Relative safety profiles of high dose statin regimens

Escobar, Carlos; Echarri, Rocio; Barrios, Vivencio

doi:10.2147/vhrm.s2048

Cited by 31 publications

(6 citation statements)

References 70 publications

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“…The most important adverse events related to the use of atorvastatin are muscle toxicity and the effects on liver enzymes. However, rhabdomyolysis and creatinine kinase or transaminase level were not significantly increased in trials of intensive statin therapy or at high dose of AVA (80 mg/day) for periods ranging from 2 weeks to 5 years and were not age related [ 45 - 48 ]. The administration doses of AVA in humans at 120 mg daily did not induce rhabdomyolysis [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin as a potential anti-malarial drug: in vitro synergy in combinational therapy with quinine against Plasmodium falciparum

Parquet

Henry

Wurtz

et al. 2010

Malar J

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BackgroundQuinine (QN) remains the first line anti-malarial drug for the treatment of complicated malaria in Europe and Africa. The emergence of QN resistance has been documented. QN resistance is not yet a significant problem, but there is an urgent need to discover partners for use in combination with QN. The aim of the study was to assess the in vitro potentiating effects of atorvastatin (AVA), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in combination with QN against Plasmodium falciparum and to evaluate whether the effects of AVA could be associated with gene copy number or mutations in genes involved in QN resistance, such as pfcrt, pfmdr1, pfmrp and pfnhe.MethodsThe susceptibilities to combination of AVA with QN were assessed against 21 parasite strains using the in vitro isotopic microtest. Genotypes and gene copy number were assessed for pfcrt, pfmdr1, pfmdr2, pfmrp genes. In addition, the number of DNNND, DDNHNDNHNN repeats in pfnhe-1 ms4760 and the ms4760 profile were determined for each strains of P. falciparum.ResultsAVA demonstrated synergistic effects in combination with QN against 21 P. falciparum strains. The QN IC50 was reduced by 5% (0% to 15%; 95%CI: 1%-8%), 10% (3% to 23%; 95%CI: 7%-14%) and 22% (14% to 40%; 95%CI: 19%-25%) in presence of AVA at concentrations of 0.1, 0.5 and 1.0 μM, respectively. These reductions were all significant (p < 0.009). The reduction in the QN IC50 in presence of AVA was not significantly correlated with the QN IC50 (r = 0.22, P = 0.3288) or the AVA IC50 (r = 0.03, P = 0.8946). The synergistic effect of AVA in combination with QN was not significantly associated with polymorphisms in the pfcrt, pfmdr1, pfmrp, and pfnhe-1 genes that could be involved in QN resistance. The synergistic effect of AVA on QN responses was not significantly associated with pfmdr1 copy number (P = 0.0428).ConclusionThe synergistic effect of AVA in combination with QN was found to be unrelated to mutations occurring in transport protein genes involved in QN drug resistance. The different mechanisms of drug uptake and/or mode of action for AVA compared to the other anti-malarial drugs, as well as the AVA-mediated synergy of the anti-malarial effect of QN, suggests that AVA will be a good candidate for combinatorial malaria treatment. All of these observations support calls for both an in vivo evaluation with pharmacokinetic component and clinical trials of AVA as an anti-malarial therapy.

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Section: Discussionmentioning

confidence: 99%

Atorvastatin as a potential anti-malarial drug: in vitro synergy in combinational therapy with quinine against Plasmodium falciparum

Parquet

Henry

Wurtz

et al. 2010

Malar J

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“…Currently, lifestyle modification is the first method of treating atherosclerosis while medicine is the next step, where statins are the most popular and widely prescribed drug. However, there are issues pertaining to the usage of statins such as escalating cost and side effects, especially elevated liver enzymes and skeletal muscle damage or myopathy [16]. Thus, new strategies are needed for the prevention of atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Gynura procumbens Standardised Extract Reduces Cholesterol Levels and Modulates Oxidative Status in Postmenopausal Rats Fed with Cholesterol Diet Enriched with Repeatedly Heated Palm Oil

