Digoxin raised risk for death in ROCKET AF subanalysis

BARCELONA, Spain — Patients with atrial fibrillation who used digoxin at baseline in the ROCKET AF trial had increased risks for all-cause mortality, vascular mortality and sudden cardiac death.

“Our findings suggest that digoxin is an agent that should be considered cautiously in this population until we have randomized trial data,” Manesh R. Patel, MD, director of interventional cardiology and catheterization labs at Duke University Health System, told Cardiology Today.

Digoxin is a commonly used rate-controlling drug, but has not been well studied in patients with AF, according to Patel. The researchers performed a retrospective analysis of ROCKET AF, a trial aimed at stroke prevention, to determine the effect of baseline digoxin use on the risk for death in patients with nonvalvular AF.

The overall ROCKET AF trial included 14,171 patients with nonvalvular AF at increased risk for stroke. The study was conducted at 1,178 sites in 45 countries. Patients were randomly assigned rivaroxaban (Xarelto, Janssen Pharmaceuticals) or warfarin. Previously published results indicated that rivaroxaban was noninferior to warfarin for the prevention of stroke/systemic embolism in this patient population.

For the current analysis, Patel and colleagues examined the risks for death in 5,239 patients who were taking digoxin at baseline in ROCKET AF vs. 8,932 who were not taking digoxin.

According to findings presented by Patel at ESC Congress, 37% of patients were using digoxin at baseline. “This showed us that digoxin is still commonly used by patients with AF,” Patel told Cardiology Today.

Digoxin use was associated with a 22% increased risk for all-cause mortality (adjusted HR=1.22; 95% CI, 1.08-1.37), 22% increased risk for CV mortality (adjusted HR=1.22; 95% CI, 1.05-1.42) and 29% increased risk for sudden cardiac death (adjusted HR=1.29; 95% CI, 1.03-1.61). The risk for all-cause hospitalization was similar among patients who did and did not use digoxin (adjusted HR=1.04; 95% CI, 0.97-1.12).

“Importantly, there was no difference in stroke/systemic embolism and no difference in MI, which makes us think that the signal was not just associated with sick patients. Although we cannot rule out unmeasured confounders, there was increased risk present after adjustment,” Patel said.

Therapy with rivaroxaban or warfarin also had no difference in the effect of digoxin on clinical events.

The researchers also evaluated the use of digoxin in patients with and without HF. Those with HF had a higher risk for clinical events, but the researchers observed no interaction between HF and digoxin use.

In addition, there was a trend toward increased risk in men who used digoxin compared with women.

Of note, at baseline, patients who were using digoxin had a higher rate of NYHA class III/IV HF (26.5% vs. 14.1%) and a higher heart rate (78 bpm vs. 75 bpm). Patients taking digoxin were equally likely to be on a beta-blocker, Patel said.

“The question is, is this hazard real? We don’t want to cause panic and say that digoxin is clearly harmful, but we see a risk that may provide impetus for randomized clinical trials and possible caution for routine use of digoxin in AF patients. There are agents other than digoxin that are useful for rate-controlling patients,” he said. – by Katie Kalvaitis

For more information:

Patel MR. Abstract #4873. Presented at: the European Society of Cardiology Congress; Aug. 30-Sept. 3, 2014; Barcelona, Spain.

Disclosure: Patel reports consulting/serving on advisory boards for Janssen Pharmaceuticals and research grants from Janssen Pharmaceuticals and Johnson & Johnson.