LAUSR

Objective: To evaluate the benefits and harms of Sacubitril/Valsartan (LCZ696) for controlling hypertension and reducing the risk of adverse cardiovascular events (MACE) in Asians by synthesising data from randomised controlled trials. Design and method: This is a systematic review and meta-analysis. We searched PubMed, ScienceDirect, Cochrane databases, trial registries HERDINPlus, ClinicalTrials.gov, and forward and backward citations to identify applicable articles. All randomised controlled trials with data of Asian patients comparing the effect of Sacubitril/Valsartan (LCZ696) against an active control for cardiovascular mortality, heart failure hospitalisation, blood pressure control, and adverse events were included without language or date restrictions. We did separate fixed-effects meta-analysis for major adverse cardiovascular events (MACE), hypertension control, serious and non-serious adverse events. Evidences were synthesised as pooled hazards ratio(HR) for MACE, pooled odds ratio for blood pressure control, and safety outcomes. The quality of evidence was assessed with the Cochrane risk of bias tool. Results: Ten of 2249 articles were included involving 6,120 patients. With high certainty of evidence, pooled data showed that Asians with mild to moderate hypertension had better hypertension control with LCZ696 against olmesartan (OR 1.63; CI 1.38, 1.92; p < 0.00001; I2 = 7%) (Figure1). However, the risk for MACE was not significantly reduced for Asians with reduced ejection fraction (HR 0.89; CI 0.73, 1.08; p = 0.22; I2 = 0%) or acute myocardial infarction (HR 0.90; CI 0.65,1.24; p 0.50; I2 = 0%) given LCZ696 (Figure2). The overall safety of LCZ696 was comparable to conventional ACEi/ARB but subgroup analysis revealed greater pooled odds ratios for hypotension (OR 1.59; 95% CI 1.19, 2.13; p = 0.002; I2 0%) and dizziness (OR 3.54; 95% CI 1.61, 7.81; p = 0.002; I2 0%) with LCZ696 and reduced pooled odds for cough occurrence(OR 0.70; 95% CI0.56, 0.87; p = 0.002; I2 0%) (Figure 3&4). Conclusions: Among Asians, LCZ696 is strongly associated with better hypertension control against olmesartan. However, its efficacy in reducing MACE is not as robust. Finally, the overall safety profile of sacubitril/valsartan is comparable to conventional ACEi/ARBs but it is associated with hypotension and dizziness with a lower risk for cough.