Triptans and the risk of stroke or MI

Jenny is a 33-year-old lady presenting with acute migraine. She reports the classic aura, followed by disabling unilateral pounding headache. She has tried paracetamol and NSAIDS with limited effect. The pharmacist suggested trialling a triptan; first line as per SIGN guidelines (click here for useful summary). However, Jenny is sceptical as her cousin was cautioned by the GP that triptans were not advisable for her due to increased risk of stroke.

‘What do you think?’ asks Jenny. ‘The nurse said I shouldn’t have the combined pill because of the risk of stroke. Does that mean I shouldn’t have a triptan either?’

Triptans are vasoconstrictors. Contraindications include uncontrolled hypertension or known vascular disease (IHD, PVD, previous TIA,CVA or MI). Cautions include CVD risk factors, elderly, history/ risk of seizures and mild, controlled hypertension (BNF).

Is Jenny right to be wary? The nurse correctly advised against the COCP for as it is UKMEC 4  for migraine with aura. Aside from migraines Jenny has no significant co-morbidities. She is normotensive, and her only medication is the mirena coil. 

The April edition of the Drugs and Therapeutics Bulletin contains a review of a Danish study that investigated the risk of MI, ischaemic or unspecified stroke after triptan initiation. This was a self-controlled cross-over study using adult data from a nationwide health registry between January 1995 and August 2022. Nearly 430 000 adults were initiated on triptans during the study; with a median age of 38, 76% female. In this study design each patient acted as their own control. Triptan prescription redemption in the 14-day focal window immediately prior to MI or CVA was compared with four 14-day reference windows in the same patient. 

They did find a link between triptan initiation and adverse outcome. A total of 11 people had an MI (0.003%), 18 had an ischaemic stroke (0.004%), and 35 had an ischaemic/unspecified stroke (0.008%).  Patients with MI were more likely to have been exposed the triptans in the 14-day focal window prior to event (OR 3.3; 95% CI 1-10.9). Similarly, patients suffering a CVA were more likely to have been exposed to a triptan (OR 3.2 ischaemic stroke, OR 3.0 combined ischaemic or unspecified stroke). 

Whilst this sounds alarming, the key headline is that the total number of CVS events was tiny, and only 13 events were thought attributable to triptan use. This equates to a very low absolute risk of roughly 1 in 30 000 patients starting a triptan medication. Further, patients with adverse events were more likely to have cardiovascular risk factors such as hypertension or previous ACS and were mostly over 60yrs old. Overall the study does not indicate cause for concern in low risk patients, but supports established guidance for caution in patients with a higher CVS risk profile. When considering triptans we should be assessing cardiovascular history and blood pressure to inform decision making.

So where does this leave Jenny? We can reassure her that in the absence of cardiovascular risk factors evidence suggests that her risk of a vascular event related to triptan use is very low. Jenny recalls that her cousin is ‘on pills for her blood pressure and cholesterol’, likely accounting for the different risk/ benefit profile in her case. She asks what the risks are associated with the COCP, to help contextualise the risk (number of strokes per year in patients <35yrs on the COCP with migraine with aura is quoted as 28/100 000 (PIL Oxford Health NHS Foundation Trust). On balance she decides the likely benefits for her outweigh possible risks, and opts for a trial of sumatriptan.