Colchicine for the Prevention of Vascular Events After an Acute Intracerebral Hemorrhage: A Placebo-Controlled Trial

 Oh, your incompetent? doctor doesn't know about colchicine already? WOW!

Ask your doctor to come up with EXACT PROTOCOLS ON COLCHICINE USE! Can't do that; you DON'T have a functioning stroke doctor!

'No Hint of Benefit' in Large Colchicine Trial  November 2024

colchicine (27 posts to December 2011)

 

Colchicine for the Prevention of Vascular Events After an Acute Intracerebral Hemorrhage: A Placebo-Controlled Trial

Aristeidis H. Katsanos, MD https://orcid.org/0000-0002-6359-0023 ar.katsanos@gmail.com, Kelvin K.H. Ng, MD https://orcid.org/0000-0002-1603-9634, Thalia S. Field, MD https://orcid.org/0000-0002-1176-0633, Aravind Ganesh, MD https://orcid.org/0000-0001-5520-2070, Joanna D. Schaafsma, MD https://orcid.org/0000-0003-4326-5597, Shirin Jalini, MD https://orcid.org/0009-0007-7548-6702, Ashfaq Shuaib, MD https://orcid.org/0000-0002-3380-7068, … Show All … , and Ashkan Shoamanesh, MD https://orcid.org/0000-0002-2802-1626Author Info & Affiliations

Stroke

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https://doi.org/10.1161/STROKEAHA.126.055934

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Abstract

BACKGROUND:

There is a need for novel treatments that lower the risk of major adverse cardiovascular events and secondary inflammatory brain injury after an intracerebral hemorrhage (ICH).

METHODS:

We performed a double-blind, placebo-controlled, pilot randomized clinical trial at 11 centers across Canada to determine the feasibility of testing colchicine after an acute ICH. We recruited adults presenting within 48 hours of ICH onset with vascular neuroimaging evidence or risk factors for atherosclerosis. Participants were randomized to oral colchicine 0.5 mg daily or placebo and followed to a common study termination date. The primary feasibility outcome was the recruitment rate (participants/center per year). Secondary feasibility outcomes included retention of participants at 6 months and medication adherence at 12 months. This trial is registered (ClinicalTrials.gov ID: REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05159219).

RESULTS:

Between August 2022 and March 2024, 52 participants were allocated to colchicine 0.5 mg daily and 48 participants to placebo daily. Participants were, on average, 68 years old, and 60% were male. The mean time from ICH onset to randomization was 35 hours. The average recruitment rate was 8.9 participants/site per year. Retention at 6 months was 92% (colchicine 91% versus placebo 93%). Following randomization, 14 participants (27%) in the colchicine group and 13 participants (27%) in the placebo group permanently discontinued the study drug. Excluding participants who died or permanently discontinued the study intervention, 12-month medication adherence was 97%, with similar rates between the colchicine and placebo groups (100% versus 93%). We detected no difference in predefined exploratory efficacy or safety end points between the 2 groups over the median follow-up time of 364 days.

CONCLUSIONS:

It is feasible to test low-dose colchicine after an acute ICH. Future randomized clinical trials should account for the high rates of early permanent study drug discontinuation in this patient population.

REGISTRATION:

URL: https://www.clinicaltrials.gov; Unique identifier: NCT05159219.

Graphical Abstract

Thromboinflammation is believed to worsen neurological outcomes and contribute to ischemic vascular events in patients with small vessel disease, including intracerebral hemorrhage (ICH). The management of patients with ICH is challenging and requires balancing the benefit of ischemic vascular preventive treatments against any possible increase in bleeding risk.¹ ICH survivors have a constant risk of rebleeding, with the annual rate of ICH recurrence ranging from 1.3% to 7.4%.² Because of their preexisting vascular risk factors and comorbidities, ICH survivors are at considerably higher risk of major adverse cardiovascular events (MACE),^3–5 which is further aggravated by the cessation of antithrombotic medications for significant periods after ICH.⁶ These findings highlight the need for novel treatments that lower the high vascular risk over the long term in ICH survivors, particularly in the early post-ICH period when patients are not receiving antithrombotic medications.

Randomized-controlled clinical trials (RCTs) have established that colchicine reduces the risk of MACE (risk ratio, 0.73 [95% CI, 0.65–0.90]) and ischemic stroke (risk ratio, 0.73 [95% CI, 0.58–0.90]) in patients with a history of coronary artery disease, with no increase in ICH risk.⁷ Results from an observational study further suggest that patients with diabetes receiving colchicine treatment have lower risks of stroke, with the risk reduction for both ischemic and hemorrhagic stroke being proportionate to the duration of colchicine use.⁸ In an experimental murine collagenase-induced ICH model, we provided proof of concept for the safety of oral colchicine after ICH, detecting no increase in hematoma volume and less perihematomal brain inflammation at a scaled dose equivalent to the 0.5 mg daily that was used in trials testing colchicine in patients with coronary artery disease, when compared with placebo.⁹

We initiated the CoVasc-ICH trial (Colchicine for the Prevention of Vascular Events After an Acute Intracerebral Hemorrhage) to determine the feasibility of testing colchicine for reducing the risk of MACE and secondary inflammatory brain injury following an acute spontaneous ICH.

NSAIDs May Pose Greater Heart Risks Than Colchicine in Gout

 Your competent? doctor knows precisely what to do with colchicine for your recovery. Right?

colchicine (27 posts to December 2011)

And knows about the association of gout with dementia?

Your doctor has a lot of explaining to do. All this other information.

Ask your doctor to compare this research for the best course of action.

