Aernoud Fiolet

361 Clinical implications and future perspectives CLINICAL IMPLICATIONS AND FUTURE PERSPECTIVES T he aim of this thesis is to prove that anti-inflammatory therapy improves outcomes in patients with coronary disease. This clinical goal is combined with a methodological goal. This methodological goal aims to show that conducting research for drug repurposing is possible to the highest scientific standards and that there are efficient methods of trial conduct and data collection that can facilitate such, often low-cost, research. This chapterwill elaborate on the implications of the research froma clinical, health care, and societal perspective. Secondly, we will describe the future directions of such research and discuss howwe can improve trial efficacy in general and in drug repurposing research in particular. TRANSLATING TO CLINICAL PRACTICE AND RECOMMENDATIONS The results of our clinical research that are described in part I and II of this thesis add to the existing body of evidence and unequivocally demonstrate the clinical efficacy of modulating inflammatory pathways in coronary disease. With this, we provide solid proof of principle of the inflammatory hypothesis in atherosclerotic disease.When pooled, the results of the low-dose colchicine studies show a relative risk reduction of 25% (relative risk 0.75, 95% confidence interval 0.61 to 0.91) for the occurrence of any major cardiovascular event, with consistent effects on the individual components myocardial infarction, ischemia-driven coronary revascularisation, and stroke. 1,2 ( Chapters 5 and 7 ) This additional risk reduction, achieved in patients on optimal medical therapy, is a clinically relevant effect that is equal to the risk reduction reached with intensive lipid-lowering therapy and antithrombotic therapy. 3,4 (Table 1) When trying to translate such effect sizes to daily practice, consider a typical outpatient clinic example of a cigarette smoking 65-year-old man with coronary disease. If he is treated with acetylsalicylic acid, with antihypertensive drugs to achieve a systolic blood pressure below 140 mm Hg, and with lipid-lowering drugs to achieve a low-density lipoprotein–cholesterol level of 1.8 mmoles/liter, he remains to have a 10-year risk of 36% for a major cardiovascular event and his lifetime risk will approach 65%. The addition of anti-inflammatory treatment with low-dose colchicine could provide an 8.4% absolute risk reduction in his 10‑year