Journal of General Internal Medicine

, Volume 14, Issue 12, pp 763–774 | Cite as

Effecacy of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors for prevention of stroke

  • Stephen Warshafsky
  • David Packard
  • Stephen J. Marks
  • Neeraj Sachdeva
  • Dawn M. Terashita
  • Gabriel Kaufman
  • Koky Sang
  • Albert J. Deluca
  • Stephen J. Peterson
  • William H. Frishman
Clinical Review

Abstract

OBJECTIVE: To determine if 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in preventing fatal and nonfatal strokes in patients at increased risk of coronary artery disease.

DESIGN: Meta-analysis of randomized controlled trials. Clinical trials were identified by a computerized search of medline (1983 to June 1996), by an assessment of the bibliographies of published studies, meta-analyses and reviews, and by contacting pharmaceutical companies that manufacture statins. Trials were included in the analysis if their patients were randomly allocated to a statin or placebo group, and reported data on stroke events. Thirteen of 28 clinical trials were selected for review. Data were extracted for details of study design, patient characteristics, interventions, duration of therapy, cholesterol measurements, and the number of fatal and nonfatal stroke events in each arm of therapy. Missing data on stroke events were obtained by contacting the investigators of the clinical trials.

MAIN RESULTS: Among 19,921 randomized patients, the rate of total stroke in the placebo group was 2.38% (90% nonfatal and 10% fatal). In contrast, patients who received statins had a 1.67% stroke rate. Using an exact stratified analysis, the pooled odds ratio (OR) for total stroke was 0.70 (95% confidence interval [CI] 0.57, 0.86; p=.0005). The pooled OR for nonfatal stroke was 0.64 (95% CI 0.51, 0.79; p=.00001), and the pooled OR for fatal stroke was 1.25 (95% CI 0.71, 2.24; p=.4973). In separate analyses, reductions in total and nonfatal stroke risk were found to be significant only for trials of secondary coronary disease prevention. Regression analysis showed no statistical association between the magnitude of cholesterol reduction and the relative risk for any stroke outcome.

CONCLUSIONS: The available evidence clearly shows that HMG-CoA reductase inhibitors reduce the morbidity associated with strokes in patients at increased risk of cardiac events. Data from 13 placebo-controlled trials suggest that on average one stroke is prevented for every 143 patients treated with statins over a 4-year period.

