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Risk Of Mortality In Patients with Type 2 and Prior CV Event

New study finds that adults with type 2 diabetes and atherosclerotic cardiovascular disease have increased risk of mortality with a prior nonfatal cardiovascular (CV) event.

The objective of the new study was to evaluate specific causes of death and their associated risk factors in a contemporary cohort of patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD).

The data used was from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study. TECOS was a double blind, multinational, placebo-controlled CV safety study that evaluated the long-term effect of adding sitagliptin to usual care in patients with type 2 diabetes and ASCVD.

Of the 14,671 patients in the TECOS intention-to-treat population, 1,084 died during a median follow-up period of 3 years. There were 530 CV deaths (49% of all deaths), 338 non-CV deaths (31% of all deaths), and 216 unknown deaths (20% of all deaths). The largest subcategory was sudden deaths, followed by acute myocardial infarction (MI)/stroke and heart failure. Among the non-CV causes of death, malignancy was the most common.

Out of all the categories of CV death, patients who died of sudden death had the youngest median age (67 years), had an HbA1c ≥ 7.5%, and were most likely to use insulin. The patients who died from heart failure had the oldest median age (70 years), longest median duration of diabetes (13.0 years), lowest median eGFR (60 mL/min/1.73 m2), and highest prevalence of CAD. The patients who died as a result of malignancy were more likely to be male, mostly white and least likely to have an HbA1c ≥ 7.5% and had the highest median BMI (29.5 kg/m2).

More patients who died from a CV cause experienced a nonfatal CV event (17%) than those who died from a non-CV death (13%) or an unknown cause (9%). The risk for all-cause death was increased with baseline age (per 5-year increase, P< 0.0001), prior MI (P=0.0005) and increased HbA1c (per 1% increase, p=0.0014). The risk for all-cause death was reduced with baseline absence of heart failure (P<0.0001), female sex (P<0.0001), history of percutaneous coronary intervention (P<0.0001) and higher eGFR (P<0.0001). Lastly, absence of prior heart failure was associated with reduced risks of sudden death (P=0.0036), heart failure (P=0.0057) and acute MI/stroke (P=0.0486).

Overall, the analysis of the data from the study showed that older patients with type 2 diabetes and ASCVD suffered from sudden death, which was the most common cause of CV mortality. These patients were usually relatively younger with less-well-controlled glycemia. The study does note that given the sizeable burden of deaths from malignancy, deaths attributable to unknown causes may not primarily be CV causes, thus there should be caution when combining CV and unknown causes of death in clinical mortality data.

This study did have some limitations such as an adjudicated cause of death not obtainable in 20% of patients. The population enrolled in TECOS may not reflect the overall diabetes population, so the results may not be directly generalizable. The strengths of this study were the large sample size and the independent blinded adjudication processes1.

In a previous study, researchers evaluated risk of CV death in all Examination of Cardiovascular Outcomes With Alogliptin vs. Standard Care (EXAMINE) study participants and those that experienced a major nonfatal CV event. The first nonfatal CV event was MI in 316 patients (5.9%), hospitalization for heart failure in 159 (3.0%), nonfatal stroke in 57 (1.1%) and hospitalization for unstable angina in 204 (3.8%) during a median follow up of 18.8 months. About 4,4644 patients did not experience any major nonfatal CV events, 233 of these patients died with 172 of CV causes. Compared to those who had not experienced a nonfatal CV event, risk of death increased significantly after MI, hospitalization for heart failure, stroke and unstable angina. In this study, although development of heart failure was lower than MI, the rate of death was much higher in patients with hospitalization for heart failure 2.

Overall, more preventative measures should be taken in patients with type 2 diabetes and high CV risks.

Practice Pearls:

  • The most common CV death was sudden death, followed by acute MI/stroke and heart failure.
  • Patients with no prior heart failure had reduced risks for sudden death, heart failure and acute MI/stroke.
  • Patients with type 2 diabetes who had ASCVD and who experienced sudden death all had similar profiles such as being relatively younger and having less-well-controlled glycemia.

References:

Sharma 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. 2017; doi: 10.2337/dc17-1091.

White, WB, et al. Cardiovascular mortality in patients with type 2 diabetes and recent acute coronary syndromes from the EXAMINE trial. Diabetes Care. 2017 Jul; 39(7): 1267-1273.

Jessica Quach, Doctor of Pharmacy Candidate 2018, GA-PCOM School of Pharmacy