Blood Pressure Treatment Goals

Blood Pressure Treatment Goals Kenneth Izuora, MD, MBA, FACE Associate Professor UNLV School of Medicine November 18, 2017

Learning Objectives Discuss the recent studies on treating hypertension Review the AACE hypertension guidelines. Does the evidence support the guidelines? What should the blood pressure goal be for people with type 2 DM?

Definition Sustained elevation of blood pressure above a given goal. BP = Cardiac Output x Peripheral Resistance

Hypertension Hypergylcemia Hyperlipidemia ASCVD ACS/MI Angina CAD Stroke/TIA PVD

Screening and Diagnosis Measure BP during every routine clinic visit. Repeat BP on separate day (within 1 month) if elevated to confirm diagnosis. Monitor BP at home to identify white coat HTN Orthostatic BP at initial visit and if symptomatic.

Why bother?

Too High? https://theskepticalcardiologist.com/2014/11/06/examining-the-heart-of-franklin-delano-roosevelt/

Too Low? 43% risk of hip fracture in first 45 days of treatment Population: 301,591 patients, 66 years, first anti-htn prescription Arch Intern Med. 2012;172(22):1739-1744. doi:10.1001/2013.jamainternmed.469

CV mortality rate Per 10,000 person-years Association of SBP and CV Mortality in Men with T2DM 250 200 No diabetes Diabetes 150 100 50 0 <120 120-139 140-159 160-179 180-199 SBP (mmhg) 200 CV = cardiovascular; SBP = systolic blood pressure; T2DM = type 2 diabetes mellitus. Stamler J, et al. Diabetes Care. 16:434-444, 1993.

Patients with events (%) Hypertension in Diabetes, UKPDS 50 40 Less tight control (mean BP 154/87 mmhg) Tight control (mean BP 144/82 mmhg) 30 20 10 Tight BP control: 24% reduction of events (95% CI 8-38) UKPDS Study Group. BMJ 317:703-13, 1998. 0 0 1 2 3 4 5 6 7 8 9 Years from randomization BP = blood pressure; UKPDS = United Kingdom Prospective Diabetes Study Group.

What is an optimal BP target?

The Hypertension J curve CVD (Hazard Ratio) 1.5 1 0.5? Blood Pressure

Key Studies

ACCORD BP 4733 T2DM patients 40 79 y/o with prior CVD or multiple CVD risk factors Blood pressure target: <120 vs. 130 140 Blood pressure achieved: 119/64 vs. 133/70 Outcomes: Primary: Major CVD event [composite of nonfatal MI, nonfatal stroke or CVD death]

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

ACCORD Conclusions No benefit in primary end point [Nonfatal MI, nonfatal stroke and CVD death]. Intensive treatment reduced the rate of total stroke and nonfatal stroke. Elevated creatinine and electrolyte abnormalities more common in intensive group.

SPRINT Participants: 9,361 persons with increased CVD risk (without DM or stroke). Planned for 5 years but stopped at 3.26 years. Blood Pressure Standard Intensive Target <140 <120 Achieved 136 121

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

25% MI ACS Stroke HF CVD death 27% Death from any cause The SPRINT Research Group. N Engl J Med 2015;373:2103-2116.

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

SPRINT Conclusion Intensive SBP treatment lowered risk for [MI,ACS, Stroke, HF, and CVD death] by 25% Intensive target reduced risk of all cause mortality by 27% Rates of hypotension, syncope, electrolyte abnormalities and AKI higher in intensive treatment group.

HOPE 3 12,705 intermediate risk patients without CVD randomized to candesartan + HCTZ or placebo. Baseline blood pressure: 138.1/81.9 mm Hg Post treatment blood pressure: 132/79 Co-primary outcomes: [CVD death, non-fatal MI, non-fatal stroke] Resuscitated cardiac arrest, HF and revascularization

Lonn EM et al. N Engl J Med 2016;374:2009-2020.

HOPE 3 Conclusion Therapy with candesartan + HCTZ was not associated with a lower rate of major cardiovascular events than placebo in intermediate risk patients without CVD.

Hypertension Optimal Treatment (HOT) Study Aim: Assess relationship between [MI, stroke, CVD death] and diastolic BP N=18790, 1501 with DM, baseline BP 169/105 Blood pressure target: 80, 85 or 90 Blood pressure achieved: 140/81, 141/83 and 144/85 Lancet 1998; 351: 1755 62

Overall

DM Patients

HOT Lowest Points of Risk Diastolic BP Systolic BP Major CV event 82.6 138.5 Myocardial Infarction - 142.2 Stroke <80 142.2 CV Mortality 86.5 138.8

HOT Results No cardiovascular benefit of lower BP target in overall trial. In DM patients, there was a 51% reduction in major CVD events with intensive control.

