Mortality and CVD Decline in Patients With Diabetes, but Biggest Strides Seen for Nonfatal Outcomes

While one expert sees the temporal changes as good news, others question why fatal events weren’t affected to a larger extent.

Mortality and CVD Decline in Patients With Diabetes, but Biggest Strides Seen for Nonfatal Outcomes

Cardiovascular and coronary heart disease deaths, as well as deaths from any cause, have declined among patients with type 1 and type 2 diabetes in Sweden, according to the results of a 15-year study. Hospitalizations for cardiovascular disease are also down.

When compared with a matched control population, patients with type 1 and type 2 diabetes also had significantly larger reductions in the risk of hospitalization for cardiovascular disease, acute MI, coronary heart disease, and stroke. But of note, reductions in all-cause, cardiovascular, and coronary heart disease mortality were not significantly different from those seen among nondiabetic controls.

For researchers, the paradoxical finding between fatal and nonfatal outcomes was a surprise.

“Patients with type 1 and type 2 diabetes traditionally die from cardiovascular-associated disease, and even most of the diabetes-related complications are actually cardiovascular disease,” lead investigator Aidin Rawshani, MD (University of Gothenburg, Sweden), told TCTMD. “Still, in the context of outcomes that have improved to a greater degree among diabetes patients, the lack of similar trends among fatal outcomes are difficult to explain.”

Rawshani said that clinical advancements in the treatment of diabetes, including management of cardiovascular risk factors and glycated hemoglobin levels, as well as advances in revascularization and use of glucose-monitoring systems, might have altered the risk of nonfatal outcomes but had less of an impact on fatal events.

“It’s important to figure out what factors influenced the character of these trends to distinguish which factors are most important for fatal outcomes and nonfatal outcomes since there is such a strong difference between the trends, both in the type 1 and type 2 population,” said Rawshani. 

Martin Rutter, MD (University of Manchester, England), who was not involved in the analysis, took a glass-half-full approach to the findings, saying they are good news for people with diabetes. “Mortality rates are going down and in some areas patients with diabetes are doing better than the general population, which is really fantastic,” he told TCTMD.

He noted that there remains “residual risk” in the diabetic population, pointing out that these patients still do worse than the general population, “even though everybody is doing a little bit better overall.” For example, in the type 2 diabetes patients, 12% were current smokers and just 37% were taking a statin. Additionally, blood pressure was 140/79 mm Hg, which he said wasn’t bad, but could be better considering their overall risk.

“There are still things we can do,” said Rutter. “I don’t think we should be complacent.” 

The results of the study were published April 13, 2017, in the New England Journal of Medicine.

Capturing Diabetes Outcomes Over 15 Years

Using data from the Swedish National Diabetes Register (NDR), the researchers identified 36,869 patients with type 1 diabetes and 457,473 patients with type 2 diabetes. The mean age of patients with type 1 and type 2 diabetes was 35.3 years and 65.2 years, respectively, and the mean duration of diabetes prior to entry into the registry was 20.0 and 5.7 years, respectively. The mean duration of follow-up was 11.2 years for patients with type 1 diabetes and 6.5 years for those with type 2 diabetes.

When expressed as a hazard ratio during a 10-year period, there was a significant 29%, 42%, and 44% reduction in the risk of all-cause, cardiovascular, and coronary heart disease mortality, respectively, among patients with type 1 diabetes. For those with type 2 diabetes, there was a corresponding 21%, 46%, and 48% reduction in the same outcomes. However, as the researchers noted, the reduction in mortality in both type 1 and type 2 diabetics was not significantly different when compared with the reductions observed in matched controls.

Regarding nonfatal outcomes, there was a 36% reduction in hospitalizations for cardiovascular disease, a 37% reduction in acute MI, a 44% reduction in hospitalizations for coronary heart disease, and a 35% reduction in stroke among type 1 diabetics. Similarly, for patients with type 2 diabetes, there was a 44% reduction in hospitalizations for cardiovascular disease, a 50% reduction in MI, a 45% reduction in coronary heart disease, and a 39% reduction in stroke. These reductions in nonfatal events were significantly larger than the reductions observed in the matched controls.

