Novel dual-action drug can tackle hypertension
The scientists from Canada, Germany, Slovakia, Spain and the US say the single-molecule LCZ696 is an angiotensin-II-receptor and neprilysin inhibitor (ARNI) that works in two ways. Not only does LCZ696 block the action of angiotensin II a protein that triggers the constriction of blood vessels and fuels blood pressure to ease the flow of blood, but it successfully neutralises neprilysin, thereby causing the blood vessels to widen and relax, which in turn leads to a drop in blood pressure.
Led by the Professor Luis M. Ruilope of the Hospital 12 de Octubre in Madrid, Spain, the researchers evaluated 1 328 patients from 18 countries suffering from mild to moderate hypertension. The research team randomly assigned each patient to one of eight groups, for a period of eight weeks. The treatments for each respective group were: 100 mg LCZ696; 200 mg LCZ696; 400 mg LCZ696; 80 mg valsartan; 160 mg valsartan; 320 mg valsartan; 200 mg AHU377 (a neprilysin blocker); or placebo.
Their findings showed that the treatments used helped lower the mean sitting diastolic blood pressure. In particular, three pairwise comparison doses of LCZ696 versus valsartan (i.e. 100 mg vs. 80 mg; 200 mg vs. 160 mg; 400 mg vs. 320 mg) delivered solid results.
A breakdown of the results for the eight-week period showed substantial reductions in blood pressure for patients treated with LCZ696 compared with patients treated 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).
Furthermore, the scientists found that over the eight-week period the reduction in mean sitting diastolic blood pressure was very different for 200 mg LCZ696 versus 160 mg valsartan (-2.97 mm Hg) as well as for 400 mg LCZ696 versus 320 mg valsartan (-2.70 mm Hg).
According to the team, using LCZ696 to treat high blood pressure is safe for patients, and all doses are well-tolerated. Concerning side effects, they were mild, infrequent and more or less the same across the eight treatment groups. Most patients reported headaches, and the placebo group had the highest number of headache cases. The scientists found no cases of swelling (angio-oedema) of the skin.
'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,' the researchers said. 'Future research should identify hypertensive patient populations that would most benefit from LCZ696 (including elderly patients and those with diabetes.'
Professors Bernard Waeber and Francois Feihl from Université de Lausanne in Switzerland wrote in an accompanying article that LCZ696 has a lot of potential because patients suffering from hypertension currently have to take more than one antihypertensive drug to keep their blood pressure in check.
'To date, clinical experience with LCZ696 was limited,' they wrote. '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.'
Also contributing to this study were scientists from Comenius University in Slovakia, Universität des Saarlandes in Germany, Centre Hospitalier de l'Université Laval in Canada, and Novartis Pharmaceuticals in the US.