Hypertension Controversies: SPRINTing to New Goalsc.ymcdn.com/.../Handouts_and_Slides/9_Isaacs,_Wolfe_-_Hypertensi.pdfHypertension Controversies: SPRINTing to New Goals Diana Isaacs,

Hypertension Controversies:

SPRINTing to New Goals

Diana Isaacs, PharmD, BCPS, BC-ADM, CDE Clinical Pharmacy Specialist Cleveland Clinic Lauren Wolfe, PharmD Primary Care Clinical Specialist Cleveland Clinic

Disclosures

• Lauren Wolfe and Diana Isaacs have nothing to

disclose.

Objectives

• Compare and contrast published guidelines for the

treatment of patients with hypertension.

• Evaluate the literature utilized to determine guideline

recommendations.

• Discuss the implications of the SPRINT trial in

establishing blood pressure goals for different patient

populations.

• Design a patient centered therapy plan based on

published guidelines and clinical trials.

AL is a 65 year old African American male. AL’s in-office BP today is 148/88mmHg and same on repeat. One month ago, AL’s BP was 146/88mmHg.

• PMH: Sleep apnea, allergic rhinitis

• Meds: Loratadine 10mg po daily

• No known drug allergies/ADR’s

• Height: 5’11” 225lbs, BMI=31.4

• Family history: mother with type 2 diabetes

• Social history: non-smoker, frequently eats out at restaurants, adds salt to food

Patient Case

• What is AL’s BP goal?

• How would you treat AL’s BP?

• How would your treatment plan differ if AL had diabetes? CAD?

• Would the goal BP change if AL was over 80 years old?

Questions to Think About

Definition/Epidemiology

• HTN defined: BP≥140/90mm Hg on repeated exam

• About 1/3 of adults have HTN

– Most common condition seen in primary care

• Close relationship with high BP and risk of MI, stroke,

renal failure and death

• Events lowest at BP=115/75 mmHg

– CV and stroke events double for each increase of 20/10mmHg

in SBP/DBP

Weber MA, et al. J Clin Hypertens. 2014 Jan;16(1):14-26.

James PA, et al. JAMA. 2014;311(5):507-520.

Trends in Awareness, Treatment, and Control of HTN

Egan BM, et al. Circulation 2014;130:1692‐1699

Go A S et al. Circulation. 2014;129:e28-e292

Prevalence of high blood pressure in adults ≥20 years of age by age and

sex (National Health and Nutrition Examination Survey: 2007–2010)

Joint National Committee (JNC7) Guidelines

-Published in 2003

We anxiously waited for JNC8, but the years

kept passing…

And then all of a

sudden!

A Flood of HTN Guidelines

• Kidney Disease: Improving Global Outcomes (KDIGO)-2012

• European Society of Cardiology/European Society of Hypertension(ESC/ESH)-2013

• American College of Cardiology/American Heart Association/Centers for Disease Control (ACC/AHA/CDC) Scientific Advisory-2013

• 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults-2013 (“JNC8”)

• American Society of Hypertension/International Society of Hypertension (ASH/ISH)-2013

• AHA/ACC/ASH Treatment of Hypertension and Coronary Artery Disease-2015

• Canadian Hypertension Educational Program (CHEP)-2016

• American Diabetes Association (ADA) Standards of Care-2017

• American College of Physicians/American Association of Family Physicians (ACP/AAFP) Pharmacologic Treatment of Hypertension in Adults Aged ≥ 60 Ann Intern Med-2017

Blood Pressure through the Ages

N Engl J Med 2016;375:1756-66.

