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Legacy effects in extension studies: standing the test of time

heartjnl · 2025-07-28 · canonical JSON source

5 visible annotations · policy: published · automated confidence ≥ 75.00%

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The legacy effect refers to the long-lasting benefits of an early intensive treatment that persist even after the cessation of the intervention.1–3 In the prevention setting, it means that a timely control of risk factors leads to more favourable long-term outcomes. One of the first pieces of evidence for this phenomenon comes from the post-trial follow-up study of the United Kingdom Prospective Diabetes Study (UKPDS) trial. In the UKPDS, patients with newly diagnosed type 2 diabetes were randomised to intensive versus conventional glycaemic control. In the intensive glycaemic control group, there was a 25% decrease in microvascular complications over the 10-year period of the active trial. Reports at 10 years after the end of the trial confirmed a persistent treatment effect, despite mean glycated haemoglobin values becoming no different between study groups by 1 year after the trial end, and then decreasing progressively over time in both groups with increasing use of other glucose-lowering medications.1 The biological explanation behind this phenomenon has been attributed to ‘metabolic memory’, which clinically translates to the importance of adequate and early risk factor control.