LCZ696, a promising novel agent in treating hypertension (a meta-analysis of randomized controlled trials)

Abstract

BackgroundTo determine the effectiveness and safety of LCZ696 for the clinical treatment of hypertension, we performed a meta-analysis of the previous clinical trials.MethodsRelevant English articles and randomized controlled trials were searched in Pubmed, Embase, EBSCO, Cochrane base and ClinicalTrials.gov. The last search date was July 20th, 2017.ResultsCompared with 20mg olmesartan, 200mg and 400mg LCZ696 outperformed olmesartan in terms of reducing mean sitting systolic blood pressure, mean ambulatory systolic blood pressure, mean sitting diastolic blood pressure and mean ambulatory diastolic blood pressure. Compared with 20mg olmesartan, 200mg and 400mg LCZ696 was better than olmesartan in terms of reducing mean sitting pulse pressure. And these studies showed that 400mg LCZ696 was better than 20mg olmesartan in terms of reducing mean ambulatory pulse pressure, however, there was no significant difference between 200mg LCZ696 and 20mg olmesartan in terms of redducing mean ambulatory pulse pressure. In addition, 200mg and 400mg LCZ696 was better than placebo in terms of reducing blood pressure parameters mentioned above. Compared with placebo or 20 mg olmesartan, LCZ696 showed no superiority in terms of reducing adverse events or serious adverse events.ConclusionsLCZ696 at 200 mg or 400 mg was better at reducing most of blood pressure parameters than 20 mg olmesartan or placebo. Compared with placebo or 20 mg olmesartan, 200 mg or 400 mg LCZ696 do not result in more adverse events in treating hypertension.

Effects of LCZ696 (Sacubitril/Valsartan) on Blood Pressure in Patients with Hypertension: A Meta-Analysis of Randomized Controlled Trials

“…In our meta-analysis, we found that LCZ696 (100, 200, and 400 mg) produced significantly greater reductions in SBP, DBP, 24 h ASBP, and 24 h ADBP than ARBs alone in hypertensive patients. These results are consistent with the meta-analyses of Ye et al [21] and Zhao et al [23]. Compared with ARBs alone, LCZ696 causes a greater reduction in blood pressure, mainly attributed to RAS inhibition occurring simultaneously with neprilysin inhibition.…”

“…Ruilope et al [6] were the first to demonstrate the antihypertensive efficacy of LCZ696. Ye et al [21] showed that LCZ696 is more effective in reducing blood pressure than placebo. Ito et al [22] suggested that LCZ696 administration may be a promising therapeutic approach for Japanese patients with hypertension and renal dysfunction.…”

The renin–angiotensin system in cardiovascular autonomic control: recent developments and clinical implications

“…Sacubitril/valsartan (LCZ696) is a first-in-class dual NEP inhibitor and ARB approved to reduce risk of cardiovascular death and hospitalizations in heart failure [100]. Sacubitril/valsartan produces greater blood pressure-lowering effects when compared with an ARB alone or placebo in controlled trials in essential hypertension [101], and may produce insulin-sensitizing effects in obesity hypertension [102]. The specific mechanisms underlying beneficial effects of this combination drug remain unclear but may include sympathoinhibition, improved endothelial and cardiac function, and anti-arrhythmic, antiatherosclerotic, and anti-thrombotic effects [103].…”

The Antihypertensive Effects and Safety of LCZ696 in Patients with Hypertension: A Systemic Review and Meta-Analysis of Randomized Controlled Trials

“…Most of these prospective and double-blind clinical trials showed that LCZ696 achieved the target blood pressure better without significant adverse effects. In addition, several meta-analyses have concluded that LCZ696 may reduce arterial pressure more efficaciously than placebo, particularly the angiotensin receptor blocker (ARB), without increasing overall adverse events [17][18][19]. However, some meta-analyses included non-RCTs, retrospective articles, or unpublished studies [17,18].…”

“…In addition, several meta-analyses have concluded that LCZ696 may reduce arterial pressure more efficaciously than placebo, particularly the angiotensin receptor blocker (ARB), without increasing overall adverse events [17][18][19]. However, some meta-analyses included non-RCTs, retrospective articles, or unpublished studies [17,18]. We performed a meta-analysis including high quality RCTs to precisely determine the effectiveness and safety of LCZ696 for the treatment of high arterial pressure.…”