BP Goals: Guideline Comparison

JNC7

2003

ESH/ESC

2013

ASH/ISH

2013

JNC8

2014

CHEP

2016

Disease

Specific

General

HTN

<140/90 <140/90

<140/90 <140/90

<140/90 SPRINT data:

<120/80 is better

Diabetes <130/80 <140/85 <140/90 <140/90

<130/80 ADA: <140/90

AACE: <130/80

CKD <130/80 <140/90

Proteinurea:

<130/80

<140/90

Proteinurea:

consider

<130/80

<140/90

<140/90 KDIGO: <140/90

Proteinurea:

<130/80

CAD <140/90 <140/90 <140/90 <140/90 <140/90 AHA: <140/90

Elderly <140/90 Age≥80

<150/90

Age≥80

<150/90

Age≥60

<150/90

Age≥80

<150/90

ACF/AAFP: Age≥60

<150/90

Stroke/TIA<140/90

Chobanioan AV et al. JAMA. 2003;289(19):2560-2572 Mancia G et al. J. Hypertension 2013;31:1281-357 Weber MA et al. J Clin Hypertens. 2014 Jan;16(1):14-26. James PA et al. JAMA. 2014;311(5):507-520.. Diabetes Care 2017. (Suppl 1).Vol 38:. SS1-92 Kidney Intl Suppl 2012;2:337-414. CHEP 2016. Available at: http://guidelines.hypertension.ca/chep-resources/ Qaseem et al. Ann Intern Med. 2017;166(6):430-437.

JNC: Joint National Committee ASH/ISH: American Society of Hypertension/International Society of Hypertension ESH/ESC: European Society of Cardiology/European Society of Hypertension CHEP: Canadian Hypertension Education Program ADA: American Diabetes Association KDIGO: Kidney Disease: Improving Global Outcomes

Antihypertensive Agents

• First line: ACEI, ARB, CCB, thiazide diuretics

Condition First Drug(s) Add On

Diabetes Historically ACEI or ARB

If no albuminurea, may

use any 1st line agent

CCB or thiazide

CKD ACEI or ARB CCB or thiazide

Clinical

CAD

Beta blocker + ACEI or

ARB

CCB or thiazide

Stroke ACEI or ARB CCB or thiazide

Heart

Failure

ACEI or ARB + beta

blocker + diuretic +

spironolactone

Dihydropyridine CCB

Weber MA et al. J Clin Hypertens. 2014 Jan;16(1):14-26

JNC8 vs. ASH/ISH

ASH/ISH

<140/90 for most

<150/90 if age>80

JNC8

<140/90 for most

<150/90 if age>60

JNC8: A Unanimous Consensus?

• Agreement on all but 1 recommendation

– SBP from 140 to 150 mm Hg in persons aged 60 years or older without DM or CKD

• “The majority embraced the view that in the absence of definitive evidence, increasing the SBP goal was the optimum approach”

• The minority “concluded that the evidence for increasing a BP target in high-risk populations should be at least as strong as the evidence required to decrease the recommended BP target”

– BP goal should be <140/90 in patients <80 and <150/90 in patients ≥80

Ann Intern Med, 2014;160:499-503.

Definition of Elderly

• Merriam-Webster: “being past middle age”

• Most countries have accepted the age of 65 years as

the definition of 'elderly’

• Lack of United Nations standard numerical criterion,

however agreed cutoff is ≥ 60 years of age

• By 2050,1/5 people will be ≥ 60 years of age

World Health Organization. http://www.who.int/healthinfo/survey/ageingdefnolder/en/. Accessed 2017 April 4.

Merriam-Webster . https://www.merriam-webster.com/dictionary/elderly. Accessed 2017 April 4.

Hypertension in the Elderly

• Systolic blood pressure (SBP) increases steadily with age

– Diastolic BP (DBP) increases until age 55, then declines

• Importance of BP as a cardiovascular risk has been

demonstrated to shift from DBP to SBP with advancing age

• Isolated systolic hypertension

– Most common form by age 50

– Increased risk of target organ damage and adverse health outcomes

– Treatment associated with reduced risk for dementia, stroke, MI, and CHF

Circulation. 2011;124:e175.

How Low is Too Low?

• Consistent relationship between degree of BP

elevation and risk of CVD and stroke

– Treating to lower target levels may not result in fewer CV events

–J-shaped association: CV risk at both low and high BP

– Overaggressive treatment can lead to organ hypoperfusion

• Excessive BP lowering may impair quality of life

– Orthostatic hypotension more common and associated with

increased CV risk and fall risk

– In the U.S., almost 40% of people age 60 years and older take

at least 5 medications

Clinical Interventions in Aging 2013:8;1505-1517. Circulation. 2011;124:e175.

