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Hypertension And the Sprint Trial

What does it mean? What do we do?

Flow of Talk

• Setting context heading into 2016– Brief Epidemiology– ACCORD Trial Review– Guideline Recommendations (JNC-8 and others)

– Recent Meta-analyses• SPRINT trial—What does it mean? Does it

matter?• What to do now ???

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Hypertension:Epidemiology Factoids

• 78 million adults have hypertension• 66% adults over 60 years old have hypertension• 10 mm lower BP reduces lifetime CV risk 25-40%

Lancet 2002; 360: 1902‐13

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(n=2,255)

Reference

INVEST: Outcomes – Tight Control Group

JAMA. 304(1):61‐68, July 7, 2010.

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Hypertension TherapyBenefits (>50 yrs)

• CHF reduction (50%)• Stroke reduction (35%)• MI reduction (25%)• CV Mortality reduction* (21%)

*HYVET – 2008

ACCORD Trial(Action to Control Cardiovascular Risk in Diabetics)

10,251 high‐risk diabetics

Intense vs. standardglycemic control

4733 pts                                    5518 pts

SBP ≤ 120           SBP ≤140         simvastatin  simvastatin+

fenofibrate

[NEJM April, 2010]

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ACCORD Trial(Action to Control Cardiovascular Risk in Diabetics)

10,251 high‐risk diabetics

Intense vs. standardglycemic control

4733 pts                                    5518 pts

SBP ≤ 120           SBP ≤140         simvastatin  simvastatin+

fenofibrate

[NEJM April 2010]

ACCORD TRIAL:Really Lowered BP

[NEJM April 2010]

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ACCORD TrialResults

[NEJM April 2010]

• The results provide no conclusive evidence that the intensive BP control strategy reduces the rate of a composite endpoints of major CVD events in diabetics at HIGH CV risk

NEJM: April 2010

ACCORD Trial:Conclusions

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Hypertension Management

JNC – 7 JNC – 8

>60 years old <140 <150

<60 years old <140 <140

Diabetes/CKD <130 <140

Guidelines 2015Guidelines: Year of

PublicationBP target

>80 y/o 60-80 y/o CKD,DMJNC 81 2014 <150/90 <150/90 <140/90

NICE2 2011 <150/90 <140/90 None Made

CHEP3 2013 <150 <140/90 <140/90-CKD<130/80-DM

ESH/ESC4 2013 <150 <140 <140/85

ASH/ISH5 2014 <150/90 <140/90 <140/90

AHA/ACC6 2013 <140/90 <140/90 <140/90

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©

Stratified by Attained Blood Pressure : Brunström, and Carlberg BMJ 2016;

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<140

<120

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SPRINT Trial

• 9361 non-diabetic hypertensives at increased CV risk

• Randomized to SBP target 120 vs 140• 102 clinical sites in U.S.• Sponsored by NHLBI• Treatment protocols were identical to ACCORD

[NEJM, Nov 26, 2016]

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SPRINT TrialInclusion Criteria

• ≥ 50 y/o• SBP >130• One of the following

– History of CVD– Stage 3 CKD– CVD 10 yr risk >15% (Framingham)– >75 years old with or without risk factor

SPRINT Trial

• Definition of hypertension (SBP)

Number of Meds

Range (SBP)

0‐1 130‐180

2 130‐170

3 130‐160

4 130‐150

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SPRINT Trial

• Definition of CV risk– Clinical

• Previous MI• Previous revascularization• (+) ETT or ACS• 50% stenosis of major artery• AAA ≥5 cm

– Subclinical• Coronary CT score ≥ 400• ABI < 0.9• LVH

SPRINT TrialExclusions

• Diabetes – no benefit (ACCORD, NEJM 2010)

• PCKD – no ∆ GFR (HALT, NEJM 2014)

• ≥ 1 gm proteinuria (REIN-2 Lancet 2005)

– less protein– No ∆ GFR

• Stroke - no benefit (SPS3 Lancet Neurol 2014)

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Systolic Blood Pressure in the Two Treatment Groups over the Course of the Trial.