Key Words

cholesterol HMG-CoA reductase inhibitors meta-analysis stroke prevention 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Grundy SM. Cholesterol and coronary heart disease: the 21st century. Arch Intern Med. 1997;157:1177–84.PubMedCrossRefGoogle Scholar
  2. 2.
    Iso H, Jacobs DR, Wentworth D, Neaton JD, Cohen JD. Serum cholesterol levels and six year mortality from stroke in 350,977 men screened for the multiple risk factor intervention trial (MRFIT). N Engl J Med. 1989;320:904–10.PubMedCrossRefGoogle Scholar
  3. 3.
    Yano K, Reed DM, MacLean CJ. Serum cholesterol and hemorhagic stroke in the Honolulu Heart Program. Stroke. 1989;20:1460–5.PubMedGoogle Scholar
  4. 4.
    Ooneda G, Yoshida Y, Suzuki K, et al. Smooth muscle cells in the development of plasmatic arterionecrosis, arteriosclerosis, and arterial contraction. Blood Vessels. 1978;15:148–56.PubMedGoogle Scholar
  5. 5.
    Yamori Y, Horie R, Ohtaka M, Nara Y, Fukase M. Effect of hypercholesterolemic diet on the incidence of cerebrovascular and myocardial lesions in spontaneously hypertensive rats (SHR). Clin Exp Pharmacol Physiol. 1976;3(suppl 3):205–8.Google Scholar
  6. 6.
    Atkins D, Psaty BM, Koepsell TD, Longstreth WT Jr, Larson EB. Cholesterol reduction and the risk for stroke in men: a meta-analysis of randomized, controlled trials. Ann Intern Med. 1993;119: 136–45.PubMedGoogle Scholar
  7. 7.
    Hebert PR, Gaziano JM, Hennekens CH. An overview of trials of cholesterol lowering and risk of stroke. Arch Intern Med. 1995;155:50–5.PubMedCrossRefGoogle Scholar
  8. 8.
    Furberg CD, Adams HP Jr, Applegate WB, et al, for the Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Circulation. 1994;90:1679–87.PubMedGoogle Scholar
  9. 9.
    Salonen R, Nyyssonen K, Porkkala E, et al. Kuopio Atherosclerosis Prevention Study (KAPS): a population-based primary preventative trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries. Circulation. 1995;92:1758–64.PubMedGoogle Scholar
  10. 10.
    Crouse JR III, Byington RP, Bond MG, et al. Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II). Am J Cardiol. 1995;75:455–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Mercuri M, Bond MG, Sirtori CR, et al. Pravastatin reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic Mediterranean population: the Carotid Atherosclerosis Italian Ultrasound Study (CAIUS). Am J Med. 1996;101:627–34.PubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedGoogle Scholar
  13. 13.
    Breslow NE, Day NE. The Analysis of Case-Control Studies. Statistical Methods in Cancer Research; vol 1. Lyon, France: IARC Scientific Publications; 1980:139.Google Scholar
  14. 14.
    Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev. 1987;9:1–30.PubMedGoogle Scholar
  15. 15.
    Shepherd J, Cobbe SM, Ford I, et al, for the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Weintraub WS, Boccuzzi SJ, Klein JL, et al. Lack of effect of lovastatin on restenosis after coronary angioplasty. N Engl J Med. 1994;331:1331–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Blankenhorn DH, Azen SP, Kramsch DM, et al. Coronary angiographic changes with lovastatin therapy: the Monitored Atherosclerosis Regression Study (MARS). Ann Intern Med. 1993;119:969–76.PubMedGoogle Scholar
  18. 18.
    Pitt B, Mancini GB, Ellis SG, Rosman HS, Park JS, McGovern ME. Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC-I): reduction in atherosclerosis progression and clinical events. J Am Coll Cardiol. 1995;26:1133–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Bradford RH, Shear CL, Chremos AN, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I; efficacy in modifying plasma lipoproteins and adverse event profile in 8,245 patients with moderate hypercholesterolemia. Arch Intern Med. 1991;151: 43–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Kane JP, Malloy MJ, Ports TA, Phillips NR, Diehl JC, Havel RJ. Regression of coronary atherosclerosis during treatment of familial hypercholesterolemia with combined drug regimens. JAMA. 1990;264:3007–12.PubMedCrossRefGoogle Scholar
