Sacubitril/Valsartan for Prevention of Cancer Therapy-Related Cardiac Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Figure 1. Forest plot showing the pooled between-group mean difference (MD) in final global longitudinal strain (GLS) values between sacubitril/valsartan and control groups across three randomized controlled trials (n = 350). Effect sizes are expressed as mean differences (%) with 95% confidence intervals (CIs). The pooled estimate was calculated using a random-effects model with restricted maximum likelihood (REML) estimation and Hartung–Knapp–Sidik–Jonkman (HKSJ) adjustment for small-sample inference. Each square represents the point estimate of an individual trial, with its size proportional to the trial’s weight in the meta-analysis, and the horizontal lines denote the 95% CIs; the diamond represents the overall pooled effect, with its width indicating the 95% CI. The dashed vertical line indicates the line of no effect (MD = 0). More negative values indicate greater GLS preservation, favoring sacubitril/valsartan. The pooled MD was −0.95% (95% CI −1.40 to −0.50; p = 0.012; I2 = 0%; τ2 = 0; Q = 0.41, p for heterogeneity = 0.81). Included trials: Hsu et al. [20], PRADA II [21], and SARAH [22].

Figure 2. Forest plot showing the pooled between-group mean difference (MD) in final left ventricular ejection fraction (LVEF) values between sacubitril/valsartan and control groups across three randomized controlled trials (n = 350). Effect sizes are expressed as mean differences (%) with 95% confidence intervals (CIs). The pooled estimate was calculated using a random-effects model with restricted maximum likelihood (REML) estimation and Hartung–Knapp–Sidik–Jonkman (HKSJ) adjustment for small-sample inference. Each square represents the point estimate of an individual trial, with its size proportional to the trial’s weight in the meta-analysis, and the horizontal lines denote the 95% CIs; the diamond represents the overall pooled effect, with its width indicating the 95% CI. The dashed vertical line indicates the line of no effect (MD = 0). Positive values indicate higher LVEF, favoring sacubitril/valsartan. The pooled MD was 1.53% (95% CI −0.47 to 3.52; p = 0.082; I2 = 0.0%; τ2 = 0.00; p for heterogeneity = 0.432). Included trials: Hsu et al. [20], PRADA II [21], and SARAH [22].