Gout may lessen Alzheimer risk March 2015

Study finds no association between gout and neurodegenerative diseases in the general population March 2023

 

Gout unveiled as surprising culprit in neurodegenerative diseases May 2023

The latest here:

NSAIDs May Pose Greater Heart Risks Than Colchicine in Gout

TOPLINE:

In patients with gout starting allopurinol as a long-term urate-lowering therapy, the prophylactic use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a higher risk for major adverse cardiovascular events (MACEs) than the use of colchicine or no prophylaxis.

METHODOLOGY:

• Researchers followed a target trial framework to emulate a randomized clinical trial using data from administrative databases in British Columbia, Canada, to compare the cardiovascular safety of the prophylactic use of NSAIDs vs colchicine in patients with gout who started allopurinol between 1995 and 2022.
• They included 9060 patients who were prescribed NSAIDs (mean age, 60.9 years; 83.5% men) who were propensity score-matched with 9060 patients prescribed colchicine on the same day as allopurinol.
• The primary outcome was MACE, a composite of myocardial infarction, ischemic stroke, or cardiovascular death. Secondary outcomes included the individual components of MACE and all-cause mortality.
• Sensitivity analyses were also conducted with follow-up truncated after 3 months or 6 months and using inverse probability treatment weighting.
• Additionally, the cardiovascular safety of NSAIDs and colchicine was compared with that of no prophylaxis after propensity matching.

TAKEAWAY:

• The risk for MACE was higher in patients using NSAIDs than in those using colchicine (hazard ratio [HR], 1.56; 95% CI, 1.11-2.17). Findings were consistent in sensitivity analyses.
• The use of NSAIDs was associated with significantly higher risks for cardiovascular death (HR, 2.50; 95% CI, 1.14-5.26) and all-cause mortality (HR, 2.00; 95% CI, 1.19-3.45) than the use of colchicine.
• Compared with no prophylaxis, the use of NSAIDs was associated with a 50% higher risk for MACE (HR, 1.50; 95% CI, 1.17-1.91) and a 93% higher risk for myocardial infarction (HR, 1.93; 95% CI, 1.35-2.75), whereas the use of colchicine was not associated with risk for MACE or its individual components.

IN PRACTICE:

“The findings of this present study have the potential to impact clinical care as well as current guidelines, as they highlight the real potential dangers of NSAID use, even short-term, among patients with gout and provide additional evidence in support of colchicine as the preferred paradoxical gout flare prophylaxis agent,” the authors wrote.

SOURCE:

This study was led by Chio Yokose, MD, MSc, Massachusetts General Hospital, Boston. It was published online on May 26, 2025, in Arthritis & Rheumatology.

LIMITATIONS:

The risk for residual confounding factors remained owing to the observational nature of this study. Data on key cardiovascular risk factors such as use of tobacco, BMI, or lipid panel were unavailable. Cardiovascular risk associated with different types of NSAID was not analyzed.

DISCLOSURES:

Some authors reported receiving support from the National Institutes of Health and the Canadian Institutes of Health Research. Several authors reported receiving personal fees, consulting fees, royalties, and grants, and having board positions and other financial ties with multiple pharmaceutical and healthcare companies.

Familiar Anti-Inflammatory Felled by Strokes in TAVR Trial

 

 Ask your doctor to come up with EXACT PROTOCOLS ON COLCHICINE USE! Can't do that; you DON'T have a functioning stroke doctor or hospital!

'No Hint of Benefit' in Large Colchicine Trial  November 2024

Colchicine prevents rise in total plaque volume for patients with stable CAD April 2025

colchicine (26 posts to December 2011)

I bet your incompetent doctor and hospital DID NOTHING WITH THIS EARLIER RESEARCH! That's why they are incompetent! DOING NOTHING!

Familiar Anti-Inflammatory Felled by Strokes in TAVR Trial

Colchicine showed some favorable results reducing new-onset arrhythmias after TAVR

Key Takeaways

• The Co-STAR trial tested the performance of colchicine in preventing new-onset arrhythmias and subclinical leaflet thrombosis after TAVR.
• The choice of periprocedural treatment with colchicine was related to its targeting of the inflammatory pathway of cardiac arrhythmias.
• Colchicine showed a reduction in rhythm disturbances, albeit with excess strokes.

The inflammation suppressant colchicine could show more promise in transcatheter aortic valve replacement (TAVR) -- if not for excess strokes, as seen in one small randomized study.

In the Co-STAR double-blind trial, periprocedural treatment with colchicine resulted in favorable 30-day results indicative of reduced new-onset arrhythmias relative to placebo:

• Composite of new-onset atrial fibrillation (Afib) or atrioventricular conduction disturbances requiring the implantation of a permanent pacemaker: 10% with colchicine vs 25% with placebo (P=0.031)
• New-onset Afib alone: 5.0% vs 6.7%
• Conduction disturbances requiring permanent pacemaker: 8.3% vs 18.3%

Imaging also showed less post-TAVR subclinical leaflet thrombosis after a colchicine regimen (27% vs 54%, P=0.007), according to Thomas Pilgrim, MD, of Bern University Hospital in Switzerland, and colleagues.

However, the trial was prematurely stopped on account of strokes: three strokes (5.0%) in the colchicine group and none in the placebo group at 30 days, reaching five strokes (8.3%) with colchicine at maximal follow-up (vs 0, P=0.022), according to the Co-STAR report published in Nature Communications.

"As the study was prematurely stopped and the event rates of the primary outcome were lower than anticipated, the trial was underpowered, the observed treatment effect may be overestimated and chance findings cannot be excluded," Pilgrim's group cautioned.

Colchicine, derived from the autumn crocus plant used medicinally for thousands of years in Egypt, is an anti-inflammatory available generically. Name-brand colchicine (Lodoco) was FDA approved for cardiovascular prevention in 2023.

Pilgrim told MedPage Today that he was not aware of any established mechanism that would link colchicine treatment to an increased risk of stroke -- in fact, colchicine was previously tied to a reduced stroke risk in people with coronary artery disease.

