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Tight BP Control Flops for Most CKD Patients
  MedPage Today
Published: September 01, 2010
Intensive blood pressure control doesn't slow progression of chronic kidney disease (CKD) in hypertensive patients overall but may help those with baseline proteinuria, according to a randomized trial.
Achieving a target below 130/80 mm Hg didn't prevent a doubling of serum creatinine, end-stage diagnosis, or death in hypertensive CKD patients compared with a standard target of 140/90 mm Hg (hazard ratio 0.91, P=0.27), Lawrence J. Appel, MD, MPH, of Johns Hopkins, and colleagues found.
Only the one-third of patients with clinically significant proteinuria at baseline appeared to benefit from the lower target (HR 0.73, P=0.01), the researchers reported in the Sept. 2 issue of the New England Journal of Medicine.
Action Points
* Explain to interested patients that intensive blood pressure control doesn't slow progression of chronic kidney disease (CKD) in hypertensive patients overall but may help those with baseline proteinuria.
* Note that the study included only African-American men and may or may not be generalizable to other populations.
These results from more than a decade of follow-up in the African-American Study of Kidney Disease and Hypertension (AASK) largely mirror the initial presentation at the American Society of Hypertension meeting in 2008.
Although national guidelines recommend 130/80 mm Hg as the target for high risk patients -- those with diabetes or CKD -- tight control has failed to demonstrate cardiovascular or renal benefits in either group in recent studies.
"We are finally obtaining the data on which to evaluate the validity of the recommendations," explained coauthor Jackson T. Wright Jr., MD, PhD, of Case Western Reserve Medical School in Cleveland, in an interview.
Now that the answer is emerging as a negative, physicians can safely refocus their efforts on getting the large number of uncontrolled patients down to the standard 140/90 mm Hg goal rather than pushing even lower, he suggested.
"For those patients without protein in their urine, this study suggests and provides fairly convincing evidence that the additional expense of more medications, the potential side effects of those medications, the greater monitoring, more office visits, is probably not [worthwhile]," Wright told MedPage Today.
The study included only black men, who are more likely to have microalbuminuria as a feature of chronic kidney disease than non-Hispanic whites, noted Julie R. Ingelfinger, MD, of Massachusetts General Hospital in Boston, in an editorial accompanying the NEJM paper.
However, the study results likely generalize to other populations, Wright said.
Prior studies also provide support for baseline proteinuria as a predictor of CKD progression and of benefit from treatment, Ingelfinger agreed.
The explanation may be that patients with baseline proteinuria were somewhat younger, she wrote in the editorial, "and one might speculate that they had less vascular disease and less inflammation and thus could benefit from blood pressure control."
The AASK study included 1,094 African-American men with non-diabetic, hypertensive chronic kidney disease who were randomized in the initial phase to treatment to a low blood pressure goal (mean arterial pressure less than 92 mm Hg, corresponding to less than 130/80 mm Hg) or the usual goal (mean arterial pressure 107 mm Hg, corresponding to 140/90 mm Hg).
During an average of four years in this initial phase, the lower goal performed as expected, with patients achieving blood pressure down to an average of 130/78 mm Hg compared with 141/86 mm Hg in the control group.
Patients without an event then rolled over into a cohort phase in which all were treated to a goal of less than 130/80 mm Hg with follow-up through a total of more than 12 years. During this phase, blood pressures averaged 131/78 mm Hg in those previously in the intensive group and 134/78 mm Hg in the former control group.
But similar to the overall cohort, intensive blood pressure control had no effect on progression of chronic kidney disease over the combined phases (hazard ratio 1.18, P=0.16) in those with a baseline protein-to-creatinine ratio of 0.22 or less, corresponding to the threshold for proteinuria of more than 300 mg/day
Among those with baseline proteinuria above this threshold, though, intensive control consistently improved outcomes over the combined trial and cohort phases as follows:
* For the primary outcome measure of progression of chronic kidney disease (HR 0.73, P=0.01)
* For doubling of the serum creatinine level or end-stage renal disease (HR 0.76, P=0.04)
* For end-stage renal disease or death (HR 0.67, P=0.002).
These benefits for those with baseline proteinuria appeared to have emerged, though not yet significantly, in the trial phase and then persisted through the cohort phase, the researchers noted, based on the Kaplan–Meier plots.
They noted that although the study also included randomization to three different drug regimens -- beta-blockers, calcium channel blockers, and ACE-inhibitors -- use of renin-angiotensin system medications was similar between blood pressure groups in both phases.
Nor was insufficient statistical power a likely explanation for lack of benefit in most patients, they added.
The study was limited by adjustment of therapy based on standard office blood pressure readings rather than ambulatory readings, they acknowledged.
The study was supported by grants to each clinical center and the coordinating center from the National Institute of Diabetes and Digestive and Kidney Diseases; by the Office of Research in Minority Health (now the National Center on Minority Health and Health Disparities); by institutional grants from the National Institutes of Health; by King Pharmaceuticals, which provided monetary support and antihypertensive medications to each clinical center; and by Pfizer, AstraZeneca, GlaxoSmithKline, Forest Laboratories, Pharmacia, and Upjohn, which donated antihypertensive medications.
Appel and Wright reported having received grant funding to his institution from King Pharmaceuticals and support in the form of provision of medications to his institution by King Pharmaceuticals, Pfizer, AstraZeneca, GlaxoSmithKline, Forest Laboratories, Pharmacia, and Upjohn.
Wright also reported consulting for CVRx, Novartis, Daiichi-Sankyo, and sanofi-aventis.
Ingelfinger reported having received royalties from Elsevier for Current Pediatric Therapy, from Up-to-Date, and from St. Martin's Press. She also reported being employed by the New England Journal of Medicine as a deputy editor.
Primary source: New England Journal of Medicine
Source reference:
Appel LJ, et al "Intensive blood-pressure control in hypertensive chronic kidney disease" N Engl J Med 2010; 363: 918-29.
Additional source: New England Journal of Medicine
Source reference:
Ingelfinger JR "Hypertension control in African-American patients with chronic kidney disease" N Engl J Med 2010; 363: 974-76.
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