medwireNews: Type 2 diabetes and polyvascular disease are additive risk factors for cardiovascular events in patients with acute coronary syndromes, a secondary analysis of the IMPROVE-IT trial suggests.
“The analyses show a clear gradient of risk within an acute coronary syndrome population, with both polyvascular disease and diabetes associated with similar heightened risk and with the combination of both translating into a particularly malignant phenotype,” Marc Bonaca (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and co-authors report in The Lancet Diabetes & Endocrinology.
For the trial, 18,144 patients who had been stabilized after an acute coronary syndrome were randomly assigned to receive simvastatin 40 mg/day plus ezetimibe 10 mg/day or placebo for a median duration of 6 years.
Polyvascular disease – defined as concomitant peripheral artery disease, stroke or transient ischemic attack, or both – was present in 11% of patients at baseline, while 27% had type 2 diabetes, and 4% had both.
At 7 years, the rate of the primary composite endpoint of cardiovascular death, a major coronary event (nonfatal myocardial infarction, documented unstable angina requiring hospital admission, or coronary revascularization occurring at least 30 days after randomization), or stroke was 39.8% among the patients with polyvascular disease and 39.9% among those with type 2 diabetes.
This was higher than the 29.6% observed in patients without polyvascular disease or diabetes but significantly lower than the rate of 60.0% seen in patients with polyvascular disease and concomitant diabetes.
Indeed, the researchers calculated that, after adjustment for baseline variables, patients with polyvascular disease and diabetes had a significant 60% higher 7-year risk for the composite cardiovascular outcome than those with polyvascular disease without diabetes.
In addition, the risks for each component of the composite outcome were a significant 37–87% higher in patients with polyvascular disease with versus without diabetes, while the risk for heart failure was a significant 70% higher.
Bonaca and team note that ezetimibe consistently lowered low-density lipoprotein (LDL) cholesterol by approximately 14 mg/dL regardless of concomitant polyvascular disease or type 2 diabetes.
However, because patients with both polyvascular disease and type 2 diabetes had the greatest cardiovascular risk overall, they also derived the greatest benefit (absolute risk reduction of 9.1%) from ezetimibe compared with those with no diabetes (3.1%) or neither condition (1.7%).
“Therefore, although all patients benefited from the addition of ezetimibe, if clinicians chose to target the use of such additional treatments at patients who would derive the greatest absolute benefit, the presence of polyvascular disease, type 2 diabetes, and the combination of both could be useful clinical indicators,” Bonaca et al conclude.
In an accompanying comment, Subodh Verma (University of Toronto, Ontario, Canada) et al say that the findings “should inform clinicians of the malignant cardiovascular phenotype that type 2 diabetes plus polyvascular disease confers,” and that physicians should have “a heightened awareness” of the coexistence of these two conditions.
They also note that “the magnitude of absolute benefit with intensive LDL cholesterol lowering in this population [is] large and clinically significant.”
By Laura Cowen
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