AIMS: An analysis was designed to determine whether chronic heart failure patients at high cardiovascular risk benefited to the same extent from high-dose lisinopril as the whole ATLAS population. METHODS AND RESULTS: A retrospective analysis was performed on high-risk heart failure patients in the Assessment of Treatment with Lisinopril And Survival (ATLAS) trial (total number of patients 3164) comparing highdose (32.5-35 mg. day(-1)) vs low-dose (2.5-5 mg. day(-1)) lisinopril for a median of 46 months. These high-risk patients included those with hypotension, hyponatraemia, compromised renal function, the elderly and patients with diabetes mellitus at baseline. In the whole study population, high-dose lisinopril led to a trend in risk reduction of all-cause mortality (primary end-point P=0.128) and a significant risk reduction in all-cause mortality plus hospitalization (principal secondary end-point P=0.002). Subgroup analyses were performed for these end-points. There were no consistent interactions between age, baseline sodium, creatinine or potassium values, and treatment effect. Diabetics showed a beneficial response to high-dose therapy that was at least as good as that in non-diabetics. The underlying higher morbidity/mortality rates in diabetics mean that high-dose lisinopril has potential for a larger absolute clinical impact in these patients. CONCLUSION: Long-term high-dose lisinopril was as effective and well-tolerated in high-risk patients, including those with diabetes mellitus, as for the ATLAS study population as a whole.