Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial

Nakamura, Haruo; Arakawa, Kikuo; Itakura, Hiroshige; Kitabatake, Akira; Gotō, Yoshio; Toyota, Takayoshi; Nakaya, Noriaki; Nishimoto, Shoji; Muranaka, M; Yamamoto, Akira; Mizuno, Kyoichi; Ohashi, Yasuo

doi:10.1016/s0140-6736(06)69472-5

Cited by 868 publications

(654 citation statements)

References 21 publications

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“…Despite overwhelming evidence that supports statin‐mediated lipid lowering to reduce CV risk,5, 6, 7, 8, 9, 10, 11, 12 dyslipidemia is often undertreated in Asian populations. A retrospective analysis of hospital medical records in China demonstrated that approximately 60% of patients with a history of atherosclerotic CVD were not prescribed a statin 13.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, CV risk reduction strategies that have proved successful in Western populations will likely have a similar impact in preventing CV events in Asian patients 3. The reduction in low‐density lipoprotein cholesterol (LDL‐C) levels with statins has been shown to be highly effective for reducing CV risk in a wide range of patient populations,5, 6 including Asian patients 7, 8, 9, 10. Recent dyslipidemia treatment guidelines have emphasized the importance of LDL‐C lowering with statins for the prevention of CVD,11, 12 including high‐intensity statin therapy to achieve ≥50% reduction in LDL‐C 12.…”

Section: Introductionmentioning

confidence: 99%

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Safety of atorvastatin in Asian patients within clinical trials

Chan

Kong

Bao

et al. 2016

Cardiovascular Therapeutics

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SummaryIntroductionData on statin safety in Asian patients are limited compared with evidence from Western populations.AimThis study assessed atorvastatin safety among Asian patients enrolled in 58 randomized clinical trials.MethodsData from 52 short‐term trials (median exposure 4–72 weeks) and six long‐term cardiovascular outcomes trials (median exposure 3.1–4.9 years) conducted across the atorvastatin 10–80‐mg dose range were analyzed retrospectively to assess the incidence of safety endpoints.ResultsA total of 77 952 patients were identified (49 974 received atorvastatin), among whom 3191 were Asian (2519 received atorvastatin). In the short‐term trials, the incidence of all‐causality adverse events (AEs) and serious AEs (SAEs) in Asian patients treated with atorvastatin was similar to or lower than that observed with other statins or placebo, and discontinuations due to treatment‐related AEs/SAEs were infrequent (2.0% across all doses). These observations were confirmed in the long‐term trials. Treatment‐related SAEs were rare (n = 4) among Asian patients receiving atorvastatin. No cases of rhabdomyolysis were observed in atorvastatin‐treated Asian patients, and the incidence of myalgia was 1.8% in the short‐term studies and 6.7% in the long‐term trials. Elevations (>3× the upper limit of normal) in liver transaminases were observed in ~2% of Asian patients receiving atorvastatin; renal AEs occurred in <2%.ConclusionThe incidence of AEs/SAEs with atorvastatin 10–40‐mg in patients of Asian origin was low and comparable to placebo. Further evaluation of atorvastatin 80‐mg is required owing to the limited number of Asian patients (n = 281; 11.2%) who received this dose.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Safety of atorvastatin in Asian patients within clinical trials

Chan

Kong

Bao

et al. 2016

Cardiovascular Therapeutics

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“…Statins are HMG-CoA reductase inhibitors that are widely used to treat hypercholesterolemia; their potential radioprotective effects have been discussed in a limited number of preclinical and clinical studies (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Clinical studies have reported that pravastatin has anti-inflammatory effects and is a safe HMG-CoA reductase inhibitor that is water soluble (5). However, the use of pravastatin to reduce radiation-induced damage to normal tissue has not been investigated thoroughly, despite its promise for use as a radioprotectant (7-10).…”

Section: Discussionmentioning

confidence: 99%

“…Pravastatin, an inhibitor of 3-hydroxy-3-methyl-glutarylconenzyme A (HMG-CoA) reductase, is widely used to treat hypercholesterolemia and has been reported to have a therapeutic applicability in a range of inflammatory conditions (5,6). Statins have previously been reported to have beneficial effects on radiation-induced toxicities, and numerous studies have demonstrated the anti-inflammatory effects of pravastatin following radiation exposure (7)(8)(9)(10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Pravastatin Reduces Radiation-Induced Damage to Normal Tissues

