We were provided access to individual patient data for each of the ACE inhibitor pediatric antihypertensive efficacy trials submitted for pediatric exclusivity from 1998 to 2005, inclusive. All 6 trials enrolled a substantial proportion of children of black or other race. At the highest dose of drug, children of white or other race demonstrated a significant systolic and diastolic blood pressure response to ACE inhibition. In contrast, at the highest dose of drug, children of black race did not show a response in aggregate to ACE inhibition.
We previously reported a racial difference in response to blood pressure of fosinopril using a different analytic method (slope of dose response in black patients compared with white patients). The present analysis differs in that, here, we have used absolute change from baseline in each trial. Our previous work is the only study to report on racial differences in blood pressure response to antihypertensive drugs in children (13
Our study demonstrates that black children do not respond as well to ACE inhibitors compared with children of white or other race. This is consistent with the well-described racial differences in responsiveness to ACE inhibitors in adult patients (3
). ACE inhibitors are less effective as monotherapy in black adults because of low renin levels and a high degree of salt sensitivity (14
). This differential response of the renin angiotensin system in blacks may be due to genetic polymorphisms in the angiotensinogen gene (15
). In black adults, the intrarenal renin–angiotensin system is not suppressed as effectively as in whites in response to high salt intake but shows the same level of activation with low salt intake. Black adults on a low-salt diet or a diuretic show a renal vascular response to renin and ACE inhibition identical to whites (17
The differential blood pressure response to ACE inhibitors according to race seen in this study could not have been demonstrated by evaluating individual trials but was discernible in the meta-analysis. We were only able to do this by having access to the data across trials. Access to protocols, final study reports, and individual patient data for each trial was therefore crucial to our investigation.
Limitations to our study include that trials of beta-blockers and calcium channel blockers were not included. We only had access to 1 trial of beta-blocker and 2 trials of calcium channel blockers compared with 6 trials of ACE inhibitors. In addition, the race group of “other” is non-specific and included children of mixed race; therefore, we could not particularly evaluate other ethnic groups besides white and black. Other limitations of this study are the small age range studied which included mainly children > 10 years of age with adult weights. Also, many patient populations that frequently use ACE inhibitors (e.g., those with cardiac disease, renal disease, or diabetes) were excluded from these studies. Hence, these data may not be applicable to younger children and/or sicker children
We have compiled the results of 6 anti-hypertensive trials in children; our analysis suggests that black children do not have as robust a response to ACE inhibitors as white children. Our analysis is limited to the dosages used in the trials; many of these trials used limited differences in the amount of product given between low- and high-dose groups (7
). Moreover, the highest doses of drug used in each trial were up to the maximum adult dose. Therefore, higher dosages of ACE inhibitors may be effective in treating hypertensive black children. The safety implications of using potentially higher doses beyond the adult maximum dose, however, require further study.