Thailand Medical Researchers Warn Low Dose Heart Failure Therapy Undermines Outcomes
Nikhil Prasad Fact checked by:Thailand Medical News Team Apr 21, 2026 1 hour, 29 minutes ago
Thailand Medical: A new and highly detailed study by Thai researchers is drawing attention to a critical issue in heart failure care: patients may not benefit fully from treatment if essential medications are prescribed at doses that are too low. The research provides rare real-world insight into how treatment strategies perform outside of controlled clinical trials and raises concerns about current practices in managing heart failure with reduced ejection fraction.
Low dosing of essential heart failure drugs may significantly increase hospitalization risk despite the use of newer treatments
What Is Heart Failure and Why Proper Treatment Is Crucial
Heart failure with reduced ejection fraction, or HFrEF, occurs when the heart’s pumping ability falls below normal levels, typically defined as an ejection fraction of 40 percent or less. This condition limits the body’s ability to circulate oxygen-rich blood, leading to fatigue, breathlessness, swelling of the legs, and frequent hospital admissions.
Because heart failure is a chronic and progressive disease, treatment must not only relieve symptoms but also reduce the risk of hospitalization and death. This is why global treatment guidelines strongly emphasize the use of multiple medications together at carefully adjusted doses.
What Is Conventional Triple Therapy
The backbone of heart failure treatment is known as conventional triple therapy, which includes three major classes of drugs that target different mechanisms of the disease.
The first group is renin–angiotensin system inhibitors, which include ACE inhibitors such as enalapril, angiotensin receptor blockers such as losartan, and newer angiotensin receptor–neprilysin inhibitors. These drugs work by relaxing blood vessels, lowering blood pressure, and reducing the strain on the heart. They also help prevent harmful structural changes in the heart over time.
The second group is beta-blockers, including medications such as carvedilol, bisoprolol, and metoprolol. These drugs slow the heart rate and reduce the effects of stress hormones like adrenaline, allowing the heart to function more efficiently and with less oxygen demand.
The third group is mineralocorticoid receptor antagonists, such as spironolactone. These medications help the body eliminate excess salt and water while blocking hormones that can worsen heart damage.
Together, these three drug classes form a powerful combination that can significantly reduce the risk of death and hospitalization when used at recommended target doses.
Role of Newer SGLT2 Inhibitors
In recent years, SGLT2 inhibitors such as dapagliflozin and empagliflozin have been added to heart failure treatment. Originally developed for diabetes, these drugs help remove excess glucose through urine and also provide benefits such as reducing fluid overload, improving kidney function, and lowering the risk of heart failure hospitalization.
Unlike conventional drugs, SGLT2 inhibitors are typically given at a fixed dose, which simplifies their use in clinical practice.
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Study Conducted Across Thai Hospitals
The study was conducted by Thailand Medical researchers from Chiang Mai University, Chiangrai Prachanukroh Hospital, Ratchaburi Hospital, and Naresuan University Hospital. It analyzed electronic medical records of 334 patients treated between 2018 and 2024.
Of these patients, 110 received SGLT2 inhibitors combined with low-dose conventional triple therapy, while 224 patients received high-dose conventional triple therapy without SGLT2 inhibitors.
The average age of participants was around 60 to 63 years, and most patients had additional health conditions such as hypertension, diabetes, atrial fibrillation, and chronic kidney disease.
Key Findings Reveal Higher Risk with Low Dose Therapy
The results showed that patients receiving SGLT2 inhibitors alongside low-dose conventional therapy experienced significantly worse outcomes. The risk of the combined endpoint of cardiovascular death or heart failure hospitalization was more than four times higher compared to those receiving high-dose conventional therapy.
Interestingly, while cardiovascular death rates alone were not significantly different, hospitalizations due to worsening heart failure were markedly higher in the low-dose group.
At this critical point, this study report highlights that simply adding newer drugs cannot compensate for insufficient dosing of foundational therapies.
Why Low Doses Lead to Poorer Outcomes
One of the most important findings was the extent of underdosing. Patients in the low-dose group were often receiving only 25 percent of the target dose for beta-blockers and about 33 percent for renin–angiotensin system inhibitors. Such low doses may fail to fully block the harmful biological pathways that drive heart failure progression. While SGLT2 inhibitors offer additional protective effects, they are not designed to replace the core benefits provided by properly dosed conventional therapy.
Furthermore, patients in the low-dose group had a higher burden of disease. They were more likely to have diabetes, high blood pressure, atrial fibrillation, and reduced kidney function. These factors increase the risk of complications and may limit the ability of doctors to increase medication doses safely.
Real World Challenges in Treatment
The study reflects real-world challenges faced in Thailand and similar healthcare systems. Many patients cannot tolerate higher medication doses due to side effects such as low blood pressure or kidney issues. In addition, access to newer medications has historically been limited, especially during the earlier years of the study.
Doctors must often make difficult decisions, balancing the risks and benefits of increasing drug doses while managing multiple health conditions.
Conclusions
This study provides strong evidence that optimizing the dose of conventional heart failure medications is just as important as choosing the right drugs. Even with the addition of advanced therapies like SGLT2 inhibitors, patients receiving low doses of foundational treatments remain at significantly higher risk of hospitalization and adverse outcomes. The findings reinforce the need for clinicians to carefully titrate medications to the highest tolerated levels whenever possible, while also considering individual patient factors. A balanced and personalized approach remains essential to improving long-term outcomes in heart failure care.
The study findings were published in the peer reviewed journal: Medicina.
https://www.mdpi.com/1648-9144/62/4/781
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