Association of mortality and use of guideline-direct medical therapy following primary prevention defibrillator implantation

Abstract Background Primary prevention implantable cardioverter-defibrillators (ICDs) are recommended for patients with heart failure with reduced ejection fraction. Previous studies have shown that a higher number of prescribed guideline-directed medical therapy (GDMT) medications improves survival rates at 2 years post-ICD implantation, though long-term data is lacking. Purpose This study investigated the impact of GDMT, and uniquely, antiarrhythmic medications, on long-term all-cause mortality following primary prevention ICD implantation. Methods A single-center, retrospective study was completed on all patients who received a primary prevention ICD between 2005 and 2024 (N=590). Baseline demographics, Charlson Comorbidity Index (CCI), GDMT (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, angiotensin receptor/neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors) and antiarrhythmic medications were recorded at the time of device implantation. The primary outcome was all-cause mortality at >5 years. Cox multivariable models were constructed, adjusting for age, sex, ejection fraction, CCI, number of GDMT, and antiarrhythmic medication use, to evaluate the impact of additional GDMT and antiarrhythmic medications on mortality, independently. Results Among 590 patients (69±12 years; 21% female), 4 (1%), 41 (7%), 223 (38%), 276 (47%), and 46 (8%) were on 0, 1, 2, 3, and 4 GDMT medications, respectively. Mortality rates were 12% (72) within 2 years, 14% (81) between 2–5 years, and 19% (111) >5 years post-implantation. The risk of death at >5 years post implantation decreased from 22% on 0/1 GDMT medication to 0% on 4 GDMT medications (p<0.01). Cox multivariable models indicated that each additional GDMT medication reduced mortality by 26% (HR: 0.74; P<0.001). Conversely, antiarrhythmic use was associated with a 27% increase in mortality (HR: 1.27; P<0.05). Conclusion Increasing GDMT medications is associated with improved long-term survival in patients post-ICD implantation, supporting escalating therapy when feasible. In contrast, antiarrhythmic use is associated with increased all-cause mortality.Figure 1