Metanalysis included 13 studies (37,736 patients) Selection criteria; Randomized control trials Enrolled at least 100 patients with T2DM or IFG At least 1 year of follow up Achieved SBP 135 in intensive group and 140 in standard group Minimum difference in SBP of 3 mm Hg Outcomes Macrovascular events; [All cause mortality], [CV mortality], [MI], [stroke], [HF], [angina] and [revascularization] Microvascular events; [microalbuminuria], [nephropathy], [ESRD/Dialysis], [neuropathy] and [retinopathy]

Intensive versus standard blood pressure control and (A) all-cause mortality and (B) cardiovascular mortality. 10% reduction in all cause mortality in intensive group. Sripal Bangalore et al. Circulation. 2011;123:2799-2810 Copyright American Heart Association, Inc. All rights reserved.

Intensive versus standard blood pressure control and (A) myocardial infarction and (B) heart failure. Sripal Bangalore et al. Circulation. 2011;123:2799-2810 Copyright American Heart Association, Inc. All rights reserved.

Intensive versus standard blood pressure control and stroke. 17% reduction in stroke with intensive treatment 47% reduction in stroke with more intensive treatment Sripal Bangalore et al. Circulation. 2011;123:2799-2810 Copyright American Heart Association, Inc. All rights reserved.

Study Conclusions No single optimal SBP can be identified in all patients with T2DM. Intensive BP control ( 135) was associated with significant reduction in all cause mortality and stroke. More intensive BP lowering was only associated with lower risk for stroke and not other CV outcomes. There was 20% increase in risk of serious adverse effects with intensive control (40% with more intensive control).

Cochrane Database of Systematic Reviews 2017, Issue 10. Art. No.: CD010315. DOI: 10.1002/14651858.CD010315.pub2.

Meta analysis of 5 studies; AASK (2002) ACCORD BP (2010) HOT (1998) Past BP (2016) SPRINT (2015) SPS3 (2013) All studies were RCT with >50 participants per group, and 6 months follow up. Objective: Determine if lower BP was associated with reduction in mortality and morbidity Population: Hypertension patients with CVD (MI, angina, stroke, PVD) BP targets: 135/85 versus 140 160/90 100) Outcome measures; Total mortality Cardiovascular events Cardiovascular mortality

Total Mortality Cochrane Database of Systematic Reviews 11 OCT 2017 DOI: 10.1002/14651858.CD010315.pub2 http://onlinelibrary.wiley.com/doi/10.1002/14651858.cd010315.pub2/full#cd010315-fig-0003

Cardiovascular Mortality There was a lower rate of cardiovascular events but no impact on CV mortality. Cochrane Database of Systematic Reviews 11 OCT 2017 DOI: 10.1002/14651858.CD010315.pub2 http://onlinelibrary.wiley.com/doi/10.1002/14651858.cd010315.pub2/full#cd010315-fig-0006

Conclusion No evidence of difference in mortality with lower BP target despite small reduction in cardiovascular events. Insufficient evidence to justify lower BP targets in this population. MORE TRIALS ARE NEEDED!!!!!

Current Recommendations

JNC 8 Population Age SBP DBP General 60 years <150 <90 <60 years <140 <90 CKD 18 years <140 <90 DM 18 years <140 <90

ADA BP recommendations Goal <140 systolic and 90 diastolic for most patients. Lower goal <130/80 or <120/80 for select patients with high ASCVD risk if lower BP can be achieved safely.

Kidney Disease Improving Global Outcomes (KDIGO) Non-DM patients with CKD (not on dialysis) 140 systolic and 90 diastolic if albumin excretion <30 130 systolic and 80 diastolic if albumin excretion >30 DM patients with CKD (not on dialysis) 140 systolic and 90 diastolic if albumin excretion <30 130 systolic and 80 diastolic if albumin excretion >30 Post transplant patients: 130 systolic and 80 diastolic KDIGO Blood Pressure Work Group. KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney inter., Suppl. 2012; 2: 337 414.

Garber AJ et al. Endocr Pract. 2017,doi:10.4158/EP161682.CS

AACE Hypertension Guidelines Hypertension Type Blood Pressure Goal Uncomplicated <140/90 Complicated Diabetes mellitus <130/80 # Kidney disease <130/80* Other high risk (stroke, MI) <130/80 #Less stringent if frail, comorbidities or adverse medication effects *Lower if proteinuria is >1 g/day ( 120/75). Alan J. Garber et al. AACE T2DM Algorithm, Executive Summary, Endocr Pract. 2017; 23(No. 2) Joseph J. Torre. AACE Hypertension Guidelines, Endocr Pract. 2006;12(No. 2)

Blood Pressure goal for T2DM? There is evidence of CVD benefit in lowering BP below 140 mm Hg in T2DM. In T2DM, BP target between 130/80 140/90 mm Hg is reasonable for most patients. Further BP lowering below 130/80 mm Hg is associated with reduced risk for stroke. Attempts to achieve lower BP goals result in increased risk for serious adverse effects. It is therefore important to balance risk of lower BP with risk for adverse effects of medication.

Summary Blood pressure is normally distributed with no specific cut off to definitely define hypertension. Variation in recommendations exists depending on the population studied. Studies on BP goals apply uniform targets to a population and do not reflect real life clinical scenarios. It is important to use clinical judgement and to individualize treatment targets.

Thank you.