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Background The atherosclerotic progression–reducing effect of LDL cholesterol (LDL-C) lowering has been established in subjects with severe atherosclerotic disease but not in persons with elevated LDL cholesterols without severe atherosclerosis. KAPS (Kuopio Atherosclerosis Prevention Study) is the first population-based trial in the primary prevention of carotid and femoral atherosclerosis. Methods and Results The eligibility requirements were serum LDL-C ≥4.0 mmol/L and total cholesterol P =.005). In the common carotid artery there was a treatment effect of 66% (95% CI, 30 to 95%; pravastatin 0.010 mm/y; placebo 0.029 mm/y; P P =.056) at the overall mean baseline IMT of 2.0 mm. The treatment effect was larger in subjects with higher baseline IMT values, in smokers and in those with low plasma vitamin E levels. There was no significant treatment effect on atherosclerotic progression in the femoral arteries. Conclusions These data establish the antiatherogenic effect of LDL-C lowering by pravastatin in hypercholesterolemic men in a primary prevention setting and suggest a greater effect in smokers than in nonsmokers.

Epidemiologic studies continue to demonstrate extremely disappointing blood pressure (BP) control rates. For this reason, the search for more effective antihypertensive agents continues. PS433540 is the first compound in a novel class of agents called Dual Acting Receptor Antagonists (DARA) which selectively block angiotensin (AT 1 ) and endothelin (ET A ) receptors. In this prospective, randomized, double blind, placebo controlled study, 234 men and women with a mean age of 56.0 years entered a 3– 4 week single blind placebo run-in period. Qualifying stage I or stage II hypertensive patients were randomized in a 1:1:1 ratio to either PS433540 200mg, 500mg or matching placebo for a period of 4 weeks. Ambulatory BP monitoring (ABPM) was performed at the start of the study and was repeated at the end of the treatment period. PS433540 lowered both 24HR Systolic BP (SBP) and Diastolic DBP (DBP) as well as mean office SBP and DBP to a greater extent than placebo, p ) PS433540 was well tolerated with 2 reported serious adverse events in the placebo group and placebo lead-in period. Three patients (all from the placebo group) were discontinued from the study for adverse events. There were no significant laboratory abnormalities. This study demonstrates that PS433540 is an effective and well tolerated new class of antihypertensive agent that may prove to be a very important addition to our armamentarium for the management of hypertension.