  21. 21.
    MAAS Investigators. Effect of simvastatin on coronary atheroma: the Multicenter Anti-Atheroma Study (MAAS). Lancet. 1994;344:633–8.CrossRefGoogle Scholar
  22. 22.
    Paterson RW, Paat JJ, Steele GH, Hathaway SC, Wong JG. Impact of intensive lipid modulation on angiographically defined coronary disease: clinical implications. South Med J. 1994;87:236–42.PubMedCrossRefGoogle Scholar
  23. 23.
    Plosker GL, McTavish D. Simvastatin: a reappraisal of its pharmacology and therapeutic efficacy in hypercholesterolemia. Drugs. 1995;50:334–63.PubMedGoogle Scholar
  24. 24.
    Jones PH. Lovastatin and simvastatin prevention studies. Am J Cardiol. 1990;66:39B-43B.PubMedCrossRefGoogle Scholar
  25. 25.
    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-126C.PubMedCrossRefGoogle Scholar
  26. 26.
    Todd PA, Goa KL. Simvastatin: a review of its pharmacological properties and therapeutic potential in hypercholesterolemia. Drugs. 1990;40:583–607.PubMedGoogle Scholar
  27. 27.
    Crouse JR, Byington RP, Bond MG, et al. Pravastatin, lipids, and atherosclerosis in the carotid arteries: design features of a clinical trial with carotid atherosclerosis outcome. Control Clin Trials. 1992;13:495–506.PubMedCrossRefGoogle Scholar
  28. 28.
    Bradford RH, Shear CL, Chremos AN, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study: design and patient characteristics of a double-blind, placebo-controlled study in patients with moderate hypercholesterolemia. Am J Cardiol. 1990;66:44B-55B.PubMedCrossRefGoogle Scholar
  29. 29.
    Tonkin AM. Management of the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study after the Scandinavian Simvastatin Survival Study (4S). Am J Cardiol. 1995;76:107C-112C.PubMedCrossRefGoogle Scholar
  30. 30.
    Foley DP, Bonnier H, Jackson G, et al. Prevention of restenosis after coronary balloon angioplasty: rationale and design of the Fluvastatin Angioplasty Restenosis (FLARE) Trial. Am J Cardiol. 1994;73:50D-61D.PubMedCrossRefGoogle Scholar
  31. 31.
    Stewart BF, Brown BG, Zhao XQ, et al. Benefits of lipid-lowering therapy in men with elevated apolipoprotein B are not confined to those with very high low density lipoprotein and cholesterol. J Am Coll Cardiol. 1994;23:899–906.PubMedCrossRefGoogle Scholar
  32. 32.
    Zhao XQ, Brown BG, Hillger L, et al. Effects of intensive lipid-lowering therapy on the coronary arteries of asymptomatic subjects with elevated apolipoprotein B. Circulation. 1993;88:2744–53.PubMedGoogle Scholar
  33. 33.
    Pfeffer MA, Sacks FM, Moye LA, et al. Cholesterol and Recurrent Events: a secondary prevention trial for normolipidemic patients. Am J Cardiol. 1995;76:98C-106C.PubMedCrossRefGoogle Scholar
  34. 34.
    Maher VM, Brown BG, Marcovina SM, Hillger LA, Zhao XQ, Albers JJ. Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein (a). JAMA. 1995;274:1771–4.PubMedCrossRefGoogle Scholar
  35. 35.
    Guptha S. Profiling a landmark clinical trial: Scandinavian Simvastatin Survival Study. Curr Opin Lipidol. 1995;6:251–3.PubMedGoogle Scholar
  36. 36.
    The West of Scotland Coronary Prevention Study Group. Screening experience and baseline characteristics in the West of Scotland Coronary Prevention Study. Am J Cardiol. 1995;76:485–91.CrossRefGoogle Scholar
  37. 37.
    Design features and baseline characteristics of the LiPID study: a randomized trial in patients with previous acute myocardial infarction and/or unstable angina pectoris. Am J Cardiol. 1995;76:474–9.Google Scholar
  38. 38.
    Stoy DB, Curtis RC, Dameworth KS, et al. The successful recruitment of elderly black subjects in a clinical trial: the CRISP [Cholesterol Reduction in Seniors Program] experience. J Natl Med Assoc. 1995;87:280–7.PubMedGoogle Scholar
