Episode 25- Procainamide for atrial fibrillation/flutter conversion
Should we be giving procainamide to patients with atrial fibrillation/ flutter? We discuss two clinical trials that may give us some answers.
“Procainamide for atrial fibrillation/flutter conversion”:
– There is a lack of data/ recommendations on how best to treat acute atrial fibrillation (AF) in the ER setting. Some advocate for attempting pharmacologic cardioversion first, and proceeding to electrical cardioversion if that fails (“drug-shock” strategy)
– A study out of Ottawa, Canada, showed that 1 g IV procainamide in 250 mL D5W given over 1 hour was successful in cardioverting 52% of patients in AF, but only 28% of patients in atrial flutter. The most common adverse drug event was hypotension
– A more recent study (RAFF2) showed that procainamide (dosed at 15 mg/kg with a max of 1500 mg given over 30 minutes) followed by electrical cardioversion if necessary (“drug-shock” group) was as effective as the “shock only” group in cardioverting patients in AF (96% vs 92%, P=0.07). Procainamide itself was successful 52% of the time, and electrical cardioversion was successful in > 90% of cases
– Overall, procainamide, especially in the setting of AF, seems to have ~50% success rate. Patients who convert with procainamide spend less time in the ER (4 hours vs 7 hours) and avoid the need for procedural sedation. However, procainamide does come with some side effects and is not very effective in the setting of atrial flutter
– Using a “drug-shock” strategy vs a “shock only” strategy should be a decision made with the patient and the provider, with full discussion of risks and benefits
Stiell IG, Sivilotti MLA, Taljaard M, et al. Electrical versus pharmacological cardioversion for emergency department patients with acute atrial fibrillation (RAFF2): a partial factorial randomized trial. Lancet. 2020; 395 (10221): 339-349
Hello and welcome to Episode 25 of ER-Rx. This week, we’re going to discuss the use of IV procainamide for patients in acute atrial fibrillation (AF) or atrial flutter. How do we best manage these patients? Should we try an anti-arrhythmic drug first, or go straight to electrical cardioversion?
AF is the most common acute arrhythmia that we will see in the ER. Patients who are in “acute,” “paroxysmal,” or “new-onset” AF are often times managed with cardioversion, in contrast to patients with “chronic” or “permanent” AF who are usually managed with a rate control strategy. Atrial flutter is less common, but also often times requires electrical cardioversion in the ER setting.
We have some data on how best to treat chronic AF. On the one hand, we have conservative treatment which consists of rate control, anticoagulation, and potentially delayed cardioversion. On the other hand, some opt for aggressive treatment with immediate cardioversion in the ER- either pharmacologically or electrically. The overall thought is that conservative, rate control therapy tends to be best for most patients in chronic AF. What is still unclear at this time is how to best treat patients who come into the ER with acute AF or atrial flutter. Well, there is one site in Ottawa, Canada that routinely uses procainamide for the pharmacologic cardioversion of AF and atrial flutter. And lucky for us, they decided to publish their experiences back in 2007.
Their retrospective study looked at a 5 ½-year period in one study site. They excluded patients with chronic AF, patients with symptoms lasting > 48 hours unless they were anticoagulated, patients with unknown durations of symptoms, and those who had other diagnoses that required admission. Basically, they left out people we wouldn’t normally cardiovert in the ER- good for them. Their protocol involved giving patients 1 g IV of procainamide in 250 mL of D5W over 1 hour, followed by electrical cardioversion if that failed. If you remember your Vaughan-Williams classifications, procainamide is a Class Ia anti-arrhythmic that works by blocking fast sodium channels, which decreases impulse conduction. They would stop the infusion if blood pressure fell to < 100 mmHg and was not responsive to a NS bolus, if the patient become bradycardic, or if the patient’s rhythm converted before the full dose was in.
This study included 341 patients, 316 with AF and 25 with atrial flutter. The mean age was 64 years, 57% were male, and the mean duration of the arrhythmia prior to presentation was 8 hours. All patients received IV procainamide, and 144 patients (42%) needed electrical cardioversion, which was successful in 91% of patients. However, the success rates for procainamide alone were 50% overall (52% for AF and only 28% for those in atrial flutter). Those who converted needed about 55 minutes to convert, with patients usually needing the full 1 g dose to see effect.
In terms of safety, adverse drug events (ADEs) occurred in 10% of patients overall, with hypotension during infusion being the most common side effect. No patient had syncope, torsades, MI, CVA, or death. Only 19 patients (5.6%) were admitted, and only 10 patients (2.9%) bounced back within 7 days.
All in all, the authors showed decent success rates in the setting of AF, and the good news was that patients spent much less time in the ER if procainamide was successful (~4 hours vs 7 hours). Their success rates and ADEs, which were mainly hypotension, correlated well with previous studies in this setting. The authors concluded that other potential agents mentioned in guidelines, such as dofetilide, flecainide, ibutilide, and propafenone are less appealing options due to FDA restrictions, high rates of arrhythmias, ineffectiveness, or the fact that IV formulations of these agents are not always available in the US.
A more recent study, published in the Lancet in February of 2020, also looked at procainamide use (this time at a dose of 15 mg/kg with a maximum dose of 1500 mg over 30 minutes) plus shock if necessary (the “drug-shock” group), versus shock alone. This was a randomized, placebo-controlled trial in 396 patients that also interestingly wanted to see if the anteroposterior or anterolateral placement of pads had any bearing on efficacy of shocks. Patient populations and exclusion criteria were similar to the previous study. They found that 96% of patients converted with the “drug-shock” strategy, and 92% converted with the shock alone strategy (p=0.07). Procainamide itself worked in 52% of patients, just like the previous study, but there were no patients with atrial flutter in this trial. ADEs were mostly once again related to hypotension in the procainamide group. At 14 days, no patients suffered a stroke, and 95% were still in normal sinus rhythm with either strategy. And for completeness, they found no differences in success rates with different pad placements (95% anterolateral and 92% anteroposterior).
My overall takeaway is that procainamide can be attempted, especially in the setting of AF. The benefit is if the patient converts with procainamide, we can avoid the need for electrical cardioversion with procedural sedation and can get them out of the ER faster. However, the fact that procainamide does cause side effects and is only 50% effective at best means that a shock-first strategy, with its > 90% success rate, is still very much a reasonable option. In the end, this should be a shared decision between providers and patients—as long as both parties know the risks and benefits of both strategies.
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