Striking underuse of therapies for HFrEF not explained by low blood pressure
Target Doses of Heart Failure Medical Therapy and Blood Pressure: Insights From the CHAMP-HF Registry
Introduction an methods
Medical therapy can substantially reduce poor CV outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Inhibition of the beta adrenergic system with beta-blockers (BBs) and of the angiotensin pathway with angiotensin-converting enzyme inhibitors (ACEi’s) or angiotensin receptor blockers (ARBs) have been central to treatment of HFrEF. The first member of the class of angiotensin II receptor blocker-neprilysin inhibitors (ARNIs), sacubitril/valsartan provides additional reduction of morbidity and mortality as compared with BB therapy alone [1,2].
Observations of dose-related relationships between ACEi and BB use and outcomes have led to recommendations on target medication doses in national guidelines [1, 3-5]. In clinical practice, target doses are often underused [6,7]. Fear of low blood pressure (BP) may be a barrier to intensifying guideline-directed medical therapy.
This study aimed to understand whether low BP is a barrier to achieving targeted doses of HFrEF therapy, by using the large, multicenter, contemporary CHAMP-HF registry of adult outpatients with HFrEF (collected at 151 US sites). Eligible patients had a primary diagnosis of HFrEF (LVEF ≤40%) within 12 months of enrollment and were taking at least one oral pharmacotherapy for HF. Patients experiencing HF medication-related side effects of with contra-indications for ACEi/ARB, ARNI or BB were excluded. 3095 Patients were included between December 2015 and August 2017.
- Median SBP was 120 mmHg (IQR: 110-130 mmHg) and median DBP was 72 mmHg (IQR: 64-80 mmHg). 70.6% Of patients were male, and 59.6% were older than 64 years old. 84% Of patients had NYHA functional class II or III. Median LVEF was 30% (IQR: 23.% - 36%).
- In those with SBP ≥110 mmHg as compared with those with <110 mmHg, use of BB was significantly lower (81.9% vs. 85.6), of ARB higher (22.6% vs. 14.7%), and of ARNI lower (11.6% vs. 17.5%). Use of ACEi was similar in both groups (1.0% vs. 42.4%).
- Of 3093 patients, 61% were receiving ACEi/ARB, 12.9% were receiving ARNI, and 82.7% a BB.
- The proportion of patients receiving target doses for these drug classes, were 10.8% (9.7%-11.9%) for ACEi/ARB, 2.0% (95%CI: 1.5%-2.5%) for ARNI and 18.7% (5%CI: 17.3-20.0) for BBs.
- Among those with SBP <110 mmHg, the proportion receiving target doses were 6.2%, 1.8% and 17.5%, respectively. In those with SBP >110 mmHg, 12.1%, 2.0% and 19.0%, respectively, received target doses of ACEi/ARB, ARNI and BB. In both SBP subgroups, more patients received <50% of the target those than >50%.
- In patients who already received 2 classes of medication (ACEi/ARB/ARNI and a BB), only 8.8% were receiving target doses of both agents. In those with SBP <110 mmHg, 5.8% received target doses of both therapies, and 9.7% of those with SBP >110 mmHg.
Analysis of the contemporary CHAMP-HF cohort of HFrEF patients revealed that an overwhelming majority of patients eligible for either BB or ACEi/ARB/ARNI were not receiving target doses. Most patients were on less than 50% of guideline-recommended target doses. Low BP did not appear to be a barrier to intensifying therapy, because undertreatment was also prevalent in those with SBP >110 mmHg. In patients who were receiving two HF medications, the proportion of patients receiving target doses was very low (8.8%) and only slightly more patients with SBP >110 mmHg received target doses than those with SBP <110 mmHg.
This study shows ample room for improvement in providing patients with the best medical therapy. Moreover, it reinforces that better understanding is needed of factors related to suboptimal dosing of important HF medications in patients who can tolerate them.