#CHC16: Hypertension Targets: How Low Should You Go?

Hypertension Canada’s 6th annual Canadian Hypertension Congress (#CHC16) is being held from Oct 19-21 2016 in Montreal. AJKD Blog will be providing some highlights from the conference; the entire program is available here.

wcushman_pic

Dr. William Cushman

The top scientific story in the nephrology and hypertension world in 2015 has surely been SPRINT (Systolic Blood Pressure Intervention Trial). The report was published in the New England Journal of Medicine, and an additional paper on the outcomes in the elderly has been published in the Journal of the American Medical Association. The dramatic results, including the benefit of a lower blood pressure (BP) target, lead to early stoppage of the trial by the National Institutes of Health (NIH); however, paradoxically, subsequent changes in guidelines and clinical practice have lagged behind. Many reasons might underlie this delay, including concerns about the trial’s BP measurement method and the ease–or perhaps difficulty–in achieving these low blood pressure targets. Therefore, it was timely to have Dr. William Cushman, one of the SPRINT investigators, present at the #CHC16 on the details and implications of the trial. In his lecture, Dr. Cushman highlighted some key aspects of SPRINT and shared some behind-the-scene pearls.

The SPRINT trial seemed to have somewhat stringent criteria, requiring hypertensive patients who were more than 50 years of age to have an additional factor placing them at high risk of cardiovascular disease (e.g., age > 75 years, chronic kidney disease [CKD] with glomerular filtration rate [GFR] 30 to 59 mL/min/1.73 m2, Framingham risk score > 15%). Chosen for reasons of equipoise, these criteria were not really stringent when it came to enrolment – indeed, at one point the NIH asked the centers to slow down with enrollment for logistic reasons! The bottom line was that doctors see patients like this almost every day in their clinics. The BP measurement method has received a lot of attention (see #NephMadness coverage here), and Dr. Cushman only stressed the need to follow proper methods for office BP measurement. The medications used are notable for their long-acting effects and potent anti-hypertensive properties. Thus, chlorthalidone (not hydrochlorothiazide) was encouraged as the primary thiazide-type diuretic, and amlodipine was the preferred calcium-channel blocker. The use of these medications at higher doses explains why the patients in the intensive treatment arm achieved lower systolic blood pressure (~15 mm Hg) with only one extra drug on average compared to controls. Dr. Cushman also showed a nice graph of the distribution of BP to tell a story beyond just the mean and median (121 and 119 mm Hg, respectively, in the intensive arm). With respect to renal outcomes, he stressed that the observed increase in acute kidney injury was mainly biochemical, with no increase in requirement for dialysis therapy. Similarly, the increase in the CKD outcome (GFR decline of >30% to <60 mL/min/1.73 m2 in those with baseline GFR >60 mL/min/1.73 m2) also did not result in a single patient requiring dialysis therapy. The last point Dr. Cushman made involved the perplexing lack of impact on stroke seen in SPRINT, as stroke is the outcome most tightly linked to hypertension. He pointed out that even in ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes – Blood Pressure Trial), the separation in arms for stroke was seen after 4 years, and SPRINT was stopped at an average follow-up of 3.26 years. (Of note, ACCORD-BP reported lack of benefit in mortality with intensive BP control but did report significant reduction in stroke.)

Group Systolic Blood Pressure Target

(mm Hg)

Grade
High risk, GFR > 20 mL/min/1.73 m2,

no dementia, not in nursing home with Systolic BP > 130

<120 (assuming 60% <120 at single visit)

<130 (assuming 80% <120 mm Hg at single visit)

A (strong)
Diabetes, post-stroke <120 or 130, as above B (moderate)
Age < 50 years, high risk <120 or 130, as above Expert opinion
Age < 50 years, low risk <140 Expert opinion
Table 1. Dr. Cushman’s thoughts on new hypertension targets.

Dr. Cushman closed with a summary slide on what BP targets he would be comfortable endorsing (Table 1). Since there is visit-to-visit variation, the thresholds vary from <120 to <130 mm Hg depending on our assumption of actual BP at a single visit. How would that compare to existing guidelines? For a side-by-side comparison, Table 2, which includes some notes on extrapolation.

KDIGO

2012

Japan

2014

JNC 8 ESH/

ESC

2013

CHEP

2016

Australia

2016

Cushman
NP-CKD <140 <140 <140 <140  <140 <140

<120#

<120 or 130

(if GFR >20)

P-CKD <130 <130 <140 <140  <140 <140

<120#

<120 or 130

(if GFR >20)

DM,

NP-CKD

<140 <130 <140 <140  <130 < 140

<120*

<120 or 130

(if GFR >20)

DM,

P-CKD

<140 <130 <140 <140  <130 <140

<120*

<120 or 130

(if GFR >20)

Elderly <150 <150 <140  <150 <120 <120 or 130
High

Risk

 <120 <120 <120
Table 2. Dr. Cushman’s recommendations for systolic BP targets (in  mm Hg) vs. those of existing guidelines for patients with CKD (GFR in mL/min/1.73 m2). Elderly defined as >80 years in CHEP, >60 years by JNC, >75 years by Australia (if lower BP well tolerated) and with no dementia or not a resident of a nursing home per Dr Cushman. Number sign (#) indicates if well tolerated, level II evidence (level I evidence for higher target of <140 mm Hg). Asterisk (*) indicates if stroke reduction prioritized (for targets in DM in Australia). Abbreviations: CHEP, Canadian Hypertension Education Program; DM, diabetes mellitus; ESH/ESC, European Society of Hypertension/European Society of Cardiology; GFR, glomerular filtration rate; JNC 8, Eighth Joint National Committee; KDIGO, Kidney Disease – Improving Global Outcomes; NP-CKD, non-proteinuric chronic kidney disease; P-CKD, proteinuric CKD.

As we can see, there is a virtual cornucopia of differing targets, hopefully some of which will get streamlined as more associations update their guidelines. As a final note, Dr. Cushman mentioned several additional analyses, some pre planned (e.g. the SPRINT-MIND study) and some post hoc, (e.g., an analyses on BP measurement methods) that will be available in the coming months.

Post written by Dr. Swapnil Hiremath, AJKD Blog Contributor.

Check out more AJKD blog coverage of the CHC 2016!

Note: Previous coverage of SPRINT can be found here (#NephJC) and here (#askASN).

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