From the Guidelines
The mechanism of action of 5-Hydroxytryptamine (5-HT) receptor agonists contraindicated in Coronary Artery Disease (CAD) and Angina Pectoris is 5-HT1B, 1D agonism, which can cause vasoconstriction of coronary arteries and exacerbate reduced blood flow to the heart muscle. These medications, known as triptans (including sumatriptan, rizatriptan, zolmitan, and others), work by selectively binding to serotonin receptors, particularly the 5-HT1B receptors on blood vessels and 5-HT1D receptors on trigeminal nerve endings, as described in the study published in the American Family Physician 1. This binding causes vasoconstriction of dilated cranial blood vessels and inhibits the release of inflammatory neuropeptides, effectively terminating migraine attacks. However, the same vasoconstrictive effect can occur in coronary arteries, which is why triptans are contraindicated in patients with coronary artery disease, angina, uncontrolled hypertension, and history of stroke or transient ischemic attack, as noted in the study 1. The risk of coronary vasospasm and potential cardiac events makes these medications dangerous for patients with existing cardiovascular conditions.
Some key points to consider when prescribing triptans include:
- Contraindications: ischemic vascular conditions, vasospastic coronary disease, uncontrolled hypertension, or other significant cardiovascular disease 1
- Mechanism of action: 5-HT1B, 1D agonism, causing vasoconstriction of dilated cranial blood vessels and inhibiting the release of inflammatory neuropeptides 1
- Examples of triptans: sumatriptan, rizatriptan, zolmitriptan, and others 1
- Potential risks: coronary vasospasm, cardiac events, and exacerbation of reduced blood flow to the heart muscle 1
It is essential to carefully evaluate the patient's medical history and current condition before prescribing triptans, and to consider alternative treatment options for patients with cardiovascular conditions, as recommended in the study 1.
From the FDA Drug Label
5-HT1 agonists including rizatriptan benzoate may cause coronary artery vasospasm (Prinzmetal's Angina), even in patients without a history of CAD. 5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina Rizatriptan benzoate should not be given to patients with ischemic or vasospastic coronary artery disease.
4 CONTRAINDICATIONS Eletriptan hydrobromide tablets are contraindicated in patients with: Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal’s angina
The mechanism of action of 5-Hydroxytryptamine (5-HT) receptor agonists contraindicated in Coronary Artery Disease (CAD) and Angina Pectoris is coronary artery vasospasm. These agonists, including rizatriptan and eletriptan, can cause Prinzmetal's Angina by inducing vasospasm in the coronary arteries, which can lead to myocardial ischemia and myocardial infarction. This is the primary reason why 5-HT1 agonists are contraindicated in patients with CAD and angina pectoris 2 3.
From the Research
Mechanism of Action of 5-Hydroxytryptamine (5-HT) Receptor Agonists
The mechanism of action of 5-HT receptor agonists, such as triptans, involves the activation of 5-HT1B and 5-HT1D receptors, which are located on cranial blood vessels and trigeminal fibers 4, 5, 6. This activation leads to:
- Cranial vasoconstriction, which helps to relieve migraine headache
- Inhibition of trigeminal CGRP release, which contributes to the antimigraine effect
- Activation of 5-HT1B/1D/1F receptors in the central nervous system, involved in (anti)nociceptive modulation
Contraindication in Coronary Artery Disease (CAD) and Angina Pectoris
Triptans are contraindicated in patients with established or clinically suspected cardiovascular disease, specifically ischemic heart disease and uncontrolled hypertension, due to their potential vasoconstrictor effects on coronary arteries 4, 5, 6, 7. The activation of 5-HT1B receptors on coronary arteries can lead to coronary vasoconstriction, which may exacerbate angina or trigger myocardial infarction in patients with CAD.
Key Findings
- Triptans, such as sumatriptan, have been shown to contract human isolated coronary artery segments in vitro, although with low efficacy 7, 8
- The Cmax/EC50 ratio, an index of coronary vasoconstriction, is higher for avitriptan compared to other triptans, suggesting a greater potential for coronary vasoconstriction 7
- Rizatriptan, a novel 5-HT1D-receptor agonist, has been found to have smaller contractile effects on human isolated coronary artery compared to sumatriptan 8
- Selective 5-HT1F receptor agonists, such as lasmiditan, have been developed as alternative antimigraine drugs with no vasoconstrictive effect on coronary arteries 5, 6