Skip to main content
SpringerLink
Log in

Fluvastatin

A Review of its Use in Lipid Disorders

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Abstract

Fluvastatin is an HMG-CoA reductase inhibitor used to treat patients with hypercholesterolaemia. Since fluvastatin was last reviewed in Drugs, trials have shown its efficacy in the secondary prevention of coronary heart disease (CHD) events and death and have expanded knowledge of its effects in primary CHD prevention and its mechanisms of activity.

In addition to reducing total (TC) and low density lipoprotein (LDL-C) cholesterol, fluvastatin has antiatherogenic, antithrombotic and antioxidant effects, can improve vascular function, and may have immunomodulatory effects. Although fluvastatin interacts with bile acid séquestrants (requiring separation of doses), its pharmacokinetics permit oral administration to most patient groups. Fluvastatin is well tolerated, with adverse effects usually mild and transient.

Use of fluvastatin to reduce lipids in patients with primary hypercholesterolaemia is well established. Its effects are similar in most patient groups, with 20 to 80 mg/day reducing LDL-C by 22 to 36%, triglycérides (TG) by 12 to 18% and apolipoprotein B by 19 to 28% and increasing high density lipoprotein cholesterol by 3.3 to 5.6%. Attempts to find fluvastatin dosages with efficacy equivalent to that of other HMG-CoA reductase inhibitors produce variable results, but larger per-milligram fluvastatin dosages are needed when patients switch from other HMG-CoA reductase inhibitors. Combinations of fluvastatin with fibric acid derivatives and bile acid séquestrants produce additive effects. Small non-comparative studies suggest fluvastatin reduces LDL-C in patients with hyper-cholesterolaemia secondary to kidney disorders by ≤40.5% and with type 2 diabetes mellitus by ⪯32%.

Three large randomised, double-blind trials show fluvastatin can help prevent CHD events or death and slow disease progression in patients with CHD with or without hypercholesterolaemia. In the Fluvastatin Angiographic Restenosis trial in patients undergoing balloon angioplasty, fluvastatin 80 mg/day for 40 weeks reduced the postangioplasty rate of deaths plus myocardial infarctions (1.5% vs 4% with placebo, p < 0.025) without altering vessel luminal diameters. In the Lipoprotein and Coronary Atherosclerosis Study in patients with coronary artery stenosis, luminal diameter reduced to a significantly lesser extent after fluvastatin 20mg twice daily than placebo after 2.5 years (−0.028 vs −0.01mm, p < 0.005). The Lescol in Symptomatic Angina study found reductions in all cardiac events or cardiac death in patients after 1 year of fluvastatin 40 mg/day (1.6% vs 5.6% for placebo, p < 0.05).

Conclusions: An evolving pattern of data suggests that, in addition to its well established efficacy and cost effectiveness in reducing hypercholesterolaemia, fluvastatin may now also be considered for use in the secondary prevention of CHD.

Pharmacology

Fluvastatin is a structurally distinct synthetic inhibitor of HMG-CoA reductase in the liver that reduces cholesterol biosynthesis, thus lowering serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). The drug also promotes concentration-dependent induction of LDL-C receptor activity, increasing catabolism of LDL-C and further reducing serum LDL-C levels. Fluvastatin can also inhibit cholesterol synthesis in peripheral tissues, although high first-pass metabolism prevents this by reducing unbound circulating drug. Further, it reduces serum apolipoprotein B levels in parallel with LDL-C levels and increases apolipoprotein A-I levels in parallel with high density lipoprotein cholesterol (HDL-C) levels.

Antiatherogenic effects of fluvastatin include reduction of collagen fibre and smooth muscle cell content of atherosclerotic plaques, inhibition of cholesterol esterification and potential plaque stabilising effects. The drug also can affect coagulation factors and fibrinolysis by reducing platelet aggregation, factor VII, von Willebrand factor antigen, tissue plasminogen activator and tissue factor. Antioxidant effects of fluvastatin appear to occur when it binds to LDL-C surface phospholipids, reducing the oxidation of LDL-C without affecting concentrations of antioxidants such as tocopherol and retinol. Fluvastatin has direct vascular effects, such as increasing aortic compliance and myocardial perfusion, improving artery structural wall properties and endothelial function, and reducing blood pressure. The drug also has potential immunological effects.

Oral fluvastatin is 98% absorbed; first-pass hepatic metabolism results in absolute bioavailability of 20 to 30%. Food reduces bioavailability and delays the peak plasma concentration, but does not alter clinical effects of fluvastatin. Plasma protein binding of fluvastatin was ≥99%. Most of the drug is taken up by the liver, where it is extensively metabolised to inactive metabolites by cytochrome P450 enzymes CYP2C9, CYP3A4 and CYP2D6, and eliminated mostly via the bile and faeces. The half-life of fluvastatin is 1.2 hours and clearance is 0.97 L/h/kg. Age and gender do not affect fluvastatin pharmacokinetics, but kinetics of the drug are affected by hepatic insufficiency.

Clinically significant interactions reducing the effectiveness of fluvastatin include those with bile acid sequestrants and rifampicin (rifampin). In vitro data suggest a potential for interaction between fluvastatin and substrates of cytochrome P450 isozymes, but in vivo this is not clinically significant, and appears to be less common than with other HMG-CoA reductase inhibitors.

