Comparison of Preventive Effect on Cardiovascular Events With Different Statins - The CIRCLE Study -

Abstract

Background: Although statins vary in their effectiveness in lowering low-density lipoprotein cholesterol (LDL-C) and increasing high-density lipoprotein cholesterol (HDL-C) levels, there is little evidence that the degree of these changes can explain cardiac risk reduction in Japan. Our objective was to compare the efficacy of statins on serum lipid levels and to explore the association between those changes and cardiac events in patients after percutaneous coronary intervention (PCI). Methods and Results:The 743 consecutive patients who underwent PCI from 2001 to 2008 were retrospectively investigated. Treatment with either atorvastatin or pitavastatin significantly reduced LDL-C compared with pravastatin or no statin. In contrast, only pitavastatin treatment significantly increased HDL-C (13.4±22.9%, P=0.01 vs. no statin). Each statin significantly prevented major adverse cardiac events (MACE) compared with no statin, and pitavastatin was the most effective of all. Multivariate-adjusted analysis revealed that percent changes of both LDL-C and HDL-C independently predicted the incidence of MACE (hazard ratio [HR]: 1.015; 95% confidence interval [CI]: 1.010-1.020, HR: 0.988; 95%CI: 0.981-0.996, respectively). This relationship was preserved in patients with a baseline HDL-C level ≤45 mg/dl, but not HDL-C level >45 mg/ml. Conclusions:The extent of changes in LDL-C and HDL-C with statin treatment would independently alter the risk of cardiac events in Japanese patients for secondary prevention. Statins with varying lipid-modifying ability might provide differing prognosis in patients after PCI. (Circ J 2011; 75: 1951 - 1959 1952MARUYAMA T et al.and Welfare of Japan, and approved by the ethics committee of the hospital.

Pitavastatin and Atorvastatin Double-Blind Randomized ComPArative Study among HiGh-Risk Patients, Including ThOse with Type 2 Diabetes Mellitus, in Taiwan (PAPAGO-T Study)

“…Moreover, pitavastatin stimulates lipoprotein lipase (LPL) activity more potently than does atorvastatin, which may facilitate an increase in HDL-C through the efficient metabolism of TG-rich lipoproteins [18]. However, in the CIRCLE study [19], there was a significantly different outcome only in patients with lower baseline HDL-C (< 45 mg/dL) levels. The high-risk cohort in the present study had a relatively higher level of baseline HDL-C (48.5 to 48.7 mg/dL), which might partially explain the insignificant difference in the change in the HDL-C level.…”

Statin-Induced Myotoxicity: Pharmacokinetic Differences among Statins and the Risk of Rhabdomyolysis, with Particular Reference to Pitavastatin

“…A summary of meta-analyses and observational studies that report the frequency of serious muscle complications with statin therapy is shown in (Table 1) [6,7,[12][13][14][15][16][17]. These studies show that statin-induced rhabdomyolysis is extremely rare with standard-dose monotherapy.…”

“…These studies have demonstrated the efficacy of this new statin for the treatment of hypercholesterolemia and combined dyslipidemia [8]. Although long-term clinical outcome data on pitavastatin are limited, the retrospective CIRCLE study (Comparison of Preventive Effect on Cardiovascular Events with Different Statins) has shown that artorvastatin, pravastatin and pitavastatin all significantly reduced the long-term risk of major cardiac events in patients after percutaneous coronary intervention, and that this effect appeared to be greatest for pitavastatin [14]. Pitavastatin has also been demonstrated to Healthy volunteers…”

Treatment Options for Hypercholesterolemia and Combined Dyslipidemia: Focus on Pitavastatin

“…This was confirmed by Maruyama et al that observed that, despite giving a similar reduction of LDL-C, pitavastatin resulted superior to atorvastatin in reducing major adverse cardiac events, due to their differing HDL-C raising ability. 36 Furthermore, differently from the majority of other statins, pitavastatin appears to be a substrate of CYP2C9, and not CYP3A4; as a result, pitavastatin is less likely to interact with drugs that are metabolized via CYP3A4, which might be important for elderly patients who need to take multiple drugs. 41 A big advantage of pitavastatin regards also the use in patients with type 2 diabetes mellitus: in the JUPITER trial, in fact, rosuvastatin significantly prevented vascular events in men and women with elevated hs-CRP, but increased the incidence of new-onset diabetes more than the placebo, 42 and a previous published meta-analysis showed that statin therapy was associated with a significantly increased risk (9%) of the development of diabetes; 43 differently from other statins, pitavastatin proved to not affect glycemic control, or insulin resistance in patients with diabetes.…”

“…36 The patients had received pravastatin (average dose: 10.3 mg), atorvastatin (average dose: 11.3 mg), pitavastatin (average dose: 2.3 mg), or no statin; the endpoint was a composite of cardiac sudden death, fatal or nonfatal myocardial infarction (MI), death from worsening of chronic heart failure (CHF), bypass surgery, target lesion revascularization (TLR) and repeated PCI for de novo lesion. As expected, compared with the no statin treatment, each statin treatment showed a significant reduction in LDL-C: −23.7% ± 15.7% with pravastatin (P , 0.001), −32.8% ± 14.4% with atorvastatin (P , 0.001), and −34.2% ± 16.6% with pitavastatin (P , 0.001).…”