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Pravastatin

A Reappraisal of its Pharmacological Properties and Clinical Effectiveness in the Management of Coronary Heart Disease

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Summary

Synopsis

Pravastatin is an HMG-CoA reductase inhibitor which lowers plasma cholesterol levels by inhibiting de novo cholesterol synthesis.

Pravastatin produces consistent dose-dependent reductions in both total and low density lipoprotein (LDL)-cholesterol levels in patients with primary hyper-cholesterolaemia. Favourable changes in other parameters such as total triglyceride and high density lipoprotein (HDL)-cholesterol levels are generally modest. Combination therapy with other antihyperlipidaemic agents such as cholestyramine further enhances the efficacy of pravastatin in patients with severe dyslipidaemias.

Available data suggest that pravastatin is effective in elderly patients and in patients with hypercholesterolaemia secondary to diabetes mellitus or renal disease.

The benefit of cholesterol-lowering in terms of patient outcomes is currently an area of considerable interest. Recently completed regression studies (PLAC I, PLACII, KAPS and REGRESS) show that pravastatin slows progression of atherosclerosis and lowers the incidence of coronary events in patients with mild to moderately severe hypercholesterolaemia and known coronary heart disease. Large scale primary (WOSCOPS) and secondary (CARE) prevention studies, moreover, demonstrate that pravastatin has beneficial effects on coronary morbidity and mortality. In WOSCOPS, all-cause mortality was reduced by 22%.

Pravastatin is generally well tolerated by most patients (including the elderly), as evidenced by data from studies of up to 5 years in duration. As with other HMG-CoA reductase inhibitors, myopathy occurs rarely (<0.1% of patients treated with pravastatin); approximately 1 to 2% of patients may present with raised serum levels of hepatic transaminases.

Thus, with its favourable effects on cardiovascular morbidity/mortality and total mortality, pravastatin should be considered a first-line agent in patients with elevated cholesterol levels, multiple risk factors or coronary heart disease who are at high risk of cardiovascular morbidity.

Pharmacodynamic Properties

Pravastatin inhibits HMG-CoA reductase, the enzyme which catalyses the rate-limiting step within the cholesterol biosynthetic pathway. By inhibiting de novo cholesterol production and reducing intracellular cholesterol stores, pravastatin stimulates the synthesis and activity of low density lipoprotein (LDL) receptors, thereby enhancing the clearance of atherogenic LDL-cholesterol. In vitro and in vivo data indicate that pravastatin exhibits hepatocellular tissue selectivity, with greatest inhibition of cholesterol synthesis occurring in the liver.

In hypercholesterolaemic patients, pravastatin produces consistent changes in total cholesterol, LDL-cholesterol, high density lipoprotein (HDL)-cholesterol and triglyceride levels; its effects on lipoprotein(a) are, however, variable.

Hypercholesterolaemic patients treated with pravastatin 10 to 20 mg/day also show decreases in apolipoprotein B (the major component of LDL) of 12 to 30%. Other major proteins found in HDL (apolipoprotein AI and AII) increase by 12 to 16%, while apolipoproteins CII, CIII and E [mainly found in chylomicrons and very low density lipoprotein (VLDL)-cholesterol] are reduced by 4 to 8%.

Pravastatin slows the progression of atherosclerosis in humans and may have beneficial effects in stabilising plaques, improving endothelial dysfunction, decreasing platelet thrombus formation, improving fibrinolytic activity and reducing the incidence of transient myocardial ischaemia. The drug appears to have no effect on adrenal and gonadal hormone production, gallstone formation or sleep patterns.

Pharmacokinetic Properties

Pravastatin is administered orally as the sodium salt of the active compound. It is rapidly absorbed with mean peak plasma concentrations (Cmax) occurring between 0.9 and 1.6 hours after single- or multiple-dose administration in hypercholesterolaemic patients. Dose-proportional increases in both Cmax and area under the plasma concentration-time curve were also observed. The drug has an oral bioavailability of 17%.

In healthy volunteers given intravenous pravastatin 10mg, the volume of distribution averaged 0.46 L/kg at steady-state. Approximately 50% of the drug is bound to plasma proteins. Tissue distribution studies in animals have demonstrated that pravastatin is selectively taken up by hepatic cells; negligible distribution into human breast milk has been reported.

The major metabolite of pravastatin, a 3α-hydroxy isomeric compound (SQ 31 906), has approximately one-tenth to one-fortieth of the HMG-CoA reductase inhibitory activity of pravastatin; 75% of the total inhibitory activity of pravastatin is attributable to the parent drug. Pravastatin undergoes extensive first-pass extraction in the liver (extraction ratio 0.66). It is rapidly excreted and has a terminal plasma elimination half-life of 1.3 to 2.6 hours. Approximately 70 and 20% of an oral dose is eliminated in faeces and urine, respectively, over 96 hours. In patients with renal or hepatic insufficiency, these dual routes of elimination may provide compensatory pathways for the excretion of pravastatin.

Clinical Effectiveness

The lipid-lowering efficacy of pravastatin has been well established in several large, controlled clinical trials evaluating patients with primary or secondary hypercholesterolaemia. Recent research has focused on assessing what benefits this has for normo- or hypercholesterolaemic patients with, or at risk of, coronary heart disease (CHD).

Recently completed regression studies (PLAC I, PLAC II, KAPS, REGRESS) show that pravastatin slows the progression of atherosclerosis and lowers the incidence of coronary events in patients with mild to moderately severe hypercholesterolaemia and evident CHD. Long term primary intervention data from WOSCOPS, moreover, demonstrate that pravastatin has beneficial effects on coronary morbidity and mortality, without associated increases in non-cardiovascular mortality. Combined primary end-points of nonfatal myocardial infarction or death from CHD were significantly reduced by 31%; all-cause mortality was lowered by 22%. The risk of recurrent nonfatal myocardial infarctions or death from CHD was also significantly reduced by 24% in patients receiving pravastatin in the CARE study (a secondary intervention trial). Relative reductions in risk were unaffected by age, presence of hypertension or diabetes, gender or smoking status. At present, pravastatin is the only HMG-CoA reductase inhibitor for which primary and secondary prevention data are available.

Combination therapy with other lipid-lowering agents such as cholestyramine, ω-3 fatty acids, gemfibrozil, nicotinic acid (niacin) or probucol enhances the efficacy of pravastatin; coadministration with cholestyramine may, however, negate the beneficial effects on triglycéride levels achieved with pravastatin monotherapy. Although concomitant use of gemfibrozil or nicotinic acid with pravastatin promotes further beneficial changes in both triglyceride and HDL-cholesterol levels, this combination should be used cautiously because of the potential increased risk of myopathy.

The lipid-lowering efficacy of pravastatin in elderly patients appears similar to that observed in younger individuals. Pravastatin has been successfully used in patients with hypercholesterolaemia secondary to other disease states such as diabetes mellitus or renal disease, in patients with hypertension, and in heart and kidney transplant recipients.

Like other HMG-CoA reductase inhibitors, pravastatin is likely to be more cost effective in secondary than in primary prevention, and in higher than in lower risk patient groups. Available pharmacoeconomic data are, however, inconclusive regarding the relative cost-effectiveness of agents within this class of drugs because of the lack of long term clinical outcomes data. Analysis of WOSCOPS and CARE will address some of these issues.

Tolerability

Data from various short and long term (5-year) studies suggest that pravastatin is generally well tolerated by most patients, including the elderly. Commonly reported events include gastrointestinal disturbances and skin rashes.

As with other HMG-CoA reductase inhibitors, myopathy occurs rarely (in <0.1% of patients treated with pravastatin). Concomitant therapy with cyclosporin, gemfibrozil, erythromycin or nicotinic acid may enhance the risk of myopathy in patients receiving HMG-CoA reductase inhibitors. Increases in hepatic transaminases occur in 1 to 2% of patients, and routine monitoring of liver function is indicated. Cataract development and sleep disturbances have not been associated with pravastatin.

The bioavailability of pravastatin was unaffected by concomitant administration with aspirin, antacids (given 1 hour before pravastatin), cimetidine, cholestyramine (given 1 hour after or 4 hours before pravastatin), colestipol (given 1 hour after pravastatin), digoxin, warfarin, probucol or nicotinic acid. Increases in plasma pravastatin concentrations have been observed with concurrent cyclosporin therapy; reductions in pravastatin clearance have also been noted in combination with gemfibrozil.

Dosage and Administration

The recommended adult dosage of pravastatin is generally 10 to 40mg taken once daily at bedtime (or divided into two daily doses). Dosages are usually initiated at 10 to 20 mg/day; in some European countries, starting dosages of 5 mg/day are also advocated. Pravastatin should be titrated according to response at intervals of not less than 4 weeks. Lower dosages may be required in patients with a history of significant renal or hepatic dysfunction, in the elderly or in patients taking concomitant cyclosporin or gemfibrozil. Pravastatin is contraindicated in patients with active liver disease or unexplained increases in hepatic transaminase levels. There are insufficient clinical data to recommend the use of pravastatin in children.

