# Presentation: 737091

## Report of NHLBI HRT Studies Other Than the WHI October 23, 2002

**Report of NHLBI HRT Studies Other Than the WHI ****October 23, 2002**

**David J. Gordon, M.D., Ph.D.**
**National Heart, Lung, and Blood Institute**

## Rationale for HRT Trials

- Pre-menopausal women are at low risk for cardiovascular disease. Estrogen?
- Oral HRT in post-menopausal women
- Reduced CV risk in observational studies
- Favorable effects on intermediate endpoints

## NHLBI HRT Trials1. QCA Regression Trials

- ERA – D. Herrington (Wake Forest)
- WAVE – D. Waters (Multi-center)
- WELL-HART – H. Hodis (Southern California)
- EAGAR – P.Ouyang (Johns Hopkins)

## NHLBI HRT Trials2. Short-Term Targeted Trials

- Effects of Acute Hormone Therapy on Recurrent Ischemia in Postmenopausal Women with Unstable Angina
-     S. Schulman (Johns Hopkins)
- Estradiol For Neurocognitive Dysfunction After CABG
-     C. Hogue (Washington, St. Louis)
- Estrogens, Cytokines, and Heart Failure
-     S. Reis (Pittsburgh)
- Efficacy of Hormone Replacement on Myocardial Ischemia in Postmemopausal Women with Minimal Coronary Artery Disease (WISE FemHRT ancillary study)
-     N. Bairey-Merz (Multi-center)

## ERA Trial

- 309 postmenopausal women with CAD
- Treatment Arms: Premarin, PremPro, Placebo
- Duration: 3 years
- Primary Endpoint: QCA
- Results: NEJM 2000; 343:522-529

| End Point | E | E+P | Placebo |
| --- | --- | --- | --- |
| MLD | -0.09 mm | -0.12 mm | -0.09 mm |
| Deaths | 8.0% | 2.9% | 5.7% |
| NF MI | 6.0% | 5.8% | 6.7% |
| CABG/PCI | 18.0% | 19.2% | 22.9% |
| DVT/PE | 5.0% | 1.9% | 1.0% |

## WAVE Trial

- 423 postmenopausal women with CAD
- Treatment Arms:
- Hysterectomy -- Premarin, Placebo
- Intact -- PremPro, Placebo
- Duration: 3 years
- Primary Endpoint: QCA
- Other Features: Antioxidant vitamin vs placebo (2x2 factorial design)
- Results: In press (Will be presented at Nov 2002 AHA Late-Breaking Trials session)

## WELL-HART

- 226 postmenopausal women with CAD
- Treatment Arms: Estrace, Estrace + MPA, Placebo
- Duration: 3 years
- Primary Endpoint: QCA.
- Other Features: 50% Hispanic, Pravastatin provided to all 3 groups per ATP II guidelines.
- Results: Will be presented at Nov 2002 AHA Late-Breaking Trials session.

## EAGAR Trial

- 99 postmenopausal women post-CABG (initially designed to enroll 200 women)
- Treatment Arms:
- Hysterectomy -- Estrace, Placebo
- Intact – Estrace + MPA, Placebo
- Planned Duration: 3 years
- Primary Endpoint: QCA, IVUS
- Impact of WHI: Trial was stopped in Aug 2002 due to low likelihood of benefit, adverse trend in PCI, and insufficient power to justify repeat angiography.

## Acute Hormone Therapy in Unstable Angina (Schulman)

- 239 postmenopausal women with acute coronary syndrome
- Treatment Arms: Acute IV Estrogen + Premarin, Acute IV Estrogen + PremPro, Placebo
- Duration: 21 days
- Primary Endpoint: 48-hr ambulatory ischemic events
- Results: JACC 2002;39:231-7

| End Point | E | E+P | Placebo |
| --- | --- | --- | --- |
| 48-hr AIE | 0.74 | 0.86 | 0.74 |
| 21-day AIE | 0.69 | 0.71 | 0.78 |
| In-hosp death | 5% | 5% | 3% |
| In-hosp NF MI | 3% | 3% | 5% |
| CABG/PCI | 36% | 37% | 34% |

## Estradiol For Neurocognitive Dysfunction After CABG (Hogue)

- 334 postmenopausal women undergoing CABG (61 randomized)
- Treatment Arms: Estrace, Placebo
- Duration: 5 days
- Primary Endpoint: Neurocognitive changes at 4-6 wk and 6 mo.
- Impact of WHI: None. Short-term treatment, no progestin.

## Estrogens, Cytokines, and Heart Failure (Reis)

- 120 postmenopausal women with CHF (5 randomized)
- Treatment Arms: FemHRT, Placebo
- Duration: 6 months
- Endpoints: Fuctional capacity, bi-ventricular mass and function, circulating cytokines.
- Impact of WHI: DSMB recommended continuation. Short-term treatment, different hormone preparation and target population.

## WISE FemHRT Ancillary Study (Bairey-Merz)

- 74 postmenopausal women with minimal CAD (< 20 randomized)
- Treatment Arms: FemHRT, Placebo
- Duration: 12 weeks
- Primary Endpoints: Induced myocardial ischemia, endothelial cell dysfunction
- Impact of WHI: DSMB recommended continuation. Short-term treatment, different hormone preparation.

## Non-NHLBI HRT Trials

- Completed
- HERS (N = 2763, clinical events, 4 yrs)
- PHOREA (N = 321, carotid IMT, 48 wks)
- PHASE (N = 255, clinical events, 3 yrs)
- EPAT (N = 199, carotid IMT, 2 yrs)
- WEST (N = 652, recurrent stroke, 3 yrs)
- Ongoing
- WISDOM (N ≈ 34,000, clinical events, 10 yrs)

##  Summary

- NHLBI has sponsored several recent small trials testing the efficacy of HRT in preventing progression of CAD in post-menopausal women and examining effects of HRT in targeted populations with cardiovascular disease (post-CABG, CHF, acute and chronic ischemia).
- 4 completed and 4 active when WHI results announced.
- 1 study stopped by DSMB and 3 continue.
- 2 published trials show no benefit of HRT – but numbers are small.
- Results of 2 other trials to be announced in November