There was a dose-dependent decrease in blood pressure for aliskiren 75 mg , 150 mg and 300 mg .
Aliskiren had no effect on blood pressure variability .
Due to very limited information available regarding change in heart rate and pulse pressure , it was not possible to meta-analyze these outcomes .Mortality and non-fatal serious adverse events were not increased .
AUTHORS ' CONCLUSIONS Compared to placebo , aliskiren lowered BP and this effect is dose-dependent .
This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme ( ACE ) inhibitors and angiotensin receptor blockers ( ARBs ) .
There is no difference in mortality , nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy .
BACKGROUND Hypertension is a chronic condition associated with an increased risk of mortality and morbidity .
Renin is the enzyme responsible for converting angiotensinogen to angiotensin I , which is then converted to angiotensin II .
Renin inhibitors are a new class of drugs that decrease blood pressure ( BP ) by preventing the formation of both angiotensin I and angiotensin II .
OBJECTIVES To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in the treatment of primary hypertension .
To determine the change in BP variability , pulse pressure , and heart rate and to evaluate adverse events ( mortality , non-fatal serious adverse events , total adverse events , withdrawal due to adverse effects and specific adverse events such as dry cough , diarrhoea and angioedema ) .
Aliskiren Reduces Blood Pressure and Suppresses Plasma Renin Activity in Combination With a Thiazide Diuretic, an Angiotensin-Converting Enzyme Inhibitor, or an Angiotensin Receptor Blocker
Thiazide diuretics , angiotensin-converting enzyme inhibitors , and angiotensin receptor blockers all cause reactive rises in plasma renin activity . We hypothesized that renin inhibition with aliskiren would prevent this reactive rise and also enhance blood pressure lowering . In 3 open-label studies in which blood pressure was assessed with ambulatory measurement , aliskiren was administered to patients with mild-to-moderate hypertension in combination with hydrochlorothiazide ( n=23 ) , ramipril  ( n=21 ) , or irbesartan  ( n=23 ) . In the diuretic combination study , the addition of 25 mg of hydrochlorothiazide to 150 mg of aliskiren daily for 3 weeks significantly lowered daytime pressure , compared with aliskiren monotherapy ( systolic/diastolic mean change from baseline [ SEM ] : daytime : −18.4 [2.1]/ −10.6 [ 1.7 ] versus −10.4 [1.8]/−5.8 [ 1.4 ] ; nighttime : −15.6 [2.7]/−8.1 [ 1.8 ] versus −8.8 [2.9]/−5.0 [ 2.2 ] ) . In the angiotensin-converting enzyme inhibitor combination study , the addition of 75 or 150 mg of aliskiren to 5 mg of ramipril alone for 3 weeks further lowered both daytime and nighttime pressures compared with ramipril monotherapy ( daytime : −10.5 [2.9]/−8.1 [ 2.1 ] and −14 [3.7]/−8.7 [ 2.3 ] versus −6.1 [2.4]/−5.9 [ 1.5 ] ; nighttime : −8.1 [2.6]/−5.3 [ 2.4 ] and −9.6 [3.4]/−5.3 [ 2.4 ] versus −2 [2.3]/−0.7 [ 2.2 ] ) . In the angiotensin receptor blocker combination study , the addition of 75 or 150 mg of aliskiren to 150 mg of irbesartan alone , for 3 weeks , result ed in significantly lower nighttime pressures compared with irbesartan monotherapy ( daytime : −14.8 [2]/−8.2 [ 1.3 ] and −13.3 [1.6]/−6.8 [ 0.9 ] versus −11.4 [1.6]/−6.5 [ 1.1 ] ; nighttime : −16.1 [2.4]/−8.6 [ 1.7 ] and −13.2 [2.7]/−7.2 [ 1.9 ] versus −9.0 [2.5]/−4.7 [ 1.9 ] ) . Aliskiren ( 150 mg ) alone significantly inhibited plasma renin activity by 65 % ( P<0.0001 ) . Ramipril and irbesartan monotherapy caused 90 % and 175 % increases in plasma renin activity , respectively . By contrast , when aliskiren was coadministered with hydrochlorothiazide , ramipril , or irbesartan  , plasma renin activity did not increase but remained similar to baseline levels or was decreased ( combination therapy versus untreated ; median [ interquartile range ] ; aliskiren and hydrochlorothiazide : 0.4 [ 0.2 to 1.1 ] versus 0.7 [ 0.5 to 1.3 ] ; ramipril and aliskiren : 0.5 [ 0.3 to 0.9 ] versus 0.6 [ 0.5 to 0.8 ] ; irbesartan and aliskiren : 0.4 [ 0.2 to 0.9 ] versus 0.6 [ 0.4 to 0.9 ] ) . These results suggest that renin inhibition with aliskiren in these combinations increases renin-angiotensin system suppression , improves 24-hour blood pressure control , and may ultimately provide better end-organ protection in patients with hypertension
There was a dose-dependent decrease in blood pressure for aliskiren 75 mg , 150 mg and 300 mg .
Aliskiren had no effect on blood pressure variability .
Due to very limited information available regarding change in heart rate and pulse pressure , it was not possible to meta-analyze these outcomes .Mortality and non-fatal serious adverse events were not increased .
AUTHORS ' CONCLUSIONS Compared to placebo , aliskiren lowered BP and this effect is dose-dependent .
This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme ( ACE ) inhibitors and angiotensin receptor blockers ( ARBs ) .
There is no difference in mortality , nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy .
BACKGROUND Hypertension is a chronic condition associated with an increased risk of mortality and morbidity .
Renin is the enzyme responsible for converting angiotensinogen to angiotensin I , which is then converted to angiotensin II .
Renin inhibitors are a new class of drugs that decrease blood pressure ( BP ) by preventing the formation of both angiotensin I and angiotensin II .
OBJECTIVES To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in the treatment of primary hypertension .
To determine the change in BP variability , pulse pressure , and heart rate and to evaluate adverse events ( mortality , non-fatal serious adverse events , total adverse events , withdrawal due to adverse effects and specific adverse events such as dry cough , diarrhoea and angioedema ) .