Why is the use of digitalis withering? Another reason that we need medical heart failure specialists

Packer, Milton

doi:10.1002/ejhf.1043

Cited by 7 publications

(5 citation statements)

References 14 publications

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“…A third comment should be made about the digoxin dose. It has been well known and documented that there is a strong association between higher doses of digoxin and increased mortality, and this was shown not only in the DIG study, but also in earlier studies with digoxin, and was reported again recently in the ARISTOTLE trial . The general consensus is that serum digoxin concentrations ≥1.0 ng/mL should be avoided, and that dosing should be aimed at reaching concentrations of 0.5–0.9 ng/mL.…”

mentioning

confidence: 84%

“…it may be considered in HF patients with reduced ejection fraction (HFrEF) who are in sinus rhythm, and still symptomatic despite treatment with an angiotensin‐converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) or an angiotensin‐receptor neprilysin inhibitor (ARNI), a beta‐blocker and a mineralocorticoid receptor antagonist (MRA), to reduce the risk of hospitalization. This IIb‐B recommendation is much lower than the IA level digoxin still had in the 2001 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, and along with this change, the use of digoxin has gradually declined from more than 60% in a large European study in the 1990s 3 to less than 10% in a more recent trial in patients with HF and sinus rhythm (data from COMMANDER HF 4 ). The use of digoxin has also declined in patients with atrial fibrillation (AF) (and HF), and in the 2016 ESC HF guidelines, digoxin is only recommended for the treatment of patients with HFrEF and AF to slow a rapid ventricular rate .…”

mentioning

confidence: 99%

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Value of digoxin in patients with heart failure: new pieces to the puzzle

Veldhuisen

Rienstra

Meer

2018

European J of Heart Fail

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mentioning

confidence: 84%

mentioning

confidence: 99%

Value of digoxin in patients with heart failure: new pieces to the puzzle

Veldhuisen

Rienstra

Meer

2018

European J of Heart Fail

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“…The drug was approved by the Chinese Food and Drug Administration in 2004 for the treatment of heart failure. 9 QLQX consists of 11 different ingredients: (1) the root of Astragalus mongholicus Bunge (milkvetch root), (2) the root of Panax ginseng C.A. Mey.…”

Section: Formulation and Active Ingredients Of Qiliqiangxinmentioning

confidence: 99%

“…Plant‐based medicines have been used for the treatment of chronic heart failure for centuries. Digitalis, diuretics and sodium–glucose cotransporter 2 (SGLT2) inhibitors have their origins in plants, whereas angiotensin‐converting enzyme and neprilysin inhibitors were derived from snake venom 1–3 . Therefore, it should not seem peculiar that new ideas about the treatment of heart failure will continue to emerge from natural sources.…”

Section: Introductionmentioning

confidence: 99%

Qiliqiangxin: A multifaceted holistic treatment for heart failure or a pharmacological probe for the identification of cardioprotective mechanisms?

