News Release

New dual action drug shows promise for treating high blood pressure and heart disease

Peer-Reviewed Publication

The Lancet_DELETED

A new dual-action drug, called LCZ696, is well tolerated and provides significantly greater reductions in blood pressure than the established angiotensin receptor blocker (ARB) valsartan in patients with hypertension (high blood pressure). LCZ696 might be superior to standard ARBs and has the potential to be a promising treatment for hypertension and heart disease, concludes an Article published Online First and in this week's edition of The Lancet.

The single-molecule LCZ696 is an angiotensin-II-receptor and neprilysin inhibitor (ARNI) that works in two ways. Like ARBs it blocks the action of angiotensin II, a hormone that causes arteries to constrict (and the drug therefore should allow blood to flow more easily), but it also neutralises a substance called neprilysin, which results in the blood vessels relaxing and widening, thereby lowering blood pressure. It has been suggested that because the drug blocks both angiotensin II and neprilysin it has the potential to offer superior benefits for the treatment of hypertension and heart failure compared with ARBs.

In this study, Luis Ruilope from Hospital 12 de Octubre, Madrid, Spain and international colleagues examine whether the dual mechanism of action of LCZ696 leads to further lowering of blood pressure compared with the ARB valsartan.

1328 patients with mild-to-moderate hypertension were recruited from 18 countries and randomly assigned to 8 weeks treatment in one of eight groups: 100 mg LCZ696, 200 mg LCZ696, 400 mg LCZ696, 80 mg valsartan, 160 mg valsartan, 320 mg valsartan, 200 mg AHU377 (which blocks neprilysin alone), or placebo. The primary outcome was the lowering of mean sitting diastolic blood pressure during treatment, calculated as the mean difference in blood pressure between three pairwise comparison doses of LCZ696 versus valsartan (100 mg vs 80 mg, 200 mg vs 160 mg, 400 mg vs 320 mg).

Overall, patients treated with LCZ696 had significant reductions in blood pressure compared with valsartan (a mean drop in sitting diastolic blood pressure of -2.17 mm Hg and sitting systolic blood pressure of -4.20 mm Hg).

Over 8 weeks, the drop in mean sitting diastolic blood pressure was significantly different for 200 mg LCZ696 vs 160 mg valsartan (-2.97 mm Hg) and for 400 mg LCZ696 vs 320 mg valsartan (-2.70 mm Hg).

LCZ696 treatment was safe and generally well tolerated at all doses. Side effects were infrequent, mild, and similar between the eight treatment groups—the most common being headaches which occurred most frequently in the placebo group. No cases of angio-oedema (swelling) were reported. There were three serious adverse events, none of which were related to treatment with LCZ696.

These findings show that: "Dual inhibition of the angiotensin II receptor and neprilysin have complementary effects…and could provide clinical benefits in a range of cardiovascular diseases including hypertension and heart failure…Future research should identify hypertensive patient populations that would most benefit from LCZ696 (including elderly patients and those with diabetes)".

In an accompanying Comment, Bernard Waeber and Francois Feihl from the Université de Lausanne in Switzerland say that there is great potential for this dual-acting drug because most people with high blood pressure currently need to take more than one antihypertensive drug to target different mechanisms that affect the cardiovascular system, and thereby manage blood pressure effectively.

They conclude: "To date, clinical experience with LCZ696 was limited. We now have sufficient encouraging data to justify the carrying out of large clinical trials in various clinical conditions, notably hypertension, diabetes, and heart or renal failure."

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Professor Luis Ruilope, Hospital 12 de Octubre, Madrid, Spain. T) +34 629 175 770 E) ruilope@ad-hocbox.com

Professor Bernard Waeber, Université de Lausanne, Lausanne, Switzerland. T) +41 21 314 07 06 E) Bernard.waeber@chuv.ch

For full Article and Comment, see: http://press.thelancet.com/lcz696.pdf


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