fluvastatina), insufficienza renale acuta, miopatia di grado medio o forte, e di cataratta. In tutti i casi, il rischio persisteva per l'intera durata del trattamento e, dopo la cessazione della terapia, tornava alla normalità in un tempo variabile da 1 a 3 anni, a seconda del sesso del paziente e del tipo di effetto avverso. I numeri necessari per il trattamento (Nnt) e per nuocere (Nnh), calcolati su 5 anni, sono risultati sovrapponibili nei maschi e nelle femmine, fatta eccezione per la miopatia (91 tra i primi vs. 259 nelle seconde). Verificati e quantificati i possibili effetti avversi delle statine, concludono le autrici, occorre migliorare gli strumenti per individuare gli assistiti ad alto rischio che necessitino di un monitoraggio più stretto.

BMJ, 2010; 340:c2197

Am J Cardiovasc Drugs. 2007;7(3):219-24.
Effects of simvastatin and metformin on inflammation and insulin resistance in individuals with mild metabolic syndrome. 2007

Bulcão C, Ribeiro-Filho FF, Sañudo A, Roberta Ferreira SG.

Division of Endocrinology, Department of Internal Medicine, Federal University of São Paulo, São Paulo, Brazil. cbulcao@uol.com.br
Abstract

BACKGROUND: In addition to lipid-lowering and insulin-sensitizing actions, statins (HMG-CoA reductase inhibitors) and metformin may have pleiotropic effects. OBJECTIVE: To study the effect of simvastatin and metformin on insulin sensitivity and inflammatory markers. METHODS: Forty-one subjects with body mass index (BMI) 25-39.9 kg/m(2) and impaired glucose tolerance were randomized to receive simvastatin or metformin for 16 weeks. Blood samples were obtained for measurement of metabolic and inflammatory parameters before and after each treatment. RESULTS: As expected, when compared with simvastatin, metformin therapy resulted in significant reductions in mean BMI, fasting plasma glucose, and homeostasis model assessment-insulin resistance (HOMA-IR), whereas simvastatin treatment resulted in significantly reduced total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and apolipoprotein B levels. Independently of the medication used, significant decreases in C-reactive protein (CRP) and interleukin (IL)-6 were detected from baseline to treatment end. CRP showed a mean reduction of 0.12 +/- 0.04 mg/dL (p = 0.002) over the 16-week intervention period and IL-6 a mean reduction was 0.35 +/- 0.17 pg/mL (p = 0.046). No change was observed in the tumor necrosis factor-alpha levels. Baseline values of CRP and IL-6 and their percentage declines were correlated (r = 0.71 and r = 0.67, respectively; p < 0.001). In simvastatin recipients, no correlation was detected between reductions in CRP or IL-6 and lipids, whereas in metformin recipients, reductions in inflammatory markers were not correlated to BMI and HOMA-IR. CONCLUSION: Our findings suggest that both metformin and simvastatin have similar beneficial effects on low-grade inflammation, in addition to their classical effects on glucose and lipid metabolism. Moreover, they confirm the importance of treating at-risk individuals even before the precipitation of overt diabetes mellitus or full-blown metabolic syndrome.

Statin adverse effects : a review of the literature and evidence for a mitochondrial mechanism. 2008
Am J Cardiovasc Drugs. 2008;8(6):373-418. doi: 10.2165/0129784-200808060-00004.
Golomb BA, Evans MA.

Department of Medicine, University of California, San Diego, California 92093-0995, USA. bgolomb@ucsd.edu
Abstract

