Further analysis of long-term follow up of patients from the AASK study found indications that intensive blood pressure (BP) control might reduce chronic kidney disease (CKD) progression in those with baseline proteinuria.

AASK tested antihypertensive regimens based on three drug groups in non-diabetic African-American patients with hypertension and signs of renal impairment, to determine whether any drug class was superior and whether more intensive BP control had advantages. Drugs used were ramipril, amlodipine, and metoprolol: the amlodipine arm was stopped early due to poorer outcomes. The results from the original trial, published in 2002 (JAMA 2002; 288(19): 2421-31), did not show any superiority for intensive BP control in the primary outcome of kidney disease progression.

Those who completed the trial without diagnosed end-stage renal disease (ESRD) were invited to join a cohort study in which they received recommended therapy with a target BP of 130/80 mmHg. Primary outcome was progression of kidney disease, defined as a doubling of the serum creatinine level (roughly, halving GFR), a diagnosis of ESRD, or death. Overall outcomes of the cohort study at conclusion with a maximum follow-up of 12.2 years have been reported (Arch Intern Med 2008;168(8):832-839) and confirmed the lack of significant benefit from intensive control. This paper reports a pre-specified subgroup analysis, the primary outcome according to proteinuria at baseline (measured as log-transformed protein-to-creatinine ratio).

There were 1,094 patients initially randomised to the study, of whom 759 were included in the cohort study. Treatment was open-label with ramipril as first-line therapy; if ramipril was not tolerated, an angiotensin receptor blocker (ARB) was used. Additional drugs were added (furosemide, beta-blockers, calcium channel blockers, centrally acting a-adrenergic blockers, and direct vasodilators) to achieve control. Across the entire study, there was a significant interaction between the randomised blood-pressure group and the protein-to-creatinine ratio for the primary outcome (P=0.02 for interaction). In patients with a protein-to-creatinine ratio of more than 0.22, those in the intensive-control group had a significant reduction in the risk of the primary outcome (hazard ratio, 0.73; 95% CI, 0.58 to 0.93; P=0.01).

Based on this analysis, the authors conclude that the evidence for intensive blood pressure control in black patients with hypertensive CKD is sparse. In their sub-group analysis, however, there was an indication that it may be beneficial in some patients, specifically those with a protein-to-creatinine ratio of more than 0.22. They comment that as a sub-group analysis the results should be interpreted with caution; however they are consistent with other study results.

An accompanying editorial discusses the study results.