Intensive Rx Similar to Standard Care for Preventing CV Events in T2D

An intensive approach for preventing coronary events and all-cause mortality in type 2 diabetes (T2D) yields results similar to those seen with standard care, according to a study published in the December issue of Lancet Diabetes & Endocrinology.

“Our results do not fully support the efficacy of further intensified multifactorial intervention compared with current standard care for the prevention of a composite of coronary events, cerebrovascular events, and all-cause mortality,” wrote first author Kohjiro Ueki, MD, of Diabetes Research Center, National Center for Global Health and Medicine, Tokyo, Japan, and colleagues with the Japan Diabetes Optimal Treatment (J-DOIT3) study group.

However, they noted that the results suggest intensified management may have a benefit for the prevention of cerebrovascular events in T2D, especially stroke.

While research suggests that tight glucose control may decrease microvascular complications in T2D,  that control alone may not be enough to decrease macrovascular complications. Also, intensive glucose control can increase the risk of severe hypoglycemia, which may trigger cardiac events.

Multipronged approach
Limited research suggests that a multifactorial approach focused on intensive control of blood glucose, lipids, and hypertension may improve macrovascular outcomes and mortality in T2D.

To further evaluate the issue, Ueki and colleagues conducted an open-label randomized study at 81 clinics in Japan between June 2006 and March 2016. 

• Participants included 2542 patients with T2D who were aged 45-69, and had hypertension, dyslipidemia and A1c ≥ 6.9%.
• Participants were randomized to standard therapy according to Japanese guidelines (n=1271), or intensive therapy (n=1271).

• Primary outcome: composite of heart attack, stroke, revascularization, and all-cause mortality. Patients were followed for a median of 8.5 years.

Please click "next" below for Key Results and Discussion

Key results:

o  Treatment goals significantly better for Intensive vs standard therapy (all p<·0001)

     - HbA1c: 6.8% vs 7.2%

     - Systolic BP: 123 mmHg vs 129 mmHg

     - Diastolic BP: 71 mmHg vs 74 mmHg

     - LDL: 85 mg/dL vs 104 mg/dL

o  Primary outcome: 19% lower risk with intensive vs standard therapy

     - Results not significant: HR 0.81, 95% CI 0.63–1.04; p=0.094

o  Post-hoc analysis:

     - Both groups had similar risk of all-cause mortality (p=0.95) and coronary events (p=0.44)

     - Significantly lower risk of cerebrovascular events (-58%) with intensive therapy (HR 0.42, 0.24–0.74; p=0.002)

o  Adverse events similar for both groups EXCEPT:

     - Non severe hypoglycemia: significantly more with intensive therapy (p<0.001)

     - Edema not associated with heart failure: significantly more with intensive therapy (p=0.001)

The authors noted that one reason the trial showed no clear benefit with intensive therapy may be because the number of events was lower than expected.  

However, they suggested that their results may support more strict blood pressure and lower LDL targets than currently recommended by the American Diabetes Association and the European Association for Diabetes.

“Since the intensive therapy in the J-DOIT3 trial showed potential benefits on cerebrovascular disease and microvascular complications compared with well controlled conventional therapy, our results could affect recommended targets for HbA1c, blood pressure control, and cholesterol reduction for the prevention of these complications in patients with type 2 diabetes in future guidelines,” the authors concluded.

They noted that the results may not generalize to patients who are treated by non-specialists in primary care settings.

The research team is currently conducting a follow-up study to evaluate the long-term effects of the intensive intervention on coronary and cerebrovascular events and mortality.

Please click "next" below for Take-home Points and Source.

Take-home Pointso  Japanese study found that an intensive approach for preventing coronary events and all-cause mortality in T2D is similar to standard care
o  Post-hoc analysis suggested that intensive therapy may have a benefit for the prevention of cerebrovascular events in T2D, especially stroke
o  Authors suggest these findings may support more strict blood pressure and lower LDL targets for the prevention of cerebrovascular events and microvascular complications in T2D

Source: Ueki K, Sasako T, Okazaki Y, Kato M, et al. Effect of an intensified multifactorial intervention on cardiovascular outcomes and mortality in type 2 diabetes (J-DOIT3): an open-label, randomised controlled trial.

Lancet Diabetes Endocrinol. 2017;5:951-964. doi: 10.1016/S2213-8587(17)30327-3.