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References

  1. Gotto AM, LaRosa JC, Hunninghake D, et al. A summary of the evidence relating dietary fats, serum cholesterol, and coronary heart disease. Circulation 1990; 81: 1721–33

    Article  PubMed  Google Scholar 

  2. 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). Circulation 1994; 89: 1333–445

    Article  Google Scholar 

  3. O’Connor P, Feely J, Shepherd J. Lipid lowering drugs. BMJ 1990; 300: 667–72

    Article  PubMed  Google Scholar 

  4. Alberts AW. Effects of HMG CoA reductase inhibitors on cholesterol synthesis. Drug Invest 1990; 2 Suppl. 2: 9–17

    Article  Google Scholar 

  5. McTavish D, Sorkin EM. Pravastatin: a review of its pharmacological properties and therapeutic potential in hypercholesterolaemia. Drugs 1991; 42: 65–89

    Article  PubMed  CAS  Google Scholar 

  6. Plosker GL, Wagstaff AJ. Fluvastatin: a review of its pharmacology and therapeutic efficacy in hypercholesterolaemia. Drugs 1996; 51: 433–59

    Article  PubMed  CAS  Google Scholar 

  7. ER Squibb & Sons Limited. Pravastatin prescribing information. Middlesex, UK, 1994-5

  8. Tsujita Y, Kuroda M, Shimada Y, et al. CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase: tissue-selective inhibition of sterol synthesis and hypolipidemic effects on various animal species. Biochim Biophys Acta 1986; 877: 50–60

    Article  PubMed  CAS  Google Scholar 

  9. Amorosa LF, Rozovski SJ, Ananthakrishnan R, et al. Effects of pravastatin on cholesterol metabolism in Watanabe heritable hyperlipidemic rabbits. Jpn Heart J 1992; 33: 451–63

    Article  PubMed  CAS  Google Scholar 

  10. Koga T, Shimada Y, Kuroda M, et al. Tissue-selective inhibition of cholesterol synthesis in vivo by pravastatin sodium, a 3-hydroxy-2-methylglutaryl coenzyme A reductase inhibitor. Biochim Biophys Acta 1990; 1045: 115–20

    Article  PubMed  CAS  Google Scholar 

  11. Reihnér E, Rudling M, Ståhlberg D, et al. Influence of pravastatin, a specific inhibitor of HMG-CoA reductase, on hepatic metabolism of cholesterol. N Engl J Med 1990; 323: 224–8

    Article  PubMed  Google Scholar 

  12. Ziegler K, Stünkel W. Tissue-selective action of pravastatin due to hepatocellular uptake via a sodium-independent bile acid transporter. Biochim Biophys Acta 1992; 1139: 203–9

    Article  PubMed  CAS  Google Scholar 

  13. Yamazaki M, Suzuki H, Hanano M, et al. Na+-independent multispecific anion transporter mediates active transport of pravastatin into rat liver. Am J Physiol 1993; 264: G36–44

    PubMed  CAS  Google Scholar 

  14. Mosley ST, Kalinowski SS, Schafer BL, et al. Tissue-selective acute effects of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase on cholesterol biosynthesis in lens. J Lipid Res 1989; 30: 1411–20

    PubMed  CAS  Google Scholar 

  15. De Vries ACJ, Cohen LH. Different effects of the hyperlipidemic drugs pravastatin and lovastatin on the cholesterol biosynthesis of the human ocular lens in organ culture and on the cholesterol content of the rat lens in vivo. Biochim Biophys Acta 1993; 1167: 63–9

    Article  PubMed  Google Scholar 

  16. De Vries ACJ, Vermeer MA, Bloemendal H, et al. Pravastatin and simvastatin differently inhibit cholesterol biosynthesis in human lens. Invest Ophthalmol Vis Sci 1993; 34: 377–84

    PubMed  Google Scholar 

  17. Kalinowski SS, Tanaka RD, Mosley ST. Effects of long-term administration of HMG-CoA reductase inhibitors on cholesterol synthesis in lens. Exp Eye Res 1991; 53: 179–86

    Article  PubMed  CAS  Google Scholar 

  18. De Vries ACJ, Vermeer MA, Bredman JJ, et al. Cholesterol content of the rat lens is lowered by administration of simvastatin, but not pravastatin. Exp Eye Res 1993; 56: 393–9

    Article  PubMed  Google Scholar 

  19. Nakaya N, Homma Y, Tamachi H, et al. The effect of CS-514, an inhibitor of HMG-CoA reductase, on serum lipids in healthy volunteers. Atherosclerosis 1986; 61: 125–8

    Article  PubMed  CAS  Google Scholar 

  20. Pan HY, Willard DA, Funke PT, et al. The clinical pharmacology of SQ 31,000 (CS 514) in healthy subjects. In Paoletti R, editor. Drugs affecting lipid metabolism, Berlin: Springer-Verlag, 1987: 255–9

    Chapter  Google Scholar 

  21. Pan HY, DeVault AR, Wang-Iverson D, et al. Comparative pharmacokinetics and pharmacodynamics of pravastatin and lovastatin. J Clin Pharmacol 1990; 30: 1128–35

    PubMed  CAS  Google Scholar 

  22. Pan HY, Triscari J, De Vault AR, et al. Pharmacokinetic interaction between propranolol and the HMG-CoA reductase inhibitors pravastatin and lovastatin. Br J Clin Pharmacol 1991; 31: 665–70

    Article  PubMed  CAS  Google Scholar 

  23. Franceschini G, Cassinotti, M, Vecchio G, et al. Pravastatin effectively lowers LDL cholesterol in familial combined hyperlipidemia without changing LDL subclass pattern. Arterioscler Thromb 1994; 14: 1569–75

    Article  PubMed  CAS  Google Scholar 

  24. Slyper AH. Low-density lipoprotein density and atherosclerosis. JAMA 1994; 272: 305–8

    Article  PubMed  CAS  Google Scholar 

  25. Fieseler H-G, Armstrong VW, Wieland E, et al. Serum Lp(a) concentrations are unaffected by treatment with the HMG-CoA reductase inhibitor pravastatin: results of a 2-year investigation. Clin Chim Acta 1991; 204: 291–300

    Article  PubMed  CAS  Google Scholar 

  26. Hunninghake DB, Stein EA, Mellies MJ. Effects of one year of treatment with pravastatin, an HMG-CoA reductase inhibitor, on lipoprotein a. J Clin Pharmacol 1993; 33: 574–80

    PubMed  CAS  Google Scholar 

  27. Klausen IC, Gerdes LU, Meinertz H, et al. Apolipoprotein(a) polymorphism predicts the increase of Lp(a) by pravastatin in patients with familial hypercholesterolaemia treated with bile acid sequestration. Eur J Clin Invest 1993; 23: 240–5

    Article  PubMed  CAS  Google Scholar 

  28. Umeda F, Watanabe J, Inoue K, et al. Effect of pravastatin on serum lipids, apolipoproteins and lipoprotein (a) in patients with non-insulin dependent diabetes mellitus. Endocrinol Jpn 1992; 39: 45–50

    Article  PubMed  CAS  Google Scholar 

  29. Roheim PS. Atherosclerosis and lipoprotein metabolism: role of reverse cholesterol transport. Am J Cardiol 1986; 57: 3C–10C

    Article  PubMed  CAS  Google Scholar 

  30. Bard JM, Parra HJ, Douste-Blazy P, et al. Changes in lipoprotein particles defined by their apolipoprotein composition on pravastatin or cholestyramine therapy. J Drug Dev 1990; 3 Suppl. 1: 111–5

    Google Scholar 

  31. Cheung MC, Austin MA, Moulin P, et al. Effects of pravastatin on apolipoprotein-specific high density lipoprotein sub-populations and low density lipoprotein subclass phenotypes in patients with primary hypercholesterolemia. Atherosclerosis 1993; 102: 107–19

    Article  PubMed  CAS  Google Scholar 

  32. Kazumi T, Yoshino G, Kasama T, et al. Effects of CS-514, a new inhibitor of HMG CoA reductase, on plasma lipids, lipoproteins and apolipoproteins in patients with primary hypercholesterolaemia. Horm Metab Res 1986; 18: 654–5

    Article  PubMed  CAS  Google Scholar 

  33. Nakaya N, Goto Y. Effect of CS514 on hypercholesterolemic patients. In Paoletti R, editor. Drugs affecting lipid metabolism, Berlin: Springer-Verlag, 1987: 274–7

    Chapter  Google Scholar 

  34. Nakaya N, Homma Y, Tamachi H, et al. The effect of CS-514 on serum lipids and apolipoproteins in hypercholesterolemic subjects. JAMA 1987; 257: 3088–93

    Article  PubMed  CAS  Google Scholar 

  35. Saito Y, Goto Y, Nakaya N, et al. Dose-dependent hypolipidemic effect of an inhibitor of HMG-CoA reductase, pravastatin (CS-514), in hypercholesterolemic subjects: a double blind test. Atherosclerosis 1988; 72: 205–11

    Article  PubMed  CAS  Google Scholar 

  36. Vega GL, Krauss RM, Grundy SM. Pravastatin therapy in primary moderate hypercholesterolaemia: changes in metabolism of apolipoprotein B-containing lipoproteins. J Intern Med 1990; 227: 81–94

    Article  PubMed  CAS  Google Scholar 

  37. Yoshino G, Kazumi T, Iwai M, et al. Effects of CS-514 on plasma lipids and lipoprotein composition in hypercholesterolemic subjects. Atherosclerosis 1988; 71: 95–101

    Article  PubMed  CAS  Google Scholar 

  38. Franceschini G, Sirtori M, Vaccarino V, et al. Plasma lipoprotein changes after treatment with pravastatin and gemfibrozil in patients with familial hypercholesterolaemia. J Lab Clin Med 1989; 114: 250–9

    PubMed  CAS  Google Scholar 

  39. Goto Y, Yasugi T, Goto Y, et al. Clinical evaluation of CS-514 (pravastatin) on hyperlipidemia: double blind study with clinofibrate. Clin Evaluation 1988; 16: 211–49

