Drugs

, Volume 68, Issue 3, pp 339–358 | Cite as

Drugs for Cardiovascular Disease Prevention in Women

Implications of the AHA Guidelines — 2007 Update
Review Article

Abstract

Lifestyle interventions constitute the initial strategy for the primary and secondary prevention of cardiovascular disease in women. However, pharmacotherapy is often indicated for control of major cardiovascular risk factors, and abundant clinical trial data support the morbidity and mortality benefit of a number of categories of drug therapy following a coronary event. Although women have increasingly been enrolled in clinical trials of pharmacotherapy, under representation of women in most research studies limits the gender-specific assessment of outcomes. Equally importantly, recent randomized clinical trial data have highlighted inappropriate preventive therapies for women (i.e. those lacking effectiveness and potentially imparting harm). Decision-making data for drug therapy for women also derive from a number of clinical trials conducted solely in women.

The drug classes reviewed in this article include omega-3 fatty acids, aspirin, ACE inhibitors and angiotensin II receptor antagonists or blockers, β-adrenoceptor antagonists (β-blockers), aldosterone antagonists, antioxidants, folic acid and vitamins B6 and B12, and menopausal hormone therapy and selective estrogen-receptor modulators.

Information is sparse regarding specific cardiovascular pharmacotherapies for elderly women, and women of racial and ethnic minorities. Owing to the under representation of the subset of women in many trials, analysis by age, race and ethnicity is not appropriate. This information gap presents a major challenge for future studies, as these subgroups constitute populations of women at high cardiovascular risk.