Clinical Efficacy

Data from 12 placebo-controlled 6-month studies in 1621 fluvastatin recipients with type IIa/IIb hyperlipidaemia showed LDL-C reduced by 22, 25 and 36%, HDL-C increased by 3.3, 4.4 and 5.6%, triglycerides (TG) reduced by 12, 13.5 and 18% and apolipoprotein B reduced by 19, 18 and 28% after 20, 40 and 80 mg/day, respectively. Greater LDL-C reductions occurred in women than men, but fluvastatin induced similar LDL-C reductions in elderly and younger patients, in patients with initially high or low LDL-C levels, and in patients with secondary or primary hypercholesterolaemia. Noncomparative studies also showed fluvastatin to be effective in decreasing LDL-C in patients with hypercholesterolaemia secondary to type 2 diabetes mellitus (by ≤32%) or nephrotic syndrome and in kidney transplant recipients and patients undergoing peritoneal dialysis (by ≤40.5%). Comparative trials found fluvastatin 20 mg/day was similar in efficacy to gemfibrozil 1200 mg/day, and fluvastatin 40 mg/day was superior to bezafibrate 400 mg/day in reducing TC and LDL-C levels, but that fibric acid derivatives were superior to fluvastatin in reducing TG and increasing HDL-C at these fluvastatin dosages. Cholestyramine 16 g/day produced slightly greater reductions in TC and LDL-C than fluvastatin 40 mg/day. When other lipid-lowering agents are added to fluvastatin, the resultant effects on TC, LDL-C, TG and HDL-C levels appear to be additive. Fluvastatin has been effectively combined with cholestyramine, nicotinic acid, bezafibrate, probucol, gemfibrozil and fenofibrate.

Comparative studies in patients with hyperlipidaemia generally suggest that a higher milligram dosage of fluvastatin is required than for other HMG-CoA reductase inhibitors, but many did not test the full fluvastatin dosage range (20 to 80 mg/day) and thus produced variable dosage equivalence results. On LDL-C levels, fluvastatin 40 to 80 mg/day was similar in efficacy to pravastatin 20 or 40 mg/day. Variable dosage ratios were seen between fluvastatin and simvastatin in trials involving reformulation of fluvastatin (≤40 mg/day). A recent well controlled trial using marketed formulations determined a 2: 1 dosage ratio for fluvastatin (40 and 80 mg/day): simvastatin (20 and 40 mg/day). A4: 1 dosage ratio was found for fluvastatin: lovastatin in trials using a maximum of fluvastatin 40 mg/day. Early fluvastatin versus atorvastatin trials failed to find equivalent dosages but did not test fluvastatin 80 mg/day. A recent trial found fluvastatin 80 mg/day and atorvastatin 40 mg/day had similar effects on LDL-C and TC, although atorvastatin 10 mg/day was superior to fluvastatin 20 mg/day in these effects, indicating that fluvastatin has a steeper dose-response effect on LDL-C than atorvastatin. Results of studies examining the ability of HMG-CoA reductase inhibitors to achieve National Cholesterol Education Program (NCEP)-recommended LDL-C targets are inconclusive, because fluvastatin dosage ranges did not reflect dosage equivalence with other agents.

Three randomised, double-blind, parallel-group, multicentre studies enrolling large numbers of patients with CHD have found that, in addition to having favourable effects on plasma lipids, fluvastatin may reduce the incidence of clinical events and slow the progression of atherosclerotic plaques. In FLARE (Fluvastatin Angiographic Restenosis trial), fluvastatin 80 mg/day was administered for 2 to 4 weeks before and 40 weeks after percutaneous transluminal coronary angioplasty (PTCA) in patients with ≥1 stenotic lesion amenable to that procedure and LDL-C levels <6 mmol/L. In LCAS (the Lipoprotein and Coronary Atherosclerosis Study), CHD patients with mild to moderate hyperlipidaemia (LDL-C 3.0 to 4.9 mmol/L) and stenosis of ≥1 coronary vessel received fluvastatin 20mg twice daily for 2.5 years. In LISA (the Lescol in Symptomatic Angina study), patients with symptomatic CHD and at least moderately elevated lipid levels (TC 6.5 mmol/L, LDL-C >4.1 mmol/L) received fluvastatin 40 or 80 mg/day for 1 year.

Fluvastatin therapy was associated with clear reductions in the occurrence of death and myocardial infarction (1.5 vs 4% with placebo, p < 0.025) in FLARE and of all cardiac events in LISA (3 of 214 patients vs 10 in 215 placebo recipients, p < 0.035). LCAS was not designed to detect differences in clinical events between groups, but a trend towards reduced events with fluvastatin emerged early in the trial. In LISA, cardiac events or cardiac death occurred in 1.6% of fluvastatin versus 5.6% of placebo recipients (p < 0.05). In LCAS, fluvastatin significantly slowed progression of CHD in patients with mildly-to-moderately elevated LDL-C levels; women and patients with higher HDL-C levels were the least likely to show progression of lesions. Also in LCAS, a smaller reduction occurred in minimal luminal diameter (MLD) after fluvastatin than placebo (−0.028mm vs −0. lmm, p < 0.005), and this was associated with fewer fluvastatin than placebo patients requiring revascularisation. However, in FLARE, the drug had no effect on restenosis or MLD (−0.23mm in both groups).

Tolerability

Adverse events associated with fluvastatin are generally mild and transient. Headache, dyspepsia, diarrhoea, abdominal pain, nausea and insomnia occurred more frequently with fluvastatin than placebo. Elevated transaminase levels have been reported during prolonged treatment, but resolved when fluvastatin was halted. In clinical trials, fluvastatin was as well tolerated as gemfibrozil, bezafibrate, cholestyramine, pravastatin, simvastatin and atorvastatin. Although rare with fluvastatin and unreported in fluvastatin clinical trials, myopathy (including myositis and rhabdomyolysis) has been reported as a class effect of HMG-CoA reductase inhibitors associated with hypothyroidism or concomitant use of fibric acid derivatives, nicotinic acid or cyclosporin. Asymptomatic elevations of creatine phosphokinase have occurred during fluvastatin therapy (0.3% of patients).

Pharmacoeconomic Considerations

Comparisons of drug acquisition costs versus expected reductions in LDL-C suggest that fluvastatin may be more cost effective than simvastatin, pravastatin and lovastatin. Cost-effectiveness studies also have found that in the treatment of hypercholesterolaemia, depending on the country and study perspective, fluvastatin costs were 13 to 57% less than those of simvastatin, 26 to 60% less than lovastatin and 60 to 64% less than pravastatin per percentage reduction in LDL-C. Another trial found 44 to 53% lower costs associated with reaching an LDL-C target of 4.5 mmol/L using fluvastatin than lovastatin. Trials comparing fluvastatin with atorvastatin failed to examine all fluvastatin dosages and found dosages of 40 mg/day to be less effective than maximum dosages of atorvastatin, simvastatin or lovastatin, or found fluvastatin (≤40 mg/day only) and simvastatin next most cost effective to atorvastatin when compared with pravastatin and lovastatin.

When patients were switched to fluvastatin from simvastatin, lovastatin or gemfibrozil, no significant change in resource utilisation, LDL-C levels or achievement of NCEP targets occurred in one managed-care organisation. Programmes to assist a switch to fluvastatin are documented in the literature and appear to be capable of reducing formulary costs. However, when patients are switched from other HMG-CoA reductase inhibitors to fluvastatin, lipid monitoring is required and fluvastatin dosage adjustments may be needed.

Dosage and Administration

Before and during fluvastatin treatment, patients should undertake dietary changes to reduce cholesterol levels. Fluvastatin is administered orally without regard to meals in dosages from 20 to 80 mg/day. Monthly monitoring should take place and dosages should be individualised to patients’ serum TC and LDL-C concentrations. Most patients require long term therapy, during which serum lipoprotein concentrations should be monitored periodically. Fluvastatin is contraindicated in patients with unexplained persistent elevated serum transaminase levels, pregnant or lactating women and patients <18 years of age. The drug should be used with caution in patients with severe renal impairment or liver disease or during heavy alcohol ingestion. Fluvastatin may be combined with cholestyramine or other bile acid séquestrants if doses are separated by >5 hours.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. National Cholesterol Education Program. Second report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Overview and summary. Circulation 1994 Mar; 89: 1333–43, 1432-45

    Google Scholar 

  2. Pyörälä K, De Backer G, Graham I, et al. Prevention of coronary heart disease in clinical practice: recommendations of the Task Force of the European Society of Cardiology, European Atherosclerosis Society and European Society of Hypertension. Atherosclerosis 1994 Oct; 110: 121–61

    Article  PubMed  Google Scholar 

  3. Stark RM. Review of the major intervention trials of lowering coronary artery disease risk through cholesterol reduction. Am J Cardiol 1996 Sep 26; 78 Suppl. 6A: 13–9

    Article  PubMed  CAS  Google Scholar 

  4. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994 Nov 19; 344: 1383–9

    Google Scholar 

  5. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996 Oct 3; 335(14): 1001–9

    Article  PubMed  CAS  Google Scholar 

  6. Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. N Engl J Med 1997 Jan 16; 336(3): 153–62

    Article  Google Scholar 

  7. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995 Nov 16; 333(20): 1301–7

    Article  PubMed  CAS  Google Scholar 

  8. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA 1998 May 27; 279(20): 1615–22

    Article  PubMed  CAS  Google Scholar 

  9. Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998 Nov 5; 339(19): 1349–57

    Article  Google Scholar 

  10. Plosker GL, Wagstaff AJ. Fluvastatin: a review of its pharmacology and use in the management of hypercholesterolaemia. Drugs 1996 Mar; 51: 433–59

    Article  PubMed  CAS  Google Scholar 

  11. Shiomi M, Ito T, Tsukada T, et al. Effect of fluvastatin sodium on the smooth muscle cells in atherosclerotic plaques: in vivo study using low-density lipoprotein receptor deficient Watanabe heritable hyperlipidemic (WHHL) rabbits. Arzneimittel Forschung 1998 Jun; 48: 680–5

    PubMed  CAS  Google Scholar 

  12. Niwa S, Totsuka T, Hayashi S. Inhibitory effect of fluvastatin, an HMG-CoA reductase inhibitor, on the expression of adhesion molecules on human monocyte cell line. Int J Immunopharmacol 1996 Nov; 18: 669–75

