Subgroup interactions in the Heart and Estrogen/Progestin Replacement Study: lessons learned.

Area of Science:

• Cardiovascular Medicine
• Endocrinology
• Women's Health

Background:

• The Heart and Estrogen/Progestin Replacement Study (HERS) found no overall benefit of postmenopausal hormone treatment in women with coronary heart disease (CHD).
• Previous analyses of HERS data did not identify specific subgroups with clear treatment benefits or harms.

Purpose of the Study:

• To analyze HERS data for specific subgroups of women who responded differently to postmenopausal hormone treatment.
• To investigate potential interactions between baseline characteristics and hormone therapy effects.

Main Methods:

• Conducted extensive post hoc analyses of 86 predefined subgroups based on baseline characteristics.
• Examined within-subgroup treatment effects for variables that significantly interacted with treatment assignment.
• Assessed treatment effects at 1 year and at trial completion.

Main Results:

• Six interaction values were nominally significant (P<0.05) at 1 year, and 3 were significant at trial completion.
• Use of digitalis, history of myocardial infarction, and lipoprotein(a) levels emerged as potential modifiers of hormone therapy effects.
• No subgroup demonstrated clear beneficial or harmful effects of hormone therapy.

Conclusions:

• Extensive post hoc analyses did not identify any subgroup where postmenopausal hormone treatment was clearly beneficial or harmful.
• Several potential modifiers of hormone therapy effects warrant further investigation in future clinical trials.