The HOPE-3-Trial investigated the effect of primary prevention on cardio- and neurovascular events in patients without known atherosclerotic disease, but with intermediate risk. In a factorial design Rosuvastatin 10 mg, Candesartan 16 mg/HCT 12.5 mg or both were compared with placebo. Rosuvastatin effectively lowered LDL-cholesterol and the rate of cardio- and neurovascular complications with a NNT of approximately 500/year without detectable effect on mortalitiy. Candesartan 16 mg/HCT 12.5 mg did not influence any endpoint, however, the predefined subgroup of patients with hypertension level I had a benefit. Patients with systolic pressure <131 mmHg even trended towards a higher risk if treated. The combination of statin and blood pressure-lowering agents showed no additive effects. The benefit was solely the result of statin therapy alone. Primary prevention with Rosuvastatin can be recommended if the cardio- and neurovascular risk is 1-2%/year, independent of the initial LDL, although the NNT of 500-1400/year is high and mortalitiy is not decreased. Possibly there will be future studies with longer term follow up to verify a reduction in mortality. Therapy with Candesartan 16 mg/HCT 12,5 mg has a beneficial effect only in patients with hypertension. Further studies with different antihypertensives and more intensive blood pressure lowering are desirable. The approach of combining all three drugs within a poly-pill for primary prevention in an intermediate risk population without elevated blood pressure is not recommended.