    Article  PubMed  CAS  Google Scholar 

  13. Corsini A, Raiteri M, Soma MR, et al. Pathogenesis of atherosclerosis and the role of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Am J Cardiol 1995 Jul 13; 76: 21A-8A

    Article  Google Scholar 

  14. Corsini A, Bernini F, Quarato P, et al. Non-lipid-related effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Cardiology 1996 Nov–Dec; 87: 458–68

    Article  PubMed  CAS  Google Scholar 

  15. Bernini F, Didoni G, Bonfidini G, et al. Requirement for mevalonate in acetylated LDL induction of cholesterol esterification in macrophages. Atherosclerosis 1993; 104: 19–26

    Article  PubMed  CAS  Google Scholar 

  16. Mitani H, Bandoh T, Ishikawa J, et al. Inhibitory effects of fluvastatin, a new HMG-CoA reductase inhibitor, on the increase in vascular ACE activity in cholesterol-fed rabbits. Br J Pharmacol 1996 Nov; 119: 1269–75

    Article  PubMed  CAS  Google Scholar 

  17. Bellosta S, Via D, Canavest M, et al. HMG-CoA reductase inhibitors reduce MMP-9 secretion by macrophages. Arterioscler Thromb Vasc Biol 1998; 18: 1671–8

    Article  PubMed  CAS  Google Scholar 

  18. Hussein O, Rosenblat M, Schlezinger S, et al. Reduced platelet aggregation after fluvastatin therapy is associated with altered platelet lipid composition and drug binding to the platelets. Br J Clin Pharmacol 1997 Jul; 44: 77–83

    Google Scholar 

  19. Aviram M, Hussein O, Rosenblat M, et al. Interactions of platelets, macrophages, and lipoproteins in hypercholesterolemia: antiatherogenic effects of HMG-CoAreductase inhibitor therapy. J Cardiovasc Pharmacol 1998 Jan; 31: 39–45

    Article  PubMed  CAS  Google Scholar 

  20. Tan KCB, Janus ED, Lam KSL. Effects of fluvastatin on prothrombotic and fibrinolytic factors in non-insulin-dependent diabetic patients with dyslipidaemia [abstract]. Atherosclerosis 1998 Mar; 136 Suppl.: 55

    Article  Google Scholar 

  21. Bevilacqua M, Bettica P, Milani M, et al. Effect of fluvastatin on lipids and fibrinolysis in coronary artery disease. Am J Cardiol 1997 Jan 1; 79: 84–7

    Article  PubMed  CAS  Google Scholar 

  22. Colli S, Eligini S, Lalli M, et al. Vastatins inhibit tissue factor in cultured human macrophages: a novel mechanism of protection against atherothrombosis. Arterioscler Thromb Vasc Biol 1997 Feb; 17: 265–72

    Article  PubMed  CAS  Google Scholar 

  23. Leonhardt W, Kurktschiev T, Meissner D, et al. Effects of fluvastatin therapy on lipids, antioxidants, oxidation of low density lipoproteins and trace metals. Eur J Clin Pharmacol 1997 Sep; 53: 65–9

    Article  PubMed  CAS  Google Scholar 

  24. Hussein O, Schlezinger S, Rosenblat M. Reduced susceptibility of low density lipoprotein (LDL) to lipid peroxidation after fluvastatin therapy is associated with the hypocholesterolemic effect of the drug and its binding to the LDL. Atherosclerosis 1997 Jan 3; 128: 11–8

    Article  PubMed  CAS  Google Scholar 

  25. Guethlin M, Kasel AM, Coppenrath K, et al. Delayed response of myocardial flow reserve to lipid-lowering therapy with fluvastatin. Circulation 1999; 9: 475–81

    Article  Google Scholar 

  26. Eichstädt H, Amthauer H, Jochens R, et al. Short-term fluvastatin therapy increases myocardial perfusion in patients with coronary artery disease [abstract]. Eur J Clin Invest 1996; 26 Suppl. 1: 3

    Google Scholar 

  27. Sidhu P, Forbat S, Naoumova R, et al. Assessment of lipid-lowering therapy by non-invasive cardiovascular imaging [abstract]. Atherosclerosis 1997 Feb 10; 128: 261

    Google Scholar 

  28. Schobel HP, Schmieder RE. Vasodilatory capacity of forearm resistance vessels is augmented in hypercholesterolemic patients after treatment with fluvastatin. Angiology 1998 Sep; 49(9): 743–8

    Article  PubMed  CAS  Google Scholar 

  29. Abetel G, Poget PN, Bonnabry JR Antihypertensive effect of a cholesterol-lowering agent (fluvastatin): pilot study [in French]. Schweiz Med Wochenschr 1998 Feb 14; 128: 272–7

    PubMed  CAS  Google Scholar 

  30. John S, Schlaich M, Langenfeld M, et al. Increased bioavailability of nitric oxide after lipid-lowering therapy in hypercholesterolemic patients: a randomized, placebo-controlled, double-blind study. Circulation 1998 Jul 21; 98: 211–6

    Article  PubMed  CAS  Google Scholar 

  31. Rothe G, Elbracht R, Hauser I, et al. Relative decrease of cytotoxic T cells under fluvastatin treatment in kidney transplanted patients [abstract]. Atherosclerosis 1997 Oct; 134(1–2): 282

    Article  Google Scholar 

  32. Rothe G, Stöhr J, Abletshauser C, et al. A more mature phenotype of blood mononuclear phagocytes is induced by fluvastatin treatment [abstract]. Atherosclerosis 1997 1–2, Oct No.; 134: 235–6

    Article  Google Scholar 

  33. Madej A, Kalina Z, Okopién B, et al. The release of tumor necrosis factor-alpha by cultured macrophages from hyperlipidemic patients treated with fluvastatin [abstract]. Eur J Clin Pharmacol 1997; 52 Suppl.: 76

    Google Scholar 

  34. Jokubaitis LA. Development and pharmacology of fluvastatin. Br J Clin Pract 1996 Jan Suppl. 77A: 11-5

  35. Lennernäs H, Fager G. Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors: similarities and differences. Clin Pharmacokinet 1997 May; 32: 403–25

    Article  PubMed  Google Scholar 

  36. Transon C, Leemann T, Dayer P. In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol 1996 May; 50: 209–15

    Article  PubMed  CAS  Google Scholar 

  37. Novartis. Lescol* data sheet. In: ABPI Compendium of data sheets and summaries of product characteristics. London: Datapharm Publications Ltd, 1998: 825-6

  38. Kronbach T, Fischer V, Meyer UA. Cyclosporine metabolism in human liver: identification of a cytochrome P-450III gene family as the major cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs. Clin Pharmacol Ther 1988; 43: 630–5

    Article  PubMed  CAS  Google Scholar 

  39. Torri A, Branchi A, Rovellini A, et al. Effect of fluvastatin on serum lipoproteins and glycémic control in hyperlipidemic patients with type II diabetes [abstract]. Atherosclerosis 1997 Oct; 134(1–2): 384

    Article  Google Scholar 

  40. Regazzi MB, Iacona I, Campana C, et al. Altered disposition of travastatin following concomitant drug therapy with cyclosporin A in transplant recipients. Transplant Proc 1993 Aug; 25(4): 2732–4

    PubMed  CAS  Google Scholar 

  41. Olbricht C, Wanner C, Eisenhauer T, et al. Accumulation of lovastatin, but not pravastatin, in the blood of cyclosporinetreated kidney graft patients after multiple doses. Clin Pharmacol Ther 1997; 62: 311–21

    Article  PubMed  CAS  Google Scholar 

  42. Arnadottir M, Eriksson L-O, Thysell H, et al. Plasma concentration profiles of simvastatin 3-hydroxy-3-methyl-glutarylcoenzyme A reductase inhibitory activity in kidney transplant recipients with and without ciclosporin. Nephron 1993; 65: 410–3

    Article  PubMed  CAS  Google Scholar 

  43. Trilli LE, Kelley CL, Aspinall SL, et al. Potential interaction between warfarin and fluvastatin. Ann Pharmacother 1996 Dec; 30: 1399–402

    PubMed  CAS  Google Scholar 

  44. Kline SS, Harrell CC. Potential warfarin-fluvastatin interaction. Ann Pharmacother 1997 Jun; 31: 790

    PubMed  CAS  Google Scholar 

  45. Kantola T, Kivisto KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics of atorvastatin. Clin Pharmacol Ther 1998; 64: 58–65

    Article  PubMed  CAS  Google Scholar 

  46. Åberg J, Eriksson U, Fager G. Effects of erythromycin on plasma fluvastatin levels: a pharmacokinetic study [abstract]. Atherosclerosis 1997 Oct; 134(1–2): 118–9

    Article  Google Scholar 

  47. Kivistö KT, Kantola T, Neuvonen PJ. Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. Br J Clin Pharmacol 1998 Jul; 46: 49–53

    Article  PubMed  Google Scholar 

  48. Meadowcroft AM, Williamson KM, Patterson JH, et al. The effects of fluvastatin, a CYP2C9 inhibitor, on losartan pharmacokinetics [abstract]. Clin Pharmacol Ther 1998 Feb; 63: 213

    Google Scholar 

  49. McMillan K. Considerations in the formulary selection of hydroxymethylglutaryl-coenzyme Areductase inhibitors. Am J Health System Pharm 1996 Sep 15; 53: 2206–14

    CAS  Google Scholar 

  50. Novartis. Data on file. Novartis Pharma AG, Basel, Switzerland

  51. Serruys PW, Foley DP, Jackson G, et al. A randomized placebocontrolled trial of fluvastatin for prevention of restenosis after successful coronary balloon angioplasty: final results of the fluvastatin angiographic restenosis (FLARE) trial. Eur Heart J 1998; 20: 58–69

    Article  Google Scholar 

  52. Widimsky J, Hulinsky V, Lanska V, et al. Czech and Slovak experience trial of fluvastatin in the treatment of hyperlipidemia [abstract]. 66th Congress of the European Atherosclerosis Society. 13–17 July, 1996. Florence, Italy

  53. Buzzi AP, Pastore MA, Argentine and Multicenter Evaluation Investigators. Argentine multicenter evaluation of fluvastatin in the treatment of patients with hypercholesterolemia. Curr Ther Res Clin Exp 1997 Dec; 58: 1013–28

    Article  CAS  Google Scholar 

  54. Beil S, Pfafferott C, Weber M. Fluvastatin lipid-lowering effect in routine practice conditions (FLIRT): results of a drug surveillance study. Clin Drug Invest 1997 Aug; 14: 146–53