"In our study, two of the five strokes occurred well after the completion of colchicine therapy, and one was directly related to the TAVR procedure itself," he noted.

Study authors reason that inflammation is still worth pursuing as a therapeutic target in TAVR, a concept bolstered by previous successes of colchicine in cardiac surgery.

"The etiopathology of TAVR-related arrhythmias is a complex interplay of local and systemic factors in which inflammatory processes are considered to be an important trigger. A systemic inflammatory response syndrome peaking between 24 and 48 hours after TAVR has been documented in 39-56% of patients, and may be causal in the development of atrial fibrillation," they wrote.

"Beyond colchicine, other anti-inflammatory agents, such as monoclonal antibodies targeting interleukin-1β or interleukin-6, may also be investigated in this context," Pilgrim said.

Co-STAR was a single-center trial that randomized TAVR patients to colchicine or placebo from 2021 to 2024. Investigators managed to enroll 120 out of 200 anticipated participants with severe aortic stenosis before the trial was stopped early. Eligible candidates were people with no history of Afib or permanent pacemakers or severe renal failure.

Per study protocol, colchicine treatment was initiated with a loading dose of 1 mg the day before TAVR and the day of the intervention, followed by a maintenance dose of 0.5 mg once daily for 12 days after TAVR.

The study cohort averaged age 80.6 years and was 64% men, with mean Society of Thoracic Surgeons predicted mortality reaching 2.5%.

Two in three participants got TAVR with balloon-expandable devices and the remainder received self-expanding devices. Factors known to be associated with the occurrence of atrioventricular block after TAVR (e.g., pre-existing right bundle branch block, prosthetic valve design, oversizing, and postdilatation) were well balanced between the two treatment groups, according to Pilgrim and colleagues.

All patients were monitored during hospitalization and got continuous electrocardiogram holter monitoring up to 7 days postdischarge. The mean duration of continuous rhythm monitoring was 10 days in the colchicine group, significantly longer than the 8.5 days in the placebo group.

For the imaging endpoint, 48 people in each group underwent a single coronary CT angiography at a mean 37 days after TAVR. Subclinical leaflet thrombosis was defined as a case of at least one leaflet with >50% motion reduction or thickening.

"It is possible, that colchicine does not prevent but rather defers the occurrence of subclinical leaflet thrombosis. Serial imaging would be required to rule out a catch-up effect of thrombus formation," Pilgrim's group acknowledged.

What's more, the clinical significance of post-TAVR leaflet thrombosis itself is unclear, as many cases have been observed to resolve on their own.

Disclosures

The study was supported by grants from the Bangerter-Rhyner Foundation and the Swiss Life Foundation.

Pilgrim reported research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the Swiss Polar Institute, the Bangerter-Rhyner Foundation, the Mach-Gaensslen Foundation, and the Monsol Foundation; research, travel, or educational grants to the institution without personal remuneration from Biotronik, Boston Scientific, Edwards Lifesciences, and ATsens; and speaker fees and consultancy fees to the institution from Biotronik, Boston Scientific, Edwards Lifesciences, Abbott, Medtronic, Biosensors, and HighLife.

Co-authors reported multiple relationships with industry.

Primary Source

Nature Communications

Source Reference: Ryffel C, et al "Colchicine in patients with aortic stenosis undergoing transcatheter aortic valve replacement: a double-blind randomized trial" Nat Commun 2025; DOI: 10.1038/s41467-025-61916-6.

Colchicine May Raise Stroke Risk in Elderly Patients With Intracranial Artery Stenosis: CHANCE-3 Trial

 Ask your doctor to come up with EXACT PROTOCOLS ON COLCHICINE USE! Can't do that; you DON'T have a functioning stroke doctor!

'No Hint of Benefit' in Large Colchicine Trial  November 2024

colchicine (24 posts to December 2011)

I bet your incompetent doctor and hospital DID NOTHING WITH THIS EARLIER RESEARCH! That's why they are incompetent! DOING NOTHING!

Colchicine May Raise Stroke Risk in Elderly Patients With Intracranial Artery Stenosis: CHANCE-3 Trial

Colchicine prevents rise in total plaque volume for patients with stable CAD

 

 I bet we don't have enough brains in stroke to say; 'Maybe this would help in stroke also!'

 Really? You have disproved this research?

'No Hint of Benefit' in Large Colchicine Trial  November 2024

colchicine (23 posts to December 2011)

I bet your incompetent doctor and hospital DID NOTHING WITH THIS EARLIER RESEARCH! That's why they are incompetent! DOING NOTHING!

Colchicine prevents rise in total plaque volume for patients with stable CAD

Key takeaways:

• For patients with stable coronary artery disease, colchicine conferred lower total plaque volume as measured by coronary CT angiography vs. placebo.
• There was no effect on volume of low attenuation plaque.

CHICAGO — Among patients with stable coronary artery disease, colchicine lowered total plaque volume compared with placebo but had no impact on low attenuation plaque volume, researchers reported.

“If we can show both outcome data and mechanistic plaque data that are concordant, we should ... get more comfortable with these interventions, and I think colchicine is going to be one that will be used more in clinical practice based on the available clinical data,” Matthew J. Budoff, MD, investigator at The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, professor of medicine at the David Geffen School of Medicine at UCLA and program director and director of cardiac CT, division of cardiology, at Harbor-UCLA Medical Center, told Healio.

Data were derived from Budoff MJ, et al. Featured clinical research IV. Presented at: American College of Cardiology Scientific Session; March 29-31, 2025; Chicago (hybrid meeting).

For the EKSTROM trial, presented at the American College of Cardiology Scientific Session, Budoff and colleagues randomly assigned 84 patients with stable CAD to the anti-inflammatory drug colchicine 0.5 mg (Lodoco, Agepha Pharma) or placebo.