Brocklehurst’s Textbook of Geriatric Medicine. 2010:880-885.

Literature Behind JNC8

SHEP Syst-Eur JATOS

VALISH HYVET CARDIO-

SIS

JAMA. 1991;265(24):3255-64.

Primary

Objective

To assess the ability of antihypertensive therapy to reduce the risk of nonfatal

and fatal stroke in isolated systolic hypertension

Inclusion N=4736

Age ≥ 60 (mean 72 years)

SBP 160-219, DBP<90mmHg

Low CV risk

Treatment SBP<160 or ↓ SBP by ≥20mmHg

Chlorthalidone +/- atenolol +/-reserpine

Mean follow-up: 4.5yrs

Outcomes ↓Non-fatal plus fatal stroke (primary): RR: 0.64, CI:0.50-0.82, p=0.0003

↓ Non-fatal MI: RR: 0.67,CI:0.47-0.96

↓ Symptomatic MI events: 63 (tx) vs 98 (placebo), p=0 .005

↓ CHD: RR:0.75,CI:0.60-0.94

↓ Non-fatal MI or CHD deaths: RR: 0.73,CI:0.57-0.94

↓Fatal and non-fatal HF:RR: 0.51, CI:0.37-0.71, p<0.001

SHEP (Systolic HTN in the Elderly Program)

Take Away Points: SHEP

• Average SBP: 143mmHg (treatment), 155mmHg (placebo)

• 36% decrease in stroke and 34% decrease in major CVD

• No difference in total or CV deaths

• Mean follow-up: 4.5yrs

Results

• Reduction below <150mmHg was not evaluated

• Patients included had low CVD risk

• Did not determine differences in adverse events

Limitations

• Treatment to SBP <150mmHg may reduce risk of stroke and major CVD

Conclusions

JAMA. 1991;265(24):3255-64.

Lancet. 1997;350(9080):757-64.

Primary

Objective

To assess the ability of antihypertensive therapy to reduce the risk of

nonfatal and fatal stroke in isolated systolic hypertension

Inclusion N=4695

Age≥60 (mean age 70 years)

SBP 160-219 and DBP<95mmHg (Mean baseline SBP=173.8mmHg)

Treatment SBP goal<150 and ↓ SBP by ≥20mmHg

Nitrendipine +/- enalapril +/- HCTZ

Median follow- up: 2 yrs

Outcomes Mean ↓ in BP: 23/7(tx) vs 13/2 (placebo) mmHg

↓ fatal and non-fatal stroke (primary): HR: 0.59, CI: 0.38-0.79, P<0.01

↓ fatal/non-fatal cardiac endpoints: HR: 0.71, CI: 0.54-0.94, P<0.05 44%

↓ non-fatal stroke , p=0.007 56%

↓ fatal MI, p=0.08

36% ↓ non-fatal HF, p= 0.06

SYST- EUR (Systolic HTN in Europe)

Take Away Points: Syst-Eur

• Treatment mean SBP: 151mmHg

• Placebo mean SBP: 173mmHg

• 42% decrease in total stroke incidence (p=0.003)

• 26% decrease in fatal and nonfatal CV endpoints (p=0.03)

Results

• Placebo group did not receive antihypertensive treatment

• Adverse events were not reported

• Further SBP reduction not evaluated

Limitations

• SBP <150mmHG had benefit in reduction of total stroke and nonfatal CV

Conclusions

Lancet. 1997;350(9080):757-64.

N Engl J Med. 2008;358(18):1887-98.

Primary

Objective

To determine the benefits/risks of antihypertensive treatment in patients ≥ 80

Inclusion N=3845

Age≥80

SBP≥160mmHg (Mean baseline SBP=173mmHg)

Treatment Treatment: indapamide ± perindopril to goal: <150/80 mmHg vs placebo

Mean follow-up: 2.1 yrs

Outcomes Mean BP 15.0/6.1 mmHg lower tx group than placebo (SBP 144 vs. 159mmhg)