    Google Scholar 

  40. Goto Y, Yamamoto A, Matsuzawa Y, et al. Clinical usefulness of pravastatin (CS-514) in the treatment of patients with hyperlipidemia: double-blind comparison with probucol. J Clin Exp Med 1988; 146: 927–55

    Google Scholar 

  41. Yoshino G, Matsushita M, Iwai M, et al. Two-year study on the effect of pravastatin (CS-514) on plasma lipoprotein and apolipoprotein concentrations in hypercholesterolemic patients. Curr Ther Res 1989; 46: 144–52

    Google Scholar 

  42. Ikeda T, Ochi H, Ohtani I, et al. Comparison of the effects of small doses of probucol and pravastatin on serum lipids and apolipoproteins in nonobese, non-insulin-dependent diabetes mellitus patients with hypercholesterolemia. Curr Ther Res 1992; 51: 593–9

    Google Scholar 

  43. Tawata M, Miwa I, Tsuchiya K, et al. Clinical efficacy of pravastatin for hyperlipidemia in patients with type 2 diabetes mellitus. Arzneimittelforschung 1995; 45: 704–8

    PubMed  CAS  Google Scholar 

  44. Yoshino G, Kazumi T, Iwai M, et al. Long-term treatment of hypercholesterolemic non-insulin dependent diabetics (NIDDM) with pravastatin (CS-514). Atherosclerosis 1989; 75: 67–72

    Article  PubMed  CAS  Google Scholar 

  45. Kazumi T, Yoshino G, Ishida Y, et al. Long-term efficacy and tolerability of pravastatin in hypercholesterolemia in patients with non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 1995; 27: 61–8

    Article  PubMed  CAS  Google Scholar 

  46. Watanabe J, Kobayashi K, Umeda F, et al. Apolipoprotein E polymorphism affects the response to pravastatin on plasma apolipoproteins in diabetic patients. Diabetes Res Clin Pract 1993; 20: 21–7

    Article  PubMed  CAS  Google Scholar 

  47. Tait GW, Shepherd J. Hyperlipidaemia: its pathogenesis, clinical significance and treatment. Pharm J 1989; 242: 134–7

    Google Scholar 

  48. Kume N, Kita T, Mikami A, et al. Induction of mRNA for low-density lipoprotein receptors in heterozygous Watanabe heritable hyperlipidemic rabbits treated with CS-514 (pravastatin) and cholestyramine. Circulation 1989; 79: 1084–90

    Article  PubMed  CAS  Google Scholar 

  49. Kuroda M, Matsumoto A, Itakura H, et al. Effects of pravastatin sodium alone and in combination with cholestyramine on hepatic, intestinal and adrenal low density lipoprotein receptors in homozygous Watanabe heritable hyperlipidemic rabbits. Jpn J Pharmacol 1992; 59: 65–70

    Article  PubMed  CAS  Google Scholar 

  50. Shiomi M, Watanabe Y, Ito Y, et al. Suppressive effect of the combination treatment with pravastatin sodium and cholestyramine of the progression of atherosclerosis and xanthoma in mature WHHL rabbits. Presented at the 8th International Symposium on Atherosclerosis, 1988 Oct 9–13; Rome, Italy

  51. Hayashi H, Naito C, Ito H, et al. The effect of pravastatin in relation to low density lipoprotein receptor activity. Curr Med Res Opin 1990; 12: 100–7

    Article  PubMed  CAS  Google Scholar 

  52. Khachadurian AK, Shimamura T, Rosovski SJ, et al. Pravastatin decreases serum lipids and vascular cholesterol in Watanabe heritable hyperlipidemic (WHHL) rabbits. Jpn Heart J 1991; 32: 675–85

    Article  PubMed  CAS  Google Scholar 

  53. Shiomi M, Ito T, Tsukada T, et al. Reduction of serum cholesterol levels alters lesional composition of atherosclerotic plaques. Effect of pravastatin sodium on atherosclerosis in mature WHHL rabbits. Arterioscler Thromb Vasc Biol 1995; 15: 1938–44

    Article  PubMed  CAS  Google Scholar 

  54. Shiomi M, Ito T, Watanabe Y, et al. Suppression of established atherosclerosis and xanthomas in mature WHHL rabbits by keeping their serum cholesterol levels extremely low. Atherosclerosis 1990; 83: 69–80

    Article  PubMed  CAS  Google Scholar 

  55. Wendelhag I, Wiklund O, Wikstrand J. Intima-media thickness after cholesterol lowering in familial hypercholesterolemia. A three-year ultrasound study of common carotid and femoral arteries. Atherosclerosis 1995; 117: 225–36

    Article  PubMed  CAS  Google Scholar 

  56. Levine GN, Keaney JF, Vita JA. Cholesterol reduction in cardiovascular disease. Clinical benefits and possible mechanisms. N Engl J Med 1995; 332: 512–21

    Article  PubMed  CAS  Google Scholar 

  57. Egashira K, Hirooka Y, Kai H, et al. Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. Circulation 1994; 89: 2519–24

    Article  PubMed  CAS  Google Scholar 

  58. Kool M, Lustermans F, Kragten H, et al. Does lowering of cholesterol levels influence functional properties of large arteries? Eur J Clin Pharmacol 1995; 48: 217–23

    Article  PubMed  CAS  Google Scholar 

  59. Corsini A, Raiteri M, Soma MR, et al. Simvastatin but not pravastatin has a direct inhibitory effect on rat and human myocyte proliferation. Clin Biochem 1992; 25: 399–400

    Article  PubMed  CAS  Google Scholar 

  60. Davies MJ, Richardson PD, Woolf N, et al. Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J 1993; 69: 377–81

    Article  PubMed  CAS  Google Scholar 

  61. Weissberg PL, Clesham GJ, Bennett MR. Is vascular smooth muscle cell proliferation beneficial? Lancet 1996; 347: 305–7

    Article  PubMed  CAS  Google Scholar 

  62. Corsini A, Mazzotti M, Raiteri M, et al. Relationship between mevalonate pathway and arterial myocyte proliferation: in vitro studies with inhibitors of HMG-CoA reductase. Atherosclerosis 1993; 101: 117–25

    Article  PubMed  CAS  Google Scholar 

  63. 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; 76: 21–8

    Article  Google Scholar 

  64. Onaka H, Hirota Y, Kita Y, et al. The effect of pravastatin on prevention of restenosis after successful percutaneous transluminal coronary angioplasty. Jpn Circ J 1994; 58: 100–6

    Article  PubMed  CAS  Google Scholar 

  65. Yui Y, Kawai C, Hosoda S, et al. Pravastatin (Mevalotin) restenosis trial after percutaneous transluminal coronary angioplasty. Cholesterol reduction rate determines the restenosis rate. Ann NY Acad Sci 1995; 748: 208–16

    Article  PubMed  CAS  Google Scholar 

  66. Sahni R, Maniet AR, Voci G, et al. Prevention of restenosis by lovastatin after successful coronary angioplasty. Am Heart J 1991; 121: 1600–8

    Article  PubMed  CAS  Google Scholar 

  67. Weintraub WS, Boccuzzi SJ, Klein, et al. Lack of effect of lovastatin on restenosis after coronary angioplasty. N Engl J Med 1994; 331: 1331–7

    Article  PubMed  CAS  Google Scholar 

  68. Lacoste LL, Lam JYT, Hung J, et al. Pravachol decreases cholesterol and platelet thrombus formation in coronary patients [abstract no. 73]. Can J Cardiol 1993; 9 Suppl. E: 83E

    Google Scholar 

  69. Lacoste L, Lam JYT, Hung J, et al. Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. Circulation 1995; 92: 3172–7

    Article  PubMed  CAS  Google Scholar 

  70. Lacoste L, Lam JYT. Comparative effect of pravastatin and simvastatin on platelet-thrombus formation in hypercholesterolaemic coronary patients [abstract no. 1045-19]. J Am Coll Cardiol 1996; 27 Suppl. A: 413A

    Article  Google Scholar 

  71. Mori Y, Noda A, Sakaguchi T, et al. Effect of pravastatin on coagulation and fibrinolytic systems in patients with hypercholesterolemia fin Japanese]. J Kessen Shiketsu 1991; 2: 501–4

    Article  CAS  Google Scholar 

  72. Wada H, Mori Y, Kaneko T, et al. Hypercoagulable state in patients with hypercholesterolemia: effects of pravastatin. Clin Ther 1992; 14: 829–34

    PubMed  CAS  Google Scholar 

  73. Barrow SE, Stratton PD, Benjamin N, et al. Reduction of LDL cholesterol by pravastatin does not influence platelet activation in patients with mild hypercholesterolaemia at risk of coronary heart disease. Br J Clin Pharmac 1991; 32: 127–9

    Article  CAS  Google Scholar 

  74. Jay RH, Rampling MW, Betteridge DJ. Abnormalities of blood rheology in familial hypercholesterolaemia: effects of treatment. Atherosclerosis 1990; 85: 249–56

    Article  PubMed  CAS  Google Scholar 

  75. Tsuda Y, Satoh K, Takahashi T, et al. Effect of medication with pravastatin sodium on hemorheological parameters in patients with hyperlipoproteinemia. Int Angiol 1993; 12: 360–4

    PubMed  CAS  Google Scholar 

  76. Tsuda Y, Satoh K, Kitadai M, et al. Effects of pravastatin sodium and simvastatin on plasma fibrinogen level and blood rheology in type II hyperlipoproteinemia. Atherosclerosis 1996; 122: 225–33

