Underuse of GDMT for Heart Failure Even Worse in Low-Income Countries

While celebrating advances in HF therapy, “the strong, strong message is it’s time for implementation,” Carolyn Lam says.

Underuse of GDMT for Heart Failure Even Worse in Low-Income Countries

A new global registry study confirms that use of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) is suboptimal, and shows that the situation is particularly bad in lower-income countries.

Across sites in 44 countries participating in the prospective REPORT-HF registry, only about one-third of patients hospitalized for acute HF were on all three classes of drugs recommended by guidelines at the time—renin-angiotensin-aldosterone system (RAAS) inhibitors, beta-blockers, and mineralocorticoid receptor antagonists (MRAs)—when they were discharged (37%), without much change in that figure among those who survived to 6 months (34%).

Patients treated in low- and middle-income countries, however, were much less likely to receive GDMT than were those treated in high-income countries, both at discharge (19% vs 41%) and at 6 months (15% vs 37%).

The overall low use of GDMT for heart failure on a worldwide scale among centers collecting data in a standard way is consistent with prior research conducted within single countries or regions, senior author Carolyn Lam, MBBS, PhD (Duke-National University of Singapore Medical School, Singapore), told TCTMD, adding, “I think the surprising part [is] just how bad we are at this as a whole.”

She noted that the recently updated US and European guidelines have added a fourth drug class—the sodium-glucose cotransporter 2 (SGLT2) inhibitors—to foundational heart failure therapy, which means it might be even harder now to get patients on all of the recommended medications.

“The paper’s coming out at a very good time when there’s a lot of press about how much we’ve advanced in heart failure, all the good therapies we have, the consistency among international guidelines that we should get every patient on four foundational medicines,” Lam said. That is “then juxtaposed to this reality check that we’re not even doing right by our patients with the basic three, and especially women, especially those from low-income regions, and especially those without any insurance.”

The study was published recently online in the European Heart Journal, with lead author Jasper Tromp, MD, PhD (Saw Swee Hock School of Public Health, National University of Singapore).

REPORT-HF Registry

For the study, the investigators turned to the REPORT-HF registry, which prospectively collected data on patients treated across 358 sites on six continents. The analysis included 8,669 patients (median age 64 years; 72% men) with HFrEF (LVEF < 40%) who were hospitalized for acute HF and survived to discharge. The study period ran from July 23, 2014, to March 24, 2017.

Having the scientific advances is one thing, and we celebrate it of course, but if we don’t implement, we actually don’t realize these benefits for patients. Carolyn Lam

Use of GDMT was worse in lower-income versus high-income countries. At discharge, for instance, they were less likely to be on a RAAS inhibitor (57% vs 71%), beta-blocker (52% vs 84%), and MRA (45% vs 59%). These patients also less frequently received at least 50% of the recommended target dose of a RAAS inhibitor (22% vs 28%) or beta-blocker (7% vs 32%), although patients in lower-income countries were more likely to receive an adequate dose of MRA (14% vs 9%). That’s “possibly driven by the low cost of spironolactone and policies encouraging its use,” the authors speculate.

Among patients with medication data available both at discharge and 6 months, uptitration of RAAS inhibitors and beta-blockers was infrequent overall, but even less common in lower-income countries. MRAs were uptitrated in 4% of patients, irrespective of where they received treatment.

Generally, use of GDMT was particularly low among people treated in Southeast Asia or lower-income countries, women, older patients, those with new-onset HF or chronic kidney disease, and the uninsured. Of note, about 20% of women in low-income countries were not taking any of the three GDMT classes at discharge, compared with just 5% of men in high-income countries.

