Hypertension: Tips for Managing Difficult to Control Blood Pressure

in the Office

G. Dodd Denton, MD, MPH, FACPMichael Elnicki, MD, FACP

Lawrence Ward, MD, MPH, FACP

Over the Next 90 Minutes…

Introductions Background discussion Case 1 (Work-up/White-coat)

- Group discussion

Case 2 (Diabetes and Diuretics)- Group discussion

Case 3 (Uncontrolled on 4 meds)- Group discussion

Wrap-Up and Questions

Over the Next 90 Minutes…1) Avoid common pitfalls and challenges in

hypertension care 2) Discuss approaches to achieve BP control in

resistant hypertension3) Implement recommendations from the

Accord trial into the care of hypertensive diabetic patients.

4) List changes to recommendations for HTN care recommended by JNC-8 (if released by the time of the meeting).

Resistant Hypertension

The Joint National Committee 7 defines resistant hypertension as failure to achieve goal BP (140/90 mm Hg for

the overall population and 130/80 mm Hg for those with diabetes mellitus or chronic kidney disease) when a patient adheres to maximum tolerated doses of 3 antihypertensive drugs including a diuretic, or anyone on 4 drugs.

First Pass Evaluation

Is the patient adherent with medications? Is the patient limiting sodium/salt intake? Has the patient been screened for

Obstructive Sleep Apnea? Does the patient have renal disease?

Use the Big Four!

1) Diuretics HCTZ, chlorthalidone, loop diuretics

2) ACE Inhibitors & Angiotensin Receptor Blockers (ARB)

3) Calcium Antagonists (CAB) Dihydropyridines (Amlodipine)

4) Beta Blockers (BB)

Obstructive Sleep Apnea

Untreated strongly associated with hypertension

May predict development of hypertension In normotensive subjects

Very common among resistant hypertensives More common and more severe in men compared with women. The more severe, the less likely BP will be controlled.

The mechanism(s) is not clear. Intermittent hypoxemia, increased upper airway resistance

induces a sustained increase in sympathetic nervous system (SNS) activity?

Sodium intake .

Average US: 3.4 mg salt (1.5 tsp) daily Optimal: 1.5 mg (<1/2 tsp); less > age 50 Resistant hypertensives

- Average dietary sodium intake >10 g/day Dietary salt reduction to 3 g/day

- Associated with modest BP reductions- More in highly salt-sensitive African-American

and elderly patients.

Adherence

40% of patients with new hypertension discontinue antihypertensives during the first year

At 5 to 10 years of follow-up, <40% persist with antihypertensives

Poor adherence may be less common in specialty clinics

Adherence

Measuring Adherence: Pill counts Validated Questionnaires Pharmacy Records

Addressing Adherence: Choose medications with low side effect profiles Choose once daily dosing Consider combination pills Use pillboxes or pharmacy blister packs Educate the patient

- emphasize safety and efficacy of the regimen

Prognostic Value of ABPM

Ambulatory BP measurements predict CV events In treated HTN patients Even after controlling for office BP

Clement. NEJM 2003

Indications for ABPM

White Coat HTN Labile or Episodic BP Resistant HTN Autonomic Dysfunction

Source: JNC 7 and AHA

Limits of Normal ABP

Systolic Diastolic

Awake <135 <85Night <120 <7524-hour <130 <80

Dipping

BP reduction <10/5 mmHg or <10% between day and night are non-dippers.

Extreme dippers >20% drop

Information Retrieved

Mean and extreme BPs Correlation with events and SX 24-hour BP control and gaps Dipping status

BP in DM: GuidelinesHypertension Optimal Treatment (HOT) (1998)

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

15,000 patients with 1,500 diabetic subgroup

Mean diastolic BP was 82.6 mmHg

51% reduction in CV events

BP in DM: Guidelines

Diabetic patients without previous coronary disease have at least as high a risk of MI as nondiabetic patients withknown coronary disease

N Engl J Med. 1998;339(4):229-234.

BP in DM: Guidelines

American Diabetes Association Goals SBP <130 mm Hg and DBP <80 mm Hg All patients with hypertension and diabetes

should be treated with a regimen that contains an ACEI or ARB

JNC VIIAmerican Diabetes Association. Diabetes Care. 2004;27(suppl 1):S65-S67.

BP in DM: ACCORD subgroup

4700 Diabetic patientsIntensive vs standard BP control

N Engl J Med 2010;362:1575-85.

BP in DM: Guidelines

In patients with type 2 diabetes at high risk for CV events, targeting a SBP <120 mm Hg, as compared with <140 mm Hg, did not reduce fatal and nonfatal major CV events.

N Engl J Med 2010;362:1575-85.

Diuretics

Hydrochlorothiazide Chlorthalidone Metolozone Indapamide Furosemide

Torsemide Triamterene Amiloride Spironolactone Epelrenone

Which do you choose?

