CARDS demonstrated that atorvastatin 10 mg reduces major cardiovascular events by 37% and stroke by 48% in patients with type 2 diabetes and normal to mildly elevated LDL-cholesterol without prior CVD, confirming that cardiovascular risk rather than LDL level should determine statin initiation and establishing universal statin use in primary cardiovascular prevention for type 2 diabetes.
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HPS demonstrated that simvastatin reduces major vascular events by 24% across all high-risk patients regardless of baseline LDL-cholesterol level, including those with diabetes without established coronary disease, eliminating the treatment threshold concept and establishing absolute cardiovascular risk as the primary criterion for statin therapy — one of the most influential results in preventive cardiology.
WOSCOPS demonstrated that pravastatin reduces the combined incidence of nonfatal MI and coronary death by 31% in men with hypercholesterolaemia and no prior MI, establishing the primary prevention indication for statin therapy and providing the first large randomised evidence for population-level lipid lowering in high-risk individuals without established cardiovascular disease.
The 4S trial demonstrated that simvastatin reduces all-cause mortality by 30%, coronary death by 42%, and major coronary events by 34% in patients with established coronary heart disease and no excess non-cardiovascular mortality, resolving the safety debate and establishing statin therapy as the standard of care in secondary cardiovascular prevention.
The DPPOS demonstrated that cumulative diabetes prevention from the DPP lifestyle intervention and metformin persists over 10 years from original randomisation, with 34% and 18% reductions in cumulative diabetes incidence despite post-DPP convergence of care, establishing a diabetes prevention legacy effect and confirming the durability of early preventive intervention.
The DREAM trial demonstrated that rosiglitazone reduces incident diabetes or death by 60% and achieves normoglycaemia in 50% of high-risk adults with impaired glucose tolerance, the largest pharmacological diabetes prevention effect documented in a large RCT, but the drug’s subsequent cardiovascular safety concerns and market withdrawal have prevented translation of these findings into clinical practice.
The Diabetes Prevention Program demonstrated that intensive lifestyle intervention reduces type 2 diabetes incidence by 58% with a NNT of 6.9 over 2.8 years in high-risk adults, outperforming metformin which reduced incidence by 31%, establishing structured lifestyle modification as the primary preventive strategy for pre-diabetes and the evidence base for national prevention programmes.
VADT demonstrated that intensive glucose control achieving a median HbA1c of 6.9% did not significantly reduce cardiovascular events or mortality in veterans with long-standing type 2 diabetes and high cardiovascular disease prevalence, completing the ACCORD/ADVANCE/VADT triptych that defined the limits of aggressive glycaemic management in advanced disease.
ADVANCE demonstrated that intensive glucose control targeting HbA1c below 6.5% using a gliclazide-based strategy reduces nephropathy by 21% and the microvascular composite by 14% in high-risk type 2 diabetes, without the mortality hazard observed in ACCORD, providing important context for how glycaemic targets and treatment strategies interact with safety outcomes.
ACCORD demonstrated that targeting an HbA1c below 6.0% in high-risk type 2 diabetes patients with established cardiovascular disease increased all-cause mortality by 22% without significantly reducing cardiovascular events, establishing that very intensive glycaemic targets are harmful in this population and reshaping international guidelines to mandate individualised HbA1c targeting.