Underscoring the seriousness of the problem, the researchers showed that better use of GDMT was associated with lower rates of 1-year mortality. Overall, mortality was higher in patients not on any of the three drug classes at discharge compared with those on at least one of them (31% vs 21%). And after adjustment for indication bias, patients who were uptitrated to at least 50% of the recommended target dose for each medication class had a reduced mortality risk:

  • RAAS inhibitors (HR 0.70; 95% CI 0.64-0.76)
  • Beta-blockers (HR 0.68; 95% CI 0.63-0.75)
  • MRAs (HR 0.88; 95% CI 0.81-0.96)

“To the authors’ knowledge, this is the first study showing underuse and sub-target dosing of lifesaving HF medications in low-income countries in a global registry with broad representation and highlights the need for targeted public health interventions to increase the quality of care and prescription of guideline-recommended therapy in HF,” the researchers write.

No Easy Fix

Commenting for TCTMD, Rolf Wachter, MD (University Hospital Leipzig, Germany), said much of what the study shows isn’t new, as it’s been known that many patients were not receiving optimal treatment, although the analyses by country-level income are novel.

Why it continues to be a challenge and what to do about it are questions without easy answers, said Wachter, who wrote an accompanying editorial with Karl-Philipp Rommel, MD (Heart Center Leipzig, Germany). This study doesn’t address whether patients had comorbidities that wouldn’t allow for use or uptitration of certain medications, he noted.

Heart failure with reduced ejection fraction is a disease that we can treat very, very well. . . .We have to better use these possibilities, and we have to better understand what are the reasons why it’s not done. Rolf Wachter

But, Wachter added, it’s likely that for many of these patients, the therapies weren’t even tried, either because there was no one to advocate for treatment or because patients actively resisted the addition of more medications. “I think that is the main problem—it was not tried,” he said. “And we probably need more education for patients that heart failure is a journey. We want to make the journey as comfortable for the patient as possible, and that means we should—especially in the very early phase of the disease—give them as many medications as possible so that we just avoid [them coming] to the hospital again.”

The European HF guideline states that after a patient is hospitalized, there should be an outpatient follow-up visit 1 to 2 weeks after discharge to look for signs of congestion and to optimize treatments, Wachter pointed out, suggesting that an early posthospitalization visit can help improve medical therapy. Indeed, the current study showed that patients who had a follow-up visit, either with a cardiologist or general practitioner, were more likely to be on GDMT at 6 months.

“Heart failure with reduced ejection fraction is a disease that we can treat very, very well because we have four or five different therapeutic approaches that each give an additional mortality benefit,” Wachter said. “We have to better use these possibilities, and we have to better understand what are the reasons why it’s not done.”

Increasing awareness of the problem and quantifying how bad the situation is are key first steps in addressing the issue, Lam indicated, adding that there is a “long way to go.”

Despite the progress that has been made in terms of treating HF, “the strong, strong message is it’s time for implementation,” she said. “Having the scientific advances is one thing, and we celebrate it of course, but if we don’t implement, we actually don’t realize these benefits for patients.”

Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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  • REPORT-HF was funded by Novartis.
  • Tromp reports receiving support from a National University of Singapore Start-up grant, the Tier 1 grant from the Ministry of Education, and the CS-IRG New Investigator Grant from the National Medical Research Council; having received personal grants or speaker fees from Us2.ai, Daiichi Sankyo, Boehringer Ingelheim, and Roche Diagnostics; and holding a patent (US patent no: 16/216,929) unrelated to the study.
  • Lam reports being supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; having received research support from AstraZeneca, Bayer, Boston Scientific, and Roche Diagnostics; having served as a consultant or on the advisory board/steering committee/executive committee for Actelion, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, Janssen R&D, Medscape/WebMD Global, Merck, Novartis, Novo Nordisk, Roche Diagnostics, Sanofi, St Luke, and Us2.ai; having received payments or honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Medscape/WebMD Global, Novartis, Radcliffe, and Roche Diagnostics; holding a patent (US patent no: 16/216,929) and having a patent pending unrelated to this work (no: 16/216,929); and serving as cofounder and nonexecutive director of Us2.ai.
  • Wachter and Rommel report no relevant conflicts of interest.