Hypertension (2) RJS Journal Club RJS Journal ClubJ Am Soci Hypertension 14:299-306, 2012
Aliskiren (trade names Tekturna) It is the first in a class of drugs called direct renin inhibitors approved by FDA in 2007 and currently licensed for Rx of RJS Journal Club RJS Journal Club essential (primary) HTN.
Ambulatory Blood Pressure Monitoring (ABPM) RJS Journal Club RJS Journal Club
ABPM National Institute for Health and Clinical Excellence (NICE 英國國健局 ) recommends that ABPM be used to confirm the diagnosis of primary hypertension as it is a RJS Journal Club RJS Journal Club better predictor of cardiovascular events than BP measured at the clinic.
Blood Pressure (BP) load BP load is defined as percentage of BP readings exceeding the upper limits of normal (130/80 mmHg) for a given time period. RJS Journal Club RJS Journal Club BP load has a strong predictive value for end-organ damage.
Nondipper HTN Pattern The blunted nocturnal fall in BP, referred to as nondippers, is mediated by activation of the renin-angiotensin-aldosterone system (RAAS). A nondipping circadian BP pattern is estimated to affect up to 40% of the HTN population; it is RJS Journal Club RJS Journal Club a marker for increased target-organ damage and cardiovascular risk. A recent prospective analysis has shown a 17% reduction in cardiovascular risk with each 5-mm Hg reduction in nighttime systolic BP.
PRA and Nocturnal BP Nocturnal systolic and diastolic BP dips are negatively correlated with basal PRA, i.e., the more the plasma level of PRA is increased, the less likely there is nocturnal RJS Journal Club RJS Journal Club fall in BP. Thus, RAAS blockers such as ACEI, ARB, and DRI (direct renin inhibitors) might be useful in this clinical setting.
RJS Journal Club RJS Journal Club Physiology of RAASThieme Publishers All rights reserved
Methods A pooled analysis of ABPM data from two randomized controlled trials was performed to compare the antihypertensive efficacy and safety of RJS Journal Club RJS Journal Club RAAS blockade with combination DRI⁄ARB (aliskiren ⁄ valsartan) vs ARB alone (valsartan) in patients stratified as nocturnal dippers or nondippers.
Definition Dippers are randomized patients whose nighttime (10 PM to 6 AM) mean ambulatory systolic BP (maSBP) dropped >10% below their daytime (6 AM to 10 RJS Journal Club RJS Journal Club PM) baseline values. Nondippers included randomized patients whose nighttime maSBP dropped <10% below their daytime baseline values.
Pertinent Findings Nondippers tended to be slightly older than dippers (54.6 vs 53.3 years), to be somewhat more obese (BMI 30.8 vs 30.0 kg ⁄m2), and to have greater baseline RJS Journal Club RJS Journal Club ambulatory BP (145.7 ⁄ 92.4 vs 142.4 ⁄ 89.9 mm Hg).
RJS Journal Club RJS Journal ClubFIGURE 3. Reductions from baseline to week 8 in mean ambulatory systolic blood pressure (maSBP) during the nighttime and daytime and during the last 4 hours of the 24-hour dosing period in nocturnal dippers and nondippers. LSM indicates least-square mean.
Combo before tx mono before tx Combo after tx mono before tx RJS Journal Club RJS Journal ClubHourly (a) mean ambulatory systolic blood pressure (maSBP) and (b) mean ambulatory diastolic blood pressure (maDBP) at baseline and week 8 in nocturnal dippers and nondippers.
Conclusions The addition of aliskiren to valsartan was associated with an incremental benefit of approximately 5 to 6 mm Hg of lowering in mean ambulatory systolic BP and approximately 3 to 4 mm Hg of lowering RJS Journal Club RJS Journal Club in mean ambulatory diastolic BP. Of note, 32% of patients were converted from a nondipper at baseline to a dipper status at the end of study.
Clinical Implications Optimal treatment of the nondipping circadian BP pattern is probably best managed with drugs that inhibit the RAAS, with the combination of a DRI and an ARB RJS Journal Club RJS Journal Club providing greater efficacy and similar safety as an ARB alone.
A Warning from Novartis RJS Journal Club RJS Journal Club 2012 / 01 / 02
Action Points ABPM is required to differentiate nocturnal dipper and non-dipper HTN patients. In nocturnal non-dipper HNT patients, anti-RAAS drugs should first be RJS Journal Club RJS Journal Club considered. Combination of DRI and ARB is effective for non-dipper HTN patients, but serious adverse side effects (stroke, renal damage, hyperkalemia, etc.) of this