References

  1. 1.
    Mosca L, Appel LJ, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women. Expert Panel/Writing Group. Circulation 2004; 109(5): 672–92PubMedCrossRefGoogle Scholar
  2. 2.
    Mosca L, Banka CL, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation 2007; 115: 1481–501PubMedCrossRefGoogle Scholar
  3. 3.
    Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289(1): 76–9PubMedCrossRefGoogle Scholar
  4. 4.
    Albert CM, Oh K, Whang W, et al. Dietary alpha-linolenic acid intake and risk of sudden cardiac death and coronary heart disease. Circulation 2005; 112(21): 3232–8PubMedCrossRefGoogle Scholar
  5. 5.
    Mozaffarian D, Ascherio A, Hu FB, et al. Interplay between different polyunsaturated fatty acids and risk of coronary heart disease in men. Circulation 2005; 111(2): 157–64PubMedCrossRefGoogle Scholar
  6. 6.
    Iso H, Kobayashi M, Ishihara J, et al., and JPHC Study Group. Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I. Circulation 2006; 113(2): 195–202PubMedCrossRefGoogle Scholar
  7. 7.
    Mozaffarian D, Lemaitre RN, Kuller LH, et al., and Cardiovascular Health Study. Cardiac benefits of fish consumption may depend on the type of fish meal consumed: the Cardiovascular Health Study. Circulation 2003; 107(10): 1372–7PubMedCrossRefGoogle Scholar
  8. 8.
    Brouwer IA, Katan MB, Zock PL. Dietary alpha-linolenic acid is associated with reduced risk of fatal coronary heart disease, but increased prostate cancer risk: a meta-analysis. J Nutr 2004; 134(4): 919–22PubMedGoogle Scholar
  9. 9.
    Whelton SP, He J, Whelton PK, et al. Meta-analysis of observational studies on fish intake and coronary heart disease. Am J Cardiol 2004; 93(9): 1119–23PubMedCrossRefGoogle Scholar
  10. 10.
    Yzebe D, Lievre M. Fish oils in the care of coronary heart disease patients: a meta-analysis of randomized controlled trials. Fundam Clin Pharmacol 2004; 18(5): 581–92PubMedCrossRefGoogle Scholar
  11. 11.
    Schneiderman N, Saab PG, Catellier RJ, et al., and ENRICHD Investigators. Psychosocial treatment within sex by ethnicity subgroups in the Enhancing Recovery in Coronary Heart Disease clinical trial. Psychosom Med 2004; 66(4): 475–83PubMedCrossRefGoogle Scholar
  12. 12.
    Carney RM, Blumenthal JA, Freedland KE, et al., and ENRICHD Investigators. Depression and late mortality after MI in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) study. Psychosom Med 2004; 66(4): 466–74PubMedCrossRefGoogle Scholar
  13. 13.
    Taylor CB, Youngblood ME, Catellier D, et al., and ENRICHD Investigators. Effect of antidepressant medication on morbidity and mortality in depressed patients after myocardial infarction. Arch Gen Psychiatry 2005; 62(7): 792–8PubMedCrossRefGoogle Scholar
  14. 14.
    Rosendorff C, Black HR, Cannon CP, et al. Treatment of hypertension in the prevention and management of ischemic heart disease: a scientific statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. Circulation 2007; 115: 2761–88PubMedCrossRefGoogle Scholar
  15. 15.
    Chobanian AV, Bakris GL, Black HR, et al., and the National High Blood Pressure Education Program Coordinating Committee. The seventh report of the Joint National Committee on Prevention Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289(19): 2560–72PubMedCrossRefGoogle Scholar
  16. 16.
    Benetos A, Thomas F, Bean KE, et al. Why cardiovascular mortality is higher in treated hypertensives versus subjects of the same age, in the general population. J Hypertens 2003; 21(9): 1635–40PubMedCrossRefGoogle Scholar
  17. 17.
    Mulrow C, Lau J, Cornell J, et al. Pharmacotherapy for hypertension in the elderly. Cochrane Database Syst Rev 2006; (1): CD000028Google Scholar
  18. 18.
    Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Collaborative Research Group. Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertension 2003; 42(3): 239–46CrossRefGoogle Scholar
  19. 19.
    Rahman M, Presssel S, Davis BR, et al. Cardiovascular outcomes in high-risk hypertensive patients stratified by baseline glomerular filtration rate. Ann Intern Med 2006; 144(3): 172–80PubMedGoogle Scholar
  20. 20.
    Staessen JA, Thijisq L, Fagard R, et al., and Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial. J Hypertens 2004; 22(4): 847–57PubMedCrossRefGoogle Scholar
  21. 21.
    Bakris GL, Gaxiola E, Messerli FH, et al., and INVEST Investigators. Clinical outcomes in the diabetes cohort of the INternational VErapamil SR-Trandolapril study. Hypertension 2004; 44(5): 637–42PubMedCrossRefGoogle Scholar
  22. 22.
    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 2001; 285(19): 2486–97CrossRefGoogle Scholar
  23. 23.
    Heart Protection Study Collaborative Group. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo controlled trial. Lancet 2002; 360(9326): 7–22CrossRefGoogle Scholar
  24. 24.
    Shepherd J, Blauw GJ, Murphy MB, et al., on behalf of the PROSPER study group. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360(9346): 1623–30PubMedCrossRefGoogle Scholar