HMG-CoA reductase inhibitors (statins) are a widely used class of drug, and like all medications, have potential for adverse effects (AEs). Here we review the statin AE literature, first focusing on muscle AEs as the most reported problem both in the literature and by patients. Evidence regarding the statin muscle AE mechanism, dose effect, drug interactions, and genetic predisposition is examined. We hypothesize, and provide evidence, that the demonstrated mitochondrial mechanisms for muscle AEs have implications to other nonmuscle AEs in patients treated with statins. In meta-analyses of randomized controlled trials (RCTs), muscle AEs are more frequent with statins than with placebo. A number of manifestations of muscle AEs have been reported, with rhabdomyolysis the most feared. AEs are dose dependent, and risk is amplified by drug interactions that functionally increase statin potency, often through inhibition of the cytochrome P450 3A4 system. An array of additional risk factors for statin AEs are those that amplify (or reflect) mitochondrial or metabolic vulnerability, such as metabolic syndrome factors, thyroid disease, and genetic mutations linked to mitochondrial dysfunction. Converging evidence supports a mitochondrial foundation for muscle AEs associated with statins, and both theoretical and empirical considerations suggest that mitochondrial dysfunction may also underlie many nonmuscle statin AEs. Evidence from RCTs and studies of other designs indicates existence of additional statin-associated AEs, such as cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction. Physician awareness of statin AEs is reportedly low even for the AEs most widely reported by patients. Awareness and vigilance for AEs should be maintained to enable informed treatment decisions, treatment modification if appropriate, improved quality of patient care, and reduced patient morbidity.

Statins improve visual field alterations related to hypercholesterolemia. 2010
Atherosclerosis. 2010 Apr;209(2):510-4. Epub 2009 Oct 12.
Alcalá A, Jansen S, Téllez T, Gómez-Huelgas R, Pérez O, Egido J, Farkouh ME.

Department of Clinical Biochemistry and Molecular Biology, Malaga University, School of Medicine, C/Liborio Garcia, 8, 29005 Malaga, Spain. glia128@telefonica.net
Abstract

OBJECTIVE: To determine whether lipid-lowering treatment with diet or statins would provide beneficial effects on visual field alterations associated with hypercholesterolemia. METHODS: 180 subjects with hypercholesterolemia were randomly assigned to a low fat diet (diet group) or to a low fat diet plus 40 mg/day of pravastatin (pravastatin group). At the beginning of the study and 6 months after the assigned treatment, all subjects underwent a computerized perimetry test and a determination of plasma concentration of glucose, total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and triglycerides. RESULTS: At 6 months, both groups showed a significant decrease in total cholesterol, LDL-C and triglycerides compared to basal values, and a significant increase in the HDL-C. The pravastatin group had a significantly greater reduction in total cholesterol (-85+/-21 mg/dl) and LDL-C (-86+/-23 mg/dl) than the diet group (-28+/-9 and -28+/-10mg/dl, respectively). All perimetry parameters improved in both groups after the intervention period, although the improvement was greater in the pravastatin group. Using a general linear model, a significant effect of treatment with pravastatin compared to diet was observed in the improvement of all the perimetry parameters, whereas the change in LDL-C concentrations only had a significant effect on the improvement of one of them. CONCLUSION: In subjects with hypercholesterolemia, the decrease of blood lipids improves visual field parameters. The major beneficial effect noted with pravastatin, compared to diet, suggests that this effect could be due to the lipid-lowering and pleiotropic actions.

Statins: under investigation for increasing bone mineral density and augmenting fracture healing. Read more... Papers Statin Bmp2

Trattamento con statine utile nella Bpco
Esistono forti evidenze che un trattamento con statine determini benefici in pazienti con broncopneumopatia cronica ostruttiva (Bpco). Lo dimostra una revisione sistematica, effettuata da ricercatori della University of British Columbia (Vancouver), di nove studi di cui uno solo randomizzato controllato e i rimanenti otto retrospettivi, caso-controllo o epidemiologici. Tutti gli studi hanno dimostrato un beneficio dall'impiego di statine per vari outcome in pazienti con Bpco, considerati sia individualmente sia collettivamente, tra cui la funzione polmonare e la capacità d'esercizio (1 studio), i tassi di riesacerbazione (3), il numero dei ricoveri e delle intubazioni correlati a Bpco (1), la mortalità da Bpco (3). In effetti le statine, oltre al comprovato ruolo ipocolesterolemizzante, posseggono anche effetti pleiotropici antinfiammatori e immunomodulatori ritenuti efficaci nella terapia della Bpco. "La maggior parte degli studi pubblicati ha il limite metodologico di essere retrospettivo e ciò impedisce di suggerire modifiche nella pratica clinica" affermano gli autori. "Al tempo stesso, la letteratura disponibile è sufficiente per finanziare ampi trial randomizzati prospettici che, se ben condotti, possono fornire elementi determinanti per supportare o scartare l'uso delle statine nella Bpco". (A.Z.)

