21-Year Follow-up of STENO-2: Reducing Strokes and Increasing Life Expectancy — ADA 2019

The results of the STENO-2 study assessing the benefit of intensified therapy on risk of stroke.

The STENO-2 study followed patients with type 2 diabetes for 21.2 years to examine if multiple risk factor interventions would reduce the risk for stroke in these patients. The results from this study were presented during Day 4 of American Diabetes Association’s (ADA’s) 79th Scientific Sessions in San Francisco held from June 7-11, 2019. The results showed that stroke is a fatal complication in individuals with type 2 diabetes and microalbuminuria.

Studies have shown that having type 2 diabetes is considered to be a modifiable risk factor for stroke. Over time, if patients with type 2 diabetes maintain high blood glucose levels, the excess glucose can build up fat deposits in blood vessels that supply blood to the brain. Eventually, if the fat deposits continue to grow, blood vessels will narrow, subsequently leading to a stroke due to the lack of blood flow to the brain. Other complications with having type 2 diabetes can lead to stroke as well, such as high blood pressure and hyperlipidemia. The importance of individualized multifactorial inventions (lowering blood glucose, blood pressure, and lipids) in the treatment of type 2 diabetes has been studied in the STENO-2 trial.

In the STENO-2 study, 160 patients with type 2 diabetes and microalbuminuria were randomized to conventional or intensified multifactorial treatment targeting atherosclerotic risk factors (each group n=80). After the treatment duration of 7.8 years, all individuals were offered intensified multifactorial treatment for an observational follow-up of an additional 13.4 years. The treatment of intensive therapy recommended 150 mg of aspirin daily, to decrease the number of cerebral hemorrhage events. The time of the first stroke event was the primary outcome of the study.

All patients had microalbuminuria, indicating higher risk for future complications from vascular damage, at baseline. During the follow-up of 21.2 years, 30 patients experienced a total of 39 stroke events. A total of 29 strokes occurred in 21 patients (26%) within the conventional-therapy group, compared to a total of 10 strokes that occurred in 9 patients (11%) in the intensive-therapy group. The stroke hazard was reduced by 69% with intensive therapy vs. conventional treatment (HR 0.31 [95% CI 0.14, 0.69]; p = 0.004). In the intensive-therapy group, the average time to stroke or death was 19.9 years, compared to conventional-therapy group of 11.4 years. Four of the 35 patients (11%) experienced a stroke as their first manifestation of cardiovascular disease with intensive treatment, whereas 14 of 51 patients with conventional treatment experienced a stroke as their first manifestation of cardiovascular disease. Of the total strokes evaluated in the study, 35 were ischemic and 4 were hemorrhagic. Patients with conventional therapy were more likely to have a recurrent stroke. One patient out of the 10 patients with intensive treatment experienced a recurrent stroke (p = 0.018). A similar percentage of patients in the conventional-therapy and intensive-therapy who experienced a stroke died during follow-up (78% vs. 71%, respectively). However, patients in the intensive-therapy group lived for a shorter period after a stroke than the conventional-therapy group (0.3 years vs. 3.1 years, respectively).

The results for this study concluded that with the increasing numbers of patients being diagnosed with diabetes, stroke should still be considered a critical risk factor amongst these patients. The intensive therapy resulted in about 8 years of life expectancy. The study provided clinical reasoning for lowering blood glucose, blood pressure, and lipids to reduce the risk of stroke. At the Scientific Session, Dr. Peter Gæde of the Steno Diabetes Center ended with stating that although the study was long and costly, the end results contributed meaningful data on the prevention of future complications.

Practice Pearls:

• The STENO-2 trial assessed intensive therapy amongst patients with type 2 diabetes during a follow-up of 21.2 years, and showed a 69% reduction in risk of stroke.
• This study concluded that intensive therapy vs. conventional therapy led to reduced risk of stroke and cardiovascular disease mortality.
• The results for the study indicate the importance of early screening for vascular risk factors in patients with type 2 diabetes.

References:

Gæde, Peter, et al. “Beneficial Impact of Intensified Multifactorial Intervention on Risk of Stroke: Outcome of 21 Years of Follow-up in the Randomised Steno-2 Study.” SpringerLink, Springer Berlin Heidelberg, 1 June 2019, link.springer.com/article/10.1007/s00125-019-4920-3.

Reported at the American Diabetes Association 79th Scientific Sessions June, 2019

Maya Rudolph, Florida A&M University, College of Pharmacy & Pharmaceutical Sciences, PharmD Candidate