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Managing Blood Pressure in 2019: Achieving New Goals

Daniel Blanchard, MDProfessor of Medicine

UC San Diego Cardiovascular CenterLa Jolla, California

The SPRINT StudyA Randomized Trial of Intensive Versus Standard Blood-Pressure

Control

NEJM 2015;373:2103-16

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SPRINTStudy Overview

• 9361 patients, >50 yrs (mean age 68 years, 28% >75 yrs), with SBP >130 and <180 mmHg & at increased CV risk but no DM.

• Pts were assigned to intensive treatment with a target of SBP<120 mm Hg or standard treatment with a target of SBP<140 mm Hg.

SPRINT Study

Primary end point : Composite of cardiac events including MI, HF or CV mortality.

After a median of 3.3 years, the Data Safety Monitoring Committee ended the study early.

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The SPRINT Research Group. N Engl J Med 2015. DOI: 10.1056/NEJMoa1511939

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

Mean # of BP medications 2.8 vs.1.8Mean SBP at 1 year 136 vs.121 mmHg

The SPRINT Research Group. N Engl J Med 2015. DOI: 10.1056/NEJMoa1511939

Primary Outcome and Death from Any Cause.

CV DeathACSHF

SPRINT Primary Outcome and its Components

Event Rates and Hazard Ratios Intensive Standard

No. of Events Rate, %/year No. of Events Rate, %/year HR (95% CI) P value

Primary Outcome

243 1.65 319 2.19 0.75 (0.64, 0.89)

<0.001

All MI 97 0.65 116 0.78 0.83 (0.64, 1.09)

0.19

Non-MI ACS 40 0.27 40 0.27 1.00 (0.64, 1.55)

0.99

All Stroke 62 0.41 70 0.47 0.89 (0.63, 1.25)

0.50

All HF 62 0.41 100 0.67 0.62 (0.45, 0.84)

0.002

CVD Death 37 0.25 65 0.43 0.57 (0.38, 0.85)

0.005

SPRINT Study

The benefit was greatest in the SENIOR group (>75 yrs):

33% v. 25%: primary endpoint (CV death, ACS, heart failure)

34% v 27%: mortality.

37% reduction in acute HF: NNT 28--(HF increased mortality rate 27-fold)--NNT to prevent a death: 41

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SPRINT Study:Serious adverse events

Intensive treatment

Standard treatment

Hazard ratio P value

> 30% reduction in GFR

1.2 %/y 0.35 %/y 3.49 <0.001

Hypotension 2.4 % 1.4 % 1.67 0.001

Electrolyte abnormalities

3.1 % 2.3 % 1.35 0.02

AKI 4.1 % 2.5 % 1.66 <0.001

Orthostatic hypotension

16.6 % 18.3 % 0.88 <0.001

Important?

Conclusions

• Among non diabetic patients at high CV risk (especially in the elderly), SBP goal of <120 mmHg resulted in lower rates of major CV events and death from any cause compared with goal of <140 mmHg,

Conclusions

• But, aggressive treatment was associated with higher rates of adverse events, including renal dysfunction, hypotension, and electrolyte abnormalities.

N Engl J MedVolume 362(17):1575-1585

April 29, 2010

The ACCORD Study Group

Effects of Intensive BP control in Type 2 DM

Study Overview

• 4733 patients, mean age 62 yrs with type 2 DM, with high CV risk received treatment aimed at a target systolic BP of <120 mm Hg or <140 mm Hg.

• Primary end point: nonfatal MI, nonfatal stroke, or CV death.

•• Mean follow-up of 4.7 years.

Mean Systolic Blood-Pressure Levels

The ACCORD Study Group. N Engl J Med 2010;362:1575-1585

At 1 y mean SBP 133 v 119 mmHg

Baseline SBP 139/76 for both groups

Number of meds: 3.4 vs. 2.1

Kaplan-Meier Analyses

The ACCORD Study Group. N Engl J Med 2010;362:1575-1585

Annual rate1.9% v 2.1%l

Event rate in the standard therapy: 50% less than expected

Primary and Secondary Outcomes

The ACCORD Study Group. N Engl J Med 2010;362:1575-1585

Number of patients treated for 5 yrs. to prevent 1 stroke = 89

The ACCORD Study: Signals of adverse effects

Intensive Therapy Standard Therapy

Elevation in Scr > 1.5Scr > 1.3

13 %11 %

8 % (p<0.001)7 % (P<0.001)