Chest, 2009; 136:734-743

BPCO: utili le statine
Nei pazienti con BPCO, il trattamento con statine può avere effetti benefici su diversi esiti negativi rilevanti, comprese le riacutizzazioni della malattia e la mortalità derivante tanto dalla BPCO che da qualsiasi altra causa. Le statine hanno dunque il potenziale di alterare la prognosi ed il declino della funzionalità polmonare in questi pazienti, un traguardo che non si ottiene in modo limpido con nessuno dei farmaci attualmente impiegati contro la BPCO. Essa è una patologia comune, che grava pesantemente sulla società in tutto il mondo, e le statine sono state recentemente riconosciute come possibili agenti in grado di modificare il decorso della malattia. Le statine sembrano influenzare l'infiammazione sistemica e la morbidità cardiovascolare in questi pazienti, ma allo stesso tempo è probabile che colpiscano direttamente l'infiammazione delle vie aeree. Molti pazienti con BPCO presentano un aumento del rischio cardiovascolare, e pertanto sono già candidati al trattamento preventivo con statine sulla base delle attuali linee guide per la gestione della lipidemia, ma comunque nella pratica clinica spesso il rischio cardiovascolare non viene valutato sistematicamente in presenza di BPCO: esso andrebbe invece valutato controllando eventuale abitudine al fumo, profilo lipidico, rischio diabetico e pressione. Attualmente non è chiaro che tipo di statine, dosaggio e durata del trattamento applicare per ottenere un effetto pleiotropico, ma dato che la maggior parte dei dati disponibili è basata su studi osservazionali, sono necessari con urgenza studi randomizzati controllati per valutare gli effetti terapeutici delle statine nella BPCO. (BMC Pulm Med. 2009; 9: 32)

Reumatologia
LES, trapianto di rene, cuore e statine
La terapia statinica migliora gli esiti cardiaci e le dislipidemie nei pazienti con LES che ricevono un trapianto di rene, senza apparenti controindicazioni. Il LES colpisce soprattutto le giovani donne in età fertile, che poi presentano un aumento del rischio di malattie cardiovascolari premature: quanto rilevato conferma gli effetti benefici della terapia statinica per la prevenzione delle malattie cardiovascolari dimostrati in varie popolazioni. Benché le dimensioni dello studio non siano eclatanti, l'entità del risultato è stata determinante. I dati rilevati sui pazienti con LES nefrotrapiantati dovrebbero probabilmente essere estesi a tutti i pazienti con LES in generale, ma è poco probabile che venga condotto uno studio controllato sulle statine in questa intera popolazione. (Arthritis Rheum 2009; 60: 1060-4)

Tromboembolie: rosuvastatina efficace in prevenzione
La rosuvastatina appare in grado di ridurre significativamente la comparsa della tromboembolia venosa in soggetti in apparente buona salute. Persiste fino ad oggi la controversia sulla misura in cui la trombosi venosa e quella arteriosa condividano gli stessi meccanismi, nonché quella sui benefici in ciascuna delle due patologie di trattamenti di comprovata efficacia in una di esse. Gli studi osservazionali in materia hanno portato a stime variabili degli effetti della terapia statinica sul rischio di tromboembolia venosa, e non sono stati finora disponibili dati da studi randomizzati. L'efficacia della rosuvastatina è risultata costante in tutti i sottogruppi di pazienti esaminati, e non sono state riscontrate differenze significative nella frequenza degli episodi emorragici. (NEJM online 2009, pubblicato il 29/3)

Statins could be divided in two groups:

• hydrophilic (pravastatin) and
• lipophilic (atorvastatin, simvastatin, fluvastatin, lovastatin, cervistatin).

The lipophilic or hydrophilic nature of statins influences at least in vitro their access to cellular membranesIt has been shown that hydrophilic statins are distributed much more selectively in hepatic than lipophilic cells (Ichihara et al, 2002). Because the membrane of extrahepatic cells consists of lipid bilayers, hydrophilic statins cannot penetrate it, and thus cannot reach the intracellular enzyme; however the hepatic cell membrane contains organic anion transporters, which take hydrophilic substances into the cells. Lipophilic statins can enter extrahepatic and hepatic cells and thus, as shown in Figure 10, inhibit not only the cholesterol synthesis but also the production of metabolic intermediates in many extrahepatic tissues. Protein binding of statins varies from 50% (pravastatin) to 98% (atorvastatin, simvastatin, fluvastatin).

