Prophylactic ICD reduces sudden cardiac death, but may not reduce all-cause mortality in adults with nonischemic heart failure with reduced ejection fraction
EBM Focus - Volume 11, Issue 36
Reference - DANISH trial (N Engl J Med 2016 early online) (level 1 [likely reliable] evidence)
- ICDs have been shown to reduce sudden cardiac death and all-cause mortality in patients with ischemic heart failure with reduced ejection fraction, but their efficacy in patients with nonischemic heart failure is not clear.
- In a randomized trial of 1,116 adults with symptomatic nonischemic heart failure with ejection fraction ≤ 35%, addition of ICD to usual care (including medication and cardiac resynchronization therapy as indicated) reduced incidence of sudden cardiac death, but did not significantly reduce all-cause mortality at a median follow-up of 67.6 months.
Heart failure with reduced ejection fraction is associated with increased 5-year mortality rates (JAMA Intern Med 2015 Jun;175(6):996). The increased mortality is due in part to sudden ventricular arrhythmias that may occur with heart failure. ICDs are generally recommended in patients with ejection fractions ≤ 35% who are expected to live more than one year (Eur J Heart Fail 2016 Aug;18(8):891, Circulation 2013 Oct 15;128(16):e240), and they have been shown to decrease sudden cardiac death and all-cause mortality (N Engl J Med 2005 Jan 20;352(3):225, Ann Intern Med 2014 Jan 21;160(2):111). However, much of the supporting evidence involves patients with an ischemic etiology. Fatal arrhythmias may be less likely with nonischemic heart failure, and the efficacy of ICDs for patients with this condition is less clear. Also, as medications and therapies such as cardiac resynchronization therapy (CRT) improve, the significance of additional benefits of ICDs is uncertain. To investigate the efficacy of ICDs in patients with nonischemic heart failure, the recent DANISH trial randomized 1,116 adults (median age 64 years, 72% male) with chronic symptomatic nonischemic heart failure with reduced ejection fraction to ICD plus usual care (including medication and CRT devices as indicated) versus usual care alone and followed them for a median of 67.6 months. All patients had left ventricular ejection fraction ≤ 35% after medication target doses were reached and had N-terminal pro-brain natriuretic peptide (NT-proBNP) levels > 200 picograms/mL. A CRT device was implanted in 58% of patients in each group (including about 9% of the patients who had an existing device upgraded), over 90% were treated with beta-blockers and either an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, and 58% had aldosterone antagonists. Patients were excluded for atrial fibrillation with a resting pulse rate > 100 beats/minute, dialysis for renal failure, or other serious conditions.
Patients treated with ICD plus usual care had a lower incidence of sudden cardiac death compared to those treated with usual care alone (4.3% vs. 8.2%, p = 0.005, NNT 26), but there were no significant differences in all-cause mortality (21.6% vs. 23.4%), death due to other cardiovascular causes (9.5% vs. 8.8%), or other outcomes including non-cardiovascular death, cardiac arrest, sustained ventricular tachycardia requiring intervention, bleeding requiring intervention, and pneumothorax. There was no significant difference between groups in rates of infection related to ICD or CRT devices (4.9% with ICD and 3.6% with usual care alone). Inappropriate shocks occurred in 5.9% of patients in the ICD group.
This trial shows that ICDs reduce the incidence of sudden cardiac death in patients with nonischemic heart failure, but the lack of a statistically significant reduction in all-cause mortality has unclear clinical implications. The 95% confidence interval for the hazard ratio for all-cause mortality with ICDs in this trial was 0.68 to 1.12, which does not exclude a clinically meaningful reduction. Also, this trial was powered to detect a 25% reduction in all-cause mortality with ICD, but a larger sample size with the potential to detect a smaller effect may have been more prudent as prior studies with patients with nonischemic heart failure failed to show a statistically significant reduction in all-cause mortality with the use of ICDs (N Engl J Med 2004 May 20;350(21):2151, J Am Coll Cardiol 2003 May 21;41(10):1707, Circulation 2002 Mar 26;105(12):1453). Thus, the possibility that ICDs reduce all-cause mortality in patients with nonischemic heart failure cannot be excluded. It is also worth noting that this trial was conducted in a setting where the treatment of heart failure adhered as close as possible to heart failure guidelines, emphasizing the importance of proper medication management along with the use of CRT when indicated.
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