Long-term outcomes of statin dose, class, and use intensity on primary prevention of cardiovascular mortality: a national T2DM cohort study

Eur J Clin Pharmacol. 2023 May;79(5):687-700. doi: 10.1007/s00228-023-03488-2. Epub 2023 Apr 3.

Abstract

Purpose: To investigate how statins reduce cardiovascular mortality in patients with type 2 diabetes (T2DM) in a dose-, class-, and use intensity-dependent manner.

Methods: We used an inverse probability of treatment-weighted Cox hazards model, with statin use status as a time-dependent variable, to estimate the effects of statin use on cardiovascular mortality.

Results: Adjusted hazard ratio [aHR; 95% confidence interval (CI)] for cardiovascular mortality was 0.41 (0.39-0.42). Compared with nonusers, pitavastatin, pravastatin, simvastatin, rosuvastatin, atorvastatin, fluvastatin, and lovastatin users demonstrated significant reductions in cardiovascular mortality [aHRs (95% CIs) = 0.11 (0.06, 0.22), 0.35 (0.32, 0.39), 0.36 (0.34, 0.38), 0.39 (0.36, 0.41), 0.42 (0.40, 0.44), 0.46 (0.43, 0.49), and 0.52 (0.48, 0.56), respectively]. In Q1, Q2, Q3, and Q4 of cDDD-year, our multivariate analysis demonstrated significant reductions in cardiovascular mortality [aHRs (95% CIs) = 0.63 (0.6, 0.65), 0.44 (0.42, 0.46), 0.33 (0.31, 0.35), and 0.17 (0.16, 0.19), respectively; P for trend < 0.0001]. The optimal statin dose daily was 0.86 DDD, with the lowest aHR for cardiovascular mortality of 0.43.

Conclusions: Persistent statin use can reduce cardiovascular mortality in patients with T2DM; in particular, the higher is the cDDD-year of statin, the lower is the cardiovascular mortality. The optimal statin dose daily was 0.86 DDD. The priority of protective effects on mortality are pitavastatin, rosuvastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, and lovastatin for the statin users compared with non-statin users.

Keywords: Class of statin; Dose-dependent; Mortality; Statin; T2DM.

MeSH terms

  • Atorvastatin / therapeutic use
  • Cardiovascular Diseases* / drug therapy
  • Cohort Studies
  • Diabetes Mellitus, Type 2* / drug therapy
  • Fluvastatin / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Lovastatin / therapeutic use
  • Pravastatin / adverse effects
  • Primary Prevention
  • Rosuvastatin Calcium / therapeutic use
  • Simvastatin / adverse effects

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Atorvastatin
  • Rosuvastatin Calcium
  • Pravastatin
  • Fluvastatin
  • Simvastatin
  • Lovastatin