↓ fatal or non-fatal stroke (primary): HR 0.7, CI: 0.49-1.01, P=0.06

↓morality: HR=0.79, CI:0.65-0.95, P=0.02

↓death from stroke: HR=0.661, CI: 0.38-0.99, P=0.046

↓ fatal or non-fatal HF: HR=0.36, CI: 0.22-0.58, P<0.001

HYVET (Hypertension in the Very Elderly)

Take Away Points: HYVET

• Mean BP 15.0/6.1 mmHg lower in the active-treatment group than in the placebo group (SBP 144 vs. 159mmhg)

• 30% reduction fatal or nonfatal stroke (95% CI: −1 to 51, p=0.06)

• 39% reduction rate of death from stroke (95% CI: 1 to 62, p=0.05)

Results

• Short duration (1.8 years)

• Unable to assess effects of BP on dementia or cognitive dysfunction

• Benefits of further BP lowering unknown

Limitations

• Indapamide (sustained release, 1.5 mg), with or without 2 to 4 mg of perindopril, significantly reduces the risks of death from stroke and death from any cause in very elderly patients

Conclusions

N Engl J Med. 2008;358(18):1887-98.

Hypertens Res. 2008;31(12):2115-27.

Hypertension. 2010;56(2):196-202.

Trial Inclusion Treatment Outcomes

JATOS (Japanese Trial to

Assess Optimal systolic BP

in Elderly Hypertensive

Patients)

N=4418

Japanese patients

Mean Age: 73.6 years

Low CV risk

SBP<140 vs SBP

<160mmHg

Efonidipine +/- others

Treatment mean BP

135.9/74.8mmHg

Control mean BP:

145.6/78.1mmHg

2 years duration

Primary endpoint:

Events: 86 vs 86, p=0.99

Death from any cause:

Events: 54 vs 42, p=0.22

Cerebrovascular disease:

Events: 52 vs 49, p=0.77

Cardiac and vascular

disease:

Events: 26 vs 28, p=0.78

VALISH

(Valsartan in Elderly

Isolated Systolic HTN)

N=3260

Japanese patients

Mean Age: 76.1 years

Low CV risk

SBP<140 vs. SBP<150

mmHg

Valsartan +/- others

Treatment Mean BP:

136.6/74.8 mmHg

Control Mean BP:

142/76.5 mmHg

2.8 years duration

Composite of CV events

(primary)

Events: 52 vs. 47, p=0.564

All cause death:

Events: 30 vs 24, p=0.362

Fatal and non-fatal MI:

Events:4 vs. 5, p=0.761

Fatal and non-fatal stroke:

Events: 23 vs. 16, p=0.237

JATOS and VALISH

Take Away Points: JATOS and VALISH

Hypertens Res. 2008;31(12):2115-27.

Hypertension. 2010;56(2):196-202.

• Short study durations

• Did not achieve power

• Lack of generalizability of patient population

Limitations

• Did not show a difference in primary endpoints including cerebrovascular disease, cardiac and vascular disease, or renal failure

Conclusions

Usual Versus Tight Control of SBP in Non-Diabetic Patients

with Hypertension (Cardio-Sis)

Lancet. 2009;374(9689):525-33.

Primary

Objective

To determine if tight control vs. usual control would be beneficial in non-diabetic

patients with hypertension

Inclusion 1,111 patients ≥55 years (Mean Age: 67 yrs)

SBP 150 mm Hg or greater (Mean SBP 163.3 mmHg)

At least 1 risk factor for CVD

• Smoker

• TC ≥5·2 mmol/L, HDL <1·0 mmol/L, LDL l ≥3·4 mmol/L,

• Family hx CVD in 1°relative [<65 yr women and <55 yr men]

• TIA or stroke

• CAD or PAD

Treatment Open-label treatment to SBP <130 (tight) or <140 mmHg (usual)

• Tight: more diuretic use (OR 1.36; 1.08–1.71; p=0·009), 17% higher ARB use (OR

1.17, 0.90–1.52; p=0.066)

• Use of BB, CCB, ACEI did not differ

Outcomes Mean ↓ in BP: 27.3 (tight) vs 23.5 (usual) mmHg

1° outcome: left ventricular hypertrophy: 17% (82/483) usual vs 11.4% (55/484) tight

(OR 0.63, 95% CI 0.43–0.91; p=0.013 )

Composite CV endpoint: 9.4% (52/483) usual vs 4.8% (27/484) tight (HR 0.5, 95% CI

0.31-0.79; p=0.003)

Take Away Points: Cardio-Sis

• Tight Mean BP: 131.9/77.4mmHg

• Standard Mean BP: 135.6/75mmHg

• 37% decrease in left ventricular hypertrophy

• 50% decrease composite endpoint

Results

• Open-label design

• 2 year duration

• Caucasian patients only

• Both groups reached BP <140/90

Limitations

• Primary endpoint improvement with lower BP

Conclusions

Lancet. 2009;374(9689):525-33.

