Clinical Trials

• Osteoporosis Data
• Invasive Breast Cancer Data
• RUTH Trial: Cardiovascular Data

Osteoporosis Data at a Glance

Invasive Breast Cancer Data at a Glance

RUTH Trial: Cardiovascular Data¹²

Trial design: RUTH was a placebo-controlled clinical trial enrolling 10,101 postmenopausal women (mean age 68 years) with coronary heart disease (CHD) or multiple risk factors for CHD.

Primary endpoint: One of the primary endpoints of the RUTH trial was to determine whether raloxifene 60 mg/day compared with placebo lowers the risk of coronary events.

Women were followed up to 7 years (median of 5.6 years).

Inclusion criteria: Participants had to be at least 55 years old, postmenopausal for at least 1 year, and have established CHD or increased risk for CHD.

RUTH Trial Results¹²

Co-primary endpoint: EVISTA did not increase or decrease the combined endpoint of nonfatal heart attack (MI), fatal heart attack, and hospitalized acute coronary syndrome compared with placebo. EVISTA should not be used for the primary or secondary prevention of cardiovascular disease.

Secondary endpoints:

• EVISTA did not increase or decrease the risk of all-cause mortality or overall cardiovascular mortality compared with placebo
• EVISTA did not increase or decrease the risk for stroke compared with placebo; however, there was an increase in stroke mortality (0.7 per 1,000 woman-years vs placebo; p=.05)
• EVISTA increased the incidence of venous thromboembolic events (VTEs) compared with placebo (1.2 per 1,000 woman-years)

Cardiovascular Incidence Rates Observed in the RUTH Trial¹²

Adapted from N Engl J Med. 2006;355:125-137.
^‡Coronary primary endpoint: coronary death, nonfatal MI, or hospitalized acute coronary syndrome (ACS) other than MI, whichever occurred first. For any participant with multiple coronary events, each first event in each subcategory was counted separately.

Important Considerations for Healthcare Professionals

• EVISTA is indicated for the prevention and treatment of osteoporosis in postmenopausal women, for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis, and for the reduction in risk of invasive breast cancer in postmenopausal women at high risk for invasive breast cancer
• EVISTA should not be used for the prevention or reduction of the risk of cardiovascular disease
• Note that women enrolled in the RUTH clinical trial had multiple risk factors for coronary disease, or prior heart attack. This represents a different patient population than the patients previously studied in clinical trials^13-15 for EVISTA
• Patient management considerations resulting from death due to stroke:
  • In a study of postmenopausal women at high risk for cardiovascular disease taking EVISTA, there was no increase in the incidence of stroke; however, there was an increase in death due to stroke. EVISTA also did not increase or decrease the incidence of overall mortality, cardiovascular mortality, or heart attack. The risk-benefit balance should be considered in women at risk for stroke, such as prior stroke or transient ischemic attack (TIA), atrial fibrillation, hypertension, or cigarette smoking
• The risk for venous thromboembolic events (VTEs), which are not arterial events, was consistent with what has been seen in previous clinical trials^1,2,16 with EVISTA and is reflected in the current label for EVISTA

1. JAMA. 1999;282:637-645.
2. J Clin Endocrinol Metab. 2002;87:3609-3617.
3. Data on file, Lilly Research Laboratories (EVI200108001).
4. J Bone Miner Res. 2005;20:1514-1524.
5. Arch Intern Med. 2000;160:3444-3450.
6. Data on file, Lilly Research Laboratories (EVI199910005).
7. Breast Cancer Res Treat. 2001;65:125-134.
8. J Natl Cancer Inst. 2004;96:1751-1761.
9. Data on file, Lilly Research Laboratories (EVI20070730).
10. Data on file, Lilly Research Laboratories (EVI20070913).
11. JAMA. 2006;295:2727-2741.
12. N Engl J Med. 2006;355:125-137.
13. Curr Med Res Opin. 2005;21:1441-1452.
14. Am J Cardiol. 2002;90:1204-1210.
15. JAMA. 2002:287;847-857.
16. Obstet Gynecol. 2004;104:837-844.

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Important Safety Information for EVISTA

Contraindications
EVISTA is contraindicated in nursing women and in women who are or may become pregnant, as it may cause fetal harm. EVISTA is also contraindicated in women with active or past venous thromboembolic events (VTEs), including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis.

Warnings and Precautions
In a study of postmenopausal women at high risk for cardiovascular disease taking EVISTA, there was no increase in the incidence of stroke; however, there was an increase in death due to stroke. EVISTA also did not increase or decrease the incidence of overall mortality, cardiovascular mortality, or heart attack. The risk-benefit balance should be considered in women at risk for stroke, such as those with prior stroke or transient ischemic attack (TIA), atrial fibrillation, hypertension, or cigarette smoking. EVISTA should be used with caution in patients with hepatic impairment or moderate/severe renal impairment since safety and efficacy have not been established in these patients. The safety of concomitant use of EVISTA with systemic estrogens has not been established and its use is not recommended.

Adverse Reactions
The common adverse reactions considered to be drug related:

Adverse reactions occurring in the clinical trials at a frequency ≥2.0% in either group and in more EVISTA-treated women than in placebo-treated women include:

The majority of adverse reactions occurring during the osteoporosis prevention and treatment studies were mild and generally did not require discontinuation of therapy.

Please see Contraindications, Warnings and Precautions, and Adverse Reactions sections of full Prescribing Information for other Important Safety Information.