  25. 25.
    Grundy SM, Cleeman JI, Merz CNB, et al., for the Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110(2): 227–39PubMedCrossRefGoogle Scholar
  26. 26.
    The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339(19): 1349–57CrossRefGoogle Scholar
  27. 27.
    Athyros VG, Papageorgiou AA, Mercouris BR, et al. Treatment with atorvastatin to the National Cholesterol Educational Program goal versus ‘usual’ care in secondary coronary heart disease prevention: the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study. Curr Med Res Opin 2002; 18(4): 220–8PubMedCrossRefGoogle Scholar
  28. 28.
    Sever PS, Dahlöf B, Poulter NR, et al., for the ASCOT Investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361(9364): 1149–58PubMedCrossRefGoogle Scholar
  29. 29.
    The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA 2002; 288(23): 2998–3007CrossRefGoogle Scholar
  30. 30.
    LaRosa JC, Grundy SM, Waters DD, et al., for the Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005; 352(14): 1425–35PubMedCrossRefGoogle Scholar
  31. 31.
    Wenger NK, Lewis SJ, Welty FK, et al., on behalf of the TNT Steering Committee and Investigators. Beneficial effects of aggressive LDL cholesterol lowering in women with stable coronary heart disease in the Treating to New Targets (TNT) study. Heart. Epub 2007 Dec 10Google Scholar
  32. 32.
    Grady D, Chaput L, Kristof M. Diagnosis and treatment of CHD in women: systematic reviews of evidence on selected topics. Evidence Report/Technology Assessment No. 81 [prepared by the University of California, San Francisco-Stanford Evidence Evidence-based Practice Center under Contract No. 290-97-0013]. AHRQ Publication No. 03-0037. Rockville (MD): Agency for Healthcare Research and Quality, 2003 MayGoogle Scholar
  33. 33.
    Schwartz GG, Olsson AG, Ezekowitz MD, et al., for the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effect of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL Study — a randomized controlled trial. JAMA 2001; 285(13): 1711–8PubMedCrossRefGoogle Scholar
  34. 34.
    Waters DD, Schwartz GG, Olsson AG, et al., for the MIRACL Study Investigators. Effects of atorvastatin on stroke in patients with unstable angina or non-Q-wave myocardial infarction: a Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) substudy. Circulation 2002; 106(13): 1690–5PubMedCrossRefGoogle Scholar
  35. 35.
    Cannon CP, Braunwald E, McCabe CH, et al., for the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350(15): 1495–504PubMedCrossRefGoogle Scholar
  36. 36.
    Blomkalns AL, Chen AY, Hochman JS, et al., for the CRUSADE Investigators. Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative. J Am Coll Cardiol 2005; 45(6): 832–7PubMedCrossRefGoogle Scholar
  37. 37.
    Rosenhamer G, Carlson LA. Effect of combined clofibrate-nicotinic acid treatment in ischemic heart disease. Atherosclerosis 1980; 37(1): 129–42PubMedCrossRefGoogle Scholar
  38. 38.
    Goldberg AC, Sapre A, Liu J, et al., for the Ezetimibe Study Group. Efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia: a randomized double-blind, placebo-controlled trial. Mayo Clin Proc 2004; 79(5): 620–9PubMedCrossRefGoogle Scholar
  39. 39.
    Walsh JME, Pignone M. Drug treatment of hyperlipidemia in women. JAMA 2004; 291(18): 2243–52PubMedCrossRefGoogle Scholar
  40. 40.
    Foody JM, Rathore SS, Galusha D, et al. Hydroxymethyl-glutaryl-CoA reductase inhibitors in older persons with acute myocardial infarction: evidence for an age-statin interaction. J Am Geriatr Soc 2006; 54(3): 421–30PubMedCrossRefGoogle Scholar
  41. 41.
    Pan W, Pintar T, Anton J, et al. Statins are associated with a reduced incidence of perioperative mortality after coronary artery bypass graft surgery. Circulation 2004; 110 Suppl. II: II45–9PubMedGoogle Scholar
  42. 42.
    Baigent C, Keech A, Kearney PM, et al., and Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins [published erratum appears in Lancet 2005; 366: 1358]. Lancet 2005; 366(9493): 1267–78PubMedCrossRefGoogle Scholar
  43. 43.
    Vrecer M, Turk S, Drinovec J, et al. Use of statins in primary and secondary prevention of coronary heart disease and ischemic stroke: meta-analysis of randomized trials. Int J Clin Pharmacol Ther 2003; 41(12): 567–77PubMedGoogle Scholar
  44. 44.
    Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med 2005; 352(13): 1293–304PubMedCrossRefGoogle Scholar
  45. 45.
    Steering Committee of the Physicians’ Health Study Research Group. Final report on the aspirin component of the ongoing Physicians’ Health Study: Steering Committee of the Physicians’ Health Study Research Group. N Engl J Med 1989; 321: 129–35CrossRefGoogle Scholar
  46. 46.
    Berger JS, Roncaglioni MC, Avanzini F, et al. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA 2006; 295(3): 306–13PubMedCrossRefGoogle Scholar
  47. 47.
    Bhatt DL, Fox KA, Hacke W, et al., and CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006; 354(16): 1706–17PubMedCrossRefGoogle Scholar