Literature Not Referenced by JNC8

FEVER SPS3

INVEST SPRINT

Literature Not Referenced by JNC8

Journal of Hypertension. 2005;23:2157-2172.

Lancet. 2013;382(9891):507-515.

J Am Coll Cardiol 2014;64:784-93.

Trial Patients Intervention Achieved

SBP

Outcomes

FEVER 9,711 Chinese

patients

Age 50-79

Mean Age:

61.5

Randomized to

felodipine 5mg/day

or placebo

Felodipine

Mean BP

137.3 mmHg

Placebo Mean

BP: 142.5

mmHg

Incidence of stroke and CV events

reduced in felodipine group by 27%

(p=0.001)

Subgroup analysis: patients ≥65

44% reduction in all strokes

(p<0.0010)

SPS3 3,020 patients

≥ 30

Mean Age: 63

Recent,

symptomatic,

MRI-confirmed

lacunar stroke

Treatment to SBP

target of 130-

149mmHg or

<130mmHg

Lower Target

Mean SBP:

127mmHg

Higher Target

Mean SBP:

138mmHg

Lower SBP target reduced

subsequent strokes by 19% (p =

0.08) and hemorrhagic strokes by

nearly 50% (p < 0.01)

INVEST 8,354 patients

≥60 with a

baseline SBP

≥150mmHg

Mean Age:

70.7

Randomized to

verapamil-

SR/trandolapril –

OR- atenolol/hctz

SBP <140

(n=4787)

SBP 140-149

(n=1747)

SBP ≥ 150

(n=1820)

Lower rates primary outcome (all

cause death, nonfatal MI, nonfatal

stroke) SBP <140 vs. higher SBPs

(9.36% vs. 12.71% vs. 21.32%;

p<0.0001)

Randomized trial of intensive versus standard

blood pressure control (SPRINT)

N Engl J Med. 2015;373:2103-16.

Inclusion • 9361 patients, age ≥ 50 years (mean age: 67.9 years)

• Risk (one or more of the following)

Presence of clinical or subclinical CVD (not stroke)

Chronic Kidney Disease (CKD), defined as eGFR 20 – 59

ml/min/1.73m2

Framingham Risk Score for 10-year CVD risk ≥ 15%

–Not needed if eligible based on preexisting CVD or

CKD

Age ≥ 75 years

• Systolic blood pressure

SBP: 130 – 180 mm Hg on 0 or 1 medication

SBP: 130 – 170 mm Hg on up to 2 medications

SBP: 130 – 160 mm Hg on up to 3 medications

SBP: 130 – 150 mm Hg on up to 4 medications

Intervention Open-label treatment to SBP <120 (intensive group) or <140

(standard group)

Endpoints Primary composite: ACS, stroke, HF, or death from CV causes

Study Design: Patient Population

N Engl J Med. 2015;373:2103-16.

Exclusion Criteria

Stroke

Diabetes

Congestive heart failure (symptoms or EF < 35%)

Proteinuria >1g/d

CKD with eGFR < 20 mL/min/1.73m2 (MDRD)

Adherence flags

Baseline Demographics: SPRINT

N Engl J Med. 2015;373:2103-16.

