Does the antihypertensive response to angiotensin converting enzyme inhibition predict the antihypertensive response to angiotensin receptor antagonism?

To test the hypothesis that the antihypertensive response to angiotensin converting enzyme (ACE) inhibition can predict the response to angiotensin II type I receptor (AT1R) antagonism, 33 hypertensive patients were randomized to receive lisinopril (20 mg) or losartan (50 mg) for 5 weeks. Patients were then crossed-over to the alternative treatment for a second 5-week period. Twenty-four-hour ambulatory BP (ABP) was measured before randomization and on the final day of each period. The agreement in ABP response between the two drugs was assessed using the following approaches: Subjects were classified as responders and nonresponders using as a threshold an arbitrary level of response (ABP fall ≥ 10 mm Hg systolic or ≥ 5 mm Hg diastolic) or the median ABP response achieved by each of the drugs. Disagreement between the two drugs in the responders-nonresponders classification was expressed as the proportion of subjects whose ABP responded to one of the drugs only. Lisinopril was more effective than losartan in reducing ABP (mean difference 4.7 ± 8.1/3.3 ± 5.7 mm Hg, systolic/diastolic, P< .05). Disagreement in the antihypertensive response between the two drugs was found in 39%/33% of subjects for systolic/diastolic ABP using the arbitrary response criterion (33%/39% using the median response criterion). Significant correlations were found between the responses to lisinopril and losartan (r = 0.47/0.59, systolic/diastolic, P< .01). We conclude that in more than one third of hypertensive subjects, the BP response to ACE inhibition fails to predict the response to AT1 R antagonism and vice versa. These data suggest that there are differences between these two drug classes that are not only of theoretical but also of practical significance.