Redefining the ACE-inhibitor dose-response relationship: substantial blood pressure lowering after massive doses.
OBJECTIVES: The blood pressure-lowering dose-response relationship for angiotensin converting enzyme (ACE) inhibitors is assumed to flatten at doses higher than those conventionally used in clinical practice. However, existing clinical trial data do not adequately address the haemodynamic effects of high ACE inhibitor dosages. Therefore, we examined the blood pressure responses in patients presenting to hospital following a deliberate ACE inhibitor overdose. METHODS: The study design was a retrospective case review, and included all patients who presented to our hospital in the past 5 years after an ACE inhibitor overdose. The data collected were heart rate and systemic blood pressure at various times after ingestion and maximum haemodynamic derangement; these were compared to baseline or recovered values. RESULTS: Data from 33 patients (24 men) were evaluated. The median (inter-quartile range, IQR) age of the patients was 49 years (IQR: 42-56 years). The median stated dose ingested was 140 mg (IQR: 60-280 mg), which is 20x (IQR: 7-42) the defined daily dose. The maximum fall in systolic blood pressure was 50 mmHg (IQR: 40-64 mmHg), diastolic blood pressure was 35 mmHg (IQR: 26-43 mmHg) and mean blood pressure was 39 mmHg (IQR: 30-47 mmHg). CONCLUSIONS: The observed reduction in blood pressure following an overdose of an ACE inhibitor was greater than anticipated based on data from therapeutic doses. We conclude that a blood pressure-lowering dose-response relationship extends to higher ACE inhibitor doses than those conventionally used in clinical practice.