Comparative effectiveness and safety of antiplatelet drugs in patients with diabetes mellitus and acute coronary syndrome

Pharmacoepidemiol Drug Saf. 2018 Dec;27(12):1361-1370. doi: 10.1002/pds.4668. Epub 2018 Oct 31.

Abstract

Purpose: Comparative outcomes of treatment with antiplatelet drugs in patients with acute coronary syndrome (ACS) and co-morbid diabetes mellitus (DM) are not well studied.

Methods: We performed a cohort study using US commercial claims data (2009-2015) and conducted the following pairwise comparisons in ACS patients with DM: prasugrel vs clopidogrel, ticagrelor vs clopidogrel, and prasugrel vs ticagrelor. Outcomes of interest included (1) a composite effectiveness endpoint including myocardial infarction, ischemic stroke, or inpatient mortality; (2) a composite safety endpoint including major bleeding events requiring hospitalization; and (3) pneumonia hospitalizations as a negative control endpoint. We used calendar time-specific propensity score matching to account for confounding and applied Cox proportional hazard models to calculate hazard ratios (HR) with 95% confidence intervals (CI).

Results: Comparative risk of the effectiveness endpoint was lower among prasugrel initiators compared to clopidogrel initiators (HR 0.82, 95% CI 0.68-0.99, N = 7011 matched pairs), but no different between ticagrelor and clopidogrel (HR 1.02, 95% CI 0.76-1.37, N = 3013 pairs) or prasugrel and ticagrelor (HR 0.83, 95% CI 0.58-1.18, N = 2207 pairs). Bleeding risk was higher among prasugrel initiators when compared to clopidogrel initiators within the first month of treatment (HR 1.85, 95% CI 1.03-3.35); no other comparison indicated any difference. No differences in the negative control outcomes were noted after PS matching for all comparisons, indicating adequate confounding control.

Conclusions: Prasugrel was associated with superior cardiovascular outcomes and a higher risk of short-term bleeding compared to clopidogrel in patients with ACS and DM. Comparative outcomes were similar between ticagrelor and clopidogrel or prasugrel and ticagrelor.

Keywords: clopidogrel; diabetes; pharmacoepidemiology; prasugrel; ticagrelor.

MeSH terms

  • Acute Coronary Syndrome / complications
  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / epidemiology
  • Aged
  • Clopidogrel / administration & dosage
  • Clopidogrel / adverse effects
  • Cohort Studies
  • Comorbidity
  • Comparative Effectiveness Research*
  • Diabetes Mellitus / epidemiology*
  • Female
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Hemorrhage / therapy
  • Hospital Mortality
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / etiology
  • Myocardial Infarction / prevention & control
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Prasugrel Hydrochloride / administration & dosage
  • Prasugrel Hydrochloride / adverse effects
  • Stroke / epidemiology
  • Stroke / etiology
  • Stroke / prevention & control
  • Ticagrelor / administration & dosage
  • Ticagrelor / adverse effects
  • Treatment Outcome
  • United States / epidemiology

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticagrelor