Use of statins in the management of Unstable

Angina

Statin Therapy in the 21st Century

American Heart Association: 1998 Heart and Stroke Statistical Update EUROASPIRE Study Group: Eur Heart J 1997;18:1569–1582

UnitedStates

Vascular Disease:A Worldwide Challenge

Europe

Perc

ent

of

at-

risk

pati

ents

on

lip

id-l

ow

eri

ng

medic

ati

on

0

10

20

30

40

30% 32%

Therapeutic Advances in the Treatment of Cardiovascular Disease

Perc

enta

ge r

educt

ion in

ris

k of

tota

l m

ort

alit

y p

ost

-MI

5-

50

15-40

25-30

35

-20

45

-10

Thrombolysis1–4 Antiplatelets2,5 -blockers6 ACE inhibitors7-11 7–

11Statins12,13

-10%–50%

-23%

-20%

-7%–27% -22%–30%

Therapy class

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

Unstable Angina: A Worldwide Challenge

0

100,000

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

MI UA

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

Nu

mb

er o

f p

atie

nts

651,000

747,000

200,000

300,000

400,000

500,000

600,000

700,000

800,000

900,000

1,000,000

Discharge diagnosis

Angiography of Unstable Angina

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

Unstable Angina With Plaque Disruption

Davies. Atlas of Coronary Artery Disease. Lippincott-Raven, Philadelphia, Pennsylvania: 1998:81

Primary Mechanism of Unstable Angina: Pathogenesis of Atherosclerosis

Stable plaque Unstable plaque

Fibrous cap formation Matrix degradation

VSMC death

VSMC recruitment

Inflammatory cell activation

Inflammatory cell migration

Endothelial activation

Exposure to modified lipids

Matrix synthesis

Adapted from Weissberg. Atherosclerosis. 1999;147:S3–S10

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

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

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% -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

Pravastatin Reduces Events in Patients With Unstable Angina as Qualifier*

* Prespecified subgroup analysis

† 95% confidence interval (12–42) The LIPID Study Group. N Engl J Med. 1998;339:1349–1357

0

10

20

CHD death or nonfatal MI

Per

cent

wit

h ev

ent

Placebo

Pravastatin

29%†

Pravastatin Benefits in MI and Unstable Angina patients

Event

Deaths 30

Nonfatal MI 28

CABG 23

PTCA 20

Hospital admissions for UA 82

Nonfatal stroke 9

Events Prevented Per1000 Patients Treated

Over 6 Years

The LIPID Study Group. N Engl J Med. 1998;339:1349–1357

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

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