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Effective prevention of cardiovascular disease and diabetes-related events with atorvastatin in Japanese elderly patients with type 2 diabetes mellitus: adjusting for treatment changes using a marginal structural proportional hazards model and a rank-preserving structural failure time model.

AbstractAIM:
To assess the preventive effect of atorvastatin on cardiovascular disease and on diabetes-related events in elderly type 2 diabetic patients enrolled in the Japanese Elderly Diabetes Intervention Trial (J-EDIT).
METHODS:
Data were obtained from 1173 patients aged 65-84 years who were enrolled in the J-EDIT. Patients were followed prospectively for 6 years to determine the effects of atorvastatin on serum cholesterol levels, and cardiovascular and diabetes-related events. Because the study protocol allowed atorvastatin to be prescribed according to the clinical needs of each patient, we regarded the J-EDIT data as if they came from a cohort study. We adjusted for clinical characteristics during the study as time-dependent confounders using two methods, inverse-probability-of-treatment (IPT) weighting and g-estimation method.
RESULTS:
The total follow-up period was 5310.8 person-years (5.7 years of median follow up), during which 202 patients received atorvastatin treatment. Atorvastatin was associated with moderate reductions in cholesterol levels: 24.2 mg/dL for total cholesterol, 22.9 mg/dL for low-density lipoprotein (LDL) cholesterol and 24.3 mg/dL for non-high-density lipoprotein cholesterol at the first post-treatment year. As a result, the proportion of patients who achieved targeted levels of LDL cholesterol clearly increased after atorvastatin treatment. Eight patients in 476.6 person-years among atorvastatin-treated and 113 untreated patients in 4721.4 person-years had cardiovascular events (the composite end-point of fatal/non-fatal myocardial infarction, angina pectoris, coronary intervention, and fatal/non-fatal cerebrovascular disease); hazard ratio (HR) = 0.48, 95% confidence interval (CI) = 0.19-1.16, P = 0.10, and HR = 0.32, 95% CI = 0.05-1.87, P = 0.21 from IPT weighting and g-estimation method, respectively. Furthermore, seven in 475.0 person-years among atorvastatin-treated and 149 untreated patients in 4682.4 person-years had diabetes-related events (the composite end-point of sudden death, renal failure death, death as a result of hyperglycemia or hypoglycemia, diabetic gangrene and congestive heart failure in addition to cardiovascular event); HR = 0.30, 95% CI = 0.12-0.77, P = 0.01, and HR = 0.40, 95% CI = 0.09-0.89, P = 0.03 from IPT weighting and g-estimation method, respectively. When cardiovascular events were further differentiated into coronary vascular and cerebrovascular events, atorvastatin especially decreased the cerebrovascular risk.
CONCLUSION:
The use of atorvastatin to lower cholesterol levels in elderly Japanese patients with type 2 diabetes mellitus appears to reduce the risk of cardiovascular and diabetes-related events.
AuthorsTomohiro Shinozaki, Yutaka Matsuyama, Satoshi Iimuro, Hiroyuki Umegaki, Takashi Sakurai, Atsushi Araki, Yasuo Ohashi, Hideki Ito, Japanese Elderly Diabetes Intervention Trial Research Group
JournalGeriatrics & gerontology international (Geriatr Gerontol Int) Vol. 12 Suppl 1 Pg. 88-102 (Apr 2012) ISSN: 1447-0594 [Electronic] Japan
PMID22435944 (Publication Type: Journal Article)
Copyright© 2012 Japan Geriatrics Society.
Chemical References
  • Anticholesteremic Agents
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Pyrroles
  • Atorvastatin
Topics
  • Aged
  • Aged, 80 and over
  • Anticholesteremic Agents (adverse effects, therapeutic use)
  • Atorvastatin
  • Cardiovascular Diseases (etiology, prevention & control)
  • Diabetes Complications (prevention & control)
  • Diabetes Mellitus, Type 2 (blood, complications)
  • Female
  • Heptanoic Acids (adverse effects, therapeutic use)
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors (adverse effects, therapeutic use)
  • Lipids (blood)
  • Male
  • Proportional Hazards Models
  • Pyrroles (adverse effects, therapeutic use)

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