Clinical evidence,mechanism, importance and management
Retrospective analysis of data from a large randomised,placebo-controlled study of HRT (conjugated estrogens/medroxyprogesterone 0.625/2.5 mg daily) in women with coronary heart disease was conducted to see if there were any subgroups of patients who responded differently. Use of digitalis was associated with a fivefold excess rate of cardiovascular events in first year in women receiving HRT, when compared with control group. A lower 1.5-fold excess rate was seen over whole duration of study (average 4.1 years). Possible mechanisms could be a drug-drug interaction or a drug-disease (HRT with congestive heart failure) interaction (See reference number 1).
However, it is impossible to say whether this represents a true effect, because number of positive sub-group analyses in this study was same as number predicted by chance alone. Confirmatory evidence is required (See reference number 1).
1. Furberg CD,Vittinghoff E, Davidson M, Herrington DM, Simon JA, Wenger NK, Hulley S.Subgroup interactions in the Heart and Estrogen/Progestin replacement study. Lessons learned.Circulation (2002) 105, 917–22.