Blog entry by Meguid El Nahas

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by Meguid El Nahas - Sunday, 17 January 2016, 10:11 PM
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N Engl J Med
.
 2015 Nov 26;373(22):2103-16. doi: 10.1056/NEJMoa1511939. Epub 2015 Nov 9.

A Randomized Trial of Intensive versus Standard Blood-Pressure Control.

Abstract

BACKGROUND: The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain.

METHODS: We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes.

RESULTS: At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group.

CONCLUSIONS: Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01206062.).

 COMMENTS

Before we get carried away...and guidelines revisited...and so much more, lets stop the SPRINT...and look critically at the data:

Whilst this long awaited clinical trial showed a significant reduction in cardiovascular events in the intensive BP control group, it also reveals that intensive BP control was of no apparent benefit in patients suffering from CKD and even potentially harmful in such high risk of CVD patients.

Of note, in SPRINT intensive BP reduction did not impact on:

Cororonary artery events 

or

Cerebrovascular accidents

It improved CHF, presumably due to more aggressive diuretic therapy use in the intensive BP group...at a cost...

In CKD patients, a quarter of all those enrolled in the SPRINT trial, intensive BP control led to:

1. No reduction in CVD event rate or related mortality

2. No impact on CKD progression

3. Increased incidence of CKD

4. Increased incidence of AKI

In other words, intensive BP control led to harm in those elderly patients with or without CKD as far as  renal function is concerned.

A number of clinical trials previously showed that intensive BP control was of little benefit in non-proteinuric CKD:

REIN2 study was negative: 

http://www.ncbi.nlm.nih.gov/pubmed/15766995

AASK was also negative:

http://www.ncbi.nlm.nih.gov/pubmed/?term=intensive+BP+control%2C+Appel

the latter RCT hinted that progression may benefit of tighter BP control in those with CKD and proteinuria, an impression previously reported in the MDRD trial.

With the above in mind, Nephrologists should be cautious of overzealous BP reduction, in elderly individuals with CKD in the absence of significant proteinuria. Whilst there is no evidence of benefit, there is growing evidence of harm in the presence of hypotension in such age group. Not only faster CKD progression but also increased susceptility to AKI

(specially when the dreaded RAAS inhiobitors are used: http://www.ncbi.nlm.nih.gov/pubmed/24223154) 

and ultimately, falls and fractures known to be associated with increased morbidity and mortality in this age group.

 

 
[ Modified: Thursday, 1 January 1970, 1:00 AM ]