    Article  PubMed  CAS  Google Scholar 

  77. Branchi A, Rovellini A, Sommariva D, et al. Effect of three fibrate derivatives and of two HMG-CoA reductase inhibitors on plasma fibrinogen level in patients with primary hypercholesterolemia. Thromb Haemost 1993; 70: 241–3

    PubMed  CAS  Google Scholar 

  78. Dobs AS, Sarma PS, Schteingart D. Long-term endocrine function in hypercholesterolemic patients treated with pravastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Metabolism 1993; 42: 1146–52

    Article  PubMed  CAS  Google Scholar 

  79. Jay RH, Sturley RH, Stirling C, et al. Effects of pravastatin and cholestyramine on gonadal and adrenal steroid production in familial hypercholesterolaemia. Br J Pharmacol 1991; 32: 417–22

    Article  CAS  Google Scholar 

  80. Ito H. The effects of CS-514 (pravastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on serum lipids and steroid hormones in the hypercholesterolemic elderly. J Clin Ther Med 1988; 4: 395–407

    Google Scholar 

  81. Dobs AS, Martin KM, Nazelrod B, et al. Is reduced vitamin D synthesis a complication of treatment with HMG-CoA reductase inhibitors? [abstract]. Arteriosclerosis 1988; 8: 635A

    Google Scholar 

  82. Hoogerbrugge-vd Linden N, de Rooy FWM, Jansen H, et al. Effect of pravastatin on biliary lipid composition and bile acid synthesis in familial hypercholesterolaemia. Gut 1990; 31: 348–50

    Article  PubMed  CAS  Google Scholar 

  83. Horiuchi I, Ohya T, Tazuma S, et al. Effects of pravastatin (CS-514) on biliary lipid metabolism in patients with hyperlipidemia. Metabolism 1991; 40: 226–30

    Article  PubMed  CAS  Google Scholar 

  84. Kajiyama G, Horiuchi I, Takata K, et al. Effects of CS-514 on biliary lipid metabolism in patients with hyperlipidemia. J Clin Ther Med 1988; 4: 191–200

    Google Scholar 

  85. Tazuma S, Ohya T, Teramen K, et al. Effects of long-term treatment with low-dose pravastatin, a competitive inhibitor of hydroxymethylglutaryl coenzyme A reductase, on biliary lipid metastability in patients with hypercholesterolemia [abstract no. 1005]. Hepatology 1993; 18: 308A

    Article  Google Scholar 

  86. Bär PR, Bredman JJ, Koot RW. Simvastatin and lovastatin, but not pravastatin, induce myopathy in young rats [abstract no. 131]. EurJ Clin Invest 1993; 23 Suppl. 1: A24

    Google Scholar 

  87. Fukami M, Maeda N, Fukushige J, et al. Effects of HMG-CoA reductase inhibitors on skeletal muscles of rabbits. Res Exp Med 1993; 193: 263–73

    Article  CAS  Google Scholar 

  88. Reijneveld JC, Koot RW, Bredman JJ, et al. Differential effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on the development of myopathy in young rats. Paediatr Res 1996; 39: 1028–35

    Article  CAS  Google Scholar 

  89. Smith PF, Eydelloth RS, Grossman SJ, et al. Myopathy associated with HMG-CoA reductase inhibitors (HMGRIs) and cyclosporin A: evaluation in a rat model. Eur Heart J 1992; 13 Suppl. B: 2–6

    Article  PubMed  CAS  Google Scholar 

  90. Harrison RWS, Ashton CH. Do cholesterol-lowering agents affect brain activity? A comparison of simvastatin, pravastatin, and placebo in healthy volunteers. Br J Clin Pharmacol 1994; 37: 231–6

    Article  PubMed  CAS  Google Scholar 

  91. Kamei Y, Shirakawa S, Ishizuka Y, et al. Effect of pravastatin on human sleep. Jpn J Psychiatry Neurol 1993; 47: 643–6

    PubMed  CAS  Google Scholar 

  92. Roth T, Richardson GR, Sullivan JP, et al. Comparative effects of pravastatin and lovastatin on nighttime sleep and daytime performance. Clin Cardiol 1992; 15: 426–32

    Article  PubMed  CAS  Google Scholar 

  93. Vgontzas AN, Kales A, Bixler EO, et al. Effects of lovastatin and pravastatin on sleep efficiency and sleep stages. Clin Pharmacol Ther 1991; 50: 730–7

    Article  PubMed  CAS  Google Scholar 

  94. Cutler N, Sramek J, Veroff A, et al. Effects of treatment with simvastatin and pravastatin on cognitive function in patients with hypercholesterolaemia. Br J Clin Pharmac 1995; 39: 333–36

    Article  CAS  Google Scholar 

  95. Eckernäs S-Å, Roos B-E, Kvidal P, et al. The effects of simvastatin and pravastatin on objective and subjective measures of nocturnal sleep: a comparison of two structurally different HMG CoA reductase inhibitors in patients with primary moderate hypercholesterolaemia. Br J Clin Pharmac 1993; 35: 284–9

    Google Scholar 

  96. Kostis JB, Rosen RC, Wilson AC. Central nervous system effects of HMG CoA reductase inhibitors: lovastatin and pravastatin on sleep and cognitive performance in patients with hypercholesterolemia. J Clin Pharmacol 1994; 34: 989–96

    PubMed  CAS  Google Scholar 

  97. Partinen M, Pihl S, Strandberg T, et al. Comparison of effects on sleep of lovastatin and pravastatin in hypercholesterolemia. Am J Cardiol 1994; 73: 876–80

    Article  PubMed  CAS  Google Scholar 

  98. Katznelson S, Kobashigawa JA. Dual roles of HMG-CoA reductase inhibitors in solid organ transplantation: lipid lowering and immunosuppression. Kidney Int 1995; 48 Suppl. 52: S112–5

    Google Scholar 

  99. Satoh K, Yamato A, Nakai T, et al. Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in ischaemic dog hearts. Br J Pharmacol 1995; 116: 1894–8

    Article  PubMed  CAS  Google Scholar 

  100. Ichihara K, Satoh K, Abiko Y. Influences of pravastatin and simvastatin, HMG-CoA reductase inhibitors, on myocardial stunning in dogs. J Cardiovas Pharmacol 1993; 22: 852–6

    Article  CAS  Google Scholar 

  101. Van Boven AJ, Jukema JW, Zwinderman AH, et al. Pravastatin reduces transient myocardial ischemia in patients with angina pectoris and significant CAD [abstract no. 751–5]. J Am Coll Cardiol 1996; 27 Suppl. A: 165A

    Article  Google Scholar 

  102. Van Boven AJ, Jukema JW, Zwinderman AH, et al. Reduction of transient myocardial ischemia with pravastatin in addition to the conventional treatment in patients with angina pectoris. Circulation 1996; 94: 1503–5

    Article  PubMed  Google Scholar 

  103. Pan HY, DeVault AR, Swites BJ, et al. Pharmacokinetics and pharmacodynamics of pravastatin alone and with cholestyramine in hypercholesterolemia. Clin Pharmacol Ther 1990; 48: 201–7

    Article  PubMed  CAS  Google Scholar 

  104. Singhvi SM, Pan HY, Morrison RA, et al. Disposition of pravastatin sodium, a tissue selective HMG-CoA reductase inhibitor, in healthy subjects. Br J Clin Pharmacol 1990; 29: 239–43

    Article  PubMed  CAS  Google Scholar 

  105. Sasahara K, Kawabata K. Phase 1 study of CS-514, an inhibitor of HMG-CoA reductase II: pharmacokinetics of CS-514 in healthy volunteers. J Clin Ther Med 1988; 4: 45–65

    Google Scholar 

  106. Pentikainen PJ, Saraheimo M, Schwartz JL, et al. Comparative pharmacokinetics of lovastatin, simvastatin and pravastatin in humans. J Clin Pharmacol 1992; 32: 136–40

    PubMed  CAS  Google Scholar 

  107. Koga T, Kawabata K, Arai K, et al. Comparative pharmacokinetics and pharmacodynamics of pravastatin and simvastatin. Bull Mol Biol Med 1995; 20: 103–5

    CAS  Google Scholar 

  108. Pan HY, DeVault AR, Brescia D, et al. Effect of food on pravastatin pharmacokinetics and pharmacodynamics. Int J Clin Pharmacol Ther Toxicol 1993; 31: 291–4

    PubMed  CAS  Google Scholar 

  109. Triscari J, Pan H, De Vault A, et al. Comparative bioavailability of pravastatin following morning and evening dosing [abstract no. PIII-19J. Clin Pharmacol Ther 1991; 49: 178

    Google Scholar 

  110. Hunninghake DB, Mellies MJ, Goldberg AC, et al. Efficacy and safety of pravastatin in patients with primary hypercholesterolemia II. Once-daily versus twice-daily dosing. Atherosclerosis 1990; 85: 219–27

    Article  PubMed  CAS  Google Scholar 

  111. Illingworth DR. Clinical implications of new drugs for lowering plasma cholesterol concentrations. Drugs 1991; 41: 151–60

    Article  PubMed  CAS  Google Scholar 

  112. Pan H, Fleiss P, Moore L, et al. Excretion of pravastatin, an HMG-CoA reductase inhibitor, in breast milk of lactating women. J Clin Pharmacol 1988; 28: 942

