Intensive CV Risk Management Failed to Curb Subsequent Events



LISBON – Early and intensive multifactorial risk factor management in patients with screen-detected type 2 diabetes does not significantly reduce their risk of first, second, or third cardiovascular events, compared with standard diabetes care, according to a subanalysis of ADDITION-Europe.

Although the risk of experiencing a first cardiovascular event was reduced by 17% with an intensive risk management strategy, and the risk of a second, third, or even fourth CV event was lowered by 30%, 70%, and 78%, respectively, none of these differences reached statistical significance.

However, intensive risk management did not increase the risk of CV death or have any other adverse CV outcome, as previously suggested by some trials such as the oft-cited ACCORD (Action to Control Cardiovascular Risk in Diabetes) study, which was conducted in patients with long-standing disease.

These findings are consistent with the main study results, which – although negative – suggested that the early identification and treatment of type 2 diabetes was more important than the intensity of treatment. "If you find people [with type 2 diabetes] early, then they appear to have a lower risk of [subsequent CV] events," said Dr. Simon Griffin, one of the investigators of ADDITION-Europe in an interview at the annual meeting of the European Society for the Study of Diabetes.

Dr. Griffin, who is a primary care practitioner and assistant director of the Medical Research Council (MRC) Epidemiology Unit in Cambridge, England, added that the trial findings show that "if you start intensive treatment early, you can reduce patients’ risk of events without apparently harming them."

ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen Detected Diabetes in Primary Care)–Europe randomized primary care patients with screen-detected diabetes to either routine care or targeted risk factor management.

Of more than 3,000 patients with screen-detected type 2 diabetes, who had a mean age of 60 years and were identified according to World Health Organization criteria, 1,379 were randomized to routine care and 1,678 to intensive risk factor management. The latter included lifestyle interventions (dietary advice, increased physical activity, and smoking cessation) and targeted blood glucose, blood pressure, and cholesterol control, as well as the prescription of daily low-dose aspirin.

As reported recently in the Lancet (2011;378:156-167), the intensive risk management strategy resulted in slight – but significant – improvement in CV risk factors such as HbA1c, total cholesterol, and blood pressure, but produced a small, nonsignificant decrease in the incidence of a first CV event and death. The aim of the present analysis was to see if there was any greater effect on the incidence of experiencing a subsequent CV event.

After a mean follow-up of 5.3 years, 167 patients experienced a single CV event and 71 had experienced multiple events. Patients who experienced more than one event were more likely to be smokers, male, older, and unemployed.

Revascularization was the most common type of CV event, occurring for the first time in 88 (37%) of patients and for the second or three or more times in 55 (77%) and 15 (60%) of patients.

First, second, and third or more CV death event occurred in 48 (20%), 8 (11%), and 4 (16%) patients, respectively, and first, second, and third or more nonfatal MI occurred in 61 (26%), 5 (7%), and 3 (12%) patients. Respective rates for nonfatal stoke were 17% (41 patients), 3% (2), and 8% (2).

Rebecca Simmons, Ph.D., also of the MRC Epidemiology Unit, presented the data, and noted that the overall hazard ratio for a first CV event was 0.82 (95% confidence interval, 0.65-1.05), which favored intensive over routine diabetes treatment in the patient population studied.

The HR for any further CV event was 0.77 (95% CI, 0.58-1.02), and specifically for a second, third, or fourth event was a respective 0.70 (95% CI, 0.43-1.12), 0.30 (95% CI, 0.10-0.97), and 0.22 (95% CI, 0.02-2.18).

Dr. Simmons said of the findings that "modest but significant increases in intensity of treatment was not associated with significant reduction in first or second CVD events." However, there were clearly differences in the distribution of subsequent CV events, she noted.

Dr. Griffin further commented on the differences between studies such as ACCORD (Action to Control Cardiovascular Risk in Diabetes): "If you take people who have had diabetes for 10 years and they’ve not got very good glucose or blood pressure control and you suddenly try and change that, in terms of the glucose it does not necessarily help people. But if you take people early and you try to keep their glucose as low as possible for as long as possible then it does not appear to harm them and it appears to be beneficial."

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