LISBON – Patients with type 2 diabetes who required insulin therapy were 19% more likely to die following a percutaneous coronary intervention than were patients who managed their disease with diet or oral antiglycemic medications, according to a registry analysis.
The higher mortality rate among insulin users remained after researchers controlled for the severity of diabetes, Dr. Anna Norhammar reported at the annual meeting of the European Association for the Study of Diabetes.
"Patients with type 2 diabetes who are taking insulin are at a very high risk after cardiac angiography, especially if they have a history of previous myocardial infarction or renal complications. We need to give these patients special attention and intensive handling," after the procedure, said Dr. Norhammar of the Karolinska Institute, Stockholm.
She and her colleagues extracted data from a combination of two large Swedish patient registries: the Swedish Coronary Angiography and Angioplasty Register (SCARR), which includes all patients who have undergone the procedures, and the National Diabetes Registry, which contains information on about 70% of Swedish citizens with the disease. They identified 14,079 patients who were included in both registries from 2001 to 2009. These patients formed the basis of the analysis.
Patients were divided into four groups: those on dietary therapy alone (2,936), those on oral agents alone (5,713), those taking both oral medications and insulin (3,008), and those taking insulin only (2,422).
The patients’ mean age was 69 years. Disease duration was shorter for those on the less intensive therapies compared with those taking insulin only (6 years vs. 15 years).
As expected, mean hemoglobin A1c rose along with treatment intensity, from 6.5% in those in the diet-only group to 7% in the oral-only group, and 7.8% in each of the combo and insulin-only groups. Retinopathy was present in 13% of the diet-managed group compared with 54% of the insulin-only group, a significant difference.
Heart failure also was significantly more common in the insulin-only group (24%) compared with the diet-only (14%), oral medications-only (12%) and combination therapy (17%) groups. Heart attacks had occurred in 39% of the insulin-only group, compared with 29% of the diet-only group, again a significant difference.
About 70% of all patients were hypertensive. Renal insufficiency was present in about 2% of the less-intensively-treated groups, 1% of those on combination therapy, and 8% of those taking only insulin, but this difference was not statistically significant. The insulin-only group also had more peripheral artery disease, but that difference also was not significant.
Angiographic results varied by treatment intensity. Those with diet-only therapy were most likely to have normal results (22%); results were normal in 17% of the insulin-only group. There also was a significant difference in the prevalence of three-vessel disease, which occurred in 23% of the diet-only group and 30% of the insulin-only group.
Diabetes treatment did not impact subsequent cardiovascular therapy, however.
By 6 months, the mortality curves were significantly different. Those on diet or oral therapy alone each had a mortality of about 5%, compared with 7% of those on combination therapy and 9% of those taking insulin-only therapy.
By 4 years – the mean follow-up time – mortality was still significantly higher among the insulin-only group (22%) compared with the diet-only and oral therapy-only groups (both 15%). This pattern continued as follow-up proceeded. By 8 years, more than 50% of the insulin-only group had died, compared with about 38% of the oral-only and diet-only groups.
Adjustment for baseline cardiovascular risk factors and diabetes complications (including more severe coronary artery disease, micro- and macrovascular disease, and renal complications) attenuated the risk of death for the most-intensively-treated patients, Dr. Norhammar said. "The risk of death for these patients fell from 1.22 to 1.19, but there was still a significant overall risk of excess mortality for those on insulin."
Whether insulin plays some mechanistic role in poorer outcomes, or whether it is simply a marker of more advanced disease, remains unclear, Dr. Norhammar said.
"We know that when patients start on insulin after [PCI], there can be some adverse reactions, including more occlusion and restenosis after stenting, and poorer response to antiplatelet drugs."
"I think this whole issue will be a lot clearer when we have the results of the ORIGIN study," she added.
The Outcome Reduction With Initial Glargine Intervention (ORIGIN) study is investigating the prevention of cardiovascular morbidity and mortality in people with type 2 diabetes or impaired glucose tolerance. The treatment variables are insulin glargine (variable dose vs. standard care), and different doses of omega-3 fatty acid, and placebo. Participants are being randomized to one of four possible treatment combinations.