For patients in whom we are initiating flecainide, what pre-testing do they need?
I can always use a refresh on anti-arrhythmic medications. This week we saw a patient in whom we wanted to start flecainide, and I knew we needed to get an echo to rule out structural heart disease, but I wasn't sure if all of these patients need an ischemic evaluation, too. At my old job at the VA, we would routinely get a stress test, but our patients were also generally older than the patients I now see at Grady (this particular patient was younger than 50). The 2014 AHA/ACC guidelines on managing afib do say we should be cautious about using flecainide in patients with HF and CAD, as well as those with sinus/AV node dysfunction, aflutter, infranodal conduction disease, Brugada, and kidney/liver dysfunction. They specifically reference patients with a history of MI, citing the CAST study.
So, I went back and reread CAST, attached, and remembered that patients with a history of MI and subsequent PVCs, but not VT, received flecainide in one arm, and that they were then followed for death or cardiac arrest. This particular group had an EF between 30 and 55% (if they were more than 90d post-MI, their EF had to be between 30 and 40%), and they did have to demonstrate PVC suppression with the drug. As you probably know, the groups receiving flecainide and encainide had a significantly higher rate of death and cardiac arrest, from arrhythmia, cardiac cause, or any cause:
Figure 2. Actuarial Probabilities of Freedom from Death or Cardiac Arrest due to Any Cause in 1498 Patients Receiving Encainde or Flecainde or Corresponding Placebo
There's also a table showing the increased incidence of VT/VF in patients who received a drug as compared to those who received placebo:
Table 3. First Monitored Rhythm in Patients with Death or Arrest Due to Arrhythmia
Some of the non-arrhythmia cardiac deaths and arrests were due to acute MI leading to shock, CHF, and/or CABG. The authors talk about the pro-arrhythmic effects of these drugs in the Discussion section, and how a lack of monitoring might have led to missing ventricular arrhythmias; they also speculate that the ischemia that occurred in drug patients might have been more likely to be fatal than that observed in placebo patients (through facilitating an arrhythmia and/or negative inotropy).
Using flecainide in patients with prior MI is a Class III recommendation according to the 2017 AHA/ACC guidelines on ventricular arrhythmias, citing this same reference. I did not find other great primary literature about this topic; it seems we've extrapolated from harm after prior MI to pre-proceeding with an ischemic evaluation based on this data. Doing an ischemic eval before initiating flecainide is also recommended in the UpToDate summary on anti-arrhythmics for afib.
So, I guess the answer is to do a stress test or a CCTA before starting flecainide, though I don't feel great about the evidence behind this practice. This week's question was a nice reminder for me of how sometimes our data is quite limited, and how the presence of significant harm can limit further investigation, even though it might be helpful. Would love to hear if any of you feel comfortable initiating flecainide in younger patents without doing an ischemic evaluation.
Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. Journal of the American College of Cardiology. 2018;72(14):e91-e220. doi:https://doi.org/10.1016/j.jacc.2017.10.054
Echt DS, Liebson PR, Mitchell LB, et al. Mortality and Morbidity in Patients Receiving Encainide, Flecainide, or Placebo. New England Journal of Medicine. 1991;324(12):781-788. doi:https://doi.org/10.1056/nejm199103213241201
January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. Journal of the American College of Cardiology. 2014;64(21):e1-e76. doi:https://doi.org/10.1016/j.jacc.2014.03.022
