Gemfibrozil in the Treatment of Dyslipidemia: An 18-Year Mortality Follow-up of the Helsinki Heart Study | Cardiology | JAMA Internal Medicine | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Frick  MHElo  OHaapa  K  et al.  Helsinki Heart Study: primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia; safety of treatment, changes in risk factors, and incidence of coronary heart disease.  N Engl J Med 1987;3171237- 1245PubMedGoogle ScholarCrossref
Manninen  VElo  OFrick  MH  et al.  Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study.  JAMA 1988;260641- 651PubMedGoogle ScholarCrossref
Heinonen  OPHuttunen  JKManninen  V  et al.  The Helsinki Heart Study: coronary heart disease incidence during an extended follow-up.  J Intern Med 1994;23541- 49PubMedGoogle ScholarCrossref
Huttunen  JKHeinonen  OPManninen  V  et al.  The Helsinki Heart Study: an 8.5 year safety and mortality follow-up.  J Intern Med 1994;23531- 39PubMedGoogle ScholarCrossref
Manninen  VTenkanen  LKoskinen  P  et al.  Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study.  Circulation 1992;8537- 45PubMedGoogle ScholarCrossref
Tenkanen  LMänttäri  MManninen  V Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil: experience from the Helsinki Heart Study.  Circulation 1995;921779- 1785PubMedGoogle ScholarCrossref
Robins  SJRubins  HBFaas  FH  et al.  Insulin resistance and cardiovascular events with low HDL cholesterol: the Veterans Affairs HDL Intervention Trial (VA-HIT).  Diabetes Care 2003;261513- 1517PubMedGoogle ScholarCrossref
Mäenpää  HManninen  VHeinonen  OP Compliance with medication in the Helsinki Heart Study.  Eur J Clin Pharmacol 1992;4215- 19PubMedGoogle ScholarCrossref
Mähönen  MSalomaa  VTorppa  J  et al.  The validity of the routine mortality statistics on coronary heart disease in Finland: comparison with the FINMONICA MI register data for the years 1983-1992: Finnish multinational MONItoring of trends and determinants in CArdiovascular disease.  J Clin Epidemiol 1999;52157- 166PubMedGoogle ScholarCrossref
Pietilä  KTenkanen  LMänttäri  MManninen  V How to define coronary heart disease in register-based follow-up studies: experience from the Helsinki Heart Study.  Ann Med 1997;29253- 259PubMedGoogle ScholarCrossref
Grundy  SMBrewer  HB  JrCleeman  JISmith  SC  JrLenfant  C Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition.  Circulation 2004;109433- 438PubMedGoogle ScholarCrossref
Sane  TKnudsen  PVuorinen-Markkola  HYki-Järvinen  HTaskinen  MR Decreasing triglycerides by gemfibrozil therapy does not affect the glucoregulatory or antilipolytic effect of insulin in nondiabetic subjects with mild hypertriglyceridemia.  Metabolism 1995;44589- 596PubMedGoogle ScholarCrossref
Asplund-Carlson  A Effects of gemfibrozil therapy on glucose tolerance, insulin sensitivity and plasma plasminogen activator inhibitor activity in hypertriglyceridaemia.  J Cardiovasc Risk 1996;3385- 390PubMedGoogle ScholarCrossref
Jeng  CYSheu  WHFuh  MMShich  SMChen  YDReaven  GM Gemfibrozil treatment of endogenous hypertriglyceridemia: effect on insulin-mediated glucose disposal and plasma insulin concentrations.  J Clin Endocrinol Metab 1996;812550- 2553PubMedGoogle Scholar
Avogaro  ABeltramello  PMarin  R  et al.  Insulin action and glucose metabolism are improved by gemfibrozil treatment in hypertriglyceridemic patients.  Atherosclerosis 1995;113117- 124PubMedGoogle ScholarCrossref
Jeng  JRJeng  CYSheu  WHLee  MMHuang  SHShich  SM Gemfibrozil treatment of hypertriglyceridemia: improvement on fibrinolysis without change of insulin resistance.  Am Heart J 1997;134565- 571PubMedGoogle ScholarCrossref
Nordt  TKLutzi  SRuef  J  et al.  Attenuation by fibrates of plasminogen activator inhibitor type-1 expression in human arterial smooth muscle cells.  Thromb Haemost 2001;861305- 1313PubMedGoogle Scholar
Rubins  HBRobins  SJCollins  D  et al.  Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT).  Arch Intern Med 2002;1622597- 2604PubMedGoogle ScholarCrossref
Staels  BDallongeville  JAuwerx  JSchoonjans  KLeitersdorf  EFruchart  JC Mechanism of action of fibrates on lipid and lipoprotein metabolism.  Circulation 1998;982088- 2093PubMedGoogle ScholarCrossref
Neve  BPCorseaux  DChinetti  G  et al.  PPARalpha agonists inhibit tissue factor expression in human monocytes and acrophages.  Circulation 2001;103207- 212PubMedGoogle ScholarCrossref
Stary  HC Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults.  Arteriosclerosis 1989;9 ((1)(suppl)) I19- I32PubMedGoogle Scholar
Hsing  AWGao  YTChua  S  JrDeng  JStanczyk  FZ Insulin resistance and prostate cancer risk.  J Natl Cancer Inst 2003;9567- 71PubMedGoogle ScholarCrossref
Colangelo  LAGapstur  SMGann  PHDyer  ARLiu  K Colorectal cancer mortality and factors related to the insulin resistance syndrome.  Cancer Epidemiol Biomarkers Prev 2002;11385- 391PubMedGoogle Scholar
Original Investigation
April 10, 2006