‘There is a lot of controversy’

Matthew J. Budoff

“There is a lot of controversy about colchicine use right now,” Budoff told Healio. “There have been a few positive trials and a negative trial more recently. There is a lot of unclear assessment of the clinical utility for colchicine today. Whether it improves atherosclerosis is critical in understanding its potential benefit for our patients.”

In the colchicine group, the mean age was 65.4 years and 94% were men. In the placebo group, the mean age was 63.8 years and 81% were men.

At 1 year, there was barely any change in either group in the primary outcome of low attenuation plaque (P = .344), but the key secondary outcome of total plaque volume was increased less in the colchicine group than in the placebo group (rise in percent atheroma volume, 0.3% vs. 1.4%; P = .015), Budoff said during a presentation.

“We are always interested in the vulnerable plaque, and we thought that given [colchicine’s] anti-inflammatory properties, it might affect low attenuation plaque, but we studied a stable coronary disease outpatient population,” Budoff told Healio. “The prevalence of low attenuation plaque was very low, so we couldn’t see a sizable benefit there. But percent atheroma volume, or total plaque, has been the primary outcome of every intravascular ultrasound study. And a 1% benefit translates into a 25% event reduction. So the fact that we saw a 1.1% benefit in plaque atheroma volume, we feel speaks toward the outcome data we already have from LoDoCo2 trial, which says that it reduces cardiac events by 30%. That’s very concordant with the outcome data.”

The difference was driven by changes in dense calcified plaque (rise in percent atheroma volume, 0.1% vs. 1%; P = .009), he said.

High-sensitivity C-reactive protein levels were lower in the colchicine group than in the placebo group at 1 year (0.35 mg/L vs. 0.65 mg/L), and the results were independent of baseline CRP, according to the researchers.

‘A very consistent answer’

Budoff said the researchers would like to perform a larger trial with more power to analyze individual plaque components. “It would also be interesting to do an acute coronary syndrome study, a population of patients who had high levels of inflammation, to see if there was more of an effect on low attenuation plaque that we were able to show in a stable coronary population,” he said.

Budoff said he has been giving colchicine to patients with stable CAD since the positive LoDoCo2 and COLCOT trials were published. “The EKSTROM trial further reinforces the benefits in this population,” he said. “While we still have some questions about acute myocardial infarction from other trials like CLEAR SYNERGY, I think we have a very consistent answer in patients with stable coronary disease that there’s benefit by being on low-dose colchicine.”

For more information:

Matthew J. Budoff, MD, can be reached at mbudoff@lundquist.org or on X @BudoffMd.

Colchicine prevents rise in total plaque volume for patients with stable CAD

 I bet we don't have enough brains in stroke to say; 'Maybe this would help in stroke also!'

colchicine (23 posts to December 2011)

I bet your incompetent doctor and hospital DID NOTHING WITH THIS EARLIER RESEARCH! That's why they are incompetent! DOING NOTHING!

Colchicine prevents rise in total plaque volume for patients with stable CAD

Key takeaways:

• For patients with stable coronary artery disease, colchicine conferred lower total plaque volume as measured by coronary CT angiography vs. placebo.
• There was no effect on volume of low attenuation plaque.

CHICAGO — Among patients with stable coronary artery disease, colchicine lowered total plaque volume compared with placebo but had no impact on low attenuation plaque volume, researchers reported.

“If we can show both outcome data and mechanistic plaque data that are concordant, we should ... get more comfortable with these interventions, and I think colchicine is going to be one that will be used more in clinical practice based on the available clinical data,” Matthew J. Budoff, MD, investigator at The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, professor of medicine at the David Geffen School of Medicine at UCLA and program director and director of cardiac CT, division of cardiology, at Harbor-UCLA Medical Center, told Healio.

Data were derived from Budoff MJ, et al. Featured clinical research IV. Presented at: American College of Cardiology Scientific Session; March 29-31, 2025; Chicago (hybrid meeting).     

Colchicine may Reduce CV Event Risk with Urate-Lowering Therapy for Gout: study

 Really? You have disproved this research?

'No Hint of Benefit' in Large Colchicine Trial  November 2024

 Colchicine has been researched a while, has your doctor and hospital done anything with it? Do they know about ANY of that research?

• colchicine (22 posts to December 2011)

Didn't your competent? stroke doctor start using colchicine years ago and now has quit? Or don't you have functioning stroke doctor? I'd run away from such incompetence! I'd question the ability of the board of directors to supervise a stroke hospital. You can't let incompetency continue for decades at a time!

The latest here:

Colchicine may Reduce CV Event Risk with Urate-Lowering Therapy for Gout: study

'No Hint of Benefit' in Large Colchicine Trial

 Colchicine has been researched a while, has your doctor and hospital done anything with it? Do they know about ANY of that research?

• colchicine (21 posts to December 2011)

Didn't your competent? stroke doctor start using colchicine years ago? Or don't you have functioning stroke doctor? I'd run away from such incompetence! I'd question the ability of the board of directors to supervise a stroke hospital. You can't let incompetency continue for decades at a time!

'No Hint of Benefit' in Large Colchicine Trial

WASHINGTON — Colchicine does not protect against major cardiovascular adverse events after an acute myocardial infarction, according to a multinational placebo-controlled trial of more than 7000 patients.

The CLEAR SYNERGY (OASIS 9) study, called "the largest trial ever of colchicine in acute MI," showed no hint of benefit in an adverse event curve for colchicine relative to placebo over 5 years, which suggests that the role of this drug after myocardial infarction (MI) "is uncertain," Sanjit Jolly, MD, an interventional cardiologist at Hamilton Health Sciences and a professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported here at Transcatheter Cardiovascular Therapeutics (TCT) 2024.

For the primary composite outcome — cardiovascular death, MI, stroke, and ischemia-driven revascularization — the event curves in the colchicine and placebo groups remained essentially superimposed over 5 years of follow-up, with only a slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR], 0.99; P = .93).