  39. 39.
    Waters D, Higginson L, Gladstone P, Kimball B, LeMay M, Lesperance J. Design features of a controlled clinical trial to assess the effect of an HMG-CoA reductase inhibitor on the progression of coronary artery disease. Control Clin Trials. 1993;14:45–74.PubMedCrossRefGoogle Scholar
  40. 40.
    Stehbens WE. Validity of the 4S simvastatin trial. Lancet. 1995;345:264. Letter.PubMedCrossRefGoogle Scholar
  41. 41.
    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.Google Scholar
  42. 42.
    Sacks FM, Pfeffer MA, Moye L, et al. Rationale and design of a secondary prevention trial of lowering normal plasma cholesterol levels after acute myocardial infarction: the Cholesterol and Recurrent Events trial (CARE). Am J Cardiol. 1991;68:1436–46.PubMedCrossRefGoogle Scholar
  43. 43.
    Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–9.CrossRefGoogle Scholar
  44. 44.
    Jukema JW, Bruschke AV, 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.PubMedGoogle Scholar
  45. 45.
    The 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 (200–300 mg/dl) plus two additional atherosclerotic risk factors. Am J Cardiol. 1993;72:1031–7.CrossRefGoogle Scholar
  46. 46.
    Sacks FM, Pfeffer MA, Moye LA, et al, for the Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335:1001–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990;323:1289–98.PubMedCrossRefGoogle Scholar
  48. 48.
    Sacks FM, Pasternak RC, Gibson CM, Rosner B, Stone PH, for the Harvard Atherosclerosis Reversibility Project (HARP) Group. Effect on coronary atherosclerosis of decrease in plasma cholesterol concentrations in normocholesterolaemic patients. Lancet. 1994;344:1182–6.PubMedCrossRefGoogle Scholar
  49. 49.
    Brensike JF, Levy RI, Kelsey SF, et al. Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study. Circulation. 1984;69:313–24.PubMedGoogle Scholar
  50. 50.
    Buchwald H, Varco RL, Matts JP, et al. Effect of partial ileal by-pass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. N Engl J Med. 1990;323:946–55.PubMedCrossRefGoogle Scholar
  51. 51.
    Watts GF, Lewis B, Brunt JN, et al. Effects on coronary artery disease of lipid-lowering diet or diet plus cholestyramine in St. Thomas’ Atherosclerosis Regression Study (STARS). Lancet. 1992;339:563–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Waters D, Higginson L, Gladstone P, et al. Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography: the Canadian Coronary Atherosclerosis Intervention Trial (CCAIT). Circulation. 1994;89:959–68.PubMedGoogle Scholar
  53. 53.
    The Multicenter European Research Trial with Cilazapril After Angioplasty to Prevent Transluminal Coronary Obstruction and Restenosis (MERCATOR) Study Group. Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary angioplasty? Circulation. 1992;86:100–10.Google Scholar
  54. 54.
    Waters D, Craven TE, Lesperance J. Prognostic significance of progression of coronary atherosclerosis. Circulation. 1993;87:1067–75.PubMedGoogle Scholar
  55. 55.
    Craven TE, Ryu JE, Espeland MA, et al. Evaluation of the associations between carotid artery atherosclerosis and coronary artery stenosis: a case-control study. Circulation. 1990;82:1230–42.PubMedGoogle Scholar
  56. 56.
    Salonen R, Salonen JT. Progression of carotid atherosclerosis and its determinants: a population-based ultrasonography study. Atherosclerosis. 1990;81:33–40.PubMedCrossRefGoogle Scholar
  57. 57.
    Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia: safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987;317:1237–45.PubMedCrossRefGoogle Scholar
  58. 58.
    Sahni R, Maniet AR, Voci G, Banka VS. Prevention of restenosis by lovastatin after successful coronary angioplasty. Am Heart J. 1991;121:1600–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Haskell WL, Alderman EL, Fair JM, et al. Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease: the Standford Coronary Risk Intervention Project (SCRIP). Circulation. 1994;89:975–90.PubMedGoogle Scholar