Potassium <3.2 2.1% 1.1%(P=0.01)

eGFR < 30 ml/min 4.2% 2.2% (<0.001)

Higher incidence of hypotension (0.7% vs. 0.04%, P<0.001)

• In patients with type 2 DM with high CV risk, targeting a systolic BP of <120 mm Hg as compared with <140 mm Hg did not reduce major CV events, but increased the likelihood of hypotension & adverse renal outcome.

ACCORD - Conclusions

SPRINT vs. ACCORD:Why the Difference?

ACCORD SPRINT

Population 4733 9361

Diabetes? Yes No

Mean age 62 68

Primary outcome 9 vs 10% 5 vs 7%

Major CV event 10.6 vs 11.4% 2.9 vs 3.3%

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Three times the CV event rate in ACCORD vs. SPRINT:Could this overwhelm the benefit from BP lowering?

• Bummer of a result.

• 2/3 of diabetic patients have HTN

• Are there newer treatments for pts with diabetes and HTN?

• .

ACCORD - Conclusions

Sodium-Glucose Contransporter 2 (SGLT2) Inhibitors

New agents that improve diabetic control and

decrease weight.

Recent studies of effect on blood pressure:

Sodium-Glucose Contransporter 2 (SGLT2) Inhibitors

12-week effect on BP in

T2DM pts with nocturnal

hypertension

Kario, et al. Circulation 2019;139:2089

Sodium-Glucose Contransporter 2 (SGLT2) Inhibitors

24-week effect on BP in African-American pts with T2DM & HTN

Ferdinand, et al. Circulation 2019;139:2098

How do we apply the results of SPRINT to real world practice?

BP was measured with patients seated for 5 min

in a quiet room without talking, as an average of

3 measurements with an automated device and

with the observer outside the room.

Is your practice setting like this??

How do we apply the results of SPRINT to real world practice?

BP readings were probably ~10 mmHg

lower than typical practice readings,

suggesting a <130 mmHg rather than <120

mmHg target for systolic BP.

SPRINT vs. the real world

The excess of hypotension, syncope, AKI,

and electrolyte disturbances in the intensive

arm suggests caution in targeting systolic BP

levels <120 mmHg in usual clinical practice.

New Guidelines

Normal systolic BP remains below 120 mmHg

Decrease in target BP from 140/90 to maximum of 130/80 mmHg

Goal of <120 mmHg is most useful in clinics that use the SPRINT method to measure BP.

In those that don’t (the majority), 130/80 or less may be a better goal

New Guidelines

Hypertension has been split into stage 1 (130/80 to 139/89 mm Hg) and stage 2 (140/90 mm Hg and higher)

Goals for BP lowering in stage 1 are primarily non-pharmacologic, unless ACC/AHA ASCVD 10-year risk calculation is >10%

Recommendations include: Weight loss, DASH diet, Alcohol moderation, Physical activity

“ASCVD Risk Estimator Plus” Free App from American College of Cardiology

Risk based on

– Age & Sex

– Racial background

– Blood pressure

– Total cholesterol & HDL

– History of diabetes

– History of smoking

– Use of antihypertensives, statins, & aspirin

This is a novel concept in guiding HTN treatment

New Guidelines Stage 1 Hypertension with low 10-yr CV risk

(<10%): institute lifestyle changes, f/u in 3-6 mo.

Stage 1 HTN with elevated CV risk: lifestyle changes and one antihypertensive medication, follow-up in a month.

Stage 2 HTN: lifestyle changes and TWO anti-hypertensive medications, follow-up in less than a month.

New Guidelines Before beginning antihypertensive meds, it is

reasonable to first measure home and ambulatory blood pressures

Patients with resistant HTN, sudden onset HTN, young age at onset, etc., should be screened for secondary HTN.

Almost all patients over 75 have >10% 10-year ASCVD risk

Sim J, et al. JACC 2014;64:588-97.

400,000 Kaiser Patients on Medications for Hypertension

Sim J, et al. JACC 2014;64:588-97.

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