Intensive (N=4678) Standard (N=4683)

Baseline SBP (mmHg) (mean, SD)

Distribution SBP (%)

≤132 mm Hg

>132 to<145mmHg

≥145 mm Hg

139.7±15.8

1583 (33.8)

1489 (31.8)

1606 (34.3)

139.7±15.4

1553 (33.2)

1549 (33.1)

1581 (33.8)

Age, yr (mean, SD)

Age ≥75 yr – no.(%)

67.9±9.4

1317 (28.2)

67.9±9.5

1319 (28.2)

Women – no.(%)

Black

Non-Hispanic black

Hispanic

Non-Hispanic white

Other

1684 (36.0)

1454 (31.1)

1379 (29.5)

503 (10.8)

2698 (57.7)

98 (2.1)

1648 (35.2)

1493 (31.9)

1423 (30.4)

481 (10.3)

2701 (57.7)

78 (1.7)

Estimated GFR — ml/min/1.73 m2

Among all participants

eGFR ≥60 ml/min/1.73 m2

eGFR <60 ml/min/1.73 m2

71.8±20.7

81.3±15.5

47.8±9.5

71.7±20.5

81.1±15.5

47.9±9.5

Statin use (%) 1978 (42.6) 2076 (44.7)

Aspirin use (%) 2406 (51.6) 2350 (50.4)

Body-mass index 29.9±5.8 29.8±5.7

Antihypertensive agents — no./pt 1.8±1.0 1.8±1.0

No antihypertensive agents — no. (%) 432 (9.2) 450 (9.6)

Intervention Groups

Standard

• Intensify therapy if:

– SBP ≥160 mm g at 1 visit

– ≥140 mmHg at 2

consecutive visits

• Down-titration if:

– SBP <130 mmHg at 1 visit

– <135 mmHg at 2

consecutive visits

Intensive

• Blood pressure medications are

added and/or titrated at each

study visit to achieve SBP

<120 mm Hg

• Intervention goal is to create a

minimum mean difference

between randomized groups of

at least 10 mm Hg

N Engl J Med. 2015;373:2103-16.

Primary Outcome: SPRINT

N Engl J Med. 2015;373:2103-16.

SPRINT Results: Intensive vs standard SBP

N Engl J Med. 2015;373:2103-16.

Take Away Points: SPRINT

• Mean SBP 121.5mmHg (intensive) vs. 134.6mmHg (standard) at 3.26 years

• 25% decrease in primary outcomes in lower SBP group

• NNT to prevent one primary outcome event: 61; death any cause: 90

• No difference: serious adverse event, injurious falls, bradycardia, orthostatic hypotension with dizziness

in hypotension, syncope, electrolyte abnormality, AKI/ARF in intensive treatment group (NNH of 71, 91,100, and 56 respectively)

Results

• Exclusion of patients with prior stroke and patients residing in nursing homes or assisted-living facilities

• Early cessation of trial

• Baseline use of statin 43%, aspirin 51%

• Open label

• Difficult to replicate BP monitoring techniques

Limitations

N Engl J Med. 2015;373:2103-16.

Practical Application: SPRINT

• Treatment to SBP <140mmHg

– Only achieved in 50% of population

• Treatment to SBP <120mmHg

– Required ~1 additional medication

– Achieved in less than half of strict treatment group

– More demanding, time-consuming, and costly in practice

• SPRINT-MIND

• SPRINT-SENIOR

SPRINT-Senior

• Pre-specified subgroup for analysis

• Objective: evaluate effects of intensive vs standard SBP

in patients ≥ 75 yr with HTN but without DM

– 815 participants (30.9%) were classified as frail and 1456 (55.2%)

as less fit

– Exclusion criteria: dementia, expected survival <3 years, SBP

<110mmHg after 1 min standing, unintentional weight loss >10%

6 months prior, nursing home residents

• Outcomes:

– Primary: composite of MI, ACS not resulting in MI, nonfatal stroke,

nonfatal acute decompensated HF, death from CV causes

JAMA. 2016;315(24):2673-82.

Baseline Characteristics: SPRINT-Senior

JAMA. 2016;315(24):2673-82.

