What is the treatment for malignant hypertension (HTN) caused by chemotherapy?

Treatment of Malignant Hypertension Caused by Chemotherapy

For malignant hypertension caused by chemotherapy, aggressive pharmacological management with ACE inhibitors and dihydropyridine calcium channel blockers is the first-line treatment, with early initiation to prevent severe complications and maintain cancer treatment schedules. 1

Understanding Chemotherapy-Induced Malignant Hypertension

Malignant hypertension is a hypertensive emergency characterized by severely elevated blood pressure with evidence of acute target organ damage. In cancer patients, it commonly occurs with:

• VEGF inhibitors (anti-angiogenic agents): Bevacizumab, sorafenib, and sunitinib have high risk (11-45%) of causing severe hypertension 1
• Proteasome inhibitors: Particularly carfilzomib, with incidence of 11-17% 1

Pathophysiological Mechanisms

• VEGF inhibitors cause:

  • Nitric oxide pathway inhibition
  • Vascular rarefaction (reduced microvascular density)
  • Oxidative stress
  • Glomerular injury 1

• Carfilzomib causes:

  • Reduced vasodilatory response
  • Peripheral vasoconstriction
  • Endothelial dysfunction 1

Treatment Algorithm

Immediate Management

1. Assess severity and end-organ damage:

   • Check for retinal hemorrhages/exudates, papilledema
   • Evaluate for acute heart failure
   • Assess renal function 2

2. Initiate aggressive pharmacological therapy:

   • Goal: Maintain BP <140/90 mmHg (lower if proteinuria present) 1
   • For severe cases requiring hospitalization, consider IV medications

First-Line Medications

1. ACE inhibitors (e.g., captopril):

   • Starting dose: 25 mg BID or TID 3
   • For severe malignant hypertension: May increase every 24 hours under close supervision 3
   • Benefits: Improves NO release, reduces PAI-1 expression, helps manage proteinuria 1

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

   • For rapid control in acute setting: Consider IV nicardipine (5 mg/hr, titrate by 2.5 mg/hr every 15 minutes up to 15 mg/hr) 4
   • Benefits: Effective vasodilation without significant drug interactions with chemotherapy 1

Alternative/Add-on Agents

• Beta-blockers with vasodilatory effects:

  • Nebivolol: Increases nitric oxide signaling
  • Carvedilol: Additional vasodilatory effects 1

• ARBs: Alternative when ACE inhibitors are not tolerated 1

• Phosphodiesterase-5 inhibitors (sildenafil, tadalafil):

  • May be considered as additional options 1

Important Considerations

Medications to Avoid

• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil):

  • Inhibit cytochrome P450 3A4, increasing plasma levels of many VEGF inhibitors 1

• Diuretics:

  • Use with caution due to risk of electrolyte depletion and QT prolongation 1
  • Not first-line for chemotherapy-induced hypertension

Monitoring and Follow-up

• Monitor BP frequently during chemotherapy infusion, especially with 5-FU or paclitaxel 1
• For VEGF inhibitors, monitor BP from initiation until 1 year after treatment onset 1
• Regular assessment of cardiac and renal function 1

Cancer Treatment Considerations

• If hypertension cannot be adequately controlled:
  1. Consider dose reduction of the chemotherapeutic agent
  2. If severe and uncontrollable, temporarily discontinue chemotherapy
  3. Re-challenge only after risk/benefit assessment 1

Special Situations

• Pre-existing hypertension: More aggressive monitoring and earlier intervention
• Patients with heart failure risk: Prioritize ACE inhibitors and beta-blockers 1
• Renal impairment: Adjust dosing of captopril as it is primarily excreted by kidneys 3

Early and aggressive treatment of chemotherapy-induced malignant hypertension is critical not only to prevent cardiovascular complications but also to allow continuation of potentially life-saving cancer therapy.