  48. 48.
    Verdecchia P, Reboldi G, Angeli F, et al. Angiotensin-converting enzyme inhibitors and calcium channel blockers for coronary heart disease and stroke prevention. Hypertension 2005; 46(2): 386–92PubMedCrossRefGoogle Scholar
  49. 49.
    Braunwald E, Domanski MJ, Fowler SE, et al., and PEACE Trial Investigators. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med 2004; 351(20): 2058–68PubMedCrossRefGoogle Scholar
  50. 50.
    Buch P, Rasmussen S, Abildstrom SZ, et al., and TRACE Investigators. The long-term impact of the angiotensin-converting enzyme inhibitor trandolapril on mortality and hospital admissions in patients with left ventricular dysfunction after a myocardial infarction: follow-up to 12 years. Eur Heart J 2005; 26(2): 145–52PubMedCrossRefGoogle Scholar
  51. 51.
    Daly CA, Fox KM, Remme WJ, et al., and EUROPA Investigators. The effect of perindopril on cardiovascular morbidity and mortality in patients with diabetes in the EUROPA study: results from the PERSUADE substudy. Eur Heart J 2005; 26(14): 1369–78PubMedCrossRefGoogle Scholar
  52. 52.
    Fox KM, and EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003; 362(9386): 782–8PubMedCrossRefGoogle Scholar
  53. 53.
    Krause MW, Massing M, Kshirsager A, et al. Combination therapy improves survival after acute myocardial infarction in the elderly with chronic kidney disease. Renal Fail 2004; 26(6): 715–2CrossRefGoogle Scholar
  54. 54.
    Al-Mallah MH, Tleyjen IM, Abdel-Latif AA, et al. Angiotensin-converting enzyme inhibitors in coronary artery disease and preserved left ventricular systolic function: a systematic review and meta-analysis of randomized controlled trials. J Am Coll Cardiol 2006; 47(8): 1576–83PubMedCrossRefGoogle Scholar
  55. 55.
    Danchin N, Cucherat M, Thuillez C, et al. Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials. Arch Intern Med 2006; 166(7): 787–96PubMedCrossRefGoogle Scholar
  56. 56.
    Lee VC, Rhew DC, Dylan M, et al. Meta-analysis: angiotensin-receptor blockers in chronic heart failure and high-risk acute myocardial infarction [published erratum appears in Ann Intern Med 2005; 142 (5): 391]. Ann Intern Med 2004; 141(9): 693–704PubMedGoogle Scholar
  57. 57.
    Rodrigues EJ, Eisenberg MJ, Pilote L. Effects of early and late administration of angiotensin-converting enzyme inhibitors on mortality after myocardial infarction. Am J Med 2003; 115(6): 473–9PubMedCrossRefGoogle Scholar
  58. 58.
    Demers C, McMurray JJ, Swedberg K, et al., and CHARM Investigators. Impact of candesartan on nonfatal myocardial infarction and cardiovascular death in patients with heart failure. JAMA 2005; 294(14): 1794–8PubMedCrossRefGoogle Scholar
  59. 59.
    Ellis K, Tcheng JE, Sapp S, et al. Mortality benefit of beta blockade in patients with acute coronary syndromes undergoing coronary intervention: pooled results from the Epic, Epilog, Epistent, Capture and Rapport trials. J Intervent Cardiol 2003; 16(4): 299–305PubMedCrossRefGoogle Scholar
  60. 60.
    Janosi A, Ghali JK, Herlitz J, et al., and MERIT-HF Study Group. Metoprolol CR/XL in postmyocardial infarction patients with chronic heart failure: experiences from MERIT-HF. Am Heart J 2003; 146(4): 721–8PubMedCrossRefGoogle Scholar
  61. 61.
    Wikstrand J, Wedel H, Ghali J, et al. How should subgroup analyses affect clinical practice? Insights from the Metoprolol Succinate Controlled-Release/Extended-Release Randomized Intervention Trial in Heart Failure (MERIT-HF). Card Electrophysiol Rev 2003; 7(3): 264–75PubMedCrossRefGoogle Scholar
  62. 62.
    Bunch TJ, Muhlestein JB, Bair TL, et al., and Intermountain Heart Collaborative Study Group. Effect of beta-blocker therapy on mortality rates and future myocardial infarction rates in patients with coronary artery disease but no history of myocardial infarction or congestive heart failure. Am J Cardiol 2005; 95(7): 827–31PubMedCrossRefGoogle Scholar
  63. 63.
    Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure: Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999; 341(10): 709–17PubMedCrossRefGoogle Scholar
  64. 64.
    Pitt B, Remme W, Zannad F, et al. and Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective-aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction [published erratum appears in N Engl J Med 2003; 348: 2271]. N Engl J Med 2003; 348(14): 1309–21PubMedCrossRefGoogle Scholar
  65. 65.
    Pitt B, White H, Nicolau J, et al., and EPHESUS Investigators. Eplerenone reduces mortality 30 days after randomization following acute myocardial infarction in patients with left ventricular systolic dysfunction and heart failure. J Am Coll Cardiol 2005; 46(3): 425–31PubMedCrossRefGoogle Scholar
  66. 66.
    Osganian SK, Stampfer MJ, Rimm E, et al. Vitamin C and risk of coronary heart disease in women. J Am Coll Cardiol 2003; 42(2): 246–52PubMedCrossRefGoogle Scholar
  67. 67.
