Effect of different doses of colchicine on high sensitivity C-reactive protein in patients with acute minor stroke or transient ischemic attack: A pilot randomized controlled trial

Yuan, Baoshi; Meng, Xia; Wang, Anxin; Niu, Siying; Xie, Xuewei; Jing, Jing; Li, Hao; Chang, Liguo; Wang, Yongjun; Li, Jiejie

doi:10.1016/j.ejps.2022.106288

Cited by 5 publications

(6 citation statements)

References 32 publications

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“…In people with acute cerebrovascular accident, colchicine starting 24 hours after symptom onset may lower indices of inflammation. 46…”

Section: Treatment Of Cardiovascular Disease With Colchicinementioning

confidence: 99%

Colchicine’s Role in Cardiovascular Disease Management

Buckley,

Libby

2024

ATVB

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Colchicine—an anti-inflammatory alkaloid—has assumed an important role in the management of cardiovascular inflammation ≈3500 years after its first medicinal use in ancient Egypt. Primarily used in extremely high doses for the treatment of acute gout flares during the 20th century, research in the early 21st century demonstrated that low-dose colchicine effectively treats acute gout attacks, lowers the risk of recurrent pericarditis, and can even add to secondary prevention of major adverse cardiovascular events. As the first Food and Drug Administration–approved targeted anti-inflammatory cardiovascular therapy, colchicine currently has a unique role in the management of atherosclerotic cardiovascular disease. The safe use of colchicine requires careful monitoring for drug-drug interactions, changes in kidney and liver function, and counseling regarding gastrointestinal upset. Future research should elucidate the mechanisms of anti-inflammatory effects of colchicine relevant to atherosclerosis, the potential role of colchicine in primary prevention, in other cardiometabolic conditions, colchicine’s safety in cardiovascular patients, and opportunities for individualizing colchicine therapy using clinical and molecular diagnostics.

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“…In people with acute cerebrovascular accident, colchicine starting 24 hours after symptom onset may lower indices of inflammation. 46…”

Section: Treatment Of Cardiovascular Disease With Colchicinementioning

confidence: 99%

Colchicine’s Role in Cardiovascular Disease Management

Buckley,

Libby

2024

ATVB

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“…Rarely the loading doses reach 2 mg. 53 Early treatment with low colchicine dose reduced high‐sensitivity C‐reactive protein levels in the patients with acute minor ischemic stroke and transient ischemic attack. 54 In cases of acute gout, the loading dose is 1.5–1.8 mg and those of FMF reaches to 2.4 mg. 7 , 43 , 53 However, as we demonstrated higher doses of colchicine (up to 5 mg loading dose) are required to inhibit the COVID‐19 CS. 6 , 18 , 24 , 25 , 26 , 27 , 48 …”

Section: Discussionmentioning

confidence: 99%

“…Rarely the loading doses reach 2 mg 53 . Early treatment with low colchicine dose reduced high‐sensitivity C‐reactive protein levels in the patients with acute minor ischemic stroke and transient ischemic attack 54 . In cases of acute gout, the loading dose is 1.5–1.8 mg and those of FMF reaches to 2.4 mg 7,43,53 .…”

Section: Discussionmentioning

confidence: 99%

Effect of increasing doses of colchicine on the treatment of 333 COVID‐19 inpatients