    Google Scholar 

  113. Botti RE, Triscari J, Pan HY, et al. Concentrations of pravastatin and lovastatin in cerebrospinal fluid in healthy subjects. Clin Neuropharmacol 1991; 14: 256–61

    Article  PubMed  CAS  Google Scholar 

  114. Triscari J, Swanson BN, Willard DA, et al. Steady state serum concentrations of pravastatin and digoxin when given in combination. Br J Clin Pharmacol 1993; 36: 263–5

    Article  PubMed  CAS  Google Scholar 

  115. Tsuji A, Saheki A, Tamai I, et al. Transport mechanism of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors at the blood-brain barrier. J Pharmacol Exp Ther 1993; 267: 1085–90

    PubMed  CAS  Google Scholar 

  116. Saheki A, Terasaki T, Tamai I, et al. In vivo and in vitro blood-brain barrier transport of 3-hydroxy-3-methyIglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Pharm Res 1994; 11: 305–311

    Article  PubMed  CAS  Google Scholar 

  117. Squibb & Sons, Inc. Pravastatin prescribing information. New Jersey, USA, 1995

  118. Halstenson CE, Triscari J, Devault A, et al. Single-dose pharmacokinetics of pravastatin and metabolites in patients with renal impairment. J Clin Pharmacol 1992; 32: 124–32

    PubMed  CAS  Google Scholar 

  119. Pan HY. Clinical pharmacology of pravastatin, a selective inhibitor of HMG-CoA reductase. Eur J Clin Pharmacol 1991; 40 Suppl. I: S15–8

    PubMed  Google Scholar 

  120. Pan HY, Waclawski AP, Funke PT, et al. Pharmacokinetics of pravastatin in elderly versus young men and women. Ann Pharmacother 1993; 27: 1029–33

    PubMed  CAS  Google Scholar 

  121. Betteridge DJ, Dodson PM, Durrington PN, et al. Management of hyperlipidaemia: guidelines of the British Hyperlipidaemia Association. Postgrad Med J 1993; 69: 359–69

    Article  PubMed  CAS  Google Scholar 

  122. Holme I. An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence. Circulation 1990; 82: 1916–24

    Article  PubMed  CAS  Google Scholar 

  123. 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; 344: 1383–89

    Google Scholar 

  124. McGovern ME, Mellies MJ. Long-term experience with pravastatin in clinical research trials. Clin Ther 1993; 14: 57–64

    Google Scholar 

  125. Frick MH, Elo O, Haapa K, et al. Helsinki heart study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. N Engl J Med 1987; 317: 1237–45

    Article  PubMed  CAS  Google Scholar 

  126. Lipid Research Clinics Program. The lipid research clinics coronary primary prevention trial results. I. Reduction in incidence of coronary heart disease. JAMA 1984; 251: 351–64

    Article  Google Scholar 

  127. Lipid Research Clinics Program. The lipid research clinics coronary primary prevention trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984; 251: 365–74

    Article  Google Scholar 

  128. Muldoon MF, Manuck SB, Matthews KA. Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. BMJ 1990; 301: 309–14

    Article  PubMed  CAS  Google Scholar 

  129. Shepherd J. The West of Scotland Coronary Prevention Study: a trial of cholesterol reduction in Scottish men. Am J Cardiol 1995; 76: 113C–7C

    Article  PubMed  CAS  Google Scholar 

  130. WOSCOPS Study Group. Screening experience and baseline characteristics in the West of Scotland Coronary Prevention Study. Am J Cardiol 1995; 76: 485–91

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  132. Shepherd J, Cobbe SM, Ford I. Prevention of coronary heart disease with pravastatin [letter]. N Engl J Med 1996; 334: 1334–5

    Google Scholar 

  133. Pravastatin Multinational Study Group for Cardiac Risk Patients. Effects of pravastatin in patients with serum total cholesterol levels from 5.2 to 7.8 mmol/liter (200 to 300 mg/dl) plus two additional atherosclerotic risk factors. Am J Cardiol 1993; 72: 1031–7

    Article  Google Scholar 

  134. Pfeffer MA, Sacks FM, Moyé LA, et al. Cholesterol and recurrent events: a secondary prevention trial for normolipidemic patients. Am J Cardiol 1995; 76: 98C–106C

    Article  PubMed  CAS  Google Scholar 

  135. Sacks FM, Rouleau J-L, Moye LA, et al. Baseline characteristics in the Cholesterol and Recurrent Events (CARE) trial of secondary prevention in patients with average serum cholesterol levels. Am J Cardiol 1995; 75: 621–3

    Article  PubMed  CAS  Google Scholar 

  136. Mellies MJ. Ongoing and planned clinical trials for atherosclerosis prevention and regression. Curr Opin Invest Drugs 1993; 2: 529–39

    Google Scholar 

  137. 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; 335: 1001–9

    Article  PubMed  CAS  Google Scholar 

  138. LIPID Study Group. Design features and baseline characteristics of the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) study: a randomized trial in patients with previous acute myocardial infarction and/or unstable angina pectoris. Am J Cardiol 1995; 76: 474–9

    Article  Google Scholar 

  139. Tonkin AM. Management of the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study after the Scandinavian Simvastatin Survival Study (4S). Am J Cardiol 1995;76: 107C–12C

    Article  PubMed  CAS  Google Scholar 

  140. Simes RJ. Prospective meta-analysis of cholesterol-lowering studies: the Prospective Pravastatin Pooling (PPP) project and the Cholesterol Treatment Trialists (CTT) collaboration. Am J Cardiol 1995; 76: 122C–6C

    Article  PubMed  CAS  Google Scholar 

  141. PPP Project Investigators. Design, rationale, and baseline characteristics of the Prospective Pravastatin Pooling (PPP) project — a combined analysis of three large-scale randomized trials: Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID), Cholesterol and Recurrent Events (CARE), and West of Scotland Coronary Prevention Study (WOSCOPS). Am J Cardiol 1995; 76: 899–905

    Article  Google Scholar 

  142. Byington RP, Jukema JW, Salonen JT, et al. Reduction in cardiovascular events during pravastatin therapy: pooled analysis of clinical events of the pravastatin atherosclerosis intervention program. Circulation 1995; 92: 2419–25

    Article  PubMed  CAS  Google Scholar 

  143. Salonen R, Nyyssönen K, Porkkala E, et al. Kuopio Atherosclerosis Prevention Study (KAPS): a population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries. Circulation 1995; 92: 1758–64

    Article  PubMed  CAS  Google Scholar 

  144. Pitt B, Ellis SG, Mancini GBJ, et al. Design and recruitment in the United States of a multicenter quantitative angiographie trial of pravastatin to limit atherosclerosis in the coronary arteries (PLAC I). Am J Cardiol 1993; 72: 31–5

    Article  PubMed  CAS  Google Scholar 

  145. Pitt B, Mancini GBJ, Ellis SG, et al. Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC I): reductions in atherosclerosis progression and clinical events. J Am Coll Cardiol 1995; 26: 1133–9

    Article  PubMed  CAS  Google Scholar 

  146. Byington RP, Furberg CD, Crouse JR, et al. Pravastatin, lipids, and atherosclerosis in the carotid arteries (PLAC-II). Am J Cardiol 1995; 76: 54–9C

    Article  Google Scholar 

  147. Crouse JR, Byington RP, Bond MG, et al. Pravastatin, lipids, and atherosclerosis in the carotid arteries (PLAC II). Am J Cardiol 1995; 75: 455–9

    Article  PubMed  Google Scholar 

  148. Barth JD, Zonjee MMB, REGRESS Research Group. Regression growth evaluation statin study (REGRESS): study design and baseline characteristics in 600 patients. Can J Cardiol 1992; 8: 925–32

    PubMed  CAS  Google Scholar 

  149. De Groot E, Jukema JW, van Boven AJ, et al. Effect of pravastatin on progression and regression of coronary atherosclerosis and vessel wall changes in carotid and femoral arteries: a report from the Regression Growth Evaluation Statin Study. Am J Cardiol 1995; 76: 40–6C

    Article  Google Scholar 

  150. Jukema JW, Bruschke AVG, van Boven AJ, et al. Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS). Circulation 1995; 91: 2528–40

    Article  PubMed  CAS  Google Scholar 

  151. Jukema JW, van Boven AJ, Bal ET, et al. During lipid-lowering therapy or placebo administration progression and regression of coronary lesions occur within the same patient [abstract no. 1217). Eur Heart J 1994; 15 Suppl.: 223

    Article  Google Scholar 

  152. Jukema JW, van Boven AJ, Reiber JHC, et al. Progression and regression of coronary atherosclerosis occur within the same patient during placebo treatment and during lipid-lowering therapy with pravastatin [abstract no. 769-2]. Program and abstracts of original contributions from the 44th Annual Scientific Session American College of Cardiology: 1995 March 19–22: New Orleans, Louisiana, USA; J Am Coll Cardiol (Feb) 1995; 281A

  153. Jukema JW, van Boven AJ, Reiber JHC, et al. Reduction of the beneficial effect of lipid-lowering therapy by pravastatin on coronary atherosclerosis in smoking patients (abstract no. 1584]. Abstracts from the XVIIth Congress of the European Society of Cardiology: 1995 August 20–24: Amsterdam, The Netherlands; Eur Heart J 1995; 16 Suppl.: 273

    Google Scholar 

  154. De Groot E, Jukema JW, Zwinderman AH, et al. Correlations in pravastatin treatment effect between carotid and femoral intima-media thickness, and coronary artery stenosis (abstract 988-22]. J Am Coll Cardiol 1996; 27 Suppl. A: 273A