Lowering cholesterol synthesis lowers vitamin D synthesis etc

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase fibrinolytic activity in rat aortic endothelial cells. Role of geranylgeranylation and Rho proteins. 1998

Statins W

Statin development con strutture

Antinflammatory effect and genomic mechanism 2004

Statin effect on CIITA transactivator

To get the genomic mechanism of antinflammatory effect

Papers CCAAT and statin

Papers MHC II and statins

Letteratura Sinvacor

Truth and myths about cholesterol asa risk factor 2007

Low doses of statins and coQ

The double-edged sword of statin immunomodulation. 2008

Statins as antihypertensives

Gastroenterologia
Le statine inducono l'apoptosi nel ca esofageo
Le statine possono bloccare la proliferazione e promuovere l'apoptosi delle cellule degli adenocarcinomi esofagei (EAC). Questi popolari agenti ipocolesterolemizzanti ottengono questo effetto inibendo la farnesilazione del Ras e le cascate di segnalazione ERK e AKT. In tutto il mondo è stato osservato un rapido incremento nei tassi degli EAC e nella mortalità conseguente, il che ha portato molti ricercatori a guardare alla chemioprevenzione quale mezzo per ridurre il carico della malattia. Precedenti studi hanno dimostrato che le statine, che hanno un eccellente profilo di sicurezza, possono ridurre la disponibilità di vari prodotti intermedi biosintetici di importanza critica per la segnalazione intracellulare, ma non era chiaro se ciò si potesse tradurre in un effetto benefico anticancerogeno. Al momento attuale non è possibile estrapolare questi dati di laboratorio ad uno scenario clinico, ma tali dati suggeriscono che gli effetti delle statine sui pazienti con EAC ed esofago di Barrett possano essere davvero benefici, e che sarebbe opportuno effettuare ulteriori studi sugli effetti delle statine o di altri inibitori delle farnesiltrasferasi su dinamiche epiteliali ed esiti sia nei modelli sperimentali che sui pazienti onde accertare meglio se questa classe di farmaci abbia un ruolo definito nella prevenzione o nel trattamento degli EAC. (Am J Gastroenterol 2008; 103: 825-37)

[Coronary heart disease and osteoporosis: factors related to development of both diseases]
PMID: 17941467Related Articles
Authors: Nowicka G, Panczenko-Kresowska B
Journal: Przegl Lek, 64 (3): 153-8, 2007
Nowicka G et al., Przegl Lek, 64 (3): 153-8, 2007
Coronary heart disease and osteoporosis are common diseases in aging populations.
Coronary heart disease and osteoporosis are common diseases in aging populations. Traditionally, these diseases have been considered as distinct and unrelated. However, nowadays there has been increasing evidence indicating a pathological link between these two disorders. Both diseases share etiological factors as hyperlipidemia, hypertension, diabetes, oxidative stress, inflammation, hyperhomocysteinemia. Statins, hypolipidemic drugs, not only reduce atherogenesis but also stimulate bone formation. Bisphosphonates, drugs used in osteoporosis treatment, have been shown to influence serum cholesterol levels and inhibit atherosclerotic plaque formation.
Wiki: Hyperhomocysteinemia, Atherosclerosis, Inflammation, Cholesterol, Heart_development, Osteoporosis, Heart_Diseases, Ossification, Serum, Coronary_Disease, Oxidative_stress, Oxides, Hypertension
Affiliation: Pracownia Metaboliczna, Zaklad Profilaktyki Chorób Zywieniowozaleznych, Instytut Zywności i Zywienia, Warszawa. gnowicka@izz.waw.pl