Packer

2023

European J of Heart Fail

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The active ingredients in many traditional Chinese medicines are isoprene oligomers with a diterpenoid or triterpenoid structure, which exert cardiovascular effects by signaling through nutrient surplus and nutrient deprivation pathways. Qiliqiangxin (QLQX) is a commercial formulation of 11 different plant ingredients, whose active compounds include astragaloside IV, tanshione IIA, ginsenosides (Rb1, Rg1 and Re) and periplocymarin. In the QUEST Trial, QLQX reduced the combined risk of cardiovascular death or heart failure hospitalization (hazard ratio 0.78 [95% CI 0.68‐0.90]), based on 859 events in 3119 patients over a median of 18.2 months; the benefits were seen in patients taking foundational drugs except for SGLT2 inhibitors. Numerous experimental studies of QLQX in diverse cardiac injuries have yielded highly consistent findings. In marked abrupt cardiac injury, QLQX mitigated cardiac injury by upregulating nutrient surplus signaling through the PI3K/Akt/mTOR/HIF‐1α/NRF2 pathway; the benefits of QLQX were abrogated by suppression of PI3K, Akt, mTOR, HIF‐1α or NRF2. In contrast, in prolonged measured cardiac stress (as in chronic heart failure), QLQX ameliorated oxidative stress, maladaptive hypertrophy, cardiomyocyte apoptosis, and proinflammatory and profibrotic pathways, while enhancing mitochondrial health and promoting glucose and fatty acid oxidation and ATP production. These effects are achieved by an action of QLQX to upregulate nutrient deprivation signaling through SIRT1/AMPK/PGC‐1α and enhanced autophagic flux. In particular, QLQX appears to enhance the interaction of PGC‐1α with PPARα, possibly by direct binding to RXRα; silencing of SIRT1, PGC‐1α and RXRα abrogated the favorable effects of QLQX in the heart. Since PGC‐1α/RXRα is also a downstream effector of Akt/mTOR signaling, the actions of QLQX on PGC‐1α/RXRα may explain its favorable effects in both acute and chronic stress. Intriguingly, the individual ingredients in QLQX — astragaloside IV, ginsenosides, and tanshione IIA — share QLQX's effects on PGC‐1α/RXRα/PPARα signaling. QXQL also contains periplocymarin, a cardiac glycoside that inhibits Na+‐K+‐ATPase. Taken collectively, these observations support a conceptual framework for understanding the mechanism of action for QLQX in heart failure. The high likelihood of overlap in the mechanism of action of QLQX and SGLT2 inhibitors requires additional experimental studies and clinical trials.This article is protected by copyright. All rights reserved.

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“…Today, two cardiac glycosides are still isolated for use from Digitalis: digitoxin and digoxin, and Withering's warning regarding their narrow therapeutic range holds true almost 250 years later. Due to the risks of toxicity, Digitalis derived drugs have become less popular in modern medicine [6], but it's potent toxic effects still pose risks in cases of accidental contamination.…”

Section: Introductionmentioning

confidence: 99%

Utilizing Big Data to Identify Tiny Toxic Components: Digitalis

Hunter

Literman

Handy

2021

Foods

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The botanical genus Digitalis is equal parts colorful, toxic, and medicinal, and its bioactive compounds have a long history of therapeutic use. However, with an extremely narrow therapeutic range, even trace amounts of Digitalis can cause adverse effects. Using chemical methods, the United States Food and Drug Administration traced a 1997 case of Digitalis toxicity to a shipment of Plantago (a common ingredient in dietary supplements marketed to improve digestion) contaminated with Digitalis lanata. With increased accessibility to next generation sequencing technology, here we ask whether this case could have been cracked rapidly using shallow genome sequencing strategies (e.g., genome skims). Using a modified implementation of the Site Identification from Short Read Sequences (SISRS) bioinformatics pipeline with whole-genome sequence data, we generated over 2 M genus-level single nucleotide polymorphisms in addition to species-informative single nucleotide polymorphisms. We simulated dietary supplement contamination by spiking low quantities (0–10%) of Digitalis whole-genome sequence data into a background of commonly used ingredients in products marketed for “digestive cleansing” and reliably detected Digitalis at the genus level while also discriminating between Digitalis species. This work serves as a roadmap for the development of novel DNA-based assays to quickly and reliably detect the presence of toxic species such as Digitalis in food products or dietary supplements using genomic methods and highlights the power of harnessing the entire genome to identify botanical species.

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Why is the use of digitalis withering? Another reason that we need medical heart failure specialists

Abstract: Contrary to popular opinion, William Withering did not discover digitalis nor was he the first to describe its use for heart failure. In 1785, the esteemed English botanist and physician wrote a pamphlet that summarized his experiences in 163 patients with dropsy.

Cited by 7 publications

References 14 publications

Value of digoxin in patients with heart failure: new pieces to the puzzle

Value of digoxin in patients with heart failure: new pieces to the puzzle

Qiliqiangxin: A multifaceted holistic treatment for heart failure or a pharmacological probe for the identification of cardioprotective mechanisms?

Utilizing Big Data to Identify Tiny Toxic Components: Digitalis

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