The SPRINT Research Group. N Engl J Med 2015;373:2103-2116

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SPRINT TrialAuthor’s Conclusions

“Among adults with hypertension, butwithout diabetes, lowering SBP to ≤140 resulted in significantly lower rates of fataland non-fatal CV events – also death fromany cause.”

SPRINT TrialResults

Relative Absolute(per yr)

NNT

Composite 1° endpoint 25% 0.54 185

Heart failure 38% 0.18 555

CV death 43% 0.18 555

Death (any cause) 27% 1.2 83

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Serious Side Effects

Absolute Risk Increase (per 100)

Hypotension 1.4  (<0.001)

Syncope 1.1  (0.005)

Bradycardia 0.4  (0.05)

Injurious fall NS

AKI 1.8  (< 0.001)

[NEJM Nov 26, 2015, Suppl 5]

Sprint Trail: Risks and Benefits

NNT NNH

Primary Endpoint

185

Heart Failure 385

CV Death 555

Overall Death 270

Hypotension 71

Syncope 91

Bradycardia 250

Injury Fall NS

AKI 56

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Sprint Trail: Risks and Benefits

NNT NNH

Primary Endpoint

185

Heart Failure 385

CV Death 555

Overall Death 270

Hypotension 71

Syncope 91

Bradycardia 250

Injury Fall NS

AKI 56

For 1000 Sprint‐like participants treated to 120 for 3.3 years:

‐16 people will benefit‐22 people will be harmed‐962 will neither benefit or be harmed

Ortiz et alAnnals of Internal MedicineFebruary 23, 2016

SPRINT TrialCaveats from Authors

• Significant populations excluded: diabetics, h/o CVA, severe/resistant HTN + additional clinic resources (30% more visits)

• One additional medicine required to achieve intensive goal

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SPRINT TrialComposite Endpoints NOT Improved

• Female patients (HR 0.84)• Black patients (HR 0.77)• Pre-existing CKD (HR 0.82)• Patients <75 y/o (HR 0.80)• SBP >132-144 (HR 0.77)

< 145 (HR 0.83)

SPRINT TrialQuestions NOT Answered

• To whom do these results apply?• What about diastolic blood pressure?• Long-term impact on renal function?• Impact on cognition in the elderly?• What about patients with CHF?

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SPRINT vs ACCORD

SPRINT ACCORD

No diabetics Only diabetics

# participants 9361 4733

Age (mean) 68 yr 62 yr

Populations No diabetics or previous stroke

Only diabeticsExcluded >80 years & 

Creat.>1.5

Diuretic Chlorthalidone HCTZ

Overall Event Rate (control group)

2.2% 2.1%

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Journal of Hypertension. 34(4):613‐622, April 2016

Journal of Hypertension. 34(4):613‐622, April 2016

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Published on line April 2nd 2016

• 12,000 middle aged, intermediate risk• Randomized to Valsartan/HCTZ vs placebo

(without regard to pre-existing BP)

• Baseline BP 138• Reduced by 10mm in treatment, 4mm in placebo• Followed for average of 5 years

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Lonn EM et al. N Engl J Med 2016. DOI: 10.1056/NEJMoa1600175

Cumulative Incidence of Major Cardiovascular Events, According to Trial Group.

Lonn EM et al. N Engl J Med 2016. Prepublication On‐Line April 2nd 2016

Forest Plots, According to Subgroup of Systolic Blood Pressure for the CoprimaryOutcomes.

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Conclusions:

• Hypertension should be treated.. Confusion is not a cause for inaction

• When goals should be below 140 remains unclear• Best support for SBP goals 120-125

– High Risk, non diabetics, without significant side effects with intensive treatment

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SPRINT TrialExclusion Criteria

• Known secondary hypertension

• Orthostatic BP at baseline

• Proteinuria (≥ 1 gm/day)

• Diabetes

• History of stroke

• CV event within 3 mos

• GFR <20 ml/min/mL

• Symptomatic heart failure within 6 mos

• Ejection fraction <35%

• Projected survival <3 yrs

• Factors projected to limit adherenc3e