miércoles, 9 de diciembre de 2015

Could Old Gout Drug Offer New CV Benefits?

Colchicine use was associated with fewer cardiovascular events and lower all-cause mortality

The elevated risk of cardiovascular events among patients with gout declined in those who used colchicine, an observational study found.
The incidence rate ratios among colchicine users compared with non-users were 0.52 (95% CI 0.29-0.92) for myocardial infarction, 0.34 (95% CI 0.14-0.71) for stroke, and 0.79 (95% CI 0.24-2.39) for transient ischemic attack, according to Daniel H. Solomon, MD, and colleagues from Brigham and Women's Hospital in Boston.
After adjustment for all covariates including age, sex, race, history of CV disease, diabetes, and hypertension, and the use of medications such as statins and aspirin, the risk of a composite CV endpoint that included all these events was 49% lower among gout patients who took colchicine (HR 0.51, 95% CI 0.30-0.88, P=0.016), the researchers reported online in Annals of the Rheumatic Diseases.
"While we are unable to confirm a causal link in a non-randomized observational study, this study provides justification for a randomized controlled trial of colchicine to reduce CV risk among patients with gout," Solomon and colleagues stated.
Because atherosclerosis is strongly associated with inflammation, there are current efforts to explore the possibility of using immunomodulatory medications including colchicine, methotrexate, and canakinumab (Ilaris) for prevention.
Colchicine "downregulates inflammation through blocking microtubule spindle formation, disrupting inflammasome function, inhibiting cytokine production, and hindering neutrophil chemotaxis," the researchers explained.
Previous studies have suggested that the drug -- used in gout for hundreds of years -- was beneficial for secondary CV prevention in the general population, but little is known about its CV prevention effects in gout patients themselves.
Therefore, the researchers analyzed data from the Brigham and Women's Hospital electronic medical records and the linked Medicare databases for the years 2006 to 2011.
They identified 501 patients with gout who had a first prescription for colchicine during that time, matching them by age, gender, and index date with gout patients without colchicine prescriptions.
Average age was 73, and two-thirds of the study participants were men. The cases and controls were similar in history of heart failure, CV disease, and chronic kidney disease, but cases had more hypertension (77% versus 28%, P<0 .0001="" 16="" allopurinol="" and="" anti-inflammatory="" body="" commonly="" drugs="" em="" especially="" had="" higher="" index="" mass="" more="" nbsp="" nonsteroidal="" statins="" style="border: 0px; box-sizing: border-box; font-family: inherit; font-size: inherit; font-stretch: inherit; font-variant: inherit; font-weight: inherit; line-height: inherit; margin: 0px; padding: 0px; vertical-align: baseline;" used="" versus="">P
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While the rates of myocardial infarction, stroke, and transient ischemic attack were lower in the colchicine group, the rates of revascularization procedures were similar. For coronary artery bypass grafts, the incidence rate ratio was 3.11 (95% CI 0.71-18.62), and for percutaneous coronary intervention the ratio was 1.03 (95% CI 0.59-1.78).
In an additional analysis using all-cause mortality as the outcome, colchicine users had a lower risk, with a hazard ratio of 0.27 (95% CI 0.17-0.43, P<0 .0001="" p="">
Colchicine typically is not used for extended periods, but rather is given for the acute attack or at the initiation of urate-lowering therapy, but some patients with frequent flares have used it long term.
"These results, along with those from prior studies, suggest that long-term colchicine may provide CV risk protection among patients with gout with and without known cardiovascular disease, a group known to experience a 30% to 60% increased risk of CV events," Solomon and colleagues observed.
However, they advised that their findings should be interpreted with caution, noting that prescriptions for colchicine may have been more commonly given to patients willing to take medications, or that providers may have hesitated to prescribe the drug to the sickest patients. There also could have been residual confounding.
"Results from this study may be considered hypothesis-generating for a formal test of whether colchicine reduces CV risk in the setting of a randomized controlled trial," they concluded.
If the drug does succeed in decreasing CV risk in a formal study, it is likely that the effects derive from colchicine's immunomodulatory effects, as it does not lower uric acid, the investigators noted.
The study was supported by the National Institutes of Health.
The authors reported financial relationships with Lilly, Pfizer, Amgen, and AstraZeneca.
  • Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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