sprint, royal columbian hospital medicine rounds, nov 10, 2015

SPRINT FROM @NEJMBP TARGET < 120 VS < 140 MM HG

Daniel Schwartz, MD Nov 13, 2015

BP TARGETSTHEY KEEP CHANGING

WHAT’S YOUR TARGET?

BACKGROUND

WHY TREAT HYPERTENSION

▸ Treatment to reduce elevated blood pressure can lead to reduction in

▸ coronary artery disease (CAD)

▸ congestive heart failure

▸ stroke

▸ chronic kidney disease

irrespective of age, sex, race or ethnic background and HTN severity

BACKGROUND

OBSERVATIONAL

▸ Observational studies

▸ linear relationship between blood pressure and cardiovascular risk down to 115/75 mm Hg

▸ J-curve - is it confounded?

BACKGROUND

CURRENT CHEP GUIDELINES: BP TARGETS

▸ <130/80 mm Hg: Diabetes

▸ <150 mm Hg systolic: >80 years

▸ <140/90: All else

BACKGROUND

IN DIABETES

▸ Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial

▸ Systolic BP < 120 mm Hg vs <140 mm Hg

▸ no difference in cardiovascular events in DM2

TRIAL

METHODOLOGY

TRIAL

TRIAL DESIGN

▸ randomized, controlled, open-label trial

▸ multicenter

▸ randomization stratified by site

▸ blinded outcome adjudicators (patients/researchers not blinded)

▸ primary analysis compared time to 1st occurrence of primary outcome event with intention-to-treat

▸ independent data and safety monitoring board monitored unblinded trial results and safety events

TRIAL

FUNDING

▸ NIH

▸ no industry funds

TRIAL

INCLUSION

▸ age >= 50 years

▸ Systolic blood pressure

▸ 130 – 180 mm Hg on 0 or 1 medication

▸ 130 – 170 mm Hg on up to 2 medications

▸ 130 – 160 mm Hg on up to 3 medications

▸ 130 – 150 mm Hg on up to 4 medications

▸ increased risk of cardiovascular events

▸ clinical or subclinical cardiovascular disease other than stroke

▸ CKD excluding polycystic kidney disease (eGFR 20-60)

▸ 10-year risk of cardiovascular disease >= 15% (Framingham)

▸ age >= 75 years

TRIAL

EXCLUSION

▸ Diabetes

▸ Hx of stroke

▸ An indication for a specific BP lowering medication

▸ Secondary hypertension

▸ Orthostatic BP < 110

▸ PKD, GN needing immunosuppression

▸ >1gm/day proteinuria

▸ EF < 35%

▸ Recent heart failure < 6 months, cardiac event < 3 months

TRIAL

INTERVENTION

▸ BP target <140 vs 120

▸ Treatment algorithm

▸ lifestyle

▸ drugs

TRIAL

PRIMARY OUTCOME

▸ Composite

▸ myocardial infarction

▸ acute coronary syndrome

▸ stroke

▸ acute decompensated heart failure

▸ death from cardiovascular causes

RESULTS

RESULTS

STOPPED EARLY

▸ 9361 patients enrolled

▸ Aug 20, 2015 - terminated early due to improved outcome with intensive target

RESULTS

BLOOD PRESSURES

▸ Baseline

▸ 139.7/78.2 mm Hg (intensive)

▸ 139.7/78.0 mm Hg (standard)

▸ 1 year

▸ 121.4/68.7 mm Hg (intensive) with 2.8 meds

▸ 136.2/76.3 mm Hg (standard) with 1.8 meds

RESULTS

RESULTS

▸ Intensive-treatment

▸ 25% RRR of major cardiovascular events (95% CI, 11 to 36)

▸ 27% RRR of death (95% CI, 10 to 40)

RESULTS

NNT

TO PREVENT A PRIMARY OUTCOME EVENT: 61

DEATH FROM ANY CAUSE: 90 DEATH FROM CARDIOVASCULAR CAUSES: 172OVER MEDIAN 3.26 YEARS

RESULTS

SERIOUS ADVERSE EVENTS

▸ Intensive arm: 4.7%vs

▸ Standard arm: 2.5% serious adverse events (HR, 1.88; P<0.001)

METHODS

METHODOLOGIC ISSUES?

▸ Stopping early

▸ can overestimate benefit in small trials

▸ unlikely with > 500 primary outcome events

▸ Lack of blinding (BP can be measured)

▸ mitigated by structured assessment of outcomes and adverse events

METHODS

GENERALIZABILITY

▸ Cannot apply to those with

▸ Diabetes

▸ History of Stroke

▸ Institutionalized Elderly

▸ Advanced/highly proteinuric CKD

METHODS

RISK VS BENEFIT

▸ Do benefits outweigh risks?

CURRENT GUIDELINES … REQUIRE REVISION.

Vlado Perkovic, for the NEJM

TAKE AWAY

REAL WORLD

▸ BP goal of 140/90 mm Hg

▸ US: 33-50% not at target

▸ Many developing countries: >90% not at target

16.8 MILLION US ADULTSMEET INCLUSION CRITERIA

J Am Coll Cardiol. 2015;():. doi:10.1016/j.jacc.2015.10.037

TAKE AWAY

NEPHROLOGY PRACTICE

▸ 28% had GFR 20-60 ml/min

▸ Excluded

▸ GFR < 20

▸ Proteinuria > 1gm

▸ Excluded highest risk for progression to ESRD

TAKE AWAY

SIGNIFICANT EFFORT

▸ in SPRINT

▸ initial combination therapy

▸ monthly visits until BP at target

CLINICAL TRIALS ARE DIFFERENT FROM REAL LIFE

TAKE AWAY

REAL WORLD

▸ Adoption of lower BP targets would mean

▸ more cautious titration of medications

▸ more combination treatment

▸ more care watching for adverse effects

▸ more frequent visits

▸ addressing lifestyle issues (physical activity, salt intake, obesity, sleep apnea, and alcohol use)

▸ population-level initiatives (eg sodium in food)

TAKE AWAY

MORE HELP

▸ People

▸ Nurse practitioners

▸ Physician assistants,

▸ Pharmacists

▸ Others?

▸ Treatment algorithms

▸ Algorithmic monitoring/EHRs?

TWITTER: POLL REFERENCES@nephrologynow

WHAT’S YOUR TARGET?