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Hypertension Combination TherapyAka: Combination Antihypertensive Therapy, Resistant Hypertension, Refractory Hypertension

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  1. See Also
    1. Hypertension
    2. Hypertension Criteria
    3. Hypertension Evaluation
    4. Antihypertensive Selection
    5. Refractory Hypertensive Populations
  2. Indications for Combination Antihypertensive Therapy
    1. Failed Hypertension Monotherapy
    2. Hypertension
  3. Protocol
    1. Consider reasons for resistant Hypertension (see below)
    2. Review Hypertension Risk Stratification
    3. Determine Hypertension Reduction Goal
    4. Advance to next step if BP>15/10 above goal
    5. Consolidate medications into combination agents
  4. Causes: Resistant Hypertension
    1. Noncompliance with current regimen (most common)
      1. Recent drug holiday
      2. Unfilled prescription
    2. Inaccurate Blood Pressure measurement (see BP Examination regarding pitfalls)
    3. White coat Hypertension (consider Ambulatory Blood Pressure Monitoring)
    4. Progression of disease
    5. Treatment program not optimized
      1. Example: Thiazide Diuretics are ineffective at GFR <30 ml/min (use Loop Diuretics instead)
    6. Medications or drugs counteracting antihypertensive (e.g. NSAIDS, Sympathomimetics)
    7. Comorbid condition (e.g. Sleep Apnea, morbid Obesity, Alcohol Abuse, anxiety, Chronic Pain)
    8. Secondary Hypertension
      1. Hyperaldosteronism represents 20% of refractory cases (consider if Hypokalemia)
    9. Reference
      1. O'Rorke (2001) BMJ 322:1230
  5. Preparations: Combinations (assist with cost and compliance)
    1. Prinizide (Lisinopril 10-20 mg with Hydrochlorothiazide 12.5-25 mg)
    2. Diovan-Hct (Valsartan 80-160 mg with Hydrochlorothiazide 12.5 mg)
    3. Ziac (Bisoprolol with Hydrochlorothiazide 6.25)
    4. Lotrel (Benzapril 10-20 mg with Amlodipine 2.5-10 mg)
    5. Tarka (Trandolopril 1-2 mg with Verapamil 180-240 mg)
    6. Exforge (Valsartan and Amlodipine)
    7. Reserpine 1.25-2.5 mg with Hydrochlorothiazide 25 mg
    8. Tenoretic (Atenolol 50-100 mg with Chlorthalidone 25 mg)
  6. Protocol: Combinations that add 4 drugs in 2 pills for $50-60
    1. Tenoretic 100/25 with Lotrel 10/20
    2. Tenoretic 100/25 with Prinizide 20/12.5
  7. Protocol: Step 1
    1. Serum Creatinine <1.8 mg/dl
      1. ACE Inhibitor and Thiazide Diuretic
    2. Serum Creatinine >1.8 mg/dl
      1. ACE Inhibitor and Loop Diuretic
  8. Protocol: Step 2
    1. Add Non-Dihydropyridine Calcium Channel Blocker
  9. Protocol: Step 3
    1. Heart Rate >83
      1. Add Low dose Beta Blocker
      2. Caution regarding Atrioventricular Block
    2. Heart Rate <84
      1. Add Dihydropyridine Calcium Channel Blocker
  10. Protocol: Step 4
    1. Add long acting Alpha adrenergic blocker (at night)
    2. Add Spironolactone 12.5 to 50 mg po qd
    3. Consult Nephrology or Cardiology
  11. Protocol: Additional Measures
    1. Consider Tekturna (Aliskiren), a Direct renin inhibitor
  12. References
    1. Woolley (2007) Park Nicollet Primary Care Conference, Minneapolis, MN
    2. Schwartz (2008) Mayo Selected Topics in Internal Medicine, Lecture
    3. Garg (2005) Am J Hypertens 18:619

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