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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