Losartan intervention for endpoint reduction in hypertension (the life study)

AII-blockade (selective blockade of the AT1-receptor subtype) is the first new drug class in the treatment of hypertension for a decade. Like any novel therapy AII-blockers should establish their ability to prevent hypertension related cardiovascular (CV) complications. Of currently available antihypertensive drugs only beta-blockers and diuretics have proven effects on CV mortality and morbidity. However the treatment effect on CHD is still suboptimal. Left Ventricular Hypertrophy (LVH) is the strongest independent risk indicator in hypertension. Angiotensin II (AII) is an important growth factor, and blockade of the Renin-Angiotensin-System may be of cardinal importance for LVH reversal and cardioprotection. Selective and complete blocking of AII mediated effects through the AT1-receptor therefore offers a window of opportunity to establish improved cardiovascular protection. Against this background the LIFE study is performed. Hypothesis: Compared to atenolol (established Rx), losartan (novel, orally active, selective AT1-blocker) will reduce the incidence of CV mortality and morbidity by 15% in patients with essential hypertension and LVH. Design: Multinational (Scandinavia and US), triple-blind, randomised, prospective, follow-up ≥ 4 years. Patients: 8,300 men and women, 55-80 years of age, blood pressure sitting 200-160 and/or 115-95 mmHg, ECG-verified LVH (Cornell voltage duration product). Primary endpoints: Non-fatal MI and stroke, all CV mortality (in at least 1,040 patients). Conclusion: The LIFE study will provide mortality documentation early in the history of a new drug class with an opportunity of improving CV care. The study has a novel approach since it selects the hypertensive patients on the basis of target organ damage (LVH). It is also the first prospective study with the potential of linking reversal of LVH to reduction in CV events. Patient enrollment is ongoing.