Long term impact of RAS inhibition on cardio-renal outcomes: a comparative trial of angiotensin converting enzyme inhibitors, angiotensin receptor blockers or combined therapy with both agents in patients with one or more cardiovascular risk factors and microalbuminuria, diabetic or not diabetic.

INTERVENTION: ACE‐inhibitor (ACEi) monotherapy or angiotensin II receptor blocker (ARB) monotherapy or combined treatment with ACEi + ARB. Physicians will able to choose any commercially available ACEi or ARB of ACEi or ARB commercially available provided a blood pressure target of <130/80 mmHg is addressed. The dose depends on the drug(s) selected by the investigator; the administration is by mouth (per os). Duration of intervention/s: daily for the duration of the trial (4 years). It is not possible to define a standard dose: the randomization decides which drug class will be assigned; the investigators must choose one of the drugs included in the class. The dose will be the standard dose of the selected drug. Therefore as the investigators can choose among about 85 ACEi and 36 ARB, it is not possible to define a standard dose. CONDITION: Patients with one or more cardiovascular risk factors and microalbuminuria, diabetic or not diabetic. PRIMARY OUTCOME: To evaluate the comparative efficacy for cardiac and cerebrovascular outcomes of ACEi monotherapy versus ARB monotherapy in the same individuals with micro/macroalbuminuria and cardio‐renal risk. To evaluate the comparative efficacy for cardiovascular and cerebrovascular outcomes of combined therapy with angiotensin converting enzyme inhibitors (ACEi) and (angiotensin receptor blockers) ARB versus monotherapy with ACEi or ARB in individuals with micro/macroalbuminuria and cardio‐renal risk. SECONDARY OUTCOME: To evaluate the comparative efficacy for renal outcomes of ACEi monotherapy versus ARB monotherapy in the same individuals with micro/macroalbuminuria and cardio‐renal risk. To evaluate the comparative efficacy for renal outcomes of combined therapy with angiotensin converting enzyme inhibitors (ACEi) and (angiotensin receptor blockers) ARB versus monotherapy with ACEi or ARB in individuals with micro/macroalbuminuria and cardio‐renal risk. INCLUSION CRITERIA: Consenting individuals, with microalbuminuria or macroalbuminuria, with one or more cardiovascular risk factors (smoking, diabetes, hypertension, visceral obesity, dyslipidemia, family history of cardiovascular diseases) including those with previous major cardiovascular events provided these have occurred at least 6 months before enrolment.