COMPARATIVE STUDY
JOURNAL ARTICLE
MULTICENTER STUDY
RANDOMIZED CONTROLLED TRIAL

Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study

Luis Miguel Ruilope, Andrej Dukat, Michael Böhm, Yves Lacourcière, Jianjian Gong, Martin P Lefkowitz
Lancet 2010 April 10, 375 (9722): 1255-66
20236700

BACKGROUND: LCZ696 is a first-in-class inhibitor of the angiotensin II receptor and neprilysin. We aimed to establish whether the dual actions of LCZ696 lead to further lowering of blood pressure, compared with the angiotensin-receptor blocker valsartan.

METHODS: 1328 patients aged 18-75 years with mild-to-moderate hypertension were randomly assigned (double-blind) to 8 weeks' treatment in one of eight groups: 100 mg (n=156 patients), 200 mg (n=169), or 400 mg (n=172) LCZ696; 80 mg (n=163), 160 mg (n=166), or 320 mg (n=164) valsartan; 200 mg AHU377 (n=165); or placebo (n=173). The primary endpoint was the mean difference across the three single-dose pairwise comparisons of LCZ696 versus valsartan (100 mg vs 80 mg, 200 mg vs 160 mg, and 400 mg vs 320 mg) in mean sitting diastolic blood pressure during the 8-week treatment period. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00549770.

FINDINGS: 1215 patients completed the 8-week treatment period. The average reduction in mean sitting diastolic blood pressure across the doses of LCZ696 versus the appropriate comparator dose of valsartan showed significantly greater reductions with LCZ696 (mean reduction: -2.17 mm Hg, 95% CI -3.28 to -1.06; p<0.0001). The reduction in mean sitting diastolic blood pressure was significantly different for 200 mg LCZ696 versus 160 mg valsartan (-2.97 mm Hg, 95% CI -4.88 to -1.07, p=0.0023) and for 400 mg LCZ696 versus 320 mg valsartan (-2.70 mm Hg, -4.61 to -0.80, p=0.0055). LCZ696 was well tolerated and no cases of angio-oedema were reported; only three serious adverse events occurred during the 8-week treatment period, of which none was judged to be related to the study drug, and no patients died.

INTERPRETATION: Compared with valsartan, dual-acting LCZ696 provides complementary and fully additive reduction of blood pressure, which suggests that the drug holds promise for treatment of hypertension and cardiovascular disease.

FUNDING: Novartis.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
20236700
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"