Fig. 6. Causal diagrams of target trial specification and emulation.

Causal graphs illustrate the effects of the treat-to-target cholesterol-lowering interventions ($A$) on cardiovascular disease, all-cause mortality, and atherosclerotic cardiovascular disease ($Y$) in the presence of competing events ($C$) using the sequentially randomized trial (the upper panel, i.e., target trial specification, a in which the intervention strategy $A_k$ only depends on prior cardiovascular risk profiles ($L_k$), cholesterol levels and intervention history ($A_{k-1}$) at each time $k\left(k=\mathrm{0,\; 1},\dots ,28\right)$ and the hypothetical pragmatic trial (the bottom panel, i.e., target trial emulation, b in which $A_k$ depends on prior $L_k$, $A_{k-1}$, and the potential unmeasured confounders $U_k$. $C_{k-1}$ and $Y_k$ indicate the competing events at time interval $k-1$ and the outcome of interest at time interval $k$, respectively.