Effects of incretin treatment on cardiovascular outcomes in diabetic STEMI-patients with culprit obstructive and multivessel non obstructive-coronary-stenosis

Abstract

Background: No proper data on prognosis and management of type-2 diabetic ST elevation myocardial infarction (STEMI) patients with culprit obstructive lesion and multivessel non obstructive coronary stenosis (Mv-NOCS) exist. We evaluated the 12-months prognosis of Mv-NOCS-diabetics with first STEMI vs.to non-diabetics, and then Mv-NOCS-diabetics previously treated with incretin based therapy vs. a matched cohort of STEMI-Mv-NOCS never treated with such therapy.

Methods: 1088 Patients with first STEMI and Mv-NOCS were scheduled for the study. Patients included in the study were categorized in type 2 diabetics (n 292) and non-diabetics (n 796). Finally, we categorized diabetics in current-incretin-users (n 76), and never-incretin-users (n 180). The primary end point was all cause deaths, cardiac deaths, and major adverse cardiac events (MACE) at 12 months of follow up.

Results: The study results evidenced higher percentage of all cause deaths (2.2% vs. 1.1%, p value 0.05), cardiac deaths (1.6% vs. 0.5%, p value 0.045), and MACE (12.9% vs. n 5.9%), p value 0.001) in diabetic vs. no diabetic patients at 12 months follow up. Among diabetic patients, the current vs never-incretin-users, did not present a significant difference about all cause of deaths, and cardiac deaths through 12-months. The MACE rate at 1 year was 7.4% in diabetic incretin-users STEMI Mv-NOCS patients vs. 12.9% in diabetic never-incretin-users STEMI-Mv-NOCS patients (p value 0.04). In a risk-adjusted hazard analysis, MACE through 12 months were lower in diabetic STEMI-Mv NOCS incretin-users vs never-incretin-users patients (HR 0.513, CI [0.292-0.899], p 0.021). Consequently, lower levels of glucagon-like peptide 1(GLP-1) were predictive of MACE at follow up (HR 1.528, CI [1.059-2.204], p 0.024).

Conclusion: In type 2 diabetic patients with STEMI-Mv-NOCS, we observed higher incidence of 1-year mortality and adverse cardiovascular outcomes, as compared to non-diabetic STEMI-Mv-NOCS patients. In diabetic patients, never-incretin-users have worse prognosis as compared to current-incretin-users.Trail registration Clinical trial number: NCT03312179, name of registry: clinicaltrialgov, URL: clinicalltrialgov.com, date of registration: September 2017, date of enrollment first participant: September 2009.

Keywords: Non-obstructive coronary stenosis; STEMI; Type 2 diabetes.

Fig. 1

a Kaplan–Meier curve for all cause deaths. In left part all cause deaths cumulative survival curve at 360 days follow up comparing diabetic (green color) vs. non diabetic patients (blue color). In right part all cause deaths cumulative survival curve at 360 days follow up comparing diabetic incretin users (green color) vs. diabetic never-incretin-users patients (blue color). There is a statistical significant higher number of events comparing diabetic vs.non diabetic patients (p value < 0.05). b Kaplan–Meier curve for cardiac deaths. Kaplan–Meier curve for cardiac deaths. In left part all cause deaths cumulative survival curve at 360 days follow up comparing diabetic (green color) vs. non diabetic patients (blue color). In right part all cause deaths cumulative survival curve at 360 days follow up comparing diabetic incretin users (green color) vs. diabetic never-incretin-users patients (blue color). There is a statistical significant higher number of events comparing diabetic vs.non diabetic patients (p value < 0.05)

Fig. 2

a Kaplan–Meier curve for major adverse cardiac events (MACE). Kaplan–Meier curve for major adverse cardiac events (MACE). In left part MACE cumulative survival curve at 360 days follow up comparing diabetic (green color) vs. non diabetic patients (blue color). In right part MACE cumulative survival curve at 360 days follow up comparing diabetic incretin users (green color) vs. diabetic never-incretin-users patients (blue color). There is a statistical significant higher number of events comparing diabetic vs.non diabetic patients, and incretin-users vs. never-incretin-users (p value < 0.05). b Major adverse cardiac events (MACE) outcome at 1-year follow-up stratified by GLP-1 terziles. After breakfast, blood samples for the measurement of GLP-1 were obtained every 30 min over a 2-h period. The mean of the four GLP-1 evaluations was defined as the postprandial GLP-1 value. Diabetic patients are divided by GLP-1 values in three subgroup: I terzile with GLP-1 values < 20.3 ng/ml; II terzile with GLP-1 values between 20.4 and 23.6 ng/ml; III terzile with GLP-1 values > 23.6 ng/ml. Major number of MACE are associated to I GLP-1 terzile. I GLP-1 terzile is statistical significant higher vs. II and III GLP-1 terzile (respectively marked with symbol *, and ǂ)