    Article  CAS  Google Scholar 

  55. Weiss RJ. Fluvastatin titrate-to-goal clinical practice study. Am J Therap 1998; 5(5): 281–5

    Article  CAS  Google Scholar 

  56. Sussekov A, Tvorogova M, Surkova E, et al. Fluvastatin in the treatment of NIDDM patients with hyperlipidaemia [abstract]. Atherosclerosis 1997 Oct; 134(1–2): 317

    Article  Google Scholar 

  57. Ding PY-A, Sheu WH-H, Hu C-A, et al. Efficacy and safety of fluvastatin in patients with non-insulin-dependent diabetes mellitus and hypercholesterolemia [abstract]. Atherosclerosis 1998 Mar; 136 Suppl.: 44

    Article  Google Scholar 

  58. Exaire-Murad JE, Exaire-Rodriguez JE, Salgado-Loza JL. Fluvastatin in nephrotic syndrome hypercholesterolemia [abstract no. 209]. 66th Congress of the European Atherosclerosis Society. 13 Jul 1996. Florence, Italy

  59. Scanziani R, Dozio B, Bonforte G, et al. Fluvastatin and hyperlipidemia in peritoneal dialysis [abstract]. Nephrol Dial Transplant 1997 Sep; 12: A185

    Google Scholar 

  60. Li PKT, Mak TWL, Chan TH, et al. Effect of fluvastatin on lipoprotein profiles in renal transplant patients with dyslipoproteinemia [abstract]. Kidney Int 1996 Oct; 50: 1409

    Google Scholar 

  61. Holdaas H, Hartmann A, Stenstrm J, et al. Effect of incremental doses of fluvastatin in renal recipients treated with cyclosporine [abstract no. 215]. 66th Congress of the European Atherosclerosis Society. 13 Jul 1996. Florence, Italy

  62. Hadjigavriel M, Kyriakides G. Fluvastatin in renal transplantation. Transplant Proc 1997 Nov; 29: 3050

    Article  PubMed  CAS  Google Scholar 

  63. Locsey L, Asztalos L, Kincses Z, et al. Fluvastatin (Lescol) treatment of hyperlipidaemia in patients with renal transplants. Int Urol Nephrol 1997; 29: 95–106

    Article  PubMed  CAS  Google Scholar 

  64. Lal SM, Gupta N, Georgiev O, et al. Lipid-lowering effects of fluvastatin in renal transplant patients: a clinical observation. Int J Artif Organs 1997 Jan; 20: 18–21

    PubMed  CAS  Google Scholar 

  65. Stamm G. Lescol® (fluvastatin sodium) XU 62–320 oral capsules 20 mg and 40 mg: basic prescribing information. Data on file. 18 Dec 1998. Novartis Pharma AG, Basel, Switzerland

  66. New primary prevention trial for Lescol. Scrip 1998 Nov 6(2385): 17

    Google Scholar 

  67. La Belle P, Davidson M, Wilson H, et al. A comparison of lovastatin and fluvastatin [abstract no. 217]. 66th Congress of the European Atherosclerosis Society. 13 Jul 1996. Florence, Italy

  68. Schulte K-L, Beil S. Efficacy and tolerability of fluvastatin and simvastatin in hypercholesterolaemic patients: a doubleblind, randomised, parallel-group comparison. Clin Drug Invest 1996 Sep; 12: 119–26

    Article  CAS  Google Scholar 

  69. Jones P, Kafonek S, Laurora I, et al. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (The CURVES Study). Am J Cardiol 1998 Mar 1; 81: 582–7

    Article  PubMed  CAS  Google Scholar 

  70. Schuster H, Berger J, Luft FC. Randomised, double-blind, parallel-group trial of atorvastatin and fluvastatin on plasma lipid levels in patients with untreated hyperlipidaemia. Br J Cardiol 1998 Nov; 5(11): 597–602

    Google Scholar 

  71. Pincus J. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (The CURVES Study) [letter]. Am J Cardiol 1998 Aug 1; 82: 406–7

    PubMed  CAS  Google Scholar 

  72. Nash DT. Meeting national cholesterol education goals in clinical practice — a comparison of lovastatin and fluvastatin in primary prevention. Am J Cardiol 1996 Sep 26; 78 Suppl. 6A: 26–31

    Article  PubMed  CAS  Google Scholar 

  73. Brown AS, Bakker-Arkema RG, Yellen L, et al. Treating patients with documented atherosclerosis to National Cholesterol Education Program-recommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin. J Am Coll Cardiol 1998 Sep; 32: 665–72

    Article  PubMed  CAS  Google Scholar 

  74. Hunninghake D, Bakker-Arkema RG,WigandJP, et al. Treating to meet NECP-recommended LDL cholesterol concentrations with atorvastatin, fluvastatin, lovastatin, or simvastatin in patients with risk factors for coronary heart disease. J Fam Pract 1998 Nov; 47(5): 349–56

    PubMed  CAS  Google Scholar 

  75. Sasaki S, Nakagawa M, Nakata T, et al. Efficacy and safety of the 3-hydroxy-3-methylglutaryl coenzyme Areductase inhibitor fluvastatin in hyperlipidemic patients treated with probucol. Cardiology 1997 Mar-Apr; 88: 160–5