    Article  Google Scholar 

  155. Furberg CD, Pitt B, Byington RP, et al. Reduction in coronary events during treatment with pravastatin. Am J Cardiol 1995; 76: 60–3C

    Article  Google Scholar 

  156. Sacks FM, Gibson CM, Rosner B, et al. The influence of pretreatment low density lipoprotein cholesterol concentrations on the effect of hypercholesterolemic therapy on coronary atherosclerosis in angiographie trials. Am J Cardiol 1995; 76: 78C–85C

    Article  PubMed  CAS  Google Scholar 

  157. PHYLLIS Project Group. Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS): a protocol for non-invasive evaluation of carotid atherosclerosis in hypercholesterolaemic hypertensive subjects. J Hypertens 1993; 11 Suppl. 5: S314–5

    Google Scholar 

  158. Beigel Y, Brook G, Eisenberg S, et al. Efficacy and safety of pravastatin once daily in primary moderate hypercholesterolemia: the Israeli experience. Isr J Med Sci 1993; 29: 272–7

    PubMed  CAS  Google Scholar 

  159. Jacobson TA, Chin MM, Curry CL, et al. Efficacy and safety of pravastatin in African Americans with primary hypercholesterolemia. Arch Intern Med 1995; 155: 1900–6

    Article  PubMed  CAS  Google Scholar 

  160. Rubenfire M, Maciejko JJ, Blevins RD, et al. The effect of pravastatin on plasma lipoprotein and apolipoprotein levels in primary hypercholesterolemia. Arch Intern Med 1991; 151: 2234–40

    Article  PubMed  CAS  Google Scholar 

  161. Hunninghake DB, Knopp RH, Schonfeld G, et al. Efficacy and safety of pravastatin in patients with primary hypercholesterolemia I. A dose-response study. Atherosclerosis 1990; 85: 81–9

    Article  PubMed  CAS  Google Scholar 

  162. Betteridge DJ, Bhatnager B, Bing RF, et al. Treatment of familial hypercholesterolaemia. United Kingdom lipid clinics study of pravastatin and cholestyramine. BMJ 1992; 304: 1335–8

    Article  PubMed  CAS  Google Scholar 

  163. Wiklund O, Angelin B, Fager G, et al. Treatment of familial hypercholesterolaemia: a controlled trial of the effects of pravastatin or cholestyramine therapy on lipoprotein and apolipoprotein levels. J Intern Med 1990; 228: 241–7

    Article  PubMed  CAS  Google Scholar 

  164. Arntz HR, Bönner G, Kikis D, et al. Efficacy of pravastatin and bezafibrate in primary hypercholesterolaemia [in German]. Dtsch Med Wochenschr 1991; 116: 7–12

    Article  PubMed  CAS  Google Scholar 

  165. Crepaldi G, Baggio G, Area M, et al. Pravastatin vs gemfibrozil in the treatment of primary hypercholesterolemia. The Italian Multicenter Pravastatin Study I. Arch Intern Med 1991; 151: 146–52

    Article  PubMed  CAS  Google Scholar 

  166. Malacco E, Magni A, Scandiani L, et al. Pravastatin vs gemfibrozil in the treatment of primary hypercholesterolaemia. Drug Invest 1994; 7: 331–9

    Article  Google Scholar 

  167. Jacotot B, Benghozi R, Pfister P, et al. Comparison of fluvastatin versus pravastatin treatment of primary hypercholesterolaemia. Am J Cardiol 1995; 76: 54A–6A

    Article  PubMed  CAS  Google Scholar 

  168. Kawakami Y, Tagami S, Hasegawa A, et al. Clinical efficacy of fluvastatin (XU62-320) in hyperlipidemia — a comparative study with pravastatin in a double-blind comparative method [in Japanese]. Rinsho Iyaku 1995; 11: 1679–1726

    Google Scholar 

  169. Lovastatin Pravastatin Study Group. A multicenter comparative trial of lovastatin and pravastatin in the treatment of hypercholesterolemia. Am J Cardiol 1993; 71: 810–5

    Article  Google Scholar 

  170. McPherson R, Bedard J, Connelly P, et al. Comparison of the short-term efficacy and tolerability of lovastatin and pravastatin in the management of primary hypercholesterolemia. Clin Ther 1992; 14: 276–91

    PubMed  CAS  Google Scholar 

  171. Weir MR, Berger ML, Weeks ML, et al. Comparison of the effects on quality of life and of the efficacy and tolerability of lovastatin versus pravastatin. Am J Cardiol 1996; 77: 475–9

    Article  PubMed  CAS  Google Scholar 

  172. European Study Group. Efficacy and tolerability of simvastatin and pravastatin in patients with primary hypercholesterolemia (Multicountry Comparative Study). Am J Cardiol 1992; 70: 1281–6

    Article  Google Scholar 

  173. Lambrecht LJ, Malini PL, European Study Group. Efficacy and tolerability of simvastatin 20 mg vs pravastatin 20 mg in patients with primary hypercholesterolemia. Acta Cardiol 1993; 48: 541–54

    PubMed  CAS  Google Scholar 

  174. Steinhagen-Thiessen E, Simvastatin Pravastatin European Study Group. Comparative efficacy and tolerability of 5 and 10 mg simvastatin and 10 mg pravastatin in moderate primary hypercholesterolemia. Cardiology 1994; 85: 244–54

    Article  PubMed  CAS  Google Scholar 

  175. Simvastatin Pravastatin Study Group. Comparison of the efficacy, safety and tolerability of simvastatin and pravastatin for hypercholesterolemia. Am J Cardiol 1993; 71: 1408–14

    Article  Google Scholar 

  176. Illingworth DR, Erkelens WD, Keller U, et al. Defined daily doses in relation to hypolipidaemic efficacy of lovastatin, pravastatin, and simvastatin. Lancet 1994; 343: 1554–5

    Article  PubMed  CAS  Google Scholar 

  177. Pravastatin Multicenter Study Group II. Comparative efficacy and safety of pravastatin and cholestyramine alone and in combination in patients with hypercholesterolemia. Arch Intern Med 1993; 153: 1321–9

    Article  Google Scholar 

  178. Jacob BG, Möhrle W, Richter WO, et al. Short- and long-term effects of lovastatin and pravastatin alone and in combination with cholestyramine on serum lipids, lipoproteins and apolipoproteins in primary hypercholesterolaemia. Eur J Clin Pharmacol 1992; 42: 353–8

    PubMed  CAS  Google Scholar 

  179. Contacos C, Barter PJ, Sullivan DR. Effect of pravastatin and (ω-3 fatty acids on plasma lipids and lipoproteins in patients with combined hyperlipidemia. Arterioscler Thromb 1993; 13: 1755–62

    Article  PubMed  CAS  Google Scholar 

  180. Wiklund O, Angelin B, Bergman M, et al. Pravastatin and gemfibrozil alone and in combination for the treatment of hypercholesterolemia. Am J Med 1993; 94: 13–20

    Article  PubMed  CAS  Google Scholar 

  181. Davignon J, Roederer G, Montigny M, et al. Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia. Am J Cardiol 1994; 73: 339–45

    Article  PubMed  CAS  Google Scholar 

  182. O’Keefe JH, Harris WS, Nelson J, et al. Effects of pravastatin with niacin or magnesium on lipid levels and postprandial lipemia. Am J Cardiol 1995; 76: 480–4

    Article  PubMed  Google Scholar 

  183. Davidson MH, Gwynne JT, Khachadurian AK, et al. Combination of pravastatin and probucol in the treatment of primary hypercholesterolemia. Coron Artery Dis 1991; 2: 1061–8

    Google Scholar 

  184. Anderson KM, Castelli WP, Levy D. Cholesterol and mortality: 30 years of follow-up from the Framington study. JAMA 1987; 257: 2176–80

    Article  PubMed  CAS  Google Scholar 

  185. Garber AM, Browner WS, Hulley SB. Cholesterol screening in asymptomatic adults, revisited. Ann Intern Med 1996; 124: 518–31

    PubMed  CAS  Google Scholar 

  186. Krumholz HM, Seeman TE, Merrill SS, et al. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. JAMA 1994; 272: 1335–40

    Article  PubMed  CAS  Google Scholar 

  187. Bo M, Pernigotti L, Poli L, et al. 1991. One-year experience in the treatment of elderly hypercholesterolemic patients with pravastatin. Curr Ther Res 1991; 50: 151–8

    Google Scholar 

  188. Glasser SP, DiBianco R, Effron BA, et al. The efficacy and safety of pravastatin in patients aged 60 to 85 years with low-density lipoprotein cholesterol > 160 mg/dl. Am J Cardiol 1996; 77: 83–5

    Article  PubMed  CAS  Google Scholar 

  189. Santinga JT, Rosman HS, Rubenfire M, et al. Efficacy and safety of pravastatin in the long-term treatment of elderly patients with hypercholesterolemia. Am J Med 1994; 96: 509–15

    Article  PubMed  CAS  Google Scholar 

  190. Mellies MJ, DeVault AR, Kassler-Taub K, et al. Pravastatin experience in elderly and non-elderly patients. Atherosclerosis 1993; 101: 97–110

    Article  PubMed  CAS  Google Scholar 

  191. Chan P, Lee C-B, Lin T-S, et al. The effectiveness and safety of low dose pravastatin in elderly hypercholesterolemic subjects on antihypertensive therapy. Am J Hypertens 1995; 8: 1099–104

