Can Plavix (clopidogrel) cause central sleep apnea?

Plavix (Clopidogrel) and Central Sleep Apnea

Plavix (clopidogrel) does not cause central sleep apnea, but ticagrelor, another P2Y12 receptor antagonist in the same drug class, has been associated with central sleep apnea. 1

Medication-Induced Central Sleep Apnea

Known Medications That Cause Central Sleep Apnea

• Opioids are well-established causes of central sleep apnea (CSA) through their action on μ-opioid receptors in the pontomedullary respiratory centers 1
• Non-opioid medications known to cause CSA include:
  • Sodium oxybate, baclofen, valproic acid, and gabapentin (act on GABA receptors) 1
  • Ticagrelor (P2Y12 receptor antagonist) 1, 2
• Benzodiazepines should be avoided in patients with sleep apnea as they can depress upper airway tone and worsen sleep-disordered breathing 3

Ticagrelor and Central Sleep Apnea

• Ticagrelor has been specifically linked to central sleep apnea by increasing central chemosensitivity and ventilatory response to carbon dioxide 1, 2
• A case report documented a shift from obstructive sleep apnea to central sleep apnea with Cheyne-Stokes respiration after initiation of ticagrelor 2
• A prospective study found that among patients after acute coronary syndrome:
  • 30% of patients taking ticagrelor developed central sleep apnea
  • Only 7.3% of patients not taking ticagrelor developed central sleep apnea
  • Multivariable analysis showed ticagrelor administration was significantly associated with CSA occurrence (p = 0.0006) 4

Clopidogrel (Plavix) and Sleep Apnea

• There is no evidence in the provided literature linking clopidogrel (Plavix) to central sleep apnea 5, 6
• Unlike ticagrelor, clopidogrel has not been reported to affect respiratory control centers or chemosensitivity 1
• The British Journal of Pharmacology's review of medications impacting obstructive sleep apnea does not mention clopidogrel as a medication of concern 5

Distinguishing Between Types of Sleep Apnea

Central vs. Obstructive Sleep Apnea

• Central sleep apnea is defined as the absence of naso-oral airflow due to withdrawal of respiratory center stimulation and absence of inspiratory muscle contraction 7
• Obstructive sleep apnea occurs when there is upper airway obstruction with continued activity of inspiratory muscles 7
• Polysomnography is essential for diagnosis, showing central apneas without respiratory effort 6

Risk Factors for Central Sleep Apnea

• Heart failure is the most common cause of central sleep apnea 6
• Other causes include neurological disorders (stroke), atrial fibrillation, pulmonary hypertension, and renal failure 6
• Medications are an important but potentially overlooked cause of central sleep apnea 1

Clinical Implications

Medication Management

• If a patient develops central sleep apnea while on antiplatelet therapy and requires P2Y12 inhibition, clopidogrel would be preferred over ticagrelor 1, 2, 4
• Discontinuation of offending agents has been shown to eliminate medication-induced CSA 1
• When treating insomnia in patients with central sleep apnea, avoid benzodiazepines and opt for safer alternatives like low-dose doxepin (3-6mg) or ramelteon 3

Monitoring and Diagnosis

• Patients on ticagrelor who develop symptoms of sleep apnea should be evaluated with polysomnography 6, 2
• PAP-telemonitoring can detect shifts from obstructive to central sleep apnea in patients already on PAP therapy 2

In conclusion, while ticagrelor has been associated with central sleep apnea through increased chemosensitivity to carbon dioxide, there is no evidence suggesting that clopidogrel (Plavix) causes central sleep apnea. For patients requiring antiplatelet therapy who are at risk for or have central sleep apnea, clopidogrel may be a safer alternative to ticagrelor.