Characteristic Intensive (n=1317) Standard (n=1319)

Age, mean (SD), y 79.8 (3.9) 79.9 (4.1)

Female (%)

White (%)

Black (%)

499 (37.9)

977 (74.2)

225 (17.1)

501 (38)

987 (74.8)

226 (17.1)

Seated BP mmHg (mean, SD)

Systolic

Diastolic

141.6 (15.7)

71.5 (11)

141.6 (15.8)

70.9 (11)

Orthostatic Hypotension (%) 127 (9.6) 124 (9.6)

Number of anti-HTN meds (SD) 1.9 (1) 1.9 (1)

History of CVD (%) 338 (25.7) 309 (23.4)

Estimated GFR (mean (SD)

<60 mL/min/1.73 m2, %

<45 mL/min/1.73 m2, %

584 (44.3)

207 (15.7)

577 (43.7)

212 (16.1)

Statin use (%) 682 (58.1) 697 (52.8)

Aspirin use (%) 820 (62.3 765 (58)

Outcomes: SPRINT-Senior

JAMA. 2016;315(24):2673-82.

Take Away Points: SPRINT-Senior

• Mean SBP 123.4mmHg (intensive) vs. 134.8mmHg (standard)

• NNT estimate for the primary outcome was 27 (95% CI, 19-61) and 41 (95% CI, 27-145) for all-cause mortality at 3.14 years

• Intensive group required 1 more medication to reach the lower BP

Results

• Intensive group SAEs 48.4% vs 48.3% in the standard group (HR, 0.99 [95% CI, 0.89-1.11]; P = .90).

in hypotension, syncope, electrolyte abnormality, AKI/ARF in intensive treatment group

• Absolute rate of injurious falls was lower in the intensive treatment group (4.9% vs 5.5%; HR, 0.91 [95% CI, 0.65-1.29])

Safety

JAMA. 2016;315(24):2673-82.

SBP Goal Literature Support

SBP<150

• SHEP

• Syst-Eur

SBP<140

• Cardio-Sis

• FEVER

• SPS3

• INVEST

• SPRINT

BP Goals in Diabetes

Guideline Comparison-Diabetes

JNC8

<140/90

ASH/ISH

<140/90

ADA

<140/90

AACE

<130/80

CHEP

<130/80

ESH

<140/85

Clinical Trials in Diabetes

Trial Inclusion Treatment (tx) Outcomes

ACCORD-BP

(Action to

Control

Cardiovascular

Risk in

Diabetes)

N=4733

2010

T2DM,

A1c≥7.5%,

Age≥40

SBP: 130-

180mmHg

Mean follow-up:

4.7 yrs

SBP goal<140 vs

<120mmHg

Mean SBP=119.3

vs. 133.1mmHg

ACEI or ARB or BB

or CCB or diuretic or

combo

↓Non-fatal stroke:

HR: 0.63, CI:0.41-0.96, p=0.03

↓Any stroke:

HR: 0.59, CI:0.39- 0.89, p = 0.01

↑syncope and hyperkalemia in<120 group:

(3.3% vs 1.3%, p=0.001)

No statistical difference in composite of first

occurrence of major CV event (primary), death,

non-fatal MI, major coronary disease event, fatal or

non-fatal HF, renal failure, ESRD

UKPDS

(UK

Prospective

Diabetes Study

Group)

N=1148

1998

T2DM

Age 25-65

BP≥150/85

mmHg

Mean follow-up:

8.4 yrs

SBP goal<150/85

vs. <185/105mmHg

Mean BP change:

15/12 vs. 12/7mmHg

Captopril or atenolol

Any DM related endpoint (primary):

RR:0.76, CI:0.62-0.92,p=0.0046

Stroke: RR:0.56,CI:0.35-0.89,p=0.013

HF:RR: 0.44,CI:0.20,-0.94, p=0.0043

Death related to DM:

RR:0.68,CI:0.49-0.94,p=0.019

No statistical different in all cause mortality, MI,

sudden death, death from renal failure

BMJ. 1998;317(7160):703-713.

N Engl J Med. 2010;362(17):1575-1585

Clinical Trials in Diabetes

Trial Inclusion Treatment Outcomes

HOT (Hypertension

Optimal

Treatment)

N=18790

(1501 with

DM)

1998

T2DM, age 50-

80 with DBP

100-115mmHg

Mean follow-

up: 3.8 yrs

Compared

DBP≤80 vs ≤85

vs ≤90mmHg

Mean BP not

reported for DM

subpopulation

Felopidpine +/-

ACE +/-BB +/-

diuretic

Major CV Events (Primary):

45(≤90 ) vs. 22(≤80), HR:2.06,

CI: 1.24-3.44

Total mortality: ≤ 90 vs ≤ 80:

RR: 1.77, CI:0.98-3.21

No statistical difference in MI,

stroke for ≤90 vs. ≤ 80. No

statistical difference in any

outcomes for ≤ 90 or ≤ 80 vs. ≤ 85

Lancet. 1998;351(9118):1755-1762,.

