Higher doses of ACE inhibitors are best, but even low doses improve survival

A new study from the Institute for Clinical Evaluative Sciences (ICES) shows that, although few elderly heart failure patients receive high dose ACE inhibitor therapy that has the greatest effect on reducing hospital readmissions and death, even lower doses can improve survival.

Angiotensin-converting enzyme (ACE) inhibitors are recommended as the initial therapy following heart failure. Clinical guidelines suggest that patients should gradually receive higher doses to optimize outcomes. However, little is known about how well lower doses improve survival compared to higher doses.

To further investigate this issue, ICES researchers identified over 16,000 elderly Ontario heart failure patients who survived 45 days following their first heart failure hospital discharge between 1998 and 1999. They examined the association between ACE inhibitor dose and hospital readmission and death rates after one year of follow-up. The study also looked at the initial dose dispensed and subsequent dose reduction or cessation.

Overall, 65% (10,793) of elderly heart failure patients were prescribed ACE inhibitors 45 days following hospital discharge from their initial heart failure hospitalization. At the end of one year, 85% were dispensed doses that were lower than the suggested guidelines. As well, patients put on medium or high dose therapy were significantly more likely to have their dose reduced by 50% or more relative to those on low dose therapy.

The results also showed that there was a significantly greater risk of heart failure hospital readmission or death when patients did not receive ACE inhibitors at all, compared to when they received even low doses. Higher doses reduced readmission and death rates even more, decreasing mortality by upwards of 20%.

• Implications:
• “Our study shows that, although higher doses of ACE inhibitors provide optimal survival benefits, elderly heart failure patients are better to be on a low dose rather than none at all if that’s what they can tolerate,” said lead author Dr. Paula Rochon, ICES scientist, and senior scientist at the Kunin-Lunenfeld Applied Research Unit at the Baycrest Centre for Geriatric Care. “We hope these findings will encourage physicians to keep patients who cannot tolerate high ACE inhibitor doses on lower ones, and start more heart failure patients on these drugs.”

The study, “Use of angiotensin-converting enzyme inhibitor therapy and dose-related outcomes in older adults with new heart failure in the community”, is in the June 8, 2004 issue of the Journal of General Internal Medicine.

Author affiliations: ICES (Drs. Rochon, Bronskill, Mamdani, Anderson, Tu and Laupacis, and Ms. Sykora); Kunin-Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care (Drs. Rochon and Gill); Departments of Medicine (Drs. Rochon and Gill), and Health Policy, Management and Evaluation (Drs. Rochon, Bronskill, Anderson, and Tu), and Faculty of Pharmacy (Dr. Mamdani), University of Toronto; Department of Medicine, Sunnybrook and Women’s College Health Sciences Centre (Drs. Tu and Laupacis); Meyers Primary Care Institute, Fallon Healthcare System and University of Massachusetts Medical School (Dr. Gurwitz).

This study was supported by the Canadian Institutes of Health Research (CIHR) Chronic Disease New Emerging Team (NET) program. The NET program receives joint sponsorship from the Canadian Diabetes Association, the Kidney Foundation of Canada, the Heart and Stroke Foundation of Canada, and the CIHR Institutes of Nutrition, Metabolism & Diabetes and Circulatory & Respiratory Health.

ICES is an independent, non-profit organization that uses population-based health information to produce knowledge on a broad range of healthcare issues. Our unbiased evidence provides measures of health system performance, a clearer understanding of the shifting healthcare needs of Ontarians, and a stimulus for discussion of practical solutions to optimize scarce resources. ICES knowledge is highly regarded in Canada and abroad, and is widely used by government, hospitals, planners and practitioners to make decisions about care delivery and to develop policy.

FOR FURTHER INFORMATION, PLEASE CONTACT:

• Julie Argles
• Media Relations Officer, ICES
• (416) 480-4055 ext. 3602 or cell (416) 432-8143