Female Patients Less Likely to Receive Guideline-Directed HFrEF Therapies vs Males

Although guideline-directed medical therapies (GDMTs) are crucial for the treatment of heart failure with reduced ejection fraction (HFrEF), a recent study found that use of optimal GDMT after HFrEF diagnosis is low overall, but especially among female patients compared with male patients. The findings were published in the journal Circulation.

GDMTs reduce patients’ risk of hospitalization and all-cause mortality following HFrEF diagnosis with measures including use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or angiotensin receptor neprilysin inhibitors (ARNIs); evidence-based beta-blockers such as bisoprolol, carvedilol, or metoprolol succinate; and mineralocorticoid receptor antagonists (MRAs). Sodium-glucose cotransporter 2 inhibitors were also recently recommended by the American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines for HF.

“HF GDMT benefits are incremental, accrue quickly, and can be appreciated within weeks after HF hospitalization,” the authors wrote. “All current US guidelines recommend early initiation and uptitration of multiple GDMTs after HFrEF diagnosis. However, insufficient use of these therapies persists because of low prescription and poor rates of dose uptitration to maximally tolerated guideline-recommended treatment doses.”

Although male and female patients are at similar risks of clinical HF over their lifetimes, they differ in the type of HF, risk factor burden, and clinical presentation. HFrEF is less common vs HF with preserved ejection fraction in females, who are also more likely to be older at diagnosis. The authors noted that female patients are also less likely to receive evidence-based device therapy or coronary revascularization.

Doctor holding heart | Image credit: Pana Studio - stock.adobe.com

The current study aimed to determine whether there are sex differences in the initiation of GDMT (renin-angiotensin system inhibitors, beta-blockers, and MRAs) and the intensification of therapy within 1 year or HFrEF diagnosis. Investigators utilized the deidentified Clinformatics Data Mart Database from Optum to assess use of GDMT in this population.

The final cohort included 63,759 patients, 43.2% of whom received their diagnosis in an inpatient setting. The mean patient age was 71.3 years, 56.6% were male patients, and 15.2% were non-Hispanic Black. Female patients were more likely to get their diagnosis in the inpatient setting and at an older age, had a lower prevalence of cardiometabolic comorbidities, and more frequently had Medicare insurance.

Baseline use of GDMTs was low, with 13.7% of patients receiving ACE inhibitors/ARBs/ARNIs, 17.1% receiving beta-blockers, and 6.2% receiving MRAs at the time of HFrEF diagnosis. The greatest increase in each class occurred between diagnosis and 3 months, when the use rate was 55.3% for ACE inhibitors/ARBs/ARNIs, 55.5% for beta-blockers, and 18.4% for MRAs. The use rates at 12 months were 65.2%, 64.3%, and 24.7%, respectively.

In the overall cohort, there was an increase in GDMT use from 3.0% at 3 months to 6.2% at 12 months, although only 1.4% of participants reached target doses of all 3 GDMT classes by 12 months.

The researchers identified sex differences in use patterns, finding that 81.1% of female and 84.5% of male patients received any GDMT within 12 months of HFrEF diagnosis. Female patients had a lower uptake of optimal GDMT at every time point, and a similar trend was seen with optimal doses of the 3 classes (1.0% in females vs 1.6% in males at 12 months). Overall, females with HFrEF were significantly less likely to achieve optimal GDMT compared with males (HR, 0.77; 95% CI, 0.71-0.83; P < .0001).

There were interactions observed between sex and type of insurance, as well as sex and age for the probability of optimal GDMT use, but no statistically significant interactions between sex and other covariates such as location of diagnosis or hospitalizations during follow-up.

Patients with commercial insurance were more likely to use ACE inhibitors/ ARBs/ARNIs, beta-blockers, and MRAs at baseline compared with patients covered by Medicare, with optimal use of GDMT of 11.5% among commercially insured patients and 4.9% among those with Medicare. Rates of optimal GDMT were comparable between females and males with Medicare, but female patients with commercial insurance had significantly lower optimal use vs male patients with commercial insurance (8.8% vs 12.9% at 12 months). The odds of optimal GDMT on follow-up overall differed more between males and females with commercial insurance (HR, 0.66; 95% CI, 0.58-0.76; P < .001) compared with the difference between females and males with Medicare (HR, 0.85; 95% CI, 0.77-0.92; P < .001).

Another predictor of optimal GDMT use was age, with use lower among patients 65 years or older compared with younger patients (4.8% vs 10.9% by 12-month follow-up). Younger females had lower rates of optimal GDMT vs younger males (HR, 0.65; 95% CI, 0.58-0.74; P < .001), with a lesser gap between older males and older females (HR, 0.87; 95% CI, 0.80-0.96; P = .004).

The study was limited because data were derived from International Classification of Diseases, 10th Revision codes and did not include nonclinical claims data, meaning the authors could not assess whether measures of clinical severity of HFrEF affected use rates. They also could not determine whether prescriber practices, patient nonadherence, or patient tolerability impacted GDMT use.

“Our study has important implications for HFrEF care delivery in the United States,” the authors wrote. “Female individuals with HFrEF have a higher readmission burden and greater survival loss (compared with the US population median) than male individuals. A potential driver of these differences in outcomes could be the underuse of GDMT among female (compared with male) patients. Previous data suggest a 1% increased mortality risk for each month of GDMT deferral. Thus, there is a need to improve GDMT use in all patients who are undertreated for HFrEF.”

Reference

Sumarsono A, Xie L, Keshvani N, et al. Sex disparities in longitudinal use and intensification of guideline-directed medical therapy among patients with newly diagnosed heart failure with reduced ejection fraction. Circulation. Published online January 23, 2024. doi:10.1161/CIRCULATIONAHA.123.067489