 History or evidence of severe cardiac disease, e.g. New York Heart Association NYHA Functional Class III or IV, clinical or medical history of unstable angina, acute coronary syndrome, myocardial infarction, or revascularization procedure within 6 months prior to baseline, or ventricular tachyarrhythmia requiring treatment; History or evidence of clinically significant peripheral vascular disease such as intermittent claudication or prior amputation; Renal failure requiring dialysis or renal transplant or renal insufficiency with creatinine levels 2.0 mgdl at screening; Stroke within 12 months of trial entry; Any major surgical procedure within one month before trial enrolment; 