There were no meaningful differences in any of the individual endpoint components; all 95% CIs straddled the line of unity. Rates of cardiovascular death (3.3% vs 3.2%) and stroke (1.4% vs 1.2%) were numerically higher in the colchicine group than in the placebo group. Rates of MI (2.9% vs 3.1%) and ischemia-driven revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.

No Difference

No adverse outcomes, including all-cause death (4.6% vs 5.1%), approached significance, with the exception of noncardiovascular death (13.0% vs 1.9%). For this outcome, the 95% CI stopped just short of the line of unity (HR, 0.68; 95% CI, 0.46-0.99).

Rates of adverse events (31.9% vs 31.7%; P = .86), serious adverse events (6.7% vs 7.4%; P = .22), and serious infections (2.5% vs 2.9%; P = .85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs 6.6%; P < .001).

Given these results, a panelist questioned the use of the word "uncertain" to describe the findings during the late-breaker session in which these results were presented.

"I think you are selling yourself short," said J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at the Lifespan Cardiovascular Institute, Brown University in Providence, Rhode Island. Based on the size and conduct of this trial, she called the results "definitive" and suggested that the guidelines should be adjusted.

The OASIS 9 Trial

In OASIS 9, 3528 patients were randomized to colchicine, and 3534 were randomized to placebo. A second randomization in both groups was to spironolactone or placebo; these results will be presented at the upcoming American Heart Association (AHA) 2024 meeting. Both analyses will be published in The New England Journal of Medicine at that time, Jolly reported.

The study involved 104 sites in Australia, Egypt, Europe, Nepal, and North America. Follow-up in both groups exceeded 99%. Most patients had an ST-elevation MI (STEMI), but about 5% of those enrolled had a non-STEMI. Less than 10% of patients had experienced a previous MI.

Less than 5% of patients were discharged on sodium-glucose cotransporter 2 therapy, and more than 95% were discharged on aspirin and a statin. Nearly 80% were discharged on an angiotensin-converting enzyme inhibitor, and most patients received an anticoagulant. More than 95% of patients were implanted with a drug-eluting stent.

At month 3, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker for the anti-inflammatory effect that is considered to be colchicine's primary mechanism of action. An anti-inflammatory effect has been cited as the probable explanation for the positive results shown in the COLCOT and LODOCO2 trials, published in 2019 and 2020, respectively.

In COLCOT, which randomized 4745 patients who experienced an acute MI in the previous 30 days, colchicine was associated with a 23% reduction in a composite major cardiovascular adverse events endpoint relative to placebo (HR, 0.77; P = .02). In LODOCO2, which randomized 5522 patients with chronic coronary disease, colchicine was associated with a 31% reduction in an adverse event composite endpoint (HR, 0.68; P < .0001).

However, two more recent trials — CONVINCE and CHANCE-3 — showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was relatively small, whereas CHANCE-3 randomized more than 8000 patients and showed no effect on the risk for stroke (HR, 0.98; 95% CI, 0.83-1.16).

New Data Challenge Guidelines

Of these trials, COLCOT was the most similar to OASIS 9, according to Jolly. Among the differences, OASIS 9 was initiated earlier and was larger than the other trials, so it had more power to address the study question.

Given the absence of benefit, Jolly indicated that OASIS 9 might disrupt both the joint American College of Cardiology and AHA guidelines, which gave colchicine a class 2b recommendation in 2023, and the European Society of Cardiology guidelines, which gave colchicine a 2a recommendation.

"This is a big deal for me," said Ajay J. Kirtane, director of the Interventional Cardiovascular Care program at Columbia University in New York City. As someone who is now using colchicine routinely, these data have changed his opinion, he said.

The previous data supporting the use of colchicine "were just so-so," he explained. "Now I have a good rationale" for foregoing the routine use of this therapy.

Jolly said that he had put his own father on colchicine after an acute MI on the basis of the guidelines, but immediately took him off this therapy when the data from OASIS 9 were unblinded.

"The only signal from this trial was an increased risk of diarrhea," Jolly said. The results, at the very least, suggest that colchicine "is not for everyone" after an acute MI, although he emphasized that these results do not rule out the potential for benefit from anti-inflammatory therapy. Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, he added.

Colchicine Goes Belly-Up in a More Definitive Heart Attack Trial

 

 Colchicine has been researched a while, has your doctor and hospital done anything with it? Do they know about ANY of that research?

• colchicine (20 posts to December 2011)

Didn't your competent? stroke doctor start using colchicine years ago? Or don't you have functioning stroke doctor? I'd run away from such incompetence! I'd question the ability of the board of directors to supervise a stroke hospital. You can't let incompetency continue for decades at a time!

Colchicine Goes Belly-Up in a More Definitive Heart Attack Trial

       Larger CLEAR OASIS 9 trial could not replicate past results

by Nicole Lou, Senior Staff Writer, MedPage Today October 30, 2024

Any cardiovascular protection from colchicine in heart attack survivors seemed to be debunked with a better-powered randomized trial, researchers found.

Between acute MI patients randomized to colchicine or placebo right after percutaneous coronary intervention (PCI) in the CLEAR OASIS 9 trial, there were statistically indistinguishable rates of combined cardiovascular death, myocardial infarction (MI), stroke, or ischemia-driven revascularization at 5 years (9.1% vs 9.3%, HR 0.99, 95% CI 0.85-1.16), according to Sanjit Jolly, MD, of Hamilton Health Sciences and McMaster University in Ontario, at the Transcatheter Cardiovascular Therapeutics (TCT) meetingopens in a new tab or window.

The only clinically significant signal his group reported was more diarrhea with colchicine (10.2% vs 6.6%, P<0.001).

