title: Long-term effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria:Ten years of follow-up of Prevention of Renal and Vascular End-stage Disease Intervention Trial (PREVEND IT).
abstract: BACKGROUND
  The PREVEND IT investigated whether treatment targeted at lowering urinary albumin excretion (UAE) would reduce adverse cardiovascular events. We obtained extended follow-up data to approximately 10 years to investigate the long-term effects of fosinopril 20 mg and pravastatin 40 mg on cardiovascular outcomes in subjects with UAE >15 mg per 24 hours.
  
  
  METHODS
  The original PREVEND IT consisted of 864 participants and 839 survivors after 4 years. For every survivor, the primary end point determined by the combined incidence of cardiovascular mortality and hospitalization for cardiovascular morbidity was registered in several national databases and electronic hospital systems.
  
  
  RESULTS
  Mean total follow-up of the extended PREVEND IT was 9.5 years (range 9.4-10.7 years). Four years of treatment with fosinopril was not associated with a reduction in the primary end point compared with placebo (hazard ratio 0.87, 95% CI 0.61-1.24 [P = .42]) during long-term follow-up. After 9.5 years, subjects with a baseline UAE in the upper quintile (>50 mg/24 hours) had a total event rate of 29.5% and were at a higher risk for developing cardiovascular disease compared with less UAE (hazard ratio 2.03, 95% CI 1.38-2.97 [P ≤ .01]). In addition, 4 years of fosinopril treatment resulted in a risk reduction of 45% (95% CI 6%-75% [P = .04]) in this group compared with placebo. Subjects originally assigned to pravastatin had no overall risk reduction in the primary end point (P = .99).
  
  
  CONCLUSIONS
  Elevated UAE is associated with increased cardiovascular mortality and morbidity after 9.5 years of follow-up, with a doubling of the risk if the UAE is >50 mg per 24 hours. In this group, the benefits of 4-year treatment with fosinopril were sustained during posttrial follow-up for cardiovascular mortality and morbidity. We propose that UAE be used to estimate risk in the general population and that large clinical trials be designed to confirm the hypothesis that angiotensin-converting enzyme-inhibitor treatment may be beneficial in patients with mildly elevated UAE despite the absence of other comorbidities.
authors.affiliation: Department of Cardiology, Thoraxcenter, Universitair Medical Center Groningen, University of Groningen, The Netherlands. f.p.j.brouwers@thorax.umcg.nl
authors.forename: Frank P
authors.initials: FP
authors.lastname: Brouwers
authors.forename: Folkert W
authors.initials: FW
authors.lastname: Asselbergs
authors.forename: Hans L
authors.initials: HL
authors.lastname: Hillege
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Wiek H
authors.initials: WH
authors.lastname: van Gilst
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D017328:Fosinopril / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin; D017328:Fosinopril