Doi

Matsumoto

Odawara

et al. 2016

International Journal of Radiation Oncology*Biology*Physics

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Abstract.Pravastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice were divided into two groups: The control group received ionizing radiation with no prior medication, while the pravastatin group received pravastatin prior to ionizing radiation. Pravastatin was administered orally at 30 mg/kg body weight in drinking water at 24 and 4 h before irradiation. Intestinal crypt epithelial cell survival and the incidence of apoptosis in the intestine and lung were measured post-irradiation. The effect of pravastatin on intestinal DNA damage was determined by immunohistochemistry. Finally, the effect of pravastatin on tumor response to radiotherapy was examined in a mouse mesothelioma xenograft model. Pravastatin increased the number of viable intestinal crypts and this effect was statistically significant in the ileum (P<0.0001). The pravastatin group showed significantly lower apoptotic indices in all examined parts of the intestine (P<0.0001) and tended to show reduced apoptosis in the lung. Pravastatin reduced the intestinal expression of ataxia-telangiectasia mutated and gamma-H2AX after irradiation. No apparent pravastatin-related differences were observed in the response of xenograft tumors to irradiation. In conclusion, pravastatin had radioprotective effects on the intestine and lung and reduced radiation-induced DNA double-strand breaks. Pravastatin may increase the therapeutic index of radiotherapy.

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“…17, 18 In the Japanese population, less intensive lipid-lowering therapy with low-dose pravastatin reduced the risk of CAD in low-risk patients in the setting of primary prevention of CVD. 19 In secondary prevention, there were several studies that revealed the beneficial coronary vascular effects of aggressive lipid-lowering therapy with strong statins in patients with ACS and those with CAD, 20-22 and the safety 23 and efficacy in lowering LDL-C 23 and regressing coronary atherosclerosis 21 appeared equivalent among strong statins. In addition, early intensive lipid-lowering therapy with a highdose strong statin improved long-term clinical outcomes in patients with ACS.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Rosuvastatin Improves Arterial Stiffness in High-Risk Japanese Patients With Dyslipdemia in a Primary Prevention Group - A Comparison With Fluvastatin -

Hongo

Kumazaki

Izawa

et al. 2011

Circ J

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Background:The treatment effects of rosuvastatin on arterial stiffness were assessed and compared to those of fluvastatin in high-risk Japanese patients with dyslipidemia in a primary prevention group. Methods and Results:Patients were randomly assigned to either 2.5-5 mg/day of rosuvastatin (Group A) or 20-40 mg/day of fluvastatin (Group B) and followed up for 12 months. In Group A (n=38), there was a progressive reduction in brachial-ankle pulse wave velocity (baPWV) along with a decrease in the low-density lipoprotein cholesterol/ high-density lipoprotein cholesterol (L/H) ratio and high-sensitivity C-reactive protein (hsCRP), and the change in baPWV correlated significantly with that of the L/H ratio and that of hsCRP after rosuvastatin treatment. In Group B (n=37), although fluvastatin achieved a significant improvement in baPWV, L/H ratio, and hsCRP, baPWV was significantly greater than that in Group A and showed a significant correlation with that of hsCRP alone after fluvastatin treatment. In a subgroup of patients (n=26), switching from fluvastatin to rosuvastatin further improved baPWV and the L/H ratio without altering hsCRP after 12 months. Conclusions:Low-dose rosuvastatin would be more effective than fluvastatin in improving arterial stiffness in highrisk Japanese patients with dyslipidemia. The results suggest that improvement in arterial stiffness by rosuvastatin mainly depends on its strong lipid-lowering effects, whereas that by fluvastatin is strongly dependent on the pleiotropic effects, especially an anti-inflammatory action. (Circ J 2011; 75: 2660 - 2667

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Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial

Cited by 868 publications

References 21 publications

Safety of atorvastatin in Asian patients within clinical trials

Safety of atorvastatin in Asian patients within clinical trials

Pravastatin Reduces Radiation-Induced Damage to Normal Tissues

Low-Dose Rosuvastatin Improves Arterial Stiffness in High-Risk Japanese Patients With Dyslipdemia in a Primary Prevention Group - A Comparison With Fluvastatin -

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