Gemfibrozil in the Treatment of Dyslipidemia: An 18-Year Mortality Follow-up of the Helsinki Heart Study

Author Affiliations

Author Affiliations: Helsinki Heart Study, Helsinki, Finland (Drs Tenkanen, Mänttäri, and Manninen and Ms Virkkunen); School of Public Health, Tampere University, Tampere, Finland (Dr Tenkanen and Ms Virkkunen); Helsinki University Jorvi Hospital, Espoo, Finland (Dr Mänttäri); Helsinki University Central Hospital, Helsinki (Dr Manninen); and Wihuri Research Institute, Helsinki (Drs Mänttäri and Kovanen).

Arch Intern Med. 2006;166(7):743-748. doi:10.1001/archinte.166.7.743

Background  The Helsinki Heart Study was a double-blind, placebo-controlled primary prevention trial among 4081 dyslipidemic middle-aged men to test the efficacy of gemfibrozil in the prevention of coronary heart disease (CHD). After the 5-year trial, the participants were notified of their treatment group and invited to continue or start gemfibrozil therapy free of charge through 1995. Approximately two thirds of participants in both groups chose gemfibrozil therapy. In this 18-year follow-up through 2000, we compared the CHD, cancer, and all-cause mortality among subjects in the original gemfibrozil (OG) group (n = 2046) with those in the original placebo (OP) group (n = 2035).

Methods  To provide an overview of the absolute risks in the 2 treatment groups as well as risk differences between them, we calculated crude mortality rates and presented Kaplan-Meier plots of survival with log-rank tests. We also estimated the relative risks (RRs) using Cox proportional hazards models with and without covariates.

Results  During the follow-up until 1995, subjects in the OG group had a 32% lower RR of CHD mortality (P = .03) compared with those in the OP group, and when followed up until 2000, the RR was 23% lower (P = .05). Overall, there were no differences in all-cause or cancer mortality. However, those in the OG group with both body mass index and triglyceride level in the highest tertiles had a 71% lower RR of CHD mortality (P<.001), a 33% lower RR of all-cause mortality (P = .03), and a 36% lower RR of cancer mortality (P = .22) compared with those in the OP group.

Conclusion  Long-term mortality follow-up showed that patients with dyslipidemia benefited from beginning treatment with gemfibrozil early, especially if their dyslipidemia entailed factors related to the metabolic syndrome.