Classic evidences for cardiorenal protection today

Abstract

Look AHEAD trial¹ (2001-2012), randomized 5145 obese T2DM patients to Intensive Lifestyle (I) vs diabetes support/(education (C). The primary composite outcome (PO)-(cardiovascular death, no-fatal myocardial infarction, non-fatal stroke or hospitalization for angina) was neutral at 9.6 years and was haltead early. I arm improved CRP risk factors vs C, and neutral results may reflect short duration of T2DM, moderate prospective risk and greater use of statins/ useantihypertensive with bettter lipid profile in C. Notably patients losing > 10% body weight in year one of intervention² (53% of I) significantly rduced the PO (HR 0.79, 95% CI 0.64-0.98), underscoring the impact of weight loss magnitude and speed.

Steno-2³ (1993-2001) randomized 160 T2DM with microalbuminuria intensive multifactorial treatment (I) vs conventional care (C) per Danish guidelines for risk factors. PO: CV death, nonfatalMI/stroke, revascularization, amputation, and among secondary/tertiary endpoints all-cause mortality and several microvascular events. Inerventions included lifestyle, metformin, gliclazide, metformin/gliclazide, insulin, statins, fibrates, RASi/ARBs, diuretics, CCBs, BBs and aspirin. At study end I significantly reduced the PO (HR 0.47 CI 0.22-0.74 p = 0.001)and microvascular events except peripheral neuropathy. Then a follow-up began (all patients switched to I with pharmacological agents similar to current standards, with actual CRP drugs available in the preceding 2/5 years to the study after 21 years follow-up⁴. At that time without significant differences in risk factors and despite 13 years optimization in both arms, the PO ocurred at 16.1 years in the original I arm vs 8.1 years earlier in C (95% CI 4.0 – 12.6 years) and micovascular events also favored I, with 7.9 years greater survival in this arm. This highlights that even traditional pharmacotherapy achieves CRP when applied intensively and multifactorially