How large studies may mislead: the HOPE Study

The HOPE study is widely believed to indicate that anyone over the age of 55 years with a major cardiovascular risk factor should receive prophylactic therapy with ramipril but detailed inspection of the characteristics of the patient groups suggest problems of randomisation. There was a consistent over‐representation in the placebo group of patients with each of the most potent risk factors for cardiovascular events: previous history of myocardial infarction, peripheral vascular disease, previous stoke, angina, hypertension and elevated lipids. Moreover, there was an excess of males in the placebo group. The composite end point was of death from cardiovascular cause, myocardial infarction or stoke, and 651 patients in the ramipril group and 827 in the placebo group were affected. This gave an excess of primary endpoints in the placebo group of 176 cases. However, at baseline, there was an excess in the placebo group of individuals with previous ischaemic heart disease (95), peripheral vascular disease (119), previous stroke (13) and hypertension (69). Heart failure surprisingly occurred in similar numbers in the ramipril and placebo groups (81 vs. 79) respectively. The claim that this particular ACE inhibitor protects against cardiovascular disease is unfounded because of baseline imbalance in risk.