    Article  PubMed  CAS  Google Scholar 

  192. Bierman EL. Atherogenesis in diabetes: George Lyman Duff memorial lecture. Arterioscler Thromb 1992; 12: 647–56

    Article  PubMed  CAS  Google Scholar 

  193. Garg A, Grundy SM. Management of dyslipidemia in NIDDM. Diabetes Care 1990; 13: 153–69

    Article  PubMed  CAS  Google Scholar 

  194. Anonymous. Detection and management of lipid disorders in diabetes. Diabetes Care 1993; 16 Suppl. 2: 106–12

  195. Behounek BD, McGovern ME, Kassler KB, et al. A multinational study of the effects of low-dose pravastatin in patients with non-insulin-dependent diabetes mellitus and hypercholesterolemia. Clin Cardiol 1994; 17: 558–62

    Article  PubMed  CAS  Google Scholar 

  196. Deerochanawong C, Serirat S. Clinical evaluation of pravastatin in the treatment of type II hyperlipidemia in patients with non-insulin-dependent diabetes mellitus. J Med Assoc Thai 1995; 78: 113–7

    PubMed  CAS  Google Scholar 

  197. Krempf M, Berthezene F, Wemeau JL, et al. Efficacite et tolerance de la pravastatine chez des patients presentant une hypercholesterolemie associee a un diabete de type II [abstract]. Diabete Metab 1993; 19: 44

    Google Scholar 

  198. Raskin P, Ganda OP, Schwartz S, et al. Efficacy and safety of pravastatin in the treatment of patients with type I or type II diabetes mellitus and hypercholesterolemia. Am J Med 1995; 99: 362–9

    Article  PubMed  CAS  Google Scholar 

  199. Sheu WHH, Shieh SM, Shen DDC, et al. Effect of pravastatin treatment on glucose, insulin, and lipoprotein metabolism in patients with hypercholesterolemia. Am Heart J 1994; 127: 331–6

    Article  PubMed  CAS  Google Scholar 

  200. Grundy SM. Management of hyperlipidemia of kidney disease. Kidney Int 1990; 37: 847–53

    Article  PubMed  CAS  Google Scholar 

  201. Spitalewitz S, Porush JG, Cattran D, et al. Treatment of hyperlipidemia in the nephrotic syndrome: the effects of pravastatin therapy. Am J Kidney Dis 1993; 22: 143–50

    PubMed  CAS  Google Scholar 

  202. Tokoo M, Oguchi H, Terashima M, et al. Effects of pravastatin on serum lipids and apolipoproteins in hyperlipidemia of the nephrotic syndrome. Jpn J Nephrol 1992; 34: 397–403

    CAS  Google Scholar 

  203. Moorhead JF. Lipids and progressive kidney disease. Kidney Int 1991; 39 Suppl. 31: S35–40

    Google Scholar 

  204. Mori Y, Tsuruoka A. Effect of pravastatin on microalbuminuria in patients with non-insulin-dependent diabetes mellitus [in Japanese]. J Jpn Diabetes Soc 1992; 35: 265–6

    CAS  Google Scholar 

  205. Shoji T, Nishizawa Y, Toyokawa A, et al. Decreased albuminuria by pravastatin in hyperlipidemic diabetics. Nephron 1991; 59: 664–5

    Article  PubMed  CAS  Google Scholar 

  206. Alamo C, Aranda JL, Sanchez R, et al. Treatment of proteinuria-related hyperlipidemia with pravastatin [abstract]. Kidney Int 1994; 46: 562

    Google Scholar 

  207. Motellón JL, Sánchez-Tomero A, Gruss E, et al. Treatment with pravastatin of hypercholesterolaemia in nephrological patients: effects on proteinuria and progression of renal failure [abstract]. Nephrol Dial Transplant 1994; 9: 962

    Google Scholar 

  208. Hattori M, Ito K, Kawaguchi H, et al. Treatment with a combination of low-density lipoprotein aphaeresis and pravastatin of a patient with drug-resistant nephrotic syndrome due to focal segmental glomerulosclerosis. Pediatr Nephrol 1993; 7: 196–8

    Article  PubMed  CAS  Google Scholar 

  209. Yoshimura N, Oka T, Okamoto M, et al. The effects of pravastatin on hyperlipidemia in renal transplant recipients. Transplantation 1992; 53: 94–9

    Article  PubMed  CAS  Google Scholar 

  210. Castelao AM, Grinyó JM, Castiñeiras MJ, et al. Effect of pravastatin in the treatment of hypercholesterolemia after renal transplantation under cyclosporine and prednisone. Transplant Proc 1995; 27: 2217–20

    PubMed  CAS  Google Scholar 

  211. Lye WC, Hughes K, Leong SO, et al. Abnormal lipoprotein (a) and lipid profiles in renal allograft recipients: effects of treatment with pravastatin. Transplant Proc 1995; 27: 977–8

    PubMed  CAS  Google Scholar 

  212. Katznelson S, Wilkinson AH, Kobashigawa JA, et al. The effect of pravastatin on acute rejection after kidney transplantation — a pilot study. Transplantation 1996; 61: 1469–74

    Article  PubMed  CAS  Google Scholar 

  213. Schouten JA, Rila H, Gevers Leuven J, et al. Tandem study: efficacy and safety of pravastatin in hypercholesterolemic patients with hypertension [abstract no. 470]. Atherosclerosis 1995; 115 Suppl.: S125

    Article  Google Scholar 

  214. Waeber B, Greminger P, Riesen W, et al. Combined treatment with captopril, hydrochlorothiazide and pravastatin in dyslipidemic hypertensive patients. Blood Press 1995; 4: 358–62

    Article  PubMed  CAS  Google Scholar 

  215. Fogari R, Marasi G, Zoppi A, et al. Effects of pravastatin given every other day in dyslipidemic hypertensives treated with different antihypertensive drugs [abstract no. A62]. Am J Hypertens 1994; 7 (4 Pt 2): 48A

    Google Scholar 

  216. Tsukiyama H, Otsuka K. Effects of pravastatin in dyslipidaemic patients with and without hypertension. J Hypertens 1993; 11 Suppl. 5: S346–7

    Article  CAS  Google Scholar 

  217. O’Callaghan CJ, Conway EL, Lam W, et al. Effects of pravastatin on the lipid profile of hypertensive patients receiving captopril [abstract no. 1558]. Am J Hypertens 1993; 6 (5 Pt 2): 109A

    Google Scholar 

  218. Muramatsu J, Kobayashi A, Ikeda Y, et al. Change in cardiac function after long-term treatment of hyperlipidemia by a HMG-CoA reductase inhibitor (pravastatin) in patients with hypertension and ischemic heart disease [abstract no. P979]. Jpn Circ J 1993; 57: 744

    Google Scholar 

  219. Kobashigawa JA, Katznelson S, Laks H, et al. Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med 1995; 333: 621–7

    Article  PubMed  CAS  Google Scholar 

  220. Smit JWA, Van Erpecum J, Stolk MFJ, et al. Successful dissolution of cholesterol gallstone during treatment with pravastatin. Gastroenterology 1992; 103: 1068–70

    PubMed  CAS  Google Scholar 

  221. Watanabe M, Takatori Y, Akagi S, et al. Preliminary study on the efficacy of combination therapy with pravastatin and ursodeoxycholic acid (UDCA) in gallstone dissolution [abstract no. 2594P1. World Congress of Gastroenterology, 1994 Oct 2–7; Los Angeles, USA

  222. Smit JWA, Van Erpecum KJ, Renooij W, et al. The effects of the 3-hydroxy, 3-methylglutaryl coenzyme A reductase inhibitor pravastatin on bile composition and nucleation of cholesterol crystals in cholesterol gallstone disease. Hepatology 1995; 21: 1523–9

    PubMed  CAS  Google Scholar 

  223. Kurihara T, Akimoto M, Abe K, et al. Experimental use of pravastatin in patients with primary biliary cirrhosis associated with hypercholesterolaemia. Clin Ther 1993; 15: 890–8

    PubMed  CAS  Google Scholar 

  224. Kawata S, Yamasaki E, Nagase T, et al. Long-term administration of pravastatin, a potent HMG-CoA reductase inhibitor, prolongs survival of patients with advanced hepatocellular carcinoma: a randomized controlled trial [abstract no. 476]. Hepatology 1996; 24 (4 Pt 2): 245A

    Google Scholar 

  225. Pharoah PDP, Hollingworth W. Cost effectiveness of lowering cholesterol concentration with statins in patients with and without pre-existing coronary heart disease: life table method applied to health authority population. BMJ 1996; 312: 1443–8 [letters BMJ 1996; 313: 1142–4]

    Article  PubMed  CAS  Google Scholar 

  226. Reckless JPD. The economics of cholesterol lowering. Baillieres Clin Endocrinol Metab 1990; 4: 947–72

    Article  PubMed  CAS  Google Scholar 

  227. Korman L, Borysiuk L. Replacing lovastatin with pravastatin: effect on serum lipids and costs. Am J Health-Syst Pharm 1995; 52: 1078–82

    PubMed  CAS  Google Scholar 

  228. Smart AJ, Walters L. Pharmaco-economic assessment of the HMG-CoA reductase inhibitors. S Afr Med J 1994; 84: 834–7

    PubMed  CAS  Google Scholar 

  229. Ashraf T, Hay JW, Pitt B, et al. Cost-effectiveness of pravastatin in secondary prevention of coronary artery disease. Am J Cardiol 1996; 78: 409–14

