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Resistant Hypertension

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Scott Bragg

on 9 August 2018

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Transcript of Resistant Hypertension

Treating Resistant Hypertension
Case #2
57 y/o African American female seen in a home visit with a BP of 160/90

PMH: DM2, HTN, former MI, PVD, stage IV CKD, obesity, severe peripheral neuopathy, retinitis pigmentosa-legally blind

Social hx: smokes 1/2 ppd; lives alone in 7 story low income high-rise; little friend family support; problems organizing meds
The optimization of drug effects and/or minimization of adverse drug reactions by timing medications with regard to biological rhythms

Improve effectiveness
(E.g. Statins dosed at night, PPIs prior to a meal)
Decrease side effects
(E.g. Mirtazepine at bedtime, metformin with meals)

Patient education is key!
Case #1
64 y/o Latino male with BP of 180/110

PMH: HTN, DM2, OA, obesity, HLD, poor dentition

Social history: former smoker 30 pack year hx; gambling addition; poor medication adherence

Medications: metformin 1 g BID, Lantus 12 units daily, HCTZ 25 mg daily, lisinopril 40 mg daily, Toprol 100 mg daily, aspirin 81 mg daily, amlodpine 10 mg daily, ibuprofen 600 mg TID prn
Identify causes of resistant HTN

Apply chronotherapy to improve medication effectiveness

Use appropriate meds based on BP response and patient comorbidities
Aspirin lowers BP?!?
Several studies show aspirin dosed at bedtime lowers BP ~6/4 mmHg

Theorized MOA is inhibition of renin-angiotension system and/or increase nitric oxide production

May have CV risk reduction independent of BP effects
Hermida RC, et al. Hypertension. 2005;46[part2]:1060-68.
Hermida RC, et al. Hypertension. 2003;41:1259-67.
ACE inhibitors at bedtime
Quinapril, ramipril, enalapril, and lisinopril showed greater 24 hr BP reduction with hs dosing
Physiologically RAS is more active overnight
Bradykinin concentrations did not increase with bedtime dosing of enalapril
Fujimara A, et al. Jpn J Clin Pharmacol Ther. 1999;30:741-4.
Macchiarulo C, et al. Eur Rev Med Pharmacol Sci. 1999;3:269-75.
Svensson P, et al. Hypertension. 2001;38:E28-32.
O'brien E. Medicographia. 2010;32:241-249.
Thiazide Comparisons

Use chlorthalidone or indapamide instead of HCTZ
Longer half lives (>24 hours vs 12 hrs)
More evidence of CV risk reduction (POEM data)
Better BP lowering 3–5 systolic points
Approximate potency: HCTZ 25 mg = chlorthalidone 12.5 mg = indapamide 1.25 mg
Furberg CD, et al. JAMA. 2002;288:2981–97.
Kostis JB, et al. JAMA. 2011;306(23):2588–93.
Roush GC, Hypertension. 2015;65:1041–46.
Lantus 15 units daily
Lisinopril 20 mg daily
Hydralazine 50 mg TID
Januvia 25 mg daily
Aspirin 81 mg daily
Norvasc 10 mg daily
Glipizide 5 mg BID
Pravastatin 40 mg daily
Lyrica 75 mg BID
Lasix 40 mg daily prn
Identify meds to remove and conditions to work-up if having resistant hypertension
Use medication timing to improve effectiveness
Pick drugs based on BP response and patient comorbidities
Good evidence as 4th line med for resistant HTN

ASCOT trial-added 4th line to 1411 patients
Baseline BP 156.9/85.3 mmHg (SD +/- 18/11.5 mmHg)
1 year later: mean reduction SBP 21.9 mmHg (95% CI: 20.8 to 23.0 mmHg) and DBP 9.5 mm Hg (95% CI: 9.0 to 10.1 mmHg)
Chapman N, et al. Hypertension. 2007;49:839–45.
Guanfacine (Tenex) vs Clonidine
Consider guanfacine instead of clonidine

Longer duration (~24 hrs vs 6–10 hrs)
Less chance of rebound HTN
Cheap $4 list
Minimal side effects with 1–2 mg at bedtime
Scott Bragg, PharmD
August 9, 2018
Trident/MUSC FM Residency

What Questions Do You Have?
Spironolactone Pearls
Don't use with K+ > 5 mEq/L or GFR < 30 mL/min

Cautiously use with ESRD on HD
Monitor for hyperkalemia, but can adjust K+ with HD

Start considering eplerenone as an alternative
Less gynecomastia and sexual dysfunction
Less hyperkalemia
Preferred on many insurances and cash price ~$40/month with GoodRx discount at Walmart
Definition of Resistant Hypertension
"Elevated blood pressure despite concurrent use of 3 antihypertensive drugs of different classes, including a diuretic"
Viera AJ, et al. AFP. 2010;82(12):1471–8.
Viera AJ, et al. AFP. 2010;82(12):1471–8.
Viera AJ, et al. AFP. 2010;82(12):1471–8.
Lisinopril Daily vs. Twice Daily
Retrospective cohort of 90 patients taking 20 mg daily and increasing the dose

Small baseline characteristic differences

No differences in adverese effects

Average BP reductions:
40 mg daily 6.2/1.5 mmHg
20 mg twice daily 16.5/5.9 mmHg
Tsai T, et al. J Clin Hypertens. 2017;19:868–873.
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