"I was a believer in colchicine," Jolly revealed during a TCT press conference. He shared his experience putting his own father (a retired cardiologist) on colchicine and only recently taking him off the drug, given the results of CLEAR OASIS 9. "As a patient you can decide for yourself, would you want to take this therapy? I decided to stop it in my parent."

As this is the largest trial of routine long-term colchicine in acute MI to date -- boasting 649 primary outcome events -- "the role of colchicine post myocardial infarction long term is uncertain," he concluded.

Available generically, colchicine is derived from the autumn crocus plant used medicinally for thousands of years in Egypt.

Last year, the FDA approved brand-name colchicine (Lodoco)opens in a new tab or window as the first anti-inflammatory agent indicated for cardiovascular prevention in adults with established atherosclerotic disease or multiple risk factors. Colchicine currently stands at a class IIb recommendation in American guidelines and IIa in the European ones.

TCT session discussant Roxana Mehran, MD, of Mount Sinai Health System in New York City, said she believed that colchicine's place in the guidelines may be re-evaluated based on the new data. "I would say there's some evidence to downgrade, but that would be up to the guideline group."

"Colchicine may be considered in patients under optimal medical therapy who remain at very high risk for ischemic events. It's not for everyone," Mehran said.

CLEAR OASIS 9 contradicts two major trials on the anti-inflammatory drug. In 2019, the COLCOTopens in a new tab or window group had found that low-dose colchicine worked for secondary prevention after MI, with the most substantial reductions observed for stroke and revascularization in follow-up of nearly 2 years. Colchicine again reduced cardiovascular events, this time in stable ischemic heart disease, in the LoDoCo2 trialopens in a new tab or window from 2020.

Jolly pointed out COLCOT's 301 primary endpoint events and LoDoCo2's 451 -- both lower than the present report.

"We had double the events, so I think it's just regression to the mean," he explained. "As time goes on, with more data, the truth may be there is no effect or a very modest effect [of colchicine]."

"This medicine is not well tolerated ... I would not want to start it in a patient. I never did, and now there's good rationale not to," commented Ajay Kirtane, MD, of New York-Presbyterian/Columbia University Irving Medical Center in New York City, as a panelist during the press conference.

The sentiment was echoed by fellow panelist Wayne Batchelor, MD, MHS, of Inova Health System in Fairfax, Virginia. However, Batchelor warned against "throwing the baby out with the bathwater" as the concept of suppressing inflammation may still prove clinically beneficial with a different drug such as an interleukin 6 inhibitor.

CLEAR OASIS 9 was a 2x2 factorial randomized trial that included 7,000 acute MI patients. Within 72 hours following PCI, participants were randomly assigned colchicine (0.5 mg once daily) versus placebo and spironolactone (25 mg once daily) vs placebo.

The overall cohort had a mean age just over 60 years, with only one in five being women. Reflecting the study having initially been limited to patients with ST-segment elevation myocardial infarction (STEMI) until a protocol amendment to ease enrollment, the study population ended up presenting with 95% STEMI and 5% large non-ST elevation MI. The prevalence of diabetes was around 18%, and prior MI around 9%.

For the index PCI, operators used the Synergy stent when available. The procedure consisted of a median one stent per patient, the stent averaging 23.8 mm long and having a diameter of 3.2 mm. Nearly half of patients had multivessel coronary disease, the vast majority of whom had staged procedures.

Medications at discharge were standard fare including aspirin, statins, and ticagrelor (Brilinta; 45%) as the preferred P2Y12 inhibitor over clopidogrel (Plavix; 42%) or prasugrel (Effient; 11%).

Colchicine's lack of benefit was consistent in on-treatment analysis and in the individual components of the composite primary endpoint:

• Cardiovascular death: 3.3% with colchicine vs 3.2% with placebo
• MI: 2.9% vs 3.1%
• Stroke: 1.4% vs 1.2%
• Ischemia-driven revascularization: 4.6% vs 4.7%

This was irrespective of the patient's MI type and whether they had multivessel disease, Jolly noted.

All-cause mortality was statistically similar between colchicine and placebo groups (4.6% vs 5.1%), while there was a signal of significant reduction in non-cardiovascular death by colchicine (1.3% vs 1.9%) that Jolly downplayed as a statistical anomaly.

In any case, colchicine did reduce inflammation better than placebo (-1.3 mg/L mean difference in CRP between groups at 3 months).

The medication was also not associated with excess serious adverse events (6.7% vs 7.4%).

Mehran pointed out that limitations of CLEAR OASIS 9 include its conduct during the COVID-19 pandemic and deviations from the original study protocol. She also highlighted the underrepresentation of women as a limitation of the trial, though she acknowledged that many women may have been missed due to the cutoff of acute MIs within 72 hours.

Jolly noted that the full CLEAR OASIS 9 manuscript has been accepted at the New England Journal of Medicine and will be published when the spironolactone arm of the 2x2 factorial trial is presented at the American Heart Association meeting later this month.

This is not the first negative trial for colchicine.

Cardiovascular benefits apparently did not extend to colchicine administered at the time of PCIopens in a new tab or window in an older trial, nor did the drug work as a perioperative treatmentopens in a new tab or window to reduce atrial fibrillation and myocardial injury after major non-cardiac thoracic surgery. Additionally, the CONVINCE trial had been stopped before investigators could show whether long-term colchicine use had cardiovascular benefits in stroke survivorsopens in a new tab or window.

• 

  Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

The trial was funded by grants from the Canadian Institutes of Health Research, Population Health Research Institute, and Boston Scientific.

Jolly disclosed relationships with Boston Scientific, Teleflex, Asahi, Shockwave, and Abiomed.

Mehran reported various personal ties to industry and professional societies.

