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Use of statins in the management of Unstable Angina

Statin Therapy in the 21st Century. Use of statins in the management of Unstable Angina. Vascular Disease: A Worldwide Challenge. 40. 32%. 30%. 30. Percent of at-risk patients on lipid-lowering medication. 20. 10. 0. United States. Europe.

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Use of statins in the management of Unstable Angina

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  1. Statin Therapy in the 21st Century Use of statins in the management of Unstable Angina

  2. Vascular Disease:A Worldwide Challenge 40 32% 30% 30 Percent of at-risk patients on lipid-lowering medication 20 10 0 UnitedStates Europe American Heart Association: 1998 Heart and Stroke Statistical Update EUROASPIRE Study Group: Eur Heart J 1997;18:1569–1582

  3. Therapeutic Advances in the Treatment of Cardiovascular Disease Therapy class Thrombolysis1–4 Antiplatelets2,5 b-blockers6 ACE inhibitors7-117–11 Statins12,13 -10 45 -20 35 -20% Percentage reduction in risk of total mortality post-MI -23% 25 -30 -7%–27% -22%–30% -40 15 -50 5 -10%–50% GISSI Lancet 1986, 1987; 2. ISIS 2 Lancet 1988; 3. AIMS Lancet 1988, 1990; 4. ASSET Lancet 1988, 1990; 5. Antiplatelet Trialists Collaboration BMJ 1994; 6. Yusuf et al: Cardiovasc Dis 1985;27:335–1571; 7. SAVE N Engl J Med 1992; 8. AIRE Lancet 1993; 9. GISSI 3 J Am Coll Cardiol 1996; 10. ISIS 4 Lancet 1995; 11. TRACE N Engl J Med 1995; 12. 4S Lancet 1994; 13. LIPID N Engl J Med 1998

  4. Unstable Angina: A Worldwide Challenge 1,000,000 • UA is as serious a problem as MI • 2%–10% treated UA patients will experience an MI prior to discharge • As many as 5% die despite hospital treatment for UA • 30-day event rate (death or MI) is 20% despite conventional therapy • 10%–14% of patients with UA experience an MI, death, or both within 3–6 months of onset 900,000 747,000 800,000 651,000 700,000 Number of patients 600,000 500,000 400,000 300,000 200,000 100,000 0 MI UA Discharge diagnosis White. Am J Cardiol. 1997;80:2B–10B, Landau et al. N Engl J Med.1994;330:981–993, Klootwijk et al. Lancet. 1999;353(suppl):10–15, Balsano et al. Circulation. 1990;82:17–26

  5. Angiography of Unstable Angina Davies. Atlas of Coronary Artery Disease. Lippincott-Raven, Philadelphia, Pennsylvania: 1998:79

  6. Unstable Angina With Plaque Disruption Davies. Atlas of Coronary Artery Disease. Lippincott-Raven, Philadelphia, Pennsylvania: 1998:81

  7. Primary Mechanism of Unstable Angina: Pathogenesis of Atherosclerosis Exposure to modified lipids Endothelial activation Inflammatory cell migration Inflammatory cell activation VSMC recruitment Matrix synthesis VSMC death Fibrous cap formation Matrix degradation Stable plaque Unstable plaque Adapted from Weissberg. Atherosclerosis. 1999;147:S3–S10

  8. Unstable Angina: Treatment Goals Acute • – Relieve angina • – Prevent MI • – Preserve viable myocardium if there is an infarction • – Prevent death Chronic • – Cardiac rehabilitation • – Identify and treat coronary risk factors/underlying disease • – Prevent recurrent admissions White. Unstable angina: Ischemic syndromes. In: Topol EJ (ed). Textbook of Cardiovascular Medicine. Lippincott-Raven, Philadelphia, Pennsylvania: 1998:365–393

  9. The Evidence in Unstable Angina • Only one statin trial has demonstrated benefit in patients with a history of Unstable Angina • Long Term Intervention With Pravastatin in Ischaemic Disease (The LIPID study) The LIPID Study Group: N Engl J Med 1998;339:1349–1357

  10. Pravastatin therapy in patients Post-MI or with a history of Unstable Angina: LIPID study design • 9014 men and women with post-MI or hospitalisation for unstable angina • Cholesterol 4–7 mmol/L (155–271 mg/dL) • Pravastatin 40 mg v. placebo, mean follow-up 6.1 years • 83% aspirin, 47% b-blockers, 41% PTCA/CABG at baseline Prespecified end points • CHD mortality • Total mortality • Revascularizations • Stroke The LIPID Study Group: N Engl J Med 1998;339:1349–1357

  11. Pravastatin Reduces Events in Patients With Unstable Angina as Qualifier* 20 29%† Placebo Pravastatin 10 Percent with event 0 CHD death or nonfatal MI * Prespecified subgroup analysis †95% confidence interval (12–42) The LIPID Study Group. N Engl J Med. 1998;339:1349–1357

  12. Pravastatin Benefits in MI and Unstable Angina patients Events Prevented Per1000 Patients TreatedOver 6 Years Event Deaths 30 Nonfatal MI 28 CABG 23 PTCA 20 Hospital admissions for UA 82 Nonfatal stroke 9 The LIPID Study Group. N Engl J Med. 1998;339:1349–1357

  13. Rationale for pravastatin use in patients with a history of Unstable Angina • Proven efficacy in secondary prevention • Low potential for drug interactions • Excellent long-term safety and tolerability Sacks et al. N Engl J Med. 1996;335:1001–1009, The LIPID Study Group. N Engl J Med. 1998;339:1349–1357, Quion JAV et al. Clin Pharmacokinet 1994; 27(2): 94-103

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