In a case-control study of 34 individuals with ACEi-induced angioedema and 127 control samples, Cilia La Corte et al. (2011) found that an ATG haplotype in the 5-prime region of the XPNPEP2 gene (c.-2399C-A; ; c.-1612G-T; and c.-393G-A) was significantly associated with the disorder (odds ratio of , p = ). This haplotype was associated with decreased plasma APP activity and decreased luciferase gene expression compared to other haplotypes of these SNPs. Cilia La Corte et al. (2011) concluded that the ATG haplotype of XPNPEP2 is functional and contributes to the development of ACEi-angioedema through a reduction in APP activity.
PARADIGM-HF was a multinational, randomised, double-blind study of 8,442 patients comparing Entresto to enalapril, both given to adult patients with chronic heart failure, NYHA class II-IV and reduced ejection fraction (left ventricular ejection fraction [LVEF] ≤40%, amended later to ≤35%) in addition to other heart failure therapy. The primary endpoint was the composite of cardiovascular (CV) death or hospitalisation for heart failure (HF). Patients with SBP <100 mmHg, severe renal impairment (eGFR <30 ml/min/ m 2 ) and severe hepatic impairment were excluded at screening and therefore not prospectively studied.