title: Risk factors for cardiovascular events in Japanese patients treated with fluvastatin from the long-term event monitoring (LEM) study.
abstract: OBJECTIVE
  The long-term event monitoring (LEM) study evaluated the lipid-lowering efficacy and safety of fluvastatin in Japanese patients with hypercholesterolemia. The present sub-analysis focused on the impact of risk factors on event prevention.
  
  
  METHODS
  In the LEM study, patients (n=21,139) who started fluvastatin between 2000/4/1 and 2002/3/31 in Japan were prospectively registered and followed up for 3 years (secondary prevention cohort) or 5 years (primary prevention cohort).
  
  
  RESULTS
  Of the patients registered, 19,084 were included in this sub-analysis. The secondary prevention group, demonstrated 8.27- and 2.89-fold higher incidence in cardiac events and cerebral events, respectively compared with the primary prevention group (P < 0.001). Complications of cerebrovascular disease demonstrated a 2.22- and 5.29-fold higher incidence in cardiac events and cerebral events (P < 0.01 and P < 0.001, respectively). Presence of diabetes mellitus (DM) in patients without complication significantly increased the incidence in both cardiac events (2.37) and cerebral events (2.15) as compared with non-DM patients for primary prevention (P < 0.001 and P < 0.01, respectively). For the secondary prevention, DM patients with complication of cardiac disease showed a significantly higher incidence in both cardiac events (1.59) and cerebral events (3.79) compared with non-DM patients (P < 0.05 and P < 0.01, respectively). In contrast, DM patients with complications of cerebrovascular disease showed a significantly higher incidence in cerebral events (2.58, P < 0.05), but not cardiac events compared with non-DM patients. Similarly, the presence of hypertension significantly increased the incidence in both cardiac (1.64) and cerebral events (1.81) for primary prevention (P < 0.01 and P < 0.05, respectively). For secondary prevention, hypertension in patients with complication of cardiac or cerebrovascular disease did not affect incidence in both cardiac and cerebral events. In the patients without complication, high triglycerides and low high density lipoprotein cholesterol (HDL-C), but not low density lipoprotein cholesterol (LDL-C), increased cerebral events, while only LDL-C significantly increased cardiac events. For secondary prevention, high triglycerides or low HDL-C, but not LDL-C, significantly increased the relative risk of cardiac events in the patients with complication of cardiac disease.
  
  
  CONCLUSIONS
  The LEM study, a large-scale prospective study of long-term fluvastatin treatment for hypercholesterolemia in Japanese patients, demonstrated high impact of complications such as DM and hypertension as well as high triglycerides or low HDL-C on cardiac and cerebral events. After long-term statin treatment, the control of other factors rather than LDL-C alone might be important to avoid vascular events.
authors.affiliation: Department of Clinical Gene Therapy, Osaka University, Graduate School of Medicine, Yamada-oka, Suita, Osaka, Japan. morishit@cgt.med.osaka-u.ac.jp
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Itakura
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nakaya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Masato
authors.initials: M
authors.lastname: Odawara
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Ichihara
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Mizuno
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000517:prevention & control; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000503:physiopathology; D016903:Drug Monitoring; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D006973:Hypertension / Q000150:complications; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D011322:Primary Prevention / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors; D055502:Secondary Prevention / Q000379:methods; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D000077340:Fluvastatin