Effects of fibrates on cardiovascular outcomes
Fibrates can reduce the risk of major cardiovascular events, with one of the primary mechanisms thought to be through the prevention of coronary heart disease...
Title: Effects of fibrates on cardiovascular outcomes: A systematic review and meta-analysis
Authors: M Jun, C Foote, J Lu, B Neal, et al.
Reference: Lancet 2010; 375(9729): 1875-84
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2960656-3/abstract
Reviewer: Robert Goldberg, PhD, Contributing editor, ProCor; Professor of Medicine and Epidemiology, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Reviewer comments: Fibrate therapy has been used for the management of persons with elevated serum lipid levels for several decades. While statin therapy is presently the primary medication choice for lowering serum lipids in both healthy individuals and in those with underlying cardiovascular disease (CVD), fibrate therapy has been shown to be effective in raising serum HDL cholesterol levels, lowering serum concentrations of triglycerides, and possibly reducing LDL cholesterol levels. The prior literature which has examined the effectiveness of fibrate therapy on CVD related outcomes has been mixed as some studies have shown a benefit of fibrate therapy, whereas others have not, on the development of CVD.
The results of the present summary overview suggest that fibrates can reduce the risk of major CVD events, with one of the primary mechanisms thought to be through the prevention of CHD. These medications may also have fewer side effects than other lipid lowering therapies, including statins, and appear to be safe and well tolerated by patients taking this medication. While statins have been shown to have a multiplicity of beneficial effects, and are very effective in reducing serum lipid levels, consideration should also be given to the use of fibrates in at