Identifying causes of death and related risk factors in patients with type 2 diabetes and cardiovascular disease may help with prevention.
Diabetes has been recognized as one of the major risk factors for cardiovascular (CV) disease. Results from previous studies have suggested that myocardial infarction (MI) is the most frequent cause of death among patients diagnosed with both diabetes and CV disease. However, as more research is being conducted on this topic, evidence is arising that diabetes may be associated with other causes of cardiovascular death, including sudden death, heart failure (HF), cancer, and non-CV related deaths.
The following study was conducted to identify causes of death and related risk factors in individuals with diabetes and atherosclerotic cardiovascular disease (ASCVD). Data was analyzed from a double-blind, multinational, placebo-controlled study called the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). The TECOS is a 3-year study that assessed how sitagliptin, a DPP-4 Inhibitor, would affect patients with diabetes and ASCVD when added to current drug therapy. 14,735 participants were randomized to either the sitagliptin intervention group or the placebo intervention group. Participants were included if they were older than 50 years of age and had a diagnosis of both T2DM and ASCVD. An independent committee blinded to treatment interventions was responsible for determining the causes of death. Risks associated with the causes of death were determined using Cox proportional hazard models on the TECOS population.
Out of the 14,671 participants in the TECOS, there were a total of 1,084 deaths at the 3-year follow-up. 530 deaths were CV related (49% of total deaths), 338 deaths were non-CV related (31% of total deaths), and 216 deaths were unknown cause (20% of total deaths). Among the CV-related deaths, there were 145 sudden deaths (27% of total CV deaths), 113 acute MI/stroke deaths (21% of total CV deaths), and 63 HF deaths (12% of total CV deaths). Among the non-CV related deaths, malignancy was the most frequent cause resulting in 145 deaths (46% on total non-CV deaths).
In regards to baseline characteristics, it was found that age per 5-year increase (hazard ratio (HR) 1.27; P< 0.0001), history of MI (HR 1.26; P=0.0005), and HbA1c levels per 1 % increase (HR1.23; P=0.0014) resulted in higher risk of all-cause mortality. It was also found that absence of heart failure history (HR 0.59; P< 0.0001), female sex (HR 0.69; P< 0.0001), percutaneous coronary intervention history (HR 0.74; P< 0.0001), and elevated eGFR per log10 higher (HR 0.46; P< 0.0001) resulted in a decreased risk of all-cause mortality. Absence of HF history at baseline resulted in decreased risk of CV-related deaths, including sudden death (HR 0.40; P=0.0036), acute MI/stoke death (HR 0.47; P=0.0486), and HF death (HR 0.29; P=0.0057).
This study demonstrates that among patients with both diabetes and ASCVD, the most common cause of death is sudden CV-related deaths. However, the mechanism behind sudden death is poorly understood and more research is needed. Study results suggest that HF prevention along with other modifiable CV death risks like eGFR preservation, and HbA1c reduction may aid in reducing CV mortality in this population. Limitations of this study include, unattainable cause of death in 20% of participants, lack of ejection fraction availability for the entire study, and the TECOS population may not entirely reflect the general diabetes and ASCVD population.
- The most frequent cause of mortality in patients with diabetes and ASCVD is CV-related deaths, more specifically sudden death.
- Patients with no history of heart failure at baseline had reduced risk of CV-related deaths.
- Targeting modifiable CV risk factors such as HF prevention may reduce CV deaths.
Sharma A, Green JB, Dunning A, et al. Causes of Death in a Contemporary Cohort of Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: Insights From the TECOS Trial. Diabetes Care. 201; 0:1-8.
Graciela Nieto, Pharm. D. Candidate 2018, LECOM School of Pharmacy