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Resistant Hypertension
Aka: Resistant Hypertension, Hypertension Combination Therapy, Combination Antihypertensive Therapy, Refractory Hypertension, Refractory Hypertensive Populations
- See Also
- Hypertension
- Hypertension Causes
- Hypertension Evaluation
- Hypertension Evaluation History
- Evaluation Exam
- Hypertension Evaluation Labs
- Isolated Systolic Hypertension
- Hypertension Management
- Hypertension Risk Stratification
- Resistant Hypertension
- Antihypertensive Selection
- Hypertension Management for Specific Comorbid Diseases
- Hypertension Management for Specific Populations
- Hypertension Management for Specific Emergencies
- Hypertension in Children
- Hypertension in Infants
- Hypertension in Pregnancy
- Hypertension in Athletes
- Hypertension in the Elderly
- Epidemiology
- See Refractory Hypertensive Populations
- Prevalence: May approach 20-30% of hypertensive patients
- Definitions
- Resistant Hypertension
- Blood Pressure above goal despite adherance to antihypertensive regimen of 3 medications
- Indications: Combination Antihypertensive Therapy
- Failed Hypertension Monotherapy
- Hypertension
- Risk Factors: Populations with Hypertension that is difficult to treat
- African-American
- Hispanic
- Diabetes Mellitus
- Renal Insufficiency or Renal Failure
- Elderly (especially Isolated Systolic Hypertension)
- Stage 3 Hypertension or greater
- Obese Patients
- Efficacy
- Adding a medication to protocol has five fold greater efficacy over doubling dose of current medications
- Combination agents are preferred over monotherapy esp. for BP>160/100 mmHg or >20/10 above goal
- Causes: Resistant Hypertension
- Noncompliance with current regimen (most common)
- Recent drug holiday
- Unfilled prescription
- Frequently missed doses (ask this in a non-judgemental way)
- Lifestyle modification (e.g. DASH Diet, Weight loss, Exercise) not employed
- See Lifestyle Modification in Hypertension
- Inaccurate Blood Pressure measurement (see BP Examination regarding pitfalls)
- Example: BP cuff that is too small will artificially inflate Blood Pressure readings
- White coat Hypertension
- Consider Ambulatory Blood Pressure Monitoring
- Increase regimen if average 24 hour BP > 129/79 or daytime average BP >134/84
- Pseudohypertension (elderly patients with atherosclerosis)
- Progression of disease
- Treatment program not optimized
- Example: Thiazide Diuretics are ineffective at GFR <30 ml/min (use Loop Diuretics instead)
- Medications or drugs counteracting antihypertensive (e.g. NSAIDS, Sympathomimetics)
- See Medication Causes of Hypertension
- Comorbid condition (e.g. Sleep Apnea, morbid Obesity, Alcohol Abuse, anxiety, Chronic Pain)
- Secondary Hypertension
- See Secondary Hypertension Causes
- Obstructive Sleep Apnea
- Very common cause of Resistant Hypertension
- Hyperaldosteronism
- Represents 20% of refractory cases (consider especially if Hypokalemia)
- Use Spironolactone or Eplerenone
- Check Serum Potassium and Serum Creatinine 2 weeks after start and then every 6 months
- Chronic Kidney Disease is common
- Follow a salt restricted diet
- Use Diuretics with an ACE Inhibitor or Angiotensin Receptor Blocker
- Check Serum Potassium and Serum Creatinine 2 weeks after start and then every 6 months
- Hyperuricemia
- Experimental lowering of serum Uric Acid with Allopurinol results in signficant lowering of Blood Pressure
- Reference
- O'Rorke (2001) BMJ 322:1230 [PubMed]
- Preparations: Combinations (assist with cost and compliance)
- Prinizide (Lisinopril 10-20 mg with Hydrochlorothiazide 12.5-25 mg)
- Diovan-Hct (Valsartan 80-160 mg with Hydrochlorothiazide 12.5 mg)
- Ziac (Bisoprolol with Hydrochlorothiazide 6.25)
- Lotrel (Benzapril 10-20 mg with Amlodipine 2.5-10 mg)
- Tarka (Trandolopril 1-2 mg with Verapamil 180-240 mg)
- Exforge (Valsartan and Amlodipine)
- Reserpine 1.25-2.5 mg with Hydrochlorothiazide 25 mg
- Tenoretic (Atenolol 50-100 mg with Chlorthalidone 25 mg)
- Preparations: Combinations that add 4 drugs in 2 pills for $50-60
- Tenoretic 100/25 with Lotrel 10/20
- Tenoretic 100/25 with Prinizide 20/12.5
- Protocol: Approach
- Consider reasons for Resistant Hypertension (see below)
- Review Hypertension Risk Stratification
- Determine Hypertension Reduction Goal
- Advance to next step if BP>15/10 above goal
- Consolidate medications into combination agents and once daily regimens
- Consider optimal strategies in specific populations when selecting medications
- See Hypertension Management for Specific Populations
- Protocol: Step 1 (combination agents)
- Serum Creatinine <1.5 to 1.8 mg/dl
- ACE Inhibitor and Thiazide Diuretic (Chlorthalidone is preferred as more potent then Hydrochlorothiazide)
- Serum Creatinine >1.5 to 1.8 mg/dl (or GFR <30)
- ACE Inhibitor and Loop Diuretic (Lasix typically twice daily or Torsemide once daily)
- Alternative
- Angiotensin Receptor Blocker may be used if intollerant to ACE Inhibitor
- Avoid combination of ACE Inhibitor with Angiotensin Receptor Blocker
- Protocol: Step 2
- Add Non-Dihydropyridine Calcium Channel Blocker (e.g. Diltiazem, Verapamil)
- Protocol: Step 3
- Some guidelines recommend using the step 4 agents (e.g. Spironolactone) before the step 3 agents
- Heart Rate >80-85 (or if CAD, CHF or other Beta Blocker specific indication)
- Add low dose Beta Blocker
- Consider Labetalol instead of a Beta Blocker due to its combined alpha-beta adrenergic blocker affect
- Heart Rate <80-85
- Add Dihydropyridine Calcium Channel Blocker (e.g. Amlodipine, Nifedipine)
- Protocol: Step 4
- Consider Spironolactone 12.5 to 50 mg orally daily (100 mg offers no added benefit compared with 50 mg dose)
- Consider Alpha-Beta Adrenergic blocker (Labetolol)
- Protocol: Step 5
- Consider Central Adrenergic Agonist (Clonidine)
- Consider Hydralazine (Apresoline)
- Consider Reserpine (risk of depression)
- Consider long acting Alpha adrenergic blocker at night (e.g. Terazosin)
- Protocol: Step 6
- Consult Nephrology or Cardiology
- Protocol: Additional Measures
- Consider Renal Sympathetic Denervation
- Consider Tekturna (Aliskiren), a Direct renin inhibitor
- No significant benefit in Hypertension, Chronic Kidney Disease, Heart Failure
- Risk of hyptension, Hyperkalemia and increased Serum Creatinine
- (2016) Presc Lett :3(6):34
- References
- Woolley (2007) Park Nicollet Primary Care Conference, Minneapolis, MN
- Schwartz (2008) Mayo Selected Topics in Internal Medicine, Lecture
- Garg (2005) Am J Hypertens 18:619-626 [PubMed]
- James (2014) JAMA 311(5): 507-20 [PubMed]
- Moser (2006) N Engl J Med 355(4): 385-92 [PubMed]
- Viera (2009) Am Fam Physician 79(10): 863-9 [PubMed]