  60. 60.
    Furberg CD, Pitt B, Byington RP, Park JS, McGovern ME, for the PLACI and PLACII Investigators. Reduction in coronary events during treatment with pravastatin. Am J Cardiol. 1995;76:60C-63C.PubMedCrossRefGoogle Scholar
  61. 61.
    Holme I. Cholesterol reduction and its impact on coronary artery disease and total mortality. Am J Cardiol. 1995;76:10C-17C.PubMedCrossRefGoogle Scholar
  62. 62.
    Gould AL, Rossouw JE, Santanello NC, Heyse JF, Furberg CD. Cholesterol reduction yields clinical benefit: a new look at old data. Circulation. 1995;91:2274–82.PubMedGoogle Scholar
  63. 63.
    Cummings P, Psaty BM. The association between cholesterol and death from injury. Ann Intern Med. 1994;120:848–55.PubMedGoogle Scholar
  64. 64.
    Kuo PT. Dyslipidemia and coronary artery disease. Clin Cardiol. 1994;17:519–27.PubMedGoogle Scholar
  65. 65.
    Muldoon MF, Manuck SB, Matthews KA. Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. BMJ. 1990;301:309–14.PubMedGoogle Scholar
  66. 66.
    Brown BG, Zhao XQ, Sacco DE, Albers JJ. Lipid lowering and plaque regression: new insights into prevention of plaque disruption and clinical events in coronary disease. Circulation. 1993;87:1781–91.PubMedGoogle Scholar
  67. 67.
    Holme I. Relation of coronary heart disease incidence and total mortality to plasma cholesterol reduction in randomized trials: use of meta-analysis. Br Heart J. 1993;69(suppl 1):42–7.Google Scholar
  68. 68.
    Jacobs D, Blackburn H, Higgins M, et al. Report of the conference on low blood cholesterol: mortality associations. Circulation. 1992;86:1046–60.PubMedGoogle Scholar
  69. 69.
    Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ. 1994;308:367–72.PubMedGoogle Scholar
  70. 70.
    Law MR, Thompson SG, Wald NJ. Assessing possible hazards of reducing serum cholesterol. BMJ. 1994;308:373–9.PubMedGoogle Scholar
  71. 71.
    Superko HR, Krauss RM. Coronary artery disease regression: convincing evidence for the benefit of aggressive lipoprotein management. Circulation. 1994;90:1056–69.PubMedGoogle Scholar
  72. 72.
    Marchioli R, Marfisi RM, Carinci F, Tognoni G. Meta-analysis, clinical trials, and transferability of research results into practice: the case of cholesterol-lowering interventions in the secondary prevention of coronary heart disease. Arch Intern Med. 1996;156:1158–72.PubMedCrossRefGoogle Scholar
  73. 73.
    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.PubMedGoogle Scholar
  74. 74.
    Shepherd J. Fibrates and statins in the treatment of hyperlipidaemia: an appraisal of their efficacy and safety. Eur Heart J. 1995;16:5–13.PubMedGoogle Scholar
  75. 75.
    Furberg CD, Crouse JR, Byington RP, Bond MG, Espeland MA. PLAC-II: effects of pravastatin on progression of carotid atherosclerosis and clinical events. J Am Coll Cardiol. 1993;21(suppl 2):71. Abstract.Google Scholar
  76. 76.
    Maher VM, Brown BG, Marcovina SM, et al. The adverse effect of lipoprotein (a) on coronary atherosclerosis and clinical events is eliminated by substantially lowering LDL cholesterol. J Am Coll Cardiol. 1994;23(suppl 1):131. Abstract.Google Scholar
  77. 77.
    Pitt B, Mancini J, Ellis SG, Rosman HS, McGovern ME. Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC-I). J Am Coll Cardiol. 1994;23(suppl 1):131. Abstract.Google Scholar
  78. 78.
    Thompson GR. The familial hypercholesterolemia regression study (FHRE). J Am Coll Cardiol. 1994;23(suppl 1):131. Abstract.Google Scholar
  79. 79.
    Lacoste LL, Lam JY, Hung J, Waters D. Pravachol decreases platelet thrombus formation in hypercholesterolemic coronary patients in conjunction with improvements in serum lipids. J Am Coll Cardiol. 1994;23(suppl 1):131. Abstract.Google Scholar
  80. 80.