Overall, patients with type 1 diabetes had an approximate 40% greater reduction in nonfatal cardiovascular outcomes than controls, while patients with type 2 diabetes had roughly a 20% reduction.

“Irrespective of the trends, there still remains a substantial excess overall rate of all outcomes that were analyzed in persons with type 1 and type 2 diabetes when compared with the general population,” said Rawshani.

Among type 1 diabetic patients, there was a nonsignificant 13% reduction in the risk of heart failure, and this reduction was not significantly different compared with matched controls. In contrast, there was a 29% reduction in the risk of heart failure in patients with type 2 diabetes, and this risk reduction was significantly larger than that observed in the control group.

Other Noncardiovascular Deaths

Darren McGuire, MD (University of Texas Southwestern Medical Center, Dallas), one of study authors, said the reduction in clinical outcomes observed during the study’s time period are in line with what would be expected given parallel data showing more aggressive management of cardiovascular risk factors, such as lipids and blood pressure.

“In Sweden, the adherence to prescription and achievement of therapeutic targets is really quite good, not just for hemoglobin A1c, but for cholesterol management, blood-pressure management, and smoking cessation,” he said. “What we see is what we would expect if the influence of the interventions from clinical trials pans out on a population basis.”

Regarding the lack of difference in nonfatal outcomes between controls and diabetic patients, McGuire said researchers and physicians are learning more and more about competing risks. “As we get better and better at preventing cardiovascular death, and specifically atherosclerotic-related vascular death, other mortalities emerge,” he said. “In most of the trials in the diabetes space, 30% to 40% of the deaths observed, even in an enriched cardiovascular population, are noncardiovascular. Up to a third of those deaths are malignancies.”

To TCTMD, Rutter made a similar comment, noting the registry matched patients for age, sex, and county but did not match patients for comorbid disease.

“People with type 2 diabetes will have more chronic disease,” he said. “They’ll be frailer, have more respiratory disease, more cancer, and more gastrointestinal disease. These are all going to contribute to noncardiovascular mortality. We have a strategy of managing cardiovascular risk factors in patients when they attend clinic, and that’ll have an effect of cardiovascular event rates, which appears to be the case, but it isn’t going to impact noncardiovascular mortality.”

Rutter said that the introduction of new clinical agents for the treatment of type 2 diabetes into clinical practice, specifically glucagonlike peptide-1 (GLP-1) receptor agonists and sodium glucose cotransporter-2 (SGLT-2) inhibitors, could alter future trends.

“If we were to do this study in a further 10 years and look at trends, we’d probably see a big drop in mortality rates, heart failure rates, and also cardiovascular event rates as a consequence of these new therapies that are only starting to become part of mainstream management,” he said.

In an editorial accompanying the current paper—as well as a second study by Elizabeth Myers-Davis, PhD (University of North Carolina, Chapel Hill), appearing in the same issue—Julie Ingelfinger, MD, and John Jarcho, MD, both deputy editors of the New England Journal of Medicine, note that the incidence of diabetes continues to increase in young people and new approaches are needed to reduce its burden on public health.    

Sources
  • Rawshani A, Rawshani A, Franzén S, et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes. N Engl J Med. 2017; 376:1407-1418.

  • Ingelfinger JR, Jarcho JA. Increase in the incidence of diabetes and its implications. N Engl J Med. 2017; 376:1473-1474.

Disclosures
  • Rawshani reports no disclosures.
  • McGuire reports personal fees from Boehringer Ingelheim, Janssen Research and Development LLC, Sanofi, Merck Sharp and Dohme, Eli Lilly, Novo Nordisk, GlaxoSmithKline, Takeda Pharmaceuticals North America, AstraZeneca, Lexicon, and Eisai outside the submitted work.
  • Jarcho and Ingelfinger report no conflicts of interest beyond serving as deputy editors for the New England Journal of Medicine.
  • Rutter reports receiving research funding from Novo Nordisk and educational grants from Merck Sharp & Dohme and Novo Nordisk, consultancy fees from Roche Diagnostics and Cell Catapult, and owning shares in GlaxoSmithKline.

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