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Early Lopid Treatment Reduces Heart Mortality

Administering Lopid (gemfibrozil) early significantly reduces death associated with coronary heart disease (CHD), according to an 18-year follow-up study.

The Helsinki Heart Study followed 4,081 men with dyslipidemia who received early treatment with Lopid. The original double-blind study lasted five years. After this, the researchers advised participants of their treatment group and invited them to start (or continue) treatment with gemfibrozil at no cost through 1995. About two-thirds of study participants in the treatment and control groups chose gemfibrozil therapy.

The follow-up study was published in Archives of Internal Medicine and reported by MedPage Today on April 10.

The most significant reduction in cardiac deaths occurred among participants aged 40-47 years and in a subgroup of overweight participants (BMI = 27.5) whose lipid disorder was associated with the metabolic syndrome.

Clinical Trial

The study by Leena Tenkanen, PhD, of Tampere University in Tampere, Finland, and colleagues followed participants from the original gemfibrozil and placebo groups of the Helsinki Heart Study over 18 years. Its aim was to analyze the effects of a five-year earlier start of gemfibrozil treatment on all-cause, CHD and cancer mortality.

Results showed that early treatment with Lopid was associated with lower mortality: data analysis in the year 2000 revealed that, by 1995, participants in the original Lopid treatment group had a 32% lower relative risk of CHD mortality, compared with the original placebo group.

This reduced mortality-risk decreased over time, with relative risk dropping to 23% lower by the year 2000.

Younger age also influenced the outcome: by 1995, men aged 40-47 years at the study’s outset had a 42% lower relative risk of CHD if they received Lopid treatment, compared with those in the control group. However, this difference was only 24% among men aged 48-57 years. At the 18-year follow-up point, the difference between treatment and control groups for CHD mortality was 31% and 17%, respectively.

No significant differences occurred for all-cause and cancer mortality.

Benefits for Subgroup

Lopid treatment was of greatest benefit to participants with high BMIs (=27.5) and triglycerides (184 mg/dL). Within this group, men who received Lopid had a 71% reduced relative risk of CHD mortality and a 33% reduced risk of all-cause mortality, compared with the placebo.

Additionally, for participants with low high-density lipoprotein-cholesterol levels at baseline, early treatment also showed benefits.

Dr Tenkanen noted that recent reports that Lopid is most effective in people who have insulin resistance suggest that, although the Helsinki study did not measure this parameter, BMI may play a significant role in the metabolic syndrome.

Study Limitations

Dr Tenkanen commented that the study was limited by the lack of a placebo group after the initial five-year double-blind phase. Moreover, after 1995 the researchers had no information on the participants’ medications, but they assumed consistency in treatment choice between the study groups.

The researchers concluded that, “the long-term follow-up of mortality in Helsinki Heart Study treatment groups revealed significantly reduced CHD mortality among subjects who started gemfibrozil therapy at age 40 to 47 years than among those who started the treatment 5 years later at age 48 to 57 years.”

They also noted that participants with dyslipidemia related to the metabolic syndrome particularly benefited from starting treatment earlier, in terms of significantly reduced CHD and all-cause mortality.

Editorial Comments

In an editorial published in the same issue of the Archives of Internal Medicine, Hanna Bloomfield, MD, of the Minneapolis VA Medical Center, compared the relative roles of fibrates and statins. "The fibrates may be down," she wrote, "but they are not yet out."

Dr Bloomfield noted that fibrates are undergoing “a resurgence of interest” in a world currently dominated by statins, for four main reasons:.

1) The publication of the Department of Veterans Affairs HDL Intervention Trial (VA-HIT) in 1999. This trial focused fibrates’ ability to raise HDL-C levels and lower triglyceride levels, showing for the first time that raising HDL-C levels and lowering triglyceride levels – without lowering LDL-C levels – resulted in significantly reduced major cardiovascular events.
2) The discovery in the mid-1990s that fibrates are ligands for peroxisome proliferator-activated receptors (PPARs), which regulate expression of genes involved in glucose and lipid metabolism, inflammation and endothelial function.
3) The growing awareness that statins prevent only about 20-30% of cardiac events, stirring interest in whether combination therapy with statins and fibrates may further reduce CHD morbidity and mortality.
4) The near-epidemic rise in obesity, diabetes and metabolic syndrome worldwide – conditions associated with lipid profiles for which fibrate therapy might be ideal.

Another factor is cost. According to Dr Bloomfield, "gemfibrozil is a very reasonable and less expensive alternative to statins.”

However, evidence for the superiority of statins is greater because of the larger number of patients who have been studied using statin therapy, and the fact that Lopid has not been shown to have as strong an effect on all-cause mortality.


  • Early Fibrate Therapy Found to Cut Heart Mortality, MedPage Today, April 10, 2006.
  • Gemfibrozil in the Treatment of Dyslipidemia. Leena Tenkanen, et al., Archives of Internal Medicine, volume 166, pages 743-748, 2006.
  • The Role of Fibrates in a Statin World. Hanna E Bloomfield, Archives of Internal Medicine, volume 166, pages 715-716, 2006.

Posted: April 2006