ABCD‐N 2002.

Methods	Randomized, open label controlled clinical trial. An independent end point committee, which was blinded to the study intervention arms, reviewed all cardiovascular events. The follow‐up period was 5 years.
Participants	480 participants, aged 40 ‐ 74 years, with type 2 diabetes mellitus were included. All of them had a baseline diastolic blood pressure between 80 and 89 mmHg and were not receiving antihypertensive medications at the randomization visit. The main exclusion criteria were: myocardial infarction or cerebrovascular accident within the previous 6 months, coronary artery bypass surgery within the previous 3 months, unstable angina pectoris within the previous 6 months, congestive heart failure NYHA class III or IV, a demonstrated absolute need for ACE inhibitors or CCB, and a serum creatinine level > 3 mg/dl.
Interventions	Participants were randomized into 2 treatment arms consisting of 'intensive' or 'moderate' treatment. The goal in the 'intensive' treatment group was to achieve a decrease of 10 mmHg below baseline in diastolic blood pressure (i.e. 70 ‐ 79 mmHg), whereas the goal in the 'moderate' treatment group was to maintain a diastolic blood pressure between 80 and 89 mmHg. Participants in the 'moderate' therapy group were given placebo, whereas those randomized to 'intensive' therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication. If the target blood pressure was not achieved with increasing doses, then open‐label antihypertensive medications were added in a step‐wise fashion, initially with metoprolol, then hydrochlorothiazide or additional drugs, but not a calcium channel blocker nor ACE inhibitor. Blood pressure recordings were obtained at the time when peak drug levels were expected and were an average of 3 seated readings obtained at each visit.
Outcomes	The primary end point was the change in 24‐hour creatinine clearance. Secondary end points included cardiovascular events, retinopathy, clinical neuropathy, and urinary albumin excretion.
Notes	Participants randomized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication. Participants in the moderate group were given placebo. However, by the end of the study 117 participants (48%) initially randomized to moderate therapy required treatment (systolic blood pressure > 159 and/or diastolic blood pressure > 89 mmHg on 2 consecutive visits). These individuals were started on either nisoldipine or enalapril according to randomization at entry into the study with the goal of maintaining the systolic blood pressure < 160 mmHg and diastolic blood pressure < 90 mmHg. A test for interaction between study drug assignment and blood‐pressure control strategy showed that no interaction was present
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Participants assigned to 'moderate' treatment had a greater prevalence of established vascular disease, which became significant when combined with ABCD‐N.
Allocation concealment (selection bias)	Unclear risk	Method not reported
Blinding (performance bias and detection bias) All outcomes	High risk	Blinding of participant and investigator not possible
Incomplete outcome data (attrition bias) All outcomes	High risk	Data on losses to follow‐up was not reported
Selective reporting (reporting bias)	Unclear risk	Not all outcomes reported
Other bias	Unclear risk	Funding not reported