Paradigm shifts in pathophysiology and management of atrial fibrillation—a tale of the RACE trials in the Netherlands

Figures

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  Fig. 1. Rate and rhythm control management in RACE [1]. In the rate control strategy patients with intolerable symptoms were allowed to undergo cardioversion. This was not considered a cross-over but an essential part of that strategy. The rhythm control strategy consisted of serial cardioversion supported by antiarrhythmic drugs. Drugs changed only if recurrence happened under an adequate dosage and only in case of an early recurrence, defined as happening within 6 months. Cardioversion patients resorting to rate control (‘atrial fibrillation accepted’) were not considered cross-overs since that was an essential part of the rhythm control strategy, paralleling clinical practice. Reprinted with permission of the Massachusetts Medical Society

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  Fig. 2. Main results from 5 RACE trials. a RACE: rate control is non-inferior to rhythm control [1]; b RACE-II: lenient rate control is non-inferior to strict rate control [6]; c RACE3: upstream therapy was associated with a modest improvement of rhythm control [8]; d RACE4: nurse-led care appeared not superior to usual-care provided by a cardiologist, although in proficient centres, nurse-led care was associated with significantly fewer events [9]; e RACE7-ACWAS: sinus rhythm at 4 weeks after delayed cardioversion and standard-of-care early cardioversion did not differ; f RACE7-ACWAS: sinus rhythm during index visit, according to type of cardioversion – in 69% of patients in the delayed cardioversion strategy an intervention may be avoided. In contrast, an early intervention allows only for 16% spontaneous conversion with 80% obligatory cardioversions [10]. Reprinted with permission of the Massachusetts Medical Society (RACE, RACE-II and RACE7-ACWAS) and Oxford University Press (RACE3 and RACE4)

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  Fig. 3. Over 2.3 years follow-up, RACE (published 2002) [1] had significantly more endpoint events than RACE-II (published 2010) [6], despite baseline cardiovascular risk being comparable and with an even higher intrinsic risk in permanent AF in RACE-II. This time-dependent change was likely due to the more widespread use of anticoagulants in RACE-II with far fewer thromboembolic complications but coming at the cost of (unchanged) bleeding. In addition, the more extensive prescription of renin-angiotensin system blockers in RACE-II also contributed. RACE and RACE-II included 522 and 614 patients, average age 68 and 68 years, average atrial fibrillation duration 11 and 18 months, CHA2DS2-VASc 1.4 and 1.4, all respectively. Overall anticoagulant use varied in RACE between 96–99% in rate control and 86–99% in rhythm control and in RACE-II it was constant at 99% of time