    Article  PubMed  CAS  Google Scholar 

  76. Tomlinson B, Wong S-Y, Lan W, et al. Combination treatment with fluvastatin and gemfibrozil in resistant hyperlipidaemia [abstract]. Atherosclerosis 1998 Mar; 136 Suppl.: 56

    Article  Google Scholar 

  77. Farnier M, Leneveut-Ledoux L, French Fluvastatin Study Group. Long-term efficacy and safety of a combined fluvastatin-fenofibrate therapy in primary hypercholesterolemia [abstract]. Atherosclerosis 1997 Oct; 134(1–2): 123–4

    Google Scholar 

  78. Lyakishev AA, Kozlov SG, Titov VN. Combined treatment with fluvastatin and fenofibrate in patients with severe hypercholesterolemia [abstract no. 218]. 66th Congress of the European Atherosclerosis Society. 13 Jul 1996. Florence, Italy

  79. Widimsky J, Hulinsky V, Balazovjech I, et al. Fluvastatin vs fluvastatin plus fenofibrate in CHD patients and combined hyperlipidemia [abstract]. Atherosclerosis 1997 1–2, Oct No.; 134: 63

    Google Scholar 

  80. Herd JA, Ballantyne CM, Farmer JA, et al. Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (lipoprotein and coronary atherosclerosis study [LCAS]). Am J Cardiol 1997 Aug 1; 80: 278–86

    Article  PubMed  CAS  Google Scholar 

  81. West MS, Herd JA, Ballantyne CM, et al. The Lipoprotein and Coronary Atherosclerosis Study (LCAS): design, methods, and baseline data of a trial of fluvastatin in patients without severe hypercholesterolemia. Control Clin Trials 1996 Dec; 17: 550–83

    Article  PubMed  CAS  Google Scholar 

  82. Riegger G, Abletshauser C, Ludwig M, et al. The effects of fluvastatin on cardiac events in patients with symptomatic coronary artery disease during one year of treatment. Atherosclerosis. In press

  83. Herd JA. The Lipoprotein and Coronary Atherosclerosis Study (LCAS): lipid and metabolic factors related to atheroma and clinical events. Am J Med 1998 Jun 22; 104 Suppl.: 42–9

    Article  Google Scholar 

  84. Ballantyne CM, Herd JA, Schein JR, et al. Treatment of patients with mild to moderate hypercholesterolemia: Lipoprotein and Coronary Atherosclerosis Study (LCAS). Cardiovasc Rev Rep 1998 Jan; 19: 12–24

    Google Scholar 

  85. Ballantyne CM, Schein JR, Herd JA. Influence of HDL-C on CHD progression and response to treatment. APOR Lipid Conference — Pharmacoeconomics and Outcomes Issues of Lipid Therapy 1997 Nov 6: Abstr. LC-1 (Poster)

  86. AHFS. Fluvastatin sodium. In: AHFS 98 Drug information. AHFS, 1998: 1443-5

  87. Fluvastatin and muscle disorders — a class effect. Aust Adv Drug React Bull 1996 Feb; 16: 3

    Google Scholar 

  88. Lang JE, Wang P, Glueck CJ. Myopathy associated with lipid lowering therapy in patients with previously undiagnosed or undertreated hypothyroidism. Clin Chim Acta 1996 Oct 15; 254: 85–92

    Article  CAS  Google Scholar 

  89. Tobert JA. Efficacy and long-term adverse effect pattern of lovastatin. Am J Cardiol 1988; 62: 28J-34J

    Article  Google Scholar 

  90. Jacobson TA. Preventing coronary heart disease in the managed care era: improving the cost effectiveness of lipid-lowering therapy with HMG-CoA reductase inhibitors. Am J Manage Care 1997 Sep; 3 Suppl. 1: 29–41

    Google Scholar 

  91. Jacobson TA. Cost-effectiveness of 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase inhibitor therapy in the managed care era. Am J Cardiol 1996 Sep 26; 78: 32–41

    Article  PubMed  CAS  Google Scholar 

  92. Spearman ME, Summers K, Moore V, et al. Cost-effectiveness of initial therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors to treat hypercholesterolemia in a primary care setting of a managed-care organization. Clin Ther 1997 May–Jun; 19: 582–602

    Article  PubMed  CAS  Google Scholar 

  93. Levin L-Å, Schmidt A, Schulte K-L, et al. A comparison of clinical and pharmacoeconomic properties of fluvastatin and simvastatin in the management of primary hypercholesterolaemia. Br J Med Econ 1997; 11: 23–35

    Google Scholar 

  94. Haasis R, Berger J, Andersson F, et al. A pharmacoeconomic evaluation of fluvastatin and lovastatin in primary hypercholesterolaemia. Br J Med Econ 1996; 10: 145–57

    Google Scholar 

  95. Koren MJ, Smith DG, Hunninghake DB, et al. The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients: a comparison of atorvastatin, simvastatin, lovastatin and fluvastatin. PharmacoEconomics 1998 Jul; 14: 59–70

    Article  PubMed  CAS  Google Scholar 

  96. Hilleman DE, Mohiuddin SM, Woodruff MP, et al. The CURVES trial: a pharmacoeconomic evaluation [abstract]. Pharmacotherapy 1997 Sep–Oct; 17: 1107–8

