Multimorbidity And Guideline-Directed Medical Therapy Intensification In Heart Failure: Findings From The EPIC-HF Trial

Background Despite proven benefits of guideline directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF), multiple studies have shown that rates of GDMT prescribing are suboptimal worldwide. An important potential contributor to suboptimal GDMT is the high burden of multimorbidity in the HFrEF population, with estimates showing at least 50% of patients having 5+ co-occurring chronic conditions and taking 10+ medications daily. Large registries examining GDMT prescribing demonstrate associations between individual co-morbidities and GDMT, but data is lacking on the cumulative effect of multimorbidity on GDMT prescription. Methods The recently completed 3-site EPIC-HF trial tested the effect of a pre-clinic patient activation tool on GDMT prescribing made following a visit with a cardiology provider and then over the subsequent 6 months. Using this data, we examined the effect of multimorbidity on both baseline GDMT prescription and GDMT initiation and dose intensification (the primary outcome of the EPIC-HF trial). Presence of the following 9 co-morbidities was collected: COPD or other pulmonary disease, liver disease, diabetes, cancer (excluding non-melanoma skin cancer), depression, anxiety or other psychiatric disease, atrial fibrillation or flutter, hypertension, CKD (eGFR <= 60), and obesity (BMI>=30). Results Of the 292 patients, 35.6% had 3 or more non-HFrEF comorbidities and 34.6% had 1 or fewer additional comorbidities. The most commonly occurring comorbidities were hypertension (51.7%), obesity (41.4%), CKD (32.9%), diabetes (25%) and atrial fibrillation or flutter (28.1%). Increasing burden of multimorbidity was not associated with less total prescription of GDMT at baseline, and was, in fact, associated with the prescription of higher doses of beta-blocker (median 50% target dose with 3+ additional comorbidities vs 25% with no comorbidities, p=<0.01). When controlling for study arm in the original EPIC-HF trial, the presence of additional comorbidities was associated with decreased likelihood of GDMT intensification (1 comorbidity v. 0: RR 0.61, 95% CI 0.4-0.95; 2 v. 0: RR 0.88 95% CI 0.61-1.27; 3+ v. 0: RR 0.56, 95% CI 0.36-0.86). Individual comorbidities associated with decreased likelihood of GDMT intensification were diabetes (p=0.02), hypertension (p=0.003), and CKD (p=0.047). Conclusions Increasing burden of multimorbidity was not associated with less total GDMT prescription at baseline but was associated with decreased up-titration or initiation of GDMT at the study visit. Despite proven benefits of guideline directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF), multiple studies have shown that rates of GDMT prescribing are suboptimal worldwide. An important potential contributor to suboptimal GDMT is the high burden of multimorbidity in the HFrEF population, with estimates showing at least 50% of patients having 5+ co-occurring chronic conditions and taking 10+ medications daily. Large registries examining GDMT prescribing demonstrate associations between individual co-morbidities and GDMT, but data is lacking on the cumulative effect of multimorbidity on GDMT prescription. The recently completed 3-site EPIC-HF trial tested the effect of a pre-clinic patient activation tool on GDMT prescribing made following a visit with a cardiology provider and then over the subsequent 6 months. Using this data, we examined the effect of multimorbidity on both baseline GDMT prescription and GDMT initiation and dose intensification (the primary outcome of the EPIC-HF trial). Presence of the following 9 co-morbidities was collected: COPD or other pulmonary disease, liver disease, diabetes, cancer (excluding non-melanoma skin cancer), depression, anxiety or other psychiatric disease, atrial fibrillation or flutter, hypertension, CKD (eGFR <= 60), and obesity (BMI>=30). Of the 292 patients, 35.6% had 3 or more non-HFrEF comorbidities and 34.6% had 1 or fewer additional comorbidities. The most commonly occurring comorbidities were hypertension (51.7%), obesity (41.4%), CKD (32.9%), diabetes (25%) and atrial fibrillation or flutter (28.1%). Increasing burden of multimorbidity was not associated with less total prescription of GDMT at baseline, and was, in fact, associated with the prescription of higher doses of beta-blocker (median 50% target dose with 3+ additional comorbidities vs 25% with no comorbidities, p=<0.01). When controlling for study arm in the original EPIC-HF trial, the presence of additional comorbidities was associated with decreased likelihood of GDMT intensification (1 comorbidity v. 0: RR 0.61, 95% CI 0.4-0.95; 2 v. 0: RR 0.88 95% CI 0.61-1.27; 3+ v. 0: RR 0.56, 95% CI 0.36-0.86). Individual comorbidities associated with decreased likelihood of GDMT intensification were diabetes (p=0.02), hypertension (p=0.003), and CKD (p=0.047). Increasing burden of multimorbidity was not associated with less total GDMT prescription at baseline but was associated with decreased up-titration or initiation of GDMT at the study visit.