No benefit on myocardial injury with colchicine before PCI
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PHILADELPHIA — Acute preprocedural administration of colchicine did not reduce PCI-related myocardial injury or MACE compared with placebo, but attenuation of the inflammatory response was observed in the COLCHICINE-PCI trial, which was presented at the American Heart Association Scientific Sessions.
The study evaluated oral administration of 1.8 mg of colchicine or placebo to examine the effects on myocardial injury and biomarker evidence of PCI-related inflammation in patients with suspected ischemic heart disease or ACS referred for coronary angiography with possible PCI.
The primary outcome of PCI-related myocardial injury did not differ between patients administered colchicine or placebo, at 57.3% in the colchicine group compared with 64.2% in the placebo group (P = .19), Binita Shah, MD, MS, associate director of research in the Cardiac Cath Lab and assistant professor of medicine at VA New York Harbor Healthcare System and NYU School of Medicine, reported during a Late Breaking Science session.
Results also showed no difference with colchicine or placebo in 30-day MACE (11.7% vs. 12.9%; P = .82), which was largely driven by type 4a MI, or in PCI-related MI (2.9% vs. 4.7%; P = .49), according to results presented here.
There was no heterogeneity of response in prespecified subgroups evaluated by presence of absence of ACS, intraprocedural complications or new treatment with high-intensity statin therapy within 7 days before the procedure.
Shah, a Cardiology Today Next Gen Innovator, also reported results of a nested inflammatory biomarker study, which showed no significant difference between groups in change in plasma interleukin (IL)-6 concentration from baseline to 1 hour after PCI. However, results showed significant attenuation in the rise of IL-6 (P = .02) and high-sensitivity C-reactive protein concentration (P = .001) at 22 to 24 hours after PCI in those who received colchicine. There was no difference in IL-1.
“This is the first study to demonstrate that an oral load of colchicine prevents a rise of inflammatory biomarkers in acute injury,” Shah said during her presentation.
Adverse events were low overall and did not differ between the colchicine and placebo groups, with the exception of gastrointestinal symptoms, which were more prevalent in the colchicine group (9.3% vs. 3.2%), and a greater prevalence in the placebo group of hemodynamic instability (0% vs. 1.4%) and serious adverse events (1.4% vs. 3.4%), Shah said.
COLCHICINE-PCI was an investigator-initiated, randomized, double-blind, placebo-controlled, single-center trial. Baseline assessment occurred immediately prior to drug administration and randomization occurred 1 to 2 hours before the procedure. Patients were randomly assigned to colchicine 1.2 mg followed by 0.6 mg over 1 hour (n = 366), or placebo (n = 348). For those patients who went on to undergo PCI (56% in each group), multiple assessments were made after the procedure, including troponin and inflammatory biomarkers at baseline, 1 hour, 6 to 8 hours and 22 to 24 hours.
Baseline characteristics were similar between the groups, with a mean age of 66 years, 93% men, one-fifth black, and high prevalence of hypertension, dyslipidemia and diabetes. Half of the patients presented with ACS as their indication for PCI. More than half had multivessel CAD, with predominant involvement of the left anterior descending artery. Intraprocedural complications were low in both groups. One-fifth of patients had a lesion length greater than 33 mm.
These data come on the heels of the COLCOT trial, presented earlier at the AHA Scientific Sessions, in which adults with a recent MI were less likely to experience an ischemic CV event over 2 years when assigned colchicine compared with placebo.
Colchicine, a drug commonly used to treat gout, has been shown to inhibit neutrophil chemotaxis and activity in response to vascular injury, inhibits inflammasome signaling and reduces production of active IL-1, and reduces neutrophil-platelet interaction and aggregation, Shah said during her presentation. The standard regimen of colchicine used for gout flares is 1.2 mg followed by 0.6 mg administered over an hour; this regimen has rapid onset of anti-inflammatory effects, she said.
“Vascular injury and inflammation during PCI induces rapid neutrophil recruitment to the site of mechanical trauma, is associated with endothelial cell and microvascular dysfunction, and is an independent predictor of subsequent major adverse cardiovascular events even in the contemporary era of second-generation drug eluting stents,” she said.
COLCHICINE-PCI is “an important trial with a very important question,” Subodh Verma, MD, PhD, FRCSC, FAHA, professor and cardiac surgeon, CRC Tier 1 Chair in CV Surgery, CardioLink Trials Co-Chair, University of Toronto, said during a discussion of the trial.
“Over the last several years, the importance of periprocedural PCI inflammation as a risk marker of atherosclerotic events has really exploded,” he said.
Verma said “the story is not over” for colchicine. There are ongoing, important, long-term studies evaluating the effects of colchicine, he said. One is the CLEAR-SYNERGY (OASIS 9) study, led by Sanjit S. Jolly, MD, from McMaster University and Population Health Research Institute, Hamilton, Ontario, of 4,000 patients diagnosed with STEMI referred for PCI. Patients will be randomized to colchicine or placebo in a 2x2 factorial design within 48 hours of successful PCI. The primary outcome is MACE. – by Katie Kalvaitis
Reference:
Shah B, et al. Late Breaking Science IV: State of the Art Interventional Management for ACS Patients. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2019; Philadelphia.
Disclosures: This research was funded by a VA Career Development Award, AHA Clinical Research Mentored grant, and the drug was supplied by Takeda Pharmaceuticals and the Manhattan VA Hospital Research Pharmacy. Shah reports she serves on advisory boards for Philips Volcano and Radux Devices and consults for Terumo. Verma reports he has received speaking and/or research support from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, HDL. Janssen, Lilly, Merck, Novartis, Novo Nordisk.