    van Boven AJ, Jukema JW, Bal ET, Reiber JH, Bruschke AV. Remodeling of coronary artery lesions: regression to the mean or effect of cholesterol-lowering therapy? J Am Coll Cardiol. 1994;23(suppl 1):132. Abstract.Google Scholar
  81. 81.
    Lund GK, Pfalzer B, Beisiegel U, Beil U, Greten H, Hamm CW. Treatment of severe hypercholesterolemia and coronary heart disease by simvastatin and LDL apheresis (HELP): effects on coronary lesions. J Am Coll Cardiol. 1994;23(suppl 1):132. Abstract.Google Scholar
  82. 82.
    The Scandinavian Simvastatin Survival Study Group. Design and baseline results of the Scandinavian Simvastatin Survival Study of patients with stable angina and/or previous myocardial infarction. Am J Cardiol. 1993;71:393–400.CrossRefGoogle Scholar
  83. 83.
    Bradford RH, Downton M, Chremos AN, et al. Efficacy and tolerability of lovastatin in 3390 women with moderate hypercholesterolemia. Ann Intern Med. 1993;118:850–5.PubMedGoogle Scholar
  84. 84.
    Frick MH, Heinonen OP, Huttunen JK, Koskinen P, Manttari M, Manninen V. Efficacy of gemfibrozil in dyslipidaemic subjects with suspected heart disease: an ancillary study in the Helsinki Heart Study frame population. Ann Med. 1993;25:41–5.PubMedGoogle Scholar
  85. 85.
    Furberg CD, Byington RP, Crouse JR, Espeland MA. Pravastatin, lipids, and major coronary events. Am J Cardiol. 1994;73:1133–4.PubMedCrossRefGoogle Scholar
  86. 86.
    Hodis HN, Mack WJ, Azen SP, et al. Triglyceride- and cholesterolrich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin. Circulation. 1994;90:42–9.PubMedGoogle Scholar
  87. 87.
    Bradford RH, Shear CL, Chremos AN, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: two year efficacy and safety follow-up. Am J Cardiol. 1994;74:667–73.PubMedCrossRefGoogle Scholar
  88. 88.
    Shepherd J. The West of Scotland Coronary Prevention Study: a trial of cholesterol reduction in Scottish men. Am J Cardiol. 1995;76:113C-117C.PubMedCrossRefGoogle Scholar
  89. 89.
    Heady JA, Morris JN, Oliver MF. WHO clofibrate/cholesterol trial: clarifications. Lancet. 1992;340:1405–6.PubMedCrossRefGoogle Scholar
  90. 90.
    Pitt B, Ellis SG, Mancini GBJ, Rosman HS, McGovern ME. Design and recruitment in the United States of a multicenter quantitative angiographic trial of pravastatin to limit atherosclerosis in the coronary arteries (PLAC I). Am J Cardiol. 1993;72:31–5.PubMedCrossRefGoogle Scholar
  91. 91.
    Espeland MA, Hoen H, Byington R, Howard G, Riley WA, Furberg CD. Spatial distribution of carotid intimal-medial thickness as measured by B-mode ultrasonography. Stroke. 1994;25:1812–9.PubMedGoogle Scholar
  92. 92.
    The West of Scotland Coronary Prevention Study Group. A coronary primary prevention study of Scottish men aged 45–64 years: trial design (WOSCOPS). J Clin Epidemiol. 1992;45:849–60.CrossRefGoogle Scholar
  93. 93.
    Davey Smith G, Pekkanen J. Should there be a moratorium on the use of cholesterol lowering drugs? BMJ. 1992;304:431–4.PubMedGoogle Scholar
  94. 94.
    Simes RJ, Glasziou PP. Meta-analysis and quality of evidence in the economic evaluation of drug trials. Pharmacoeconomics 1992;1:282–92.PubMedGoogle Scholar
  95. 95.
    Chalmers TC. Problems induced by meta-analyses. Stat Med. 1991;10:971–80.PubMedCrossRefGoogle Scholar
  96. 96.
    Dickersin K, Berlin JA. Meta-analysis: state-of-the-science. Epidemiol Rev. 1992;14:154–76.PubMedGoogle Scholar
  97. 97.
    Simes RJ. Publication bias: the case for an international registry of clinical trials. J Clin Oncol. 1986;4:1529–41.PubMedGoogle Scholar
  98. 98.
    Gordon DJ. Cholesterol Lowering and Total Mortality: Contemporary Issues in Cholesterol Lowering: Clinical and Population Aspects. New York, NY: Marcel Dekker Inc; 1994.Google Scholar
  99. 99.
    Oliver MF. Might treatment of hypercholesterolemia increase non-cardiac mortality? Lancet. 1991;337:1529–31.PubMedCrossRefGoogle Scholar