FulltextRDFEndnoteBibTeXPlainText
20:Statin-induced apoptosis and skeletal myopathy.
PMID: 16885396Related Articles
Authors: Dirks AJ, Jones KM
Journal: Am J Physiol Cell Physiol, 291 (6): C1208-12, 2006
Dirks AJ et al., Am J Physiol Cell Physiol, 291 (6): C1208-12, 2006
Because of the discovered pleiotropic effects of statins, the use has expanded to the treatment of many other conditions, including ventricular arrythmias, idiopathic dilated cardiomyopathy, cancer, osteoporosis, and diabetes.
Over 100 million prescriptions were filled for statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) in 2004. Statins were originally developed to lower plasma cholesterol in patients with hypercholesterolemia and are the most effective drugs on the market in doing so. Because of the discovered pleiotropic effects of statins, the use has expanded to the treatment of many other conditions, including ventricular arrythmias, idiopathic dilated cardiomyopathy, cancer, osteoporosis, and diabetes. The elderly population is growing. Therefore, it is estimated that the number of statin users will also increase. Fortunately, the use of statins is relatively safe with few side effects. Myopathy is the most common side effect with symptoms ranging from fatigue, weakness, and pain to symptoms associated with rhabdomyolysis which is a life-threatening condition. The development of statin-induced rhabdomyolysis is rare occurring in approximately 0.1% of patients; however, the occurrence of less severe symptoms is underreported and may be 1-5% or more. Physical exercise appears to increase the likelihood for the development of myopathy in patients taking statins. It is thought that as many as 25% of statin users who exercise may experience muscle fatigue, weakness, aches, and cramping due to statin therapy and potentially dismissed by the patient and physician. The mechanisms causing statin-induced myopathy have not been elucidated; however, research efforts suggest that apoptosis of myofibers may contribute. The mitochondrion is considered a regulatory center of apoptosis, and therefore its role in the induction of apoptosis will be discussed as well as the mechanism of statin-induced apoptosis and myopathy.

Un aggiornamento di parte 2008

Forte associazione contro il colesterolo
I dati del Progetto Cuore dell'Istituto Superiore di Sanità parlano chiaro. In Italia il colesterolo è una minaccia in crescita ma non sempre è trattato come dovrebbe. Il risultato è che i pazienti ad alto rischio cardiovascolare possono incorrere in eventi severi. "In questi pazienti - dice Gian Franco Gensini, ordinario di Medicina interna e Cardiologia all'Università di Firenze - per tenere il colesterolo sotto controllo sono necessari i farmaci. In particolare, le statine. I risultati degli studi DIALOGUE e LEAD, condotti in Italia su pazienti italiani, hanno evidenziato come l'associazione fissa in un'unica compressa di ezetimibe/simvastatina sia più efficace, rispetto a una dose doppia di sola simvastatina, nella riduzione dei valori di colesterolo LDL, permettendo di raggiungere valori ambiziosamente bassi in una percentuale di circa l'80% dei pazienti". "Nei diabetici - ha affermato Carlo Maria Rotella ordinario di Endocrinologia all'Università di Firenze, past-president della Società Italiana dell'Obesità e Coordinatore dello studio LEAD - valgono i medesimi obiettivi terapeutici che si adottano per chi ha già avuto un infarto: 100 mg/dL in presenza del solo diabete, 70 mg/dL se oltre al diabete sono presenti altri fattori di rischio cardiovascolare. In questi pazienti è dimostrato che l'associazione ezetimibe/simvastatina è molto più rapida ed efficace del solo raddoppio della statina.

Infarto: beta-bloccanti ostacolano statine
I livelli di CRP risultano molto più ampiamente ridotti con la sola somministrazione di statine che con l'aggiunta di beta-bloccanti dopo un infarto acuto., il che indica che questi ultimi farmaci attenuino l'effetto antiinfiammatorio delle statine. E' stato confermato che vari tipi di statine sono in grado di attenuate l'intenso incremento dell'attività infiammatoria a livello sistemico che si osserva durante la fase acuta dell'infarto miocardico, ma non era finora noto che questo effetto terapeutico delle statine potesse essere ostacolato dalla concomitante somministrazione di altri farmaci, come i beta-bloccanti. La significatività del dato rilevato permane anche tenendo conto di elementi come età o sesso del paziente e livelli base di CRP. (Am J Cardiol 2009; 103: 461-3)