Cilostazol-Induced Heart Failure Decompensation in a Patient With Peripheral Artery Disease

Patient Background

Gabriel is a 74-year-old male with a medical history of heart failure with reduced ejection fraction (HFrEF; left ventricular ejection fraction 30%), peripheral artery disease (PAD) with intermittent claudication, type 2 diabetes mellitus, hypertension, coronary artery disease with a previous myocardial infarction, and stage 3 chronic kidney disease.

His chronic heart failure had been clinically stable on guideline-directed medical therapy consisting of carvedilol 25 mg twice daily, sacubitril/valsartan 97/103 mg twice daily, spironolactone 25 mg daily, empagliflozin 10 mgdaily, furosemide 40 mg daily, aspirin 81 mg daily, and rosuvastatin 40 mg nightly.

Clinical Presentation

Despite optimal cardiovascular therapy, Gabriel continued to experience lifestyle-limiting intermittent claudication, reporting bilateral calf pain after walking approximately one block. To improve walking distance and relieve symptoms, his primary care provider initiated cilostazol 100 mg twice daily.

Approximately four weeks after starting cilostazol, Gabriel noticed mild improvement in his claudication but developed progressively worsening exertional dyspnea, orthopnea, bilateral ankle edema, and a three-pound weight gain over one week.

On presentation, his heart rate was 92 beats/min, blood pressure 108/66 mmHg, and physical examination demonstrated peripheral edema and pulmonary crackles. Laboratory evaluation revealed a marked increase in B-type natriuretic peptide (BNP) compared with baseline, while chest radiography demonstrated pulmonary vascular congestion, consistent with acute decompensated heart failure. He required hospital admission for intravenous diuretic therapy and optimization of heart failure management.

Clinical Issue Identified

During medication reconciliation, the clinical pharmacist identified the recent initiation of cilostazol, a phosphodiesterase-3 (PDE3) inhibitor, as the likely precipitating factor for the patient’s heart failure exacerbation.

Cilostazol improves symptoms of intermittent claudication through vasodilation and inhibition of platelet aggregation. However, PDE3 inhibition also increases intracellular cyclic adenosine monophosphate (cAMP) within cardiac myocytes, producing positive inotropic and chronotropic effects. In patients with established heart failure, these effects increase myocardial oxygen demand and may accelerate ventricular dysfunction, predisposing to heart failure decompensation.

Because of this class effect, cilostazol carries a boxed warning and is contraindicated in patients with heart failure of any severity

Pharmacist Intervention and Clinical Management

Identification of the Contraindicated Therapy

• Recognize cilostazol as a contraindicated medication in patients with heart failure.
• Correlate the temporal relationship between cilostazol initiation and worsening heart failure symptoms.

Reassessment of Peripheral Artery Disease Management

• Recommend a supervised exercise therapy program as first-line treatment for intermittent claudication.
• Reinforce aggressive cardiovascular risk reduction through:
  • Smoking cessation (if applicable)
  • High-intensity statin therapy
  • Antiplatelet therapy
  • Optimal diabetes and blood pressure control.
• Consider referral to vascular surgery if symptoms remain significantly lifestyle limiting despite conservative management.

Monitoring and Follow-Up

• Monitor daily weight, fluid status, renal function, electrolytes, and BNP during hospitalization.
• Reassess heart failure symptoms and functional status following discontinuation of cilostazol.
• Continue close outpatient follow-up for both heart failure and peripheral artery disease.

Patient Education

• Educate the patient regarding medications that may worsen heart failure.
• Encourage reporting of rapid weight gain, worsening dyspnea, lower extremity swelling, or reduced exercise tolerance promptly.
• Reinforce adherence to heart failure medications and dietary sodium restriction.

Clinical Rationale and Ramifications

This case illustrates the importance of reviewing medication contraindications before initiating therapy for comorbid conditions. Although cilostazol is an effective pharmacologic option for improving walking distance in patients with intermittent claudication, its PDE3 inhibitory effects make it contraindicated in patients with heart failure due to an increased risk of worsening ventricular dysfunction and adverse cardiovascular outcomes.

In Gabriel, initiation of cilostazol was followed by acute heart failure decompensation, resulting in hospitalization, intravenous diuretic therapy, and increased healthcare utilization. Recognition of the drug-related cause allowed prompt discontinuation of cilostazol and subsequent clinical improvement.

This case reinforces the importance of comprehensive medication reconciliation, particularly in patients with multiple cardiovascular comorbidities. When treating peripheral artery disease in individuals with heart failure, clinicians should prioritize supervised exercise therapy, aggressive risk factor modification, and vascular specialist referral when appropriate, while avoiding medications known to increase the risk of heart failure exacerbation.