  100. 100.
    The Asymptomatic Carotid Artery Plaque Study Group. Rationale and design for the Asymptomatic Carotid Artery Plaque Study (ACAPS). Control Clin Trials. 1992;13:293–314.CrossRefGoogle Scholar
  101. 101.
    Crouse SR, Byington PR, Furberg CD. Reductase inhibitor monotherapy prevents stroke. Circulation. 1996;94(suppl 1):540. Abstract.Google Scholar
  102. 102.
    Sacco RL, Wolf PA, Kannel WB, McNamara PM. Survival and recurrence following stroke: the Framingham Study. Stroke. 1982;13:290–5.PubMedGoogle Scholar
  103. 103.
    Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project—1981–86, 2: incidence, case fatality rates and overall outcome at one year of cerebral infarction, primary intracerebral and subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 1990;53:16–22.PubMedCrossRefGoogle Scholar
  104. 104.
    Bamford J, Sandercock, P, Dennis M, Burn J, Warlow C. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet. 1991;337:1521–6.PubMedCrossRefGoogle Scholar
  105. 105.
    Konishi M, Iso H, Komachi Y, et al. Associations of serum total cholesterol, different types of stroke, and stenosis distribution of cerebral arteries: the Akita Pathology Study. Stroke. 1993;24:954–64.PubMedGoogle Scholar
  106. 106.
    Brown RD, Whisnant JP, Sicks JD, O’Fallon WM, Wiebers DO. Stroke incidence, prevalence, and survival: secular trends in Rochester, Minnesota, through 1989. Stroke. 1996;27:373–80.PubMedGoogle Scholar
  107. 107.
    Wolf PA, D’Agostino RB, O’Neal MA, et al. Secular trends in stroke incidence and mortality: the Framingham Study. Stroke. 1992;23:1551–5.PubMedGoogle Scholar
  108. 108.
    Robins M, Baum HM. The National Survey of Stroke Incidence. Stroke. 1981;12(2 pt 2 suppl 1):I45-I57.PubMedGoogle Scholar
  109. 109.
    Howard G, Anderson R, Sorlie P, Andrews V, Backlund E, Burke GL. Ethnic differences in stroke mortality between non-Hispanic whites, Hispanic whites, and blacks: the National Longitudinal Mortality Study. Stroke. 1994;25:2120–5.PubMedGoogle Scholar
  110. 110.
    Gillum RF. Stroke in blacks. Stroke. 1988;19:1–9.PubMedGoogle Scholar
  111. 111.
    Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA. 1998;279:1643–50.PubMedCrossRefGoogle Scholar
  112. 112.
    Crouse JR III, Byington RP, Hoen HM, Furberg CD. Reductase inhibitor monotherapy and stroke prevention. Arch Intern Med. 1997;157:1305–10.PubMedCrossRefGoogle Scholar
  113. 113.
    Hebert PR, Gaziano JM, Chan KS, Hennekens CH. Cholesterol lowering with statin drugs, risk of stroke, and total mortality: an overview of randomized trials. JAMA. 1997;278:313–21.PubMedCrossRefGoogle Scholar
  114. 114.
    Blauw GJ, Lagaay AM, Smelt AH, Westendorp RG. Stroke, statins, and cholesterol: a meta-analysis of randomized, placebocontrolled, double-blind trials with HMG-CoA reductase inhibitors. Stroke. 1997;28:946–50.PubMedGoogle Scholar
  115. 115.
    Bucher HC, Griffith LE, Guyatt GH. Effect of HMG-coA reductase inhibitors on stroke: a meta-analysis of randomized, controlled trials. Ann Intern Med. 1998;128:89–95.PubMedGoogle Scholar
  116. 116.
    Fleiss JL. Statistical Methods for Rates and Proportions. 2nd ed. New York, NY: John Wiley and Sons; 1981:33–49.Google Scholar

Copyright information

© Society of General Internal Medicine 1999

Authors and Affiliations

  • Stephen Warshafsky
    • 1
  • David Packard
    • 1
  • Stephen J. Marks
    • 3
  • Neeraj Sachdeva
    • 1
  • Dawn M. Terashita
    • 1
  • Gabriel Kaufman
    • 1
  • Koky Sang
    • 1
  • Albert J. Deluca
    • 2
  • Stephen J. Peterson
    • 1
  • William H. Frishman
    • 2
  1. 1.Received from the Section of General Internal Medicine, Department of MedicineNew York Medical CollegeValhalla
  2. 2.Division of Cardiology, Department of MedicineNew York Medical CollegeValhalla
  3. 3.the Department of NeurologyNew York Medical CollegeValhalla

Personalised recommendations