    Google Scholar 

  97. Elliott WJ, Weir DR. Comparative cost-effectiveness of HMG-CoA reductase inhibitors in secondary prevention of myocardial infarction. APOR Lipid Conference — Pharmacoeconomics and Outcomes Issues of Lipid Therapy 1997 Nov 6: Abstr.LC-15

  98. Tong-Chung SM, Gilderman AM. Appropriateness and clinical outcomes with conversion to fluvastatin therapy in a managed care population. Poster presented at APOR Lipid Conference — Pharmacoeconomics and Outcomes Issues of Lipid Therapy; 1997 Nov; Orlando (FL)

  99. Algozzine TW, Whalen KM. Statin conversion initiative at a staff model health maintenance organization [abstract no. 95]. Pharmacotherapy 1998; 18(5): 1152

    Google Scholar 

  100. Moisan J, Vaillancourt R, Grégoire J-P, et al. Preferred HMG CoA reductase inhibitors: conversion and outcomes study [abstract no. LC-2]. APOR Lipid Conference — Pharmacoeconomic and Outcomes Issues of Lipid Therapy; 1997 Nov; Orlando (FL)

  101. Torborg SA, Stahl JG, Boreen DM, et al. Physician education to move lipotropic prescribing against the trends in the local market. APOR Lipid Conference — Pharmacoeconomics and Outcomes Issues of Lipid Therapy 1997 Nov 6: Abstr. LC-4

  102. Thomas M. Switching statins: can we do harm? N Z Med J 1998 Jan 23; 111: 18

    PubMed  CAS  Google Scholar 

  103. Thomas MC, Mann J, Williams S. The impact of reference pricing on clinical lipid control. N Z Med J 1998 Aug 14; 111: 292–4

    PubMed  CAS  Google Scholar 

  104. Thomas M, Mann J. Increased thrombotic vascular events after change of statin. Lancet 1998 Dec 5; 352(9143): 1830

    Article  PubMed  CAS  Google Scholar 

  105. Bennett W, McNee W. PHARMAC and statins. N Z Med J 1998 Nov 13: 439

    Google Scholar 

  106. Frohlich J, Fodor G, McPherson R, et al. Rationale for and outline of the recommendations of the Working Group on Hypercholesterolemia and other dyslipidemias: interim report. Can J Cardiol 1998 Apr; 14 Suppl. A: 17–21

    Google Scholar 

  107. Anonymous. The Lescol Intervention Prevention Study (LIPS): a randomised trial of the long-term effects of fluvastatin in patients with coronary heart disease after successful first transcatheter therapy. Novartis (Data on file)

Download references

Author information

Authors and Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Heather D. Langtry & Anthony Markham

Authors
  1. Heather D. Langtry
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anthony Markham
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heather D. Langtry.

Additional information

Various sections of the manuscript reviewed by: M. Aviram, Lipid Research Laboratory, The Bruce Rappaport Faculty of Medicine, Technion — Israel Institute of Technology, Haifa, Israel; J. Frohlich, Department of Pathology and Laboratory Medicine, University of British Columbia and Healthy Heart Program, St Paul’s Hospital Lipid Clinic, Vancouver, British Columbia, Canada; H. Holdaas, Medical Department, National Hospital, Oslo, Norway; L. Löcsey, EuroCare Health Service, Kenézy Gyula Hospital, Debrecen, Bartók, Hungary; D.T. Nash, State University of New York, Health Science Center at Syracuse, Syracuse, New York, USA; J.P. Rindone, Pharmacy Service, Veterans Affairs Medical Center, Prescott, Arizona, USA; R.E. Schmieder, Medizinische Klinik 4, Schwerpunkt Nephrologie, Klinikum Nürnberg, Nuremberg, Germany; K.-L. Schulte, Evangelisches Krankenhaus, Königin Elisabeth Herzberge, Medizinische Klinik, Berlin, Germany; M. Shiomi, Institute for Experimental Animals, Kobe University School of Medicine, Kobe, Japan.

Data Selection

Sources: Medical literature published in any language since 1966 on fluvastatin, identified using AdisBase (a proprietary database of Adis International, Auckland, New Zealand), Medline and EMBASE. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: AdisBase search terms were ‘fluvastatin’, ‘fluvastatin sodium’, ‘fluindostainin sodium’, ‘XU-62320’, ‘hypercholesterolaemia’, ‘atherosclerosis’ and ‘restenosis’. Medline and EMBASE search terms were ‘fluvastatin’, ‘fluvastatin sodium’, ‘fluindostainin sodium’, ‘SRI-62320’, ‘XU-62320’, ‘therapeutic use’, ‘pharmacokinetics’ and ‘pharmacology’. Searches were last updated 2 Mar 1999.

Selection: Studies in patients with hyperlipidaemia or previous evidence of coronary heart disease who received fluvastatin. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: fluvastatin, hypercholesterolaemia, atherosclerosis, coronary heart disease, pharmacokinetics, pharmacodynamics, therapeutic use, pharmacoeconomics.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Langtry, H.D., Markham, A. Fluvastatin. Drugs 57, 583–606 (1999). https://doi.org/10.2165/00003495-199957040-00009

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199957040-00009

Keywords

Search

Navigation