Diuretics

HCTZ

CTD

12 Hour drugT1/2 = 9-10

24 Hour drugT1/2 = 50-60

Data lacking with Conventional dosing

Survivalbenefit

Double potency without increased S/EHCTZ 25mg = CTD 12.5mg

ALLHAT, SHEP, MRFIT

Diuretics in CKD

Decision of which diuretic must also consider patient’s renal function

GFR <50 ØHCTZGFR <30 ØCTD

Use Furosemide BID or Torsemide daily

Aldosterone Independence

The most common secondary cause of hypertension 8-15% of all hypertensives >20% of resistant hypertensives (controversial) Provoked or spontaneous hypokalemia, alkalosis can be cues

Screen with early morning, fasting aldosterone and renin levels Positive is aldo/renin ratio (ARR) >20-25 Aldo>15; renin <1.0. Low renin hypertension is a separate topic

Stop meds to screen?

No! May get high false positive rate, but

confirmatory tests required. The only medication that unequivocally affects

RAAS axis is spironolactone.

Stopping antihypertensives problematic In one study, 6/50 had new AF, ICD firing,

HTN crisis, or heart failure requiring admit

Screen, then confirm

To confirm, a 24hour urine for aldosterone is one option. On

antihypertensives Concurrent sodium

measurement

Young et al. Endocrinology 2003

Diagnose subtype Subtype evaluation

only needed if surgical cure is being considered (APA or PAH)

Young et al. Endocrinology 2003

Consider empiric spironolactone

Profound BP lowering with addition of spironolactone in rHTN- At 6 months, reduction of 26.0/10.7(!)- <5% gynecomastia

Spironolactone also effective in Obstructive Sleep Apnea

Should be considered strongly as “fourth medication” to add to regimen

Take Home Tips

1) ABPM has limited but real clinical use2) Consider using more chlorthalidone3) Renal function determines diuretic choice4) Think about Aldosteronism

Screen on meds with fasting aldo/renin Consider empiric use of spironolactone

gdenton@usuhs.milelnickim@upmc.eduwardld@temple.edu

Thank you!

Suggested Reading

Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 2003;42:1206 –52.

Sarafidis PA and Bakris GL. Resistant Hypertension: An Overview of Evaluation and Treatment. J Am Coll Cardiol 2008;52:1749-57.

Calhoun DA, et al. Resistant Hypertension: Diagnosis, Evaluation, and Treatment. Hypertension. 2008;51:1403-1419.

Sarafidis PA, Bakris GL. State of hypertension management in the United States: confluence of risk factors and the prevalence of resistant hypertension. J Clin Hypertens (Greenwich) 2008;10:130 –9.

Graves JW, Bloomfield RL, Buckalew VM Jr. Plasma volume in resistant hypertension: guide to pathophysiology and therapy. Am J Med Sci 1989;298:361–5.

Logan AG, et al. High prevalence of unrecognized sleep apnoea in drug-resistant hypertension. J Hypertens. 2001;19: 2271–2277.

Van Wijk BL, Klungel OH, Heerdink ER, de Boer A. Rate and determinants of 10-year persistence with antihypertensive drugs. J Hypertens 2005;23:2101–7.

http://www.iom.edu/Reports/2010/Strategies-to-Reduce-Sodium-Intake-in-the-United-States.aspx. Last Accessed 04 February 2011

Engbaek et al. The effect of low-dose spironolactone on resistant hypertension. J Am Soc Hypertens. 2010 Nov-Dec;4(6): 290-4.

Suggested Reading

Gradman AH, Basile JN, Carter BN, Bakris GL. Combination therapy in hypertension. J Am Soc Hypertension. 2010;4(1):42–50.

Egan BM, Basile JN, Rehman SU, Davis PB, Grob CH, Riehle JF, Walters CA, Lackland DT, Merali C, Sealey JE, Laragh JH. Plasma Renin Test–Guided Drug Treatment Algorithm for Correcting Patients With Treated but Uncontrolled Hypertension: A Randomized Controlled Trial. Am J Hypertens 2009; 22:792-801.

Ernst ME, Moser M. Use of Diuretics in Patients with Hypertension. N Engl J Med 2009;361:2153-64.

Ernst ME, Carter BL, Goerdt CJ, Steffensmeier JG, Phillips BB, Zimmerman MB, Bergus GR. Comparative Antihypertensive Effects of Hydrochlorothiazide and Chlorthalidone on Ambulatory and Office Blood Pressure. Hypertension. 2006;47:352-358.

ACCORD Study Group. Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus. N Engl J Med 2010;362:1575-85.

Alvarez-Alvarez B., et al. Management of resistant arterial hypertension: role of spironolactone versus double blockade of the renin-angiotensin-aldosterone system. J Hypertens. 2010 Nov;28(11):2329-35

Fischer E., et al. Commentary on the Endocrine Society Practice Guidelines: Consequences of adjustment of antihypertensive medication in screening of primary aldosteronism. Rev Endocr Metab Disord. 2011 Feb 18. [Epub ahead of print]

Young, WF. Minireview: Primary Aldosteronism—Changing Concepts in Diagnosis and Treatment. Endocrinology 144: 2208–2213, 2003