Nazri

Fauzi

Buang

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Gynura procumbens (Lour.) Merr. (GP) has been reported in previous studies to possess antihyperlipidaemic, antioxidative, and cardioprotective properties. This study was aimed to determine the effect of standardised 80% ethanol extract of GP on lipid profiles and oxidative status of hypercholesterolemic rats. Postmenopausal (PM) Sprague-Dawley rats were ovariectomised and fed with 2% cholesterol diet fortified with five times heated palm oil to develop hyperlipidaemia status. Two doses of the extract (250 and 500 mg/kg) and atorvastatin (10 mg/kg) were administered once daily via oral gavage for 24 weeks. Systolic blood pressure (SBP) was increased during the first month in the postmenopausal group and decreased with GP supplementation. Lipid droplets accumulation was shown at the tunica media (TM) area of the aorta in the postmenopausal group and reduced with GP supplementation. Total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), and malondialdehyde (MDA) levels increased (p < 0.05) at 3 and 6 months in the postmenopausal group and were reduced with GP supplementation. GP also increased high-density lipoprotein (HDL) level in the postmenopausal group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were reduced in the postmenopausal group compared to control in the sham group but increased (p < 0.05) with GP supplementation. The results showed that the higher dose of GP (500 mg/kg) gave better effect. GP has the ability to reduce oxidative stress and prevent membrane cell damage through antioxidant enzyme activity modification and lipid profile changes in postmenopausal rats related to atherosclerosis.

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“…We noticed an influence of secondary prevention guidelines in primary prevention prescriptions, which could potentially lead to more side effects and noncompliance with statins, especially in a group of patients who are otherwise healthy. 10 …”

Section: Discussionmentioning

confidence: 99%

Use of the Joint British Society cardiovascular risk calculator before initiating statins for primary prevention in hospital medicine: experience from a large university teaching hospital

Garg¹,

Raju²,

Sondej³

et al. 2010

IJGM

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Introduction:Statin therapy is a well established treatment for hyperlipidemia. However, little is known about prescribing of statins for primary prevention in the real world, and even less about what happens to patients requiring primary prevention who are seen in a secondary care setting. The purpose of this research was to investigate the appropriateness of statin prescriptions by using the Joint British Society cardiovascular disease (JBS CVD) risk score for primary prevention in a large secondary care center.Methods:We retrospectively analyzed 500 consecutive patients in whom a statin prescription was initiated over a four-month period. We excluded patients who met secondary prevention criteria. We used the JBS CVD risk prediction chart to calculate 10-year composite risk. We also studied which statins were prescribed and their starting doses.Results:Of 500 patients consecutively started on statins in secondary care, 51 patients (10.2%) were treated for primary prevention. Of these, seven (14%) patients had a 10-year composite cardiovascular event risk of more than 20% (high-risk category), and were hence receiving appropriate therapy. Three main statins were prescribed for primary prevention, ie, atorvastatin (22 patients, 43%), simvastatin (25 patients, 49%), and pravastatin (four patients, 8%). The statins prescribed were initiated mainly at the 40 mg dose.Conclusions:Statin prescribing in secondary care for primary prevention is limited to about 10% of initiations. There is some overprescribing, because 86% of these patients did not require statins when risk-stratified appropriately. The majority of the prescriptions were for simvastatin 40 mg and atorvastatin 40 mg.

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Relative safety profiles of high dose statin regimens

Cited by 31 publications

References 70 publications

Atorvastatin as a potential anti-malarial drug: in vitro synergy in combinational therapy with quinine against Plasmodium falciparum

Atorvastatin as a potential anti-malarial drug: in vitro synergy in combinational therapy with quinine against Plasmodium falciparum

Gynura procumbens Standardised Extract Reduces Cholesterol Levels and Modulates Oxidative Status in Postmenopausal Rats Fed with Cholesterol Diet Enriched with Repeatedly Heated Palm Oil

Use of the Joint British Society cardiovascular risk calculator before initiating statins for primary prevention in hospital medicine: experience from a large university teaching hospital

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