    Article  PubMed  CAS  Google Scholar 

  230. Martens LL, Guibert R. Cost-effectiveness analysis of lipidmodifying therapy in Canada: comparison of HMG-CoA reductase inhibitors in the primary prevention of coronary heart disease. Clin Ther 1994; 16: 1052–62 [correspondence Clin Ther 1995; 17:572-80]

    PubMed  CAS  Google Scholar 

  231. Muls E, Van Ganse E, Closon MC. Cost-effectiveness of pravastatin in secondary prevention of CHD: comparison between the US and Belgium of a projected risk model [abstract]. 66th Congress of the European Atherosclerosis Society, 1996 July 13–17; Florence, Italy: 13

  232. Newman TJ, Kassler-Taub KB, Gelarden RT, et al. Safety of pravastatin in long-term clinical trials conducted in the United States. J Drug Dev 1990; 3 Suppl. 1: 275–81

    Google Scholar 

  233. Emmerich J. Comparison of the efficacy, safety and tolerability of simvastatin and pravastatin [letter]. Am JCardiol 1994; 73: 723

    Article  CAS  Google Scholar 

  234. Jungnickel PW, Cantral KA, Maloley PA. Relative safety and efficacy of pravastatin [letter]. Clin Pharm 1993; 12: 256–7

    Google Scholar 

  235. Decoulx E, Millaire A, De Groote P, et al. Rhabdomyolysis due to pravastatin and type 1 macrocreatine kinase [in French]. Ann Cardiol Angeiol 1993; 42: 267–9

    CAS  Google Scholar 

  236. Hino I, Akama H, Furuya T, et al. Pravastatin-induced rhabdomyolysis in a patient with mixed connective tissue disease. Arthritis Rheum 1996; 39: 1259–61

    Article  PubMed  CAS  Google Scholar 

  237. Perault MC, Ladouch-Bures L, Dejean C, et al. Rhabdomyolyse associée à la prise de pravastatine (Vasten®) [letter]. Therapie 1993; 48: 483–501

    Google Scholar 

  238. Rosenberg AD, Neuwirth MG, Kagen LJ, et al. Intraoperative rhabdomyolysis in a patient receiving pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor. Anesth Anaig 1995; 81: 1089–91

    CAS  Google Scholar 

  239. England JDF, Walsh JC, Stewart P, et al. Mitochondrial myopathy developing on treatment with the HMG CoA reductase inhibitors-simvastatin and pravastatin. Aust NZ J Med 1995; 25: 374–5

    Article  CAS  Google Scholar 

  240. Schalke BB, Schmidt B, Touka K, et al. Pravastatin-associated inflammatory myopathy [letter]. N Engl J Med 1992; 327: 649–50

    PubMed  CAS  Google Scholar 

  241. Ballare M, Campanini M, Airoldi G, et al. Hepatotoxic effects of hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Ital J Gastroenterol 1991; 23: 281

    Google Scholar 

  242. MacDonald JS, Gerson RJ, Kornbrust DJ, et al. Preclinical evaluation of lovastatin. Am J Cardiol 1988; 62: 16J–27J

    Article  PubMed  CAS  Google Scholar 

  243. Todd PA, Goa KL. Simvastatin: a review of its pharmacological properties and therapeutic potential in hypercholesterolaemia. Drugs 1990; 40: 583–607

    Article  PubMed  CAS  Google Scholar 

  244. Behrens-Baumann W, Thiery J, Fieseler HG, et al. Pravastatin — ocular side effects after a two year follow-up? Lens Eye Toxic Res 1990; 7: 311–8

    PubMed  CAS  Google Scholar 

  245. Schmitt C, Schmidt J, Hockwin O. Ocular drug-safety study with the HMG-CoA reductase inhibitor pravastatin. Lens Eye Tox Res 1990; 7: 631–42

    CAS  Google Scholar 

  246. Pierce LR, Wysowski DK, Gross TP. Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy. JAMA 1990; 264: 71–5

    Article  PubMed  CAS  Google Scholar 

  247. Thompson GR. Adverse reactions profile: 10. Simvastatin and pravastatin. Prescr J 1993; 33: 217–20

    Google Scholar 

  248. Garnett WR. Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Am J Health-Syst Pharm 1995; 52: 1639–45

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  250. Olbricht C, Wanner C, Eisenhauer T, et al. Pravastatin and lovastatin pharmacokinetics and pharmacodynamics in renal transplant patients receiving cyclosporine [abstract]. J Am Soc Nephrol 1995; 6: 1061

    Google Scholar 

  251. Castelao AM, Griñö JM, GilVernet S, et al. Effect of pravastatin in the treatment of hypercholesterolaemia after renal transplantation under cyclosporin immunosuppression. Nephrol Dial Transplant 1993; 8: 1037–8

    Google Scholar 

  252. Davies RA. Safety and efficacy of pravastatin after heart transplantation: preliminary patient studies [abstract]. XI International Symposium on Drugs Affecting Lipid Metabolism, 1992 May 13–16; Florence, Italy: 18

  253. Valino RN, Reiss WG, Hanes D, et al. Examination of the potential interaction between HMG-CoA reductase inhibitors and cyclosporine in transplant patients [abstract no. 139]. Pharmacotherapy 1996; 16: 511

    Google Scholar 

  254. Feher MD, Foxton J, Banks D, et al. Long-term safety of fibrate-statin combination therapy in the treatment of hypercholesterolaemia. Br J Clin Pharmacol 1994; 37: 511P

  255. Rosenson RS, Frauenheim WA. Safety of combined pravastatingemfibrozil therapy. Am J Cardiol 1994; 74: 499–500

    Article  PubMed  CAS  Google Scholar 

  256. Triscari J, Markowitz JS, McGovern MW. Pravastatin and lovastatin in cerebrospinal fluid. Clin Neuropharmacol 1993; 16: 559–60

    Article  PubMed  CAS  Google Scholar 

  257. Trenque T, Choisy H, Germain M-L. Pravastatin: interaction with oral anticoagulant? [letter]. BMJ 1996; 312: 886

    PubMed  CAS  Google Scholar 

  258. Merck & Co, Inc. Simvastatin prescribing information. Pennsylvania, USA, 1995

  259. Merck & Co, Inc. Lovastatin prescribing information. Pennsylvania, USA, 1995

  260. Simons LA, Levis G, Simons J. Apparent discontinuation rates in patients prescribed lipid-lowering drugs. Med J Aust 1996; 164: 208–11

    PubMed  CAS  Google Scholar 

  261. Schucker B, Wittes JT, Santanello NC, et al. Changes in cholesterol awareness and action: results from national physician and public surveys. Arch Intern Med 1991; 151: 666–73

    Article  PubMed  CAS  Google Scholar 

  262. Thelle DS. Epidemiology of hypercholesterolaemia and European management guidelines. Cardiology 1990; 77 Suppl. 4: 2–7

    Article  PubMed  Google Scholar 

  263. Davey Smith G, Pekkanen J. Should there be a moratorium on the use of cholesterol lowering drugs? BMJ 1992; 304: 431–4

    Article  PubMed  CAS  Google Scholar 

  264. Fey R, Pearson N. Statins and coronary heart disease. Lancet 1996; 347: 1389–90

    Article  PubMed  CAS  Google Scholar 

  265. Rogers S. Prevention of coronary heart disease with pravastatin [letter]. N Engl J Med 1996; 334: 1333

    Article  PubMed  CAS  Google Scholar 

  266. Samani NJ, De Bono DP. Prevention of coronary heart disease with pravastatin [letter]. N Engl J Med 1996; 334: 1333–4

    Article  PubMed  CAS  Google Scholar 

  267. LaRosa JC. Cholesterol-lowering and the cost-effective prevention of recurrent coronary disease. CVR & R 1996; 17: 10–28

    Google Scholar 

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    Malini Haria & Donna McTavish

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  1. Malini Haria
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Correspondence to Malini Haria.

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Various sections of the manuscript reviewed by: M. Aviram, Lipid Research Laboratory, Rambam Medical Center, Haifa, Israel; Y. Beigel, Department of Internal Medicine A, Beilinson Medical Center, Tel Aviv University, Petah Tikva, Israel; J.R. Crouse, Department of Medicine, The Bowman Gray School of Medicine, Winston-Salem, North Carolina, USA; G. Davey Smith, Department of Social Medicine, University of Bristol, Bristol, England; A.M. Gotto Jr, Baylor College of Medicine, Houston, Texas, USA; D.C. Harrison, University of Cincinnati Medical Center, Cincinnati, Ohio, USA; D.R. Illingworth, Department of Medicine, Section of Clinical Nutrition and Lipid Metabolism, Oregon Health Sciences University, Portland, Oregon, USA; L.H. Opie, Heart Research Unit, University of Cape Town Medical School, Cape Town, South Africa; W.H.H Sheu, Division of Endocrinology & Metabolism, Tri-Service General Hospital, Taipei, Taiwan; E. Steinhagen-Thiessen, Universitatsklinikum Rudolf Virchow, Berlin, Germany; G.R. Thompson, MRC Lipoprotein Team, Hammersmith Hospital, London, England; D. Waters, Division of Cardiology, Hartford Hospital, Hartford, Connecticut, USA; O. Wiklund, Wallenberg Laboratory, Sahlgrenska Hospital, Gothenburg, Sweden; N. Yoshimura, Second Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan

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Haria, M., McTavish, D. Pravastatin. Drugs 53, 299–336 (1997). https://doi.org/10.2165/00003495-199753020-00008

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