Monday, September 11, 2017

Blood pressure goals in patients with CKD: how low should we go?

- Kenny Lin, MD, MPH

In 2013, the Eighth Joint National Committee (JNC 8) recommended that adults with hypertension and chronic kidney disease (CKD) be treated to a blood pressure (BP) goal of lower than 140/90, after finding no evidence that treating to lower BP goals showed the progression of CKD. At the same time, the American College of Physicians published a guideline on screening, monitoring, and treatment of Stage 1 to 3 CKD that suggested pharmacologic therapy with an ACE inhibitor or angiotensin II receptor blocker, but noted "no difference in end-stage renal disease or mortality between strict blood pressure control (128 to 133/75 to 81 mm Hg) and standard control (134 to 141/81 to 87 mm Hg)."

Less than two years later, however, findings from the Systolic Blood Pressure Intervention Trial (SPRINT) suggested that some older adults at high risk of cardiovascular disease, including those with CKD, may experience additional benefits if treated to a systolic BP goal of 120. After reviewing SPRINT and other recent studies, the American Academy of Family Physicians and the American College of Physicians decided in a new guideline for adults aged 60 years or older to stick with a systolic BP goal of 140 for adults at high cardiovascular risk.

Two systematic reviews and meta-analyses published recently in JAMA Internal Medicine ensure that debate about BP goals for adults with CKD will continue. The first study, by Dr. Wan-Chuan Tsai and colleagues, identified 9 randomized trials (n=8127) that compared intensive BP control (less than 130/80 mm Hg) with standard BP control (less than 140/90 mm Hg) in nondiabetic patients with chronic kidney disease. They found no significant differences between the groups in annual rate of change in glomerular filtration rate (GFR), doubling of serum creatinine level, a composite renal outcome, or all-cause mortality over a median follow-up of 3.3 years.

The second study, by Dr. Rakesh Malhotra and colleagues, extracted data from 18 randomized trials that included 15,924 participants with CKD to determine if more intensive (mean systolic BP 132 mm Hg) compared with less intensive (mean systolic BP 140 mm Hg) control reduced mortality risk in persons with CKD stages 3 to 5. The authors found that more intensive BP control was associated with a statistically significant 14% lower relative risk of all-cause mortality.

An accompanying editorial by Dr. Csaba Kovesdy did a good job of putting these findings into perspective. Dr. Kovesdy pointed out that the benefits of a systolic BP goal of 120 for persons with CKD remain uncertain, and that the meta-analysis could have low external validity because trials had much lower absolute mortality rates than those in observational cohorts of adults with CKD. Finally, he observed that any incremental mortality benefit from intensive BP control is small in comparison to that already achieved by standard BP control:

We must remember that the highest risks of hypertension occur in those with extremely elevated BP levels, and the benefits accrued with treating systolic BP to levels below about 140 mm Hg are much smaller. ... More intensive vs less intensive BP lowering resulted in a [number needed to treat] to prevent 1 death of 167 based on the absolute risk reduction estimated in the meta-analysis by Malhotra et al and an NNT to prevent 1 composite renal failure event of 250 based on the results of another meta-analysis. These diminishing absolute benefits have to be weighed against the increased likelihood of adverse effects and the higher costs associated with more intensive BP lowering.

Bottom line: if family physicians choose to devote more resources to patients with CKD or other cardiovascular risk factors who might benefit from lower-than-usual BP goals, they should not lose focus on improving care for the 46% of U.S. adults with hypertension whose BPs are not adequately controlled by any standard.

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