DM BP Goal: <140/90 vs <130/80

• ACCORD-BP had similar outcomes for SBP=140 vs SBP=120

• HOT Trial supports DBP<80 over DBP<90, but was considered low quality evidence

• Post hoc analysis of a small subgroup (8% of study population)

• UKPDS: BP=150/85 had better outcomes than 180/105

• However, unable to determine if positive outcomes from SBP or DBP

• DM excluded in Sprint trial

• Are ACEI and ARB still preferred? • Large HTN trials including patients with diabetes had similar outcomes

comparing ACEI, ARB, thiazide, CCB

• ADA 2017 guidelines all 1st line agents reasonable to use except in albuminuria/CKD (ACEI/ARB preferred)

James PA, et al. JAMA. 2014;311(5):507-520

Diabetes Care 2017;40 (Suppl.1):s11-s24.

BP Goals in CAD

Most guidelines recommend <140/90 with no

separate category for CAD

SPRINT vs. ACCORD-BP

ACCORD-BP

• N=4733, 34% with a previous CV event

• BP<120/80, lower stroke rate

SPRINT

• Better outcomes with BP<120/80 vs <140/80 in high risk patients

CAD/BP Goal Comparisons

• Prospective, observational study (N=22,672)

– 45 countries represented

– Patients with Stable CAD + HN

– Median f/u: 5.0 years

• Primary Outcome: CV death, MI, stroke

• BP>140/80-worse outcomes

• SBP<120 = increased risk

– Adjusted HR 1.56, 95% CI 1·36–1·81

• DBP<70

– DBP 60-69: adjusted HR 1.41 95% CI 1.24–1.61

– DBP <60: adjusted HR 2.01 95% CI 1·.50–2.70

Vidal‐Petiot E, et al. Lancet. 2016 Aug 26..

2015 AHA/ACC/ASH Guidelines

Rosendorff C et al. J Am Coll Cardiol 2015;65:1998–2038.

Back to the Case

AL is a 65 year old African American male. AL’s in-office BP today is 148/88mmHg and same on repeat. One month ago, AL’s BP was 146/88mmHg.

• PMH: Sleep apnea, allergic rhinitis

• Meds: Loratadine 10mg po daily

• No known drug allergies/ADR’s

• Height: 5’11” 225lbs, BMI=31.4

• Family history: mother with type 2 diabetes

• Social history: non-smoker, frequently eats out at restaurants, adds salt to food

What is AL’s BP Goal?

A. <150/90

B. <140/90

C. <130/80

D. <120/80

AL is now 70 and he developed diabetes. Current BP is

136/80 and now he’s on HCTZ 25mg daily and metformin

1000mg BID. Which of the following is the best plan?

A1C=6.9%. CMP is wnl. Neg albuminurea

A. Continue current therapy

B. Add lisinopril 10mg daily

C. Add amlodipine 5mg daily

D. Add lisinopril 10mg daily and amlodipine 5mg daily

Two years later (age 72) he developed CAD and had an MI

3 months ago. Current meds: metoprolol succinate,

furosemide, metformin, sitagliptin, lisinopril, ASA. Current

BP is 132/74. What is the most appropriate BP goal?

A. <150/90

B. <140/90

C. <130/80

D. <120/80

What should his BP goal be in 10 years? (Age=82?)

In Summary

• Guidelines differ on optimal BP goals but agree <140/90 is a good

starting point for most

• Thiazides, CCB, ACE-inhibitors, ARB’s are 1st line agents

• SPRINT provides evidence that lower BP may benefit some patients

• Keep in mind SPRINT trial exclusion criteria and overall limitations

• Guidelines provide a general framework, but always consider the

individual patient