How do you treat severe hypertension (HTN) caused by chemotherapy?

Treatment of Severe Hypertension Caused by Chemotherapy

For severe hypertension caused by chemotherapy, especially VEGF inhibitors, first-line treatment should be with ACE inhibitors, ARBs, dihydropyridine calcium channel blockers (like amlodipine), or beta-blockers, with early and aggressive initiation of therapy to maintain treatment schedule and reduce complications. 1

Understanding Chemotherapy-Induced Hypertension

Mechanism and Prevalence

• VEGF inhibitors (like bevacizumab, sorafenib, and sunitinib) have a high risk (11-45%) of causing hypertension 1
• The mechanism involves:
  • Imbalance in neurohumoral factors
  • Vascular rarefaction (reduced microvascular density)
  • Altered vascular nitric oxide balance 1
• Incidence varies by:
  • Patient age and comorbidities
  • Cancer type (renal vs. non-renal cell cancer)
  • Drug type, dose, and schedule 1

Assessment and Management Algorithm

Step 1: Evaluate Severity and End-Organ Damage

• Define severe hypertension as BP ≥180/110 mmHg 2
• Assess for signs of hypertensive emergency (acute end-organ damage):
  • Cardiac: Chest pain, pulmonary edema
  • Neurological: Headache, visual disturbances, altered mental status
  • Renal: Decreased urine output, edema

Step 2: Management Based on Severity

For Hypertensive Emergency (Severe HTN with end-organ damage):

1. Admit to intensive care unit for continuous monitoring 2
2. Administer IV antihypertensive agents:
   • Nicardipine: Start 5 mg/h, increase by 2.5 mg/h every 5 minutes, maximum 15 mg/h
   • Clevidipine: Start 1-2 mg/h, double dose every 90 seconds initially
   • Labetalol: 0.3-1.0 mg/kg IV (maximum 20 mg), repeat every 10 minutes or continuous infusion
   • Sodium nitroprusside: 0.3-0.5 mcg/kg/min IV (use with caution due to toxicity) 2
3. Target BP reduction:
   • Reduce BP by no more than 25% within the first hour
   • Aim for BP <160/100 mmHg in the next 2-6 hours
   • Normalize cautiously over 24-48 hours 2

For Severe HTN without End-Organ Damage (Hypertensive Urgency):

1. Oral antihypertensive therapy is preferred
2. First-line agents (in order of preference):
   • ACE inhibitors or ARBs
   • Dihydropyridine calcium channel blockers (e.g., amlodipine 5-10 mg daily)
   • Beta-blockers 1
3. Amlodipine 5 mg daily has shown 88.5% efficacy in controlling bevacizumab-induced hypertension within 7 days 3

Medication Selection Considerations

Preferred Medications

• Dihydropyridine calcium channel blockers (e.g., amlodipine):

  • Highly effective for VEGF inhibitor-induced hypertension
  • Amlodipine inhibits calcium ion influx across cell membranes, causing vasodilation 4, 3
  • Dosing: Start with 5 mg daily, can increase to 10 mg if needed 4

• ACE inhibitors or ARBs:

  • Recommended as first-line agents for chemotherapy-induced hypertension
  • May have additional renoprotective effects 1

• Beta-blockers:

  • Particularly useful if tachycardia is present
  • Consider cardioselective agents to minimize adverse effects 1

Medications to Avoid

• Non-dihydropyridine calcium channel blockers (verapamil, diltiazem) due to potential drug interactions 1
• Immediate-release nifedipine (risk of precipitous BP drop) 5
• Hydralazine (unpredictable response) 5

Monitoring and Follow-up

1. Monitor BP closely:

   • Home BP monitoring twice daily is recommended 3
   • Target BP <140/90 mmHg for most patients 6

2. Dose adjustment strategy:

   • If BP remains uncontrolled despite maximum doses of initial therapy, add a second agent from a different class
   • If BP remains severely elevated despite optimal medical therapy, consider temporary discontinuation of the chemotherapy agent 1

3. Resumption of chemotherapy:

   • Once BP is controlled, chemotherapy can often be restarted to achieve maximum cancer efficacy 1
   • Continue antihypertensive medications throughout chemotherapy course

Special Considerations

• Early and aggressive treatment is crucial to prevent complications and maintain chemotherapy schedule 1
• Multidisciplinary approach involving oncologists, cardiologists, and hypertension specialists is recommended for complex cases 1
• For patients with pre-existing hypertension, optimization of baseline therapy before starting chemotherapy may reduce risk of severe exacerbations 1

Common Pitfalls to Avoid

1. Delaying treatment of severe hypertension (should be treated within 60 minutes of detection) 1
2. Excessive BP reduction leading to organ hypoperfusion 2
3. Failing to monitor for other cardiovascular toxicities of chemotherapy agents
4. Discontinuing effective cancer therapy prematurely instead of optimizing BP management