Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease (TNT Trial)

The Treating to New Targets (TNT) trial enrolled 10,001 patients with stable coronary artery disease and randomized them to atorvastatin 10 mg (producing LDL around 101 mg/dL) versus 80 mg (producing LDL around 77 mg/dL). The question: does driving LDL well below the then-current target of 100 mg/dL produce additional clinical benefit in patients who already have established disease?

The answer was clear. High-dose atorvastatin reduced the primary endpoint of major cardiovascular events by 22 percent compared with the moderate dose (8.7% vs 10.9%, HR 0.78). Myocardial infarction, stroke, and revascularization rates all fell. The tradeoff was a higher rate of liver enzyme elevation in the high-dose group (1.2% vs 0.2%), though serious hepatotoxicity and muscle toxicity rates were similar between arms.

TNT was one of several trials that drove the “lower is better” principle in cardiovascular medicine — the understanding that LDL targets well below 100 mg/dL are both achievable and beneficial in high-risk patients. It was instrumental in shifting secondary prevention guidelines from an LDL target of 100 mg/dL toward 70 mg/dL, a threshold that most major guidelines now endorse.

We rate the evidence strong. A landmark large RCT establishing that intensive LDL lowering in stable coronary disease produces meaningful, sustained reductions in cardiovascular events — a foundational trial in the modern statin era.