Tiholov,

Lilov,

Georgieva

et al. 2024

Immunity Inflam & Disease

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BackgroundPrevious research done in Bulgaria demonstrated a fivefold reduction in mortality from COVID‐19 with increased doses of colchicine from two hospitals in the country. We report here a further 333 cases of COVID‐19 inpatients, treated with different doses of colchicine and its effect on mortality.Materials and MethodsA case‐control comparison from two additional hospitals was conducted between increased doses of colchicine and added bromhexine to standard of care (SOC) versus current SOC. Risk and odds ratio, as well as subgroup analysis, was conducted with newly reported data, alongside aggregate data from all hospital centers to determine the extent of mortality reduction in COVID‐19 inpatients.ResultsThere was a clear reduction in the mortality of inpatients with increasing doses of colchicine—between twofold and sevenfold. Colchicine loading doses of 4 mg are more effective than those with 2 mg. Despite these doses being higher than the so‐called “standard doses,” colchicine inpatients experienced lower mortality than SOC patients (5.7% vs. 19.53%). This mortality benefit was evident in different age subgroups, with a 4‐mg loading dose of colchicine proving slightly superior to a 2‐mg loading dose. Colchicine led to an overall relative risk reduction of 70.7%, with SOC patients having 3.91 higher odds of death. The safety of the doses was not different than the reported in the summary of product characteristics.ConclusionInpatients in Bulgaria with added colchicine and bromhexine to SOC achieved better clinical and mortality outcomes than those on SOC alone. These results question the World Health Organization—recommended strategy to inhibit viral replication. We posit that our treatment strategy to inhibit the Severe acute respiratory syndrome coronavirus 2 entry into the cell with inhaled bromhexine and the hyperactivated NLRP3 inflammasome with higher doses of colchicine, prevents the development of cytokine storm. The timing of the initiation of treatment seems critical.

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“…Furthermore, in line with the recent Cochrane systematic review reporting no serious adverse effects of low-dose (0.5–1.0 mg) colchicine in patients with vascular disease, 28 our pilot study showed that acute short-term usage of 1 mg of colchicine was also well-tolerated and safe, and reduction of hsCRP level was observed at 72 h after the index event. 29 Therefore, this study will use 1 mg of colchicine on days 1–3, followed by 0.5 mg per day on days 4–90. However, given gastrointestinal intolerance has led to discontinuation in 10% to 15% of patients in prior clinical trials, 20,21 though the risk reduction of stroke was reported to be 46% by colchicine in a prior meta-analysis, 22 we conservatively apply the 25% relative risk reduction when estimating sample size.…”

Section: Discussionmentioning

confidence: 99%

Colchicine in High-risk Patients with Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3): Rationale and design of a multicenter randomized placebo-controlled trial

Wang

Johnston

et al. 2023

International Journal of Stroke

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Background: Anti-inflammatory therapy using colchicine has reduced recurrent vascular events in patients with coronary heart disease. Design: Colchicine in High-risk Patients with Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3) is a randomized, double-blind, placebo-controlled multicenter trial, in which 8,238 patients with acute minor-to-moderate ischemic stroke (NIHSS≤5) or high-risk TIA (ABCD2 score ≥ 4) and a hsCRP level of ≥2mg/L will be randomly assigned within 24 hours of symptom onset to colchicine (1 mg daily on days 1-3, followed by 0.5 mg daily for a total of 90 days) or matching placebo, on a background of optimal medical therapy. The study will have 90% power to detect a 25% reduction in the primary efficacy outcome of any stroke within 3 months of randomization. Adverse events potentially related to the use of colchicine will also be analyzed. The primary analysis will be by intention-to-treat. Discussion: The CHANCE-3 trial will evaluate the efficacy and safety of colchicine for secondary prevention after stroke and TIA. Trial registry name: Colchicine in High-risk Patients With Acute MiNor-to-moderate IschemiC Stroke or TransiEnt Ischemic Attack (CHANCE-3); URL: https://clinicaltrials.gov/ct2/show/NCT05439356?cond=CHANCE-3&draw=2&rank=1; Registration number: NCT05439356.

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Effect of different doses of colchicine on high sensitivity C-reactive protein in patients with acute minor stroke or transient ischemic attack: A pilot randomized controlled trial

Cited by 5 publications

References 32 publications

Colchicine’s Role in Cardiovascular Disease Management

Colchicine’s Role in Cardiovascular Disease Management

Effect of increasing doses of colchicine on the treatment of 333 COVID‐19 inpatients

Colchicine in High-risk Patients with Acute Minor-to-moderate Ischemic Stroke or Transient Ischemic Attack (CHANCE-3): Rationale and design of a multicenter randomized placebo-controlled trial

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