AASK 2002

Methods	Multicenter, 3 x 2 factorial design, intention‐to‐treat (ITT) strategy. Participants randomized equally to a usual mean arterial pressure goal of 102 to 107 mmHg or to a lower mean arterial pressure goal of 92 mmHg or lower, and to treatment with metoprolol, ramipril or amlodipine. When the blood pressure goal was not achieved using the randomized drug, other open‐labelled antihypertensive agents were added to participants' treatment. Participants and investigators were not masked to the blood pressure goal. The follow‐up was 3 to 6.4 years (mean 3.8 years).
Participants	African‐American men and women, aged 18 to 70 years, with hypertension defined as sitting DBP ≥ 95 mmHg and reduced kidney function, defined as glomerular filtration rate (GFR) between 20 and 65 mL/min per 1.73 m². Exclusion criteria included DBP < 95 mmHg, known history of diabetes mellitus, urinary protein to creatinine ratio > 2.5, accelerated or malignant hypertension within 6 months, secondary hypertension, evidence of non blood pressure‐related causes of chronic kidney disease (CKD), serious systemic disease or clinical congestive heart failure (CHF). Baseline characteristics for participants included in the review (%) or mean ± SD): men/women (68/32%); age (57 ± 9 years); SBP (149 ± 28 mmHg); DBP (93 ± 16 mmHg); mean blood pressure (MBP) (112 ± 19 mmHg); current smoker (31%); types of drugs at 1 year: No information available. Previous cardiovascular condition: ischaemic heart disease (IHD) (25%), stroke (69%), peripheral vascular disease (PVD) (23%). Country: USA
Interventions	Standard (usual) target: MBP 102 to 107 mmHg Lower target: MBP < 92 mmHg
Outcomes	The primary analysis was based on the rate of change in GFR (GFR slope). As a key secondary analysis, all cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions (MI), strokes, heart failure, revascularization procedures and other hospitalised cardiovascular events were reviewed and classified by a blinded endpoints committee according to a prespecified protocol
Funding sources	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Also partially funded by other National Institutes of Health grants, Office of Research in Minority Health, Pfizer, AstraZeneca and King Pharmaceuticals
Declarations of interest	"Dr Wright has no stock ownership but has received research grants, honoraria, and consult fees from Astra, Bayer, Bristol‐Myers Squibb, Eli Lilly and Co, Merck & Co, Novartis Pharma AG, Pharmacia, Pfizer, Sankyo Inc, GlaxoSmithKline, and Solvay/Unimed. Dr Appel has received honoraria from Astra and Novartis Pharma AG. Dr Cheek is a speaker for Wyeth, Novartis, and Sanofi‐Synthelabo, and investigator for Abbott Laboratories. Dr Middleton is a speaker for Merck and a consultant for King Pharmaceuticals"
Notes	The amlodipine arm was halted in September 2000. The blood pressure achieved at the end of the trial was: standard target: MBP 104 ± 7; lower target: MBP 95 ± 8 A public repository provided individual patient data from hypertensive participants with established cardiovascular disease to be used in this systematic review
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The computer screen displayed the blood pressure group to which the patient had been randomised (usual or low)" (p. S157)
Allocation concealment (selection bias)	Low risk	"The computer screen displayed the blood pressure group to which the patient had been randomised (usual or low). Random permuted blocks with randomly varying block sizes were utilized" (p. S157)
Blinding of participants and personnel (performance bias) All outcomes	High risk	The study design was not compatible with blinding of participants and personnel
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"All cardiovascular events including cardiovascular deaths and hospitalizations for myocardial infarctions, strokes, heart failure, revascularization procedures, and other hospitalised cardiovascular events were reviewed and classified by a blinded endpoints committee according to a prespecified protocol". (p. S161)
Incomplete outcome data (attrition bias) All outcomes	Low risk	There does not seem to be a significant imbalance in follow‐up flow diagram, according to Figure 1 (pp. 2421‐31)
Selective reporting (reporting bias)	Low risk	Protocol checked to cardiovascular outcomes
Other bias	Unclear risk	Subgroup of participants with basal cardiovascular disease not predefined