Kirtane disclosed grant support from Medtronic, Abbott, Boston Scientific, Amgen, CathWorks, Siemens, Philips, Recor Medical, Spectranetics, Cardiovascular Systems, Chiesi, Opens, Zoll, Regeneron, Neurotronic, Biotronik, Bolt Medical, Magenta Medical, Canon, SoniVie, Shockwave Medical, and Abiomed.

Batchelor reported grant support from Abbott and Boston Scientific on top of personal fees from Medtronic, Edwards Lifesciences, Abiomed, Chiesi, and Recor Medical.

Primary Source

Transcatheter Cardiovascular Therapeutics

Source Reference: opens in a new tab or windowJolly S "A 2x2 factorial randomized controlled trial of colchicine versus placebo and spironolactone versus placebo in patients with myocardial infarction: results of the colchicine factorial" TCT 2024.

Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE): a randomised controlled trial

 Colchicine has been researched a while, has your doctor and hospital done anything with it? Do they know about ANY of that research?

• colchicine (19 posts to December 2011)

Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE): a randomised controlled trial

• Prof Peter Kelly, MD
• Prof Robin Lemmens, MD
• Prof Christian Weimar, MD
• Prof Cathal Walsh, PhD
• Prof Francisco Purroy, MD
• Prof Mark Barber, MD
• et al.
• Show all authors

Published:June 07, 2024DOI:https://doi.org/10.1016/S0140-6736(24)00968-1

Summary

Background

Anti-inflammatory therapy with long-term colchicine prevented vascular recurrence in coronary disease. Unlike coronary disease, which is typically caused by atherosclerosis, ischaemic stroke is caused by diverse mechanisms including atherosclerosis and small vessel disease or is frequently due to an unknown cause. We aimed to investigate the hypothesis that long-term colchicine would reduce recurrent events after ischaemic stroke.

Methods

We did a randomised, parallel-group, open-label, blinded endpoint assessed trial comparing long-term colchicine (0·5 mg orally per day) plus guideline-based usual care with usual care only. Hospital-based patients with non-severe, non-cardioembolic ischaemic stroke or high-risk transient ischaemic attack were eligible. The primary endpoint was a composite of first fatal or non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation (defined as an admission to an inpatient unit or a visit to an emergency department that resulted in at least a 24 h stay [or a change in calendar date if the hospital admission or discharge times were not available]) for unstable angina. The p value for significance was 0·048 to adjust for two prespecified interim analyses conducted by the data monitoring committee, for which the steering committee and trial investigators remained blinded. The trial was registered at ClinicalTrials.gov (NCT02898610) and is completed.

Findings

3154 patients were randomly assigned between Dec 19, 2016, and Nov 21, 2022, with the last follow-up on Jan 31, 2024. The trial finished before the anticipated number of outcomes was accrued (367 outcomes planned) due to budget constraints attributable to the COVID-19 pandemic. Ten patients withdrew consent for analysis of their data, leaving 3144 patients in the intention-to-treat analysis: 1569 (colchicine and usual care) and 1575 (usual care alone). A primary endpoint occurred in 338 patients, 153 (9·8%) of 1569 patients allocated to colchicine and usual care and 185 (11·7%) of 1575 patients allocated to usual care alone (incidence rates 3·32 vs 3·92 per 100 person-years, hazard ratio 0·84; 95% CI 0·68–1·05, p=0·12). Although no between-group difference in C-reactive protein (CRP) was observed at baseline, patients treated with colchicine had lower CRP at 28 days and at 1, 2, and 3 years (p<0·05 for all timepoints). The rates of serious adverse events were similar in both groups.

Interpretation

Although no statistically significant benefit was observed on the primary intention-to-treat analysis, the findings provide new evidence supporting the rationale for anti-inflammatory therapy in further randomised trials.

Funding

Health Research Board Ireland, Deutsche Forschungsgemeinschaft (German Research Foundation), and Fonds Wetenschappelijk Onderzoek Vlaanderen (Research Foundation Flanders), Belgium.

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Low-dose colchicine for atherosclerosis: long-term safety.

Didn't your competent? stroke doctor start using colchicine years ago? Or don't you have functioning stroke doctor? I'd run away from such incompetence! I'd question the ability of the board of directors to supervise a stroke hospital. You can't let incompetency continue for decades at a time!

Colchicine reduces hospitalization, death in COVID-19 January 2021

• colchicine (18 posts to December 2011)

The latest here:

 Low-dose colchicine for atherosclerosis: long-term safety.

Stefan Nidorf, Eldad Ben-Chetrit, Paul Ridker

Low-dose colchicine (0.5 mg daily) is now FDA-approved for secondary prevention in patients with coronary disease and will be increasingly prescribed in clinical practice. In this State-of-the-Art Review, data were collated from contemporary systemic reviews of case reports, drug registries, and placebo-controlled trials that assessed specific issues of safety related to the continuous use of colchicine in a range of clinical settings to inform physicians, pharmacists, and patients of the absolute risks of continuous use of low-dose colchicine, including among individuals taking statin therapy. Based upon these collective data, it is concluded that aside mild diarrhoea on initiation of colchicine that typically subsides in the vast majority of patients within a week of therapy, continuous use of low-dose colchicine is well tolerated and very safe. It does not affect renal, liver, or cognitive function, has no adverse effects on bleeding, wound healing, fertility, or pregnancy, and does not increase risks of cancer, serious infection, or cause-specific mortality. When appropriately prescribed to patients without significant renal or hepatic impairment, reports of myelosuppression, myotoxicity, and serious drug-drug interactions are rare and no more frequent than placebo, including in patients taking statin therapy. Physicians, pharmacists, and patients can be reassured that in the absence of significant renal or hepatic impairment continuous use of low-dose colchicine can be used safely in patients with atherosclerosis for the purpose of reducing cardiovascular risk.

Atherosclerosis

Cardiology

Inflammatory Biomarkers and Stroke Subtype

Didn't your competent? stroke doctor start using colchicine and canakinumab years ago? Or don't you have functioning stroke doctor? I'd run away from such incompetence!

