Factors associated with stroke, myocardial infarction, ischemic heart disease, unstable angina, or mortality in patients from real world clinical practice with newly-diagnosed type 2 diabetes and early glycemic control

Abstract

Objectives: The objective of this study was to identify factors associated with stroke, myocardial infarction (MI), all-cause mortality, or a diagnosis of ischemic heart disease (IHD) or unstable angina (UA), among patients newly-diagnosed with type 2 diabetes (T2DM) with no recent history of cardiovascular (CV) events who rapidly achieve and maintain HbA_1c ≤8.0%.

Methods: Data were obtained from the Clinical Practice Research Datalink (CPRD) from January 1990 to December 2012. A nested case-control design was used with Cox proportional hazards analysis. Cases were identified by the first occurrence of stroke, MI, IHD, UA, or death within 5 years after HbA_1c ≤ 8.0% was first reached (index date) following T2DM diagnosis. Controls were selected using a risk-set sampling approach and were matched 4:1 to cases using index date, exposure time, age, gender, and HbA_1c at index date.

Results: A total of 11,426 T2DM patients met the inclusion criteria for cases. Of these, 5,261 experienced a CV event. Stroke was the most frequent CV event (40%), followed by IHD (29%), MI (22%), and UA (9%). Mean HbA1c ≥7.0% over the length of exposure (vs 6.5 to <7.0%) was associated with an increased risk of stroke, MI, and IHD. The use of anti-platelet medications at baseline was also associated with increased risk of stroke (HR = 1.82 [CI = 1.60–2.06]), MI (HR = 1.67 [CI = 1.38–2.03]), and IHD (HR = 1.85 [CI = 1.57–2.17]). Mean HbA1c < 6.0% was associated with increased risk of stroke (HR = 1.29 [CI = 1.02–1.63]) and IHD (HR = 1.65 [CI = 1.25–2.19]). Use of nitrate medications at baseline was associated with increased risk of MI (HR = 2.83 [CI = 2.24–3.57]), IHD (HR = 4.32 [CI = 3.57–5.22]), and UA (HR = 10.38 [CI = 7.67–14.03]).

Conclusions: Early and sustained HbA_1c control between 6.5 and <7.0% appears to be an important modifiable factor that helps reduce CV risk in patients with newly-diagnosed T2DM in real-world clinical practice.

Keywords:

• Cardiovascular events
• stroke
• myocardial infarction
• ischemic heart disease
• unstable angina
• mortality
• type 2 diabetes
• glycemic control
• real-world evidence

Transparency

Declaration of funding

This study was funded by Eli Lilly and Company.

Declaration of financial/other relationships

All authors were employed by Eli Lilly and Company at the time of manuscript development. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. CMRO peer reviewers on this manuscript have no relevant financial relationships to disclose.

BMI, Body Mass Index; CCI, Charlson Comorbidity Index; ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker.

Acknowledgments

No assistance in the preparation of this article is to be declared.