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However, the lack of significant statistical interaction between subgroups (P = 0.127) suggests that addition of the AMPLITUDE-O trial has not changed the previous scenario [5], stressing that the net separation on MACE effect between patients with or without established CV disease may be more nuanced than suggested by previous meta-analyses [3]

That does not mean every study will show the same pattern, but it does explain why dose escalation and tolerability are often discussed together