Changing Treatment Pace for Heart Failure: Why We Shouldn’t Delay Guideline-Directed Medical Therapies

As someone trained in the mid-2000s, I know the age-old adage of “start low, go slow” was preached in every class or rotation related to the care of heart failure patients. The idea behind this approach was to start guideline-directed medical therapies (GDMT) sequentially, beginning with one medication at a time at a low dose and slowly adding more meds and titrating up the doses over weeks to months. The prevailing theory was that such a practice would prevent patients from developing treatment-related adverse drug events, which would result in drug discontinuation.

Lately, this adage has come under fire from critics who say that delaying initiation and intensification of GDMT harms patients by denying them the benefits of said therapy. This criticism is born in the recently completed heart failure trials show the benefits of newer GDMT (eg, SGLT2 inhibitors) onset within 2 weeks of initiation. Indeed, some heart failure experts have now called for simultaneous initiation of “quad therapy,” whereby all 4 pillars of GDMT are initiated together on day one of treatment.

In this latest installment of Talking Therapeutics, we evaluate a new study that explores the hypothesis regarding aggressive initiation and up-titration of GDMT in patients with recently decompensated heart failure.

Talking Point: Trade in “Low and Slow” for “Fast and Furious”

New research on a post-hoc secondary analysis of the STRONG-HF randomized clinical trial, which included patients with acute heart failure who were not treated with optimal doses of GDMT before and after discharge from a hospital admission, shows aggressive initiation and up-titration of GDMT in patients may be the answer. The mean percentage of the doses of 3 classes of HF medications (renin-angiotensin system inhibitors, β-blockers, and mineralocorticoid receptor antagonists) relative to their optimal doses were computed. Patients were classified into 3 dose categories: low (<50%), medium (≥50% to <90%), and high (≥90%).

1. A total of 515 patients were included. At 2 weeks, 39 patients (7.6%) achieved low doses, 254 patients (49.3%) achieved medium doses, and 222 patients (43.1%) achieved high doses. Findings reveal 2 pertinent outcomes:
2. As a continuous time-dependent covariate, an increase of 10% in the average percentage optimal dose was associated with a reduction in 180-day heart failure-related readmission or all-cause death (adjusted hazard ratio [aHR], 0.89; 95% CI, 0.81-0.98; P=.01) and a decrease in 180-day all-cause mortality (aHR, 0.84; 95% CI, 0.73-0.95; P=.007).

Quality of life at 90 days improved more in patients treated with higher doses of GDMT (mean difference, 0.10; 95% CI, −4.88 to 5.07 and 3.13; 95% CI, −1.98 to 8.24 points in the medium- and high-dose groups relative to the low-dose group, respectively; P=.07).

Talking Point: It’s OK to be Aggressive

The study adds to the growing body of literature suggesting that patients with heart failure should be aggressively initiated and titrated on GDMT. This study shows that this is even possible after a recent hospital stay for decompensated heart failure.

It is important to note that some patients, like those with baseline hypotension or ongoing congestive symptoms, will not be good candidates for aggressive initiation of GDMT. But barring the presence of these contraindications, it’s now all systems go for simultaneous initiation and aggressive up-titration of GDMT in patients with heart failure.