AHA: Colchicine Prevents Postop Afib December 2011 

Could Old Gout Drug Offer New CV Benefits? November 2015 

Anti-inflammatory therapy for preventing stroke and other vascular events after ischaemic stroke or transient ischaemic attack November 2017

• canakinumab (5 posts to August 2012)

The latest here:

Inflammatory Biomarkers and Stroke Subtype

Seemant Chaturvedi, MD https://orcid.org/0000-0001-8660-7644, and Gian Marco De Marchis https://orcid.org/0000-0002-0342-9780Authors Info & Affiliations

January 23, 2024 issue

102 (2)

https://doi.org/10.1212/WNL.0000000000208098

 Abstract

• Disclosure
• Publication History
• References

• Information & Authors
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Abstract

Inflammation is an established pathway in the formation, growth, and rupture of atherosclerotic plaques. Inflammation is thus essential to the pathogenesis of coronary heart disease and some types of ischemic stroke.¹ The benefit of anti-inflammatory therapies, such as colchicine² and the anti-IL1β canakinumab,³ is proven in patients with coronary heart disease, yet it remains unproven for patients with ischemic stroke. Compared with coronary heart disease, the etiology of stroke is more heterogeneous. Besides arterio-arterial atherogenic embolism, possible etiologies are penetrator artery occlusion, cardioembolism, and other mechanisms. Finding a stroke etiology remains elusive in up to 30%–40% of patients despite a full evaluation. Understanding whether the stroke etiology modifies the association between inflammatory markers and recurrence risk is an important step to improve selection of patients for randomized trials on anti-inflammatory agents. IL-6 and high-sensitive CRP (hs-CRP) have been implicated in a higher recurrence risk after ischemic stroke by both an individual participant data meta-analysis⁴ and a Mendelian randomization study,⁵ but granular, in vivo results stratified by stroke etiology are lacking.

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FDA approves CV version of colchicine for patients with residual inflammatory risk

FYI.

Well, didn't your doctor start using this a long time ago? 

AHA: Colchicine Prevents Postop Afib December 2011 

Could Old Gout Drug Offer New CV Benefits? November 2015 

Anti-inflammatory therapy for preventing stroke and other vascular events after ischaemic stroke or transient ischaemic attack November 2017 

The latest here:

 

FDA approves CV version of colchicine for patients with residual inflammatory risk

Key takeaways:

• A 0.5 mg dose of colchicine has been approved for use in high-risk patients who have inflammatory risk.
• The dose is the same as that used in two successful trials, but it had not been available in the U.S.

Agepha Pharma announced that the FDA approved a 0.5 mg dose of colchicine for reduction of CV events in patients with atherosclerotic CVD or multiple CV risk factors who have residual inflammatory risk.

The 0.5 mg dose of colchicine (Lodoco) is the first anti-inflammatory agent approved as an atheroprotective CV treatment, according to a press release issued by the company.

A 0.5 mg dose of colchicine has been approved for use in high-risk patients who have inflammatory risk.
Image: Adobe Stock

The approval enables colchicine to be used alone or in combination with lipid-lowering therapy, according to the release.

Colchicine, an anti-inflammatory drug commonly used for conditions such as gout, compared with placebo was associated with reduced risk for ischemic CV events in patients with recent MI in the COLCOT trial and reduced risk for CV events in patients with chronic coronary disease in the LoDoCo2 trial. It is contraindicated in patients with chronic kidney disease (CKD) because it is excreted by the kidneys.

Major risk reduction

Paul M. Ridker

“LoDoCo2 showed a 31% relative risk reduction and COLCOT a 23% relative risk reduction. Both of these are larger than what the PCSK9 inhibitors are delivering,” Paul M. Ridker, MD, MPH, the Eugene Braunwald Professor of Medicine at Brigham and Women’s Hospital and Harvard Medical School, told Healio. “These data were published in The New England Journal of Medicine, but no one is using the drug. We have to ask some questions about why.”

One issue, he said, is that the studies were conducted with an 0.5 mg dose of colchicine, but until now, the lowest FDA-approved dose was 0.6 mg.

“You may say it doesn’t sound like a big difference, but it actually is,” Ridker told Healio. “A 20% difference in dose on a cumulative basis for a drug with a relatively narrow therapeutic window, particularly if you inadvertently give this to a person with CKD, is going to be a problem. Even though some of us are treating with colchicine, we are currently stuck using a dose that wasn’t used in the trials, which is not a good idea.”

Patients with residual risk

Other reasons why colchicine has not been widely adopted for use in U.S. patients at high CV risk include “poor physician education, limited knowledge [and] no major pharmaceutical backing for this drug,” Ridker told Healio. “It is inexpensive and has been around for a long time. I am giving colchicine to my ‘frequent flyers’: The patients who just keep coming back. Every cardiologist has a group of patients in their clinic who, despite aggressive LDL lowering [and] multiple angioplasties, they just keep coming back. A lot of them have high [C-reactive protein levels], so if the CRP is high, I am starting to put them on colchicine. It’s quite safe except in chronic kidney disease and chronic liver disease. It’s inexpensive and it works. But very few of my colleagues are doing it, and that’s unfortunate. That is just the nature of health care.”

As Healio previously reported, at the American College of Cardiology Scientific Session in March, Ridker presented a study showing that in high-risk patients on statin therapy, residual inflammatory risk as assessed by high-sensitivity CRP better predicted CV events and death than residual cholesterol risk as assessed by LDL.

The new dose is expected to be available in the second half of 2023, according to the release.

References:

• Nidorf SM, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa2021372.
• Ridker PM, et al. Lancet. 2023;doi:10.1016/S0140-6736(23)00215-5.
• Tardif JC, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1912388