Heart failure (HF) is a serious and terminal stage of various heart diseases, and it is also the most important cardiovascular disease in the 21st century, seriously endangering the health of Chinese residents. Although the current traditional drugs for the treatment of heart failure can significantly improve the prognosis, the residual risk of patients is still high, and new drugs or new treatment options are still needed to further improve the prognosis and quality of life of patients.
In recent years, new drugs for the treatment of heart failure have emerged, including angiotensin receptor-enkephalinase inhibitor (ARNI), sodium-glucose cotransporter 2 The inhibitor (SGLT-2i) and the soluble guanylate cyclase (sGC) stimulator, which was just approved on May 18 this year, have brought the treatment of chronic heart failure into a new era of multi-mechanism and multi-channel combination therapy.
The prognosis of patients with heart failure is poor, and early treatment is the key
heart failure Heart failure is a progressive disease characterized by frequent decompensation events. Each time a patient experiences a heart failure decompensation event, the heart function will drop sharply. It is difficult to return to the previous level, showing an irreversible cliff-like progress¹,². A meta-analysis of 70 randomized controlled trials showed that delaying guideline-guided medical therapy (GDMT) in newly diagnosed heart failure patients was associated with a 12.2% increase in 1-year mortality, so patients with heart failure should start treatment as soon as possible. .
A number of domestic and foreign guidelines also recommend that patients with heart failure should start treatment as soon as possible to improve their prognosis⁴, span>⁵. The 2021 ESC Guidelines for Acute and Chronic Heart Failure recommend that patients with heart failure should optimize oral drug therapy during hospitalization and early discharge >Evidence-supported oral therapy before discharge⁶; the 2021 ESC consensus on individualized medication for patients with heart failure also recommends that patients be discharged after Beforeenabling sodium glucose cotransporter-2 inhibitor (SGLT2i), mineralocorticoid receptor antagonist (MRA), angiotensin-converting enzyme inhibitor (ACEI)/ARNI, Medications such as veliximab can help relieve symptoms of congestion in patients⁷.
Early multi-channel combination to break through the bottleneck of heart failure treatment
< span>At present, more and more evidences show that heart failure includes multiple pathophysiological mechanisms and should be treated with multiple mechanisms and multiple pathways. Studies have shown that the more anti-heart failure drugs combined with different mechanisms of action, the better the patient’s prognosis⁸. However, in the current multi-drug combination of heart failure treatment drugs (mainly drugs targeting neuro-hormonal mechanism activation and metabolic-inflammatory mechanism disorders), patients still have a high residual risk, and these drugs are difficult to achieve in the real world. achieve the target dose. In the DAPA-HF study, despite receiving quadruple therapy (ARNI+β-blocker+MRA+SGLT2i), 14.3% of patients experienced a primary outcome event during the trial⁹< sup>,¹⁰. So, are there any drugs that can further improve the prognosis of patients on the existing basis and break through the bottleneck of heart failure treatment?
Veliciguat further improves the prognosis of heart failure patients based on GDMT
Velixigua (only with ® ) is a soluble sGC stimulator with a new mechanism, which was approved in my country on May 18, 2022 for patients with stable disease after recent decompensated heart failure via intravenous therapy. Adult patients with symptomatic chronic heart failure with reduced blood fraction (ejection fraction <45%) to reduce the risk of hospitalization for heart failure or the need for emergency intravenous diuretics.
Veliciguat’s mechanism of action is different from previous heart failure drugs. It can directly stimulate sGC for cell-signaling pathway disorders, and at the same time, it can stimulate sGC. Increases sGC sensitivity to nitric oxide (NO) and repairs damaged NO-sGC-cGMP pathway. On the basis of GDMT treatment, veliciguat can further improve the prognosis of heart failure patients, and significantly reduce the composite endpoint of cardiovascular death or first heart failure hospitalization risk by 10%; regardless of the basic treatment Patient benefit was consistent with or without ARNI¹¹,¹².
Figure 1: Primary endpoint cumulative event rate
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New concept of heart failure treatment: early multi-channel combination therapy
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2021ACC Consensus¹³, 2021ESC Consensus< span>⁷and the newly released 2022ACC guidelines¹⁴recommended starting combination therapy, that is, starting with a “low-dose combination “ with a drug that has been shown to improve the prognosis of heart failure, and then individualizing it according to the patient’s tolerance A subgroup study of VICTORIA showed that, compared with standard care, the earlier the use of velicigre, the more significant the clinical benefit of patients was ¹⁵,¹⁶.
Figure 2: NT-proBNP over time
A recently published review also Emphasize¹⁷, the treatment of heart failure not only requires early combined therapy, but also early multi-channel combined therapy, to prevent further aggravation of heart failure and maximize the prognosis of patients.
The treatment of stage A heart failure is the same as the guidelines, and timely adjustment may lead to or accelerated heart failure risk factors;
In stage B heart failure, the drugs in the “diamond regimen” (see Figure 3) are used in combination in the early stage , is reasonable and necessary to prevent ventricular remodeling and improve outcomes;
In the C stage of heart failure, it is more important to prevent cardiac function further deterioration, therefore, should pay more attention to the veliciacand OM (omecamtiv mecarbil) Use;
and in heart failure stage D, if the patient can tolerate it, even if only low dose, should consider treatment with all prognostic drugs (apply all “diamond regimen” drugs) and monitor closely And adjust the medication in time;For patients with stage D heart failure, the unique mechanism of action of VELICIGA may bring clinical effects beyond expectations.
Second-level professor of Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Chief Physician
Director of Hubei Cardiovascular Medical Quality Control Center
President of China Heart Failure Center Alliance
Editor-in-chief of Journal of Clinical Cardiovascular Diseases
Won the second prize of the National Science and Technology Progress Award and a total of 8 provincial and ministerial awards
Published SCI journal papers and a review of 172 articles
Editor-in-chief of HeartFour monographs including Cardiology” and “Cardiovascular Immunology”
invented ATRQβ-001 therapeutic antihypertensive vaccine< /p>
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