    Heart Protection Study Collaborative Group. MRC/BHF heart protection study of antioxidant vitamin supplementation in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360(9326): 23–33CrossRefGoogle Scholar
  68. 68.
    Waters DD, Alderman EL, Hsia J, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA 2002; 288(19): 2432–40PubMedCrossRefGoogle Scholar
  69. 69.
    The Heart Outcomes Prevention Evaluation Study Investigators. Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 2000; 342(3): 154–60CrossRefGoogle Scholar
  70. 70.
    Arad Y, Spadaro LA, Roth M, et al. Treatment of asymptomatic adults with elevated coronary calcium scores with atorvastatin, vitamin C, and vitamin E: the St Francis Heart Study randomized clinical trial. J Am Coll Cardiol 2005; 46(1): 166–72PubMedCrossRefGoogle Scholar
  71. 71.
    Lee I-M, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study — a randomized controlled trial. JAMA 2005; 294(1): 56–65PubMedCrossRefGoogle Scholar
  72. 72.
    Eidelman RS, Hollar D, Hebert PR, et al. Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch Intern Med 2004; 164(14): 1552–6PubMedCrossRefGoogle Scholar
  73. 73.
    Knekt P, Ritz J, Pereira MA, et al. Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts. Am J Clin Nutr 2004; 80(6): 1508–20PubMedGoogle Scholar
  74. 74.
    Shekelle PG, Morton SC, Jungvig LK, et al. Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease. J Gen Intern Med 2004; 19(4): 380–9PubMedCrossRefGoogle Scholar
  75. 75.
    Liu S, Stampfer MJ, Hu FB, et al. Whole-grain consumption and risk of coronary heart disease: results from the Nurses’ Health Study. Am J Clin Nutr 1999; 70(3): 412–9PubMedGoogle Scholar
  76. 76.
    Rimm EB, Willett WC, Hu FB, et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 1998; 279(5): 359–64PubMedCrossRefGoogle Scholar
  77. 77.
    Bonaa KH, Njolstad I, Ueland PM, et al., and NORVIT Trial Investigators. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006; 354(15): 1578–88PubMedCrossRefGoogle Scholar
  78. 78.
    Lonn E, Yusuf S, Arnold MJ, et al., and Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006; 354(15): 1567–77PubMedCrossRefGoogle Scholar
  79. 79.
    Lange H, Suryapranata H, De Luca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004; 350(26): 2673–81PubMedCrossRefGoogle Scholar
  80. 80.
    Schnyder G, Roffi M, Flammer Y, et al. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study — a randomized controlled trial. JAMA 2002; 288(8): 973–9PubMedCrossRefGoogle Scholar
  81. 81.
    Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002; 288(3): 321–33CrossRefGoogle Scholar
  82. 82.
    The Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 2004; 291(14): 1701–12CrossRefGoogle Scholar
  83. 83.
    Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007; 297(13): 1465–77PubMedCrossRefGoogle Scholar
  84. 84.
    Hsia J, Langer RD, Manson JE, et al., for the Women’s Health Initiative Investigators. Conjugated equine estrogens and coronary heart disease: the Women’s Health Initiative. Arch Intern Med 2006; 166(3): 357–65PubMedCrossRefGoogle Scholar
  85. 85.
    Manson JE, Hsia J, Johnson KC, et al., for the Women’s Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349(6): 523–34PubMedCrossRefGoogle Scholar
  86. 86.
    Grodstein F, Manson JE, Stampfer MJ. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. J Women Health 2006; 15(1): 35–44CrossRefGoogle Scholar
  87. 87.
    Lokkegaard E, Jovanovic Z, Heitmann BL, et al. The association between early menopause and risk of ischaemic heart disease: influence of hormone therapy. Maturitas 2006; 53(2): 226–33PubMedCrossRefGoogle Scholar
  88. 88.
    Pentti K, Honkanen R, Tuppurainen MT, et al. Hormone replacement therapy and mortality in 52- to 70-year-old women: the Kuopio Osteoporosis Risk Factor and Prevention Study. Eur J Endocrinol 2006; 154(1): 101–7PubMedCrossRefGoogle Scholar
  89. 89.
    Magliano DJ, Rogers SL, Abramson MJ, et al. Hormone therapy and cardiovascular disease: a systematic review and meta-analysis. Ann Int J Obstet Gynaecol 2006; 113(1): 5–14CrossRefGoogle Scholar
  90. 90.
    Nordenskjold B, Rosell J, Rutqvist LE, et al. Coronary heart disease mortality after 5 years of adjuvant tamoxifen therapy results from a randomized trial. J Natl Cancer Inst 2005; 97(21): 1609–10PubMedCrossRefGoogle Scholar
  91. 91.
    Hulley S, Grady D, Bush T, et al., for the Heart and Estrogen/progestin Replacement Study (HERS) Research Group. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280(7): 605–13PubMedCrossRefGoogle Scholar
  92. 92.
    Barrett-Connor E, Mosca L, Collins P, et al. for the Raloxifene Use for The Heart (RUTH) Trial Investigators. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 2006; 355(2): 125–37PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Emory University School of MedicineAtlantaUSA
  2. 2.Grady Memorial HospitalAtlantaUSA
  3. 3.Emory Heart and Vascular CenterAtlantaUSA

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