Clinicians Can Use Predictors to Identify Risk of Atherothrombosis

A recent analysis of a large international registry found that clinicians can utilize clinical descriptors to predict future ischemic events in outpatients with atherothrombosis. During a 4-year follow-up period, subgroups of atherothrombotic patients had widely varying risks, ranging from 7% in nondiabetic patients with other risk factors for atherothrombosis to 25% in patients with polyvascular disease and prior ischemic events. The results were published online in the Journal of the American Medical Association [doi:10.1001/jama.2010.1322]. Patients with atherothrombosis are at elevated risk of ischemic events, although future risk depends on the specific manifestations of atherothrombosis. It would be useful for clinicians to have accurate knowledge of the major determinants of subsequent ischemic risk, which would help triage novel preventive therapies toward those at the higher end of the risk spectrum. Identifying patients at the highest risk of cardiovascular events would also allow trials of novel therapies to focus on those patients most likely to derive benefit. To establish the risk of future ischemic events, the authors analyzed the international Reduction of Atherothrombosis for Continued Health (REACH) Registry, a contemporary data set comprising patients with various manifestations of atherosclerosis. The REACH registry includes asymptomatic adults with risk factors, patients with stable atherosclerosis, and those with prior ischemic events. Patients were enrolled if they were at least 45 years old with ≥3 risk factors for atherosclerosis and if they had established coronary artery disease, peripheral arterial disease, or cerebrovascular disease. The multiple risk factors category consisted of diabetes, diabetic nephropathy, ankle-brachial index <0.9, asymptomatic carotid stenosis of ≥70%, carotid intima-media thickness at least 2 times that at adjacent sites, systolic blood pressure of ≥150 mm Hg despite treatment, hypercholesterolemia treated with medication, current smoking of ≥15 cigarettes per day, and age ≥65 years for men or ≥70 years for women. There were 68,236 patients enrolled in the REACH registry who had baseline data. Of those, 45,227 were enrolled at 3647 centers in 29 countries and were eligible for inclusion in the 4-year followup study and contributed 4-year outcomes data; 20,980 patients enrolled at centers that did not participate in 4-year follow-up, while 2029 patients did not return after their baseline visit. The mean age of the 45,227 patients was 68.4 years and approximately two thirds were men; 48.4% had prior ischemic events, and 28.1% of those had an ischemic event within the previous year. Hypertension (81.3%) and hypercholesterolemia (70.4%) were very common, while diabetes was present in 43.6% of patients and polyvascular disease was present in 15.9%. During the follow-up period, a total of 5481 patients experienced at least 1 event, including 2315 with cardiovascular death, 1228 with myocardial infarction, 1898 with stroke, and 40 with myocardial infarction and stroke on the same day. Among patients with atherothrombosis, those with a prior history of ischemic events at baseline (n=21,890) had the highest rate of subsequent ischemic events (18.3%; 95% confidence interval [CI], 17.4%-19.1%); patients with stable coronary, cerebrovascular, or peripheral artery disease (n=15,264) had a lower risk (12.2%; 95% CI, 11.4%-12.9%); and patients without established atherothrombosis but with risk factors only (n=8073) had the lowest risk (9.1%; 95% CI, 8.3%-9.9%). P<.001 for all comparisons. In addition, using multivariable modeling, the authors found the presence of diabetes (hazard ratio [HR], 1.44; 95% CI, 1.36-1.53; P<.001), an ischemic event in the previous year (HR, 1.71; 95% CI, 1.57-1.85; P<.001), and polyvascular disease (HR, 1.99; 95% CI, 1.78-2.24; P<.001) were associated with a significantly higher risk of the primary end point. The authors mentioned that by using registries, there were certain limitations to the study, including that end points were not adjudicated. In addition, the authors could not complete the follow-up of the initial cohort enrolled because some centers and sites were unable to continue in the registry for financial reasons. However, they said the findings regarding event rates were not likely significantly influenced because there was no evidence that the sites that dropped out were those with higher or lower ischemic risk.