Clues in SCAF, a DOAC antidote trial, another negative lytic trial in stroke, JAMA changes to observational studies, and BP in stroke care are the topics John Mandrola, MD, covers in this week’s podcast.
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--TRANSCRIPT--
In This Week’s Podcast
For the week ending May 24, 2024, John Mandrola, MD, comments on the following news and features stories: Clues on which pts with subclinical atrial fibrillation (SCAF) to anticoagulate, direct oral anticoagulant (DOAC) antidote, another negative thrombolytic trial in stroke, JAMA sparks change in observational studies, and guidelines challenged in stroke care.
ARTESIA Substudy
- Sadly, ARTESIA Doesn't Answer a Common Question in Cardiology
The ARTESIA investigators presented a late breaking clinical trial at the Heart Rhythm Society (HRS) meeting looking at the relationship between CHADSVASC score and stroke risk and apixaban effect on stroke and systemic embolism.
Before I tell you about this substudy, let’s briefly review ARTESIA. The main trial randomly assigned patients with implanted cardiac devices who had short-duration AF to either apixaban or aspirin (ASA). The primary endpoint was stroke and systemic embolism.
- The average age of the 4000 patients was 77 years and mean CHADSVASC was 3.9. Median duration of AF was short at 1.5 hours. Only 20% of patients had AF longer than 6 hours.
- Stroke or systemic embolism occurred in 0.78% (apixaban) vs 1.24% (ASA) per patient-year. This difference of only 31 stroke events in a trial of more than 4000 patients yielded a statistically significant relative risk reduction of 37% (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.45- 0.88; P = .007).
- The safety endpoint of major bleeding occurred in 4.3% patients in the apixaban arm vs 2.3% patients in the ASA arm. This difference of 39 excess major bleeding events yielded a relative risk increase of 80% (HR, 1.80; 95% CI, 1.26-2.57; P = .001).
At the European Heart Rhythm Association meeting in April, ARTESIA investigators presented a provocative subanalysis finding no relationship between duration of SCAF and apixaban effect over ASA. That was weird because you’d expect OAC benefit in longer duration episodes. One problem with sorting out signal in ARTESIA (and NOAH) was the extremely low event rates.
This analysis, which was simultaneously published in the Journal of the American College of Cardiology, assessed the difference in stroke/systemic embolism and major bleeding based on CHADSVASC.
- They made three groups with about a third of patients in each. One group had CHADSVASC 4, one group had CHADSVASC = 4, and the third had CHADSVASC 4.
- For the 4 group there was no difference in stroke or bleeding in apixaban ban vs ASA (stroke rates both around 0.9% per patient-year).
- For the = 4 group the rate of stroke with apixaban vs ASA was 0.54% vs 1.2% per patient-year. But this difference did not meet significance. Same with bleeding — no difference, with 1.2% apixaban vs 0.9% ASA.
- For the 4 CHADSVASC group, the rate of stroke with apixaban was statistically lower than with ASA, basically 1% vs 2.25% per patient-year, HR 0.44 (CI 0.25-0.77). Bleeding was 2.1% vs 1.5% per patient-year but this difference did not reach statistical significance.
The authors converted this to absolute risk reduction (ARR) and wrote: “In this group, over a period of 3.5 years, apixaban prevented four strokes/systemic embolism per 100 patients compared with ASA and caused 1.70 major bleeds.
They calculated an interaction P-value to assess whether these differences between low, moderate to high, or very high CHADSVASCs were statistically significant, and the P-value was 0.06; technically not significant but very close.
The authors were quite strong in their written and spoken conclusions. They believed SCAF in patients with CHADVASC scores 4 warranted OAC.
They cited the 1.2% ARR in stroke and the lack of significance in the higher rate of bleeding in this group.
They also cited a previously published sub-analysis from ARTESIA in which patients who had a prior stroke also benefited from apixaban vs ASA.
That analysis, which was presented but not yet published, found that the risk of stroke/systemic embolism among ASA-assigned patients with a history of stroke or transient ischemic attack is 3.1% per year; suggesting that OAC should be recommended for these patients even if their CHADSVASC score is 4
Comments. The conclusion that we should use OAC in patients with SCAF when CHADSVASC is 4 makes sense. But I worry about the strong conclusions from this subgroup analysis paper.
What if the patient has 1 hour of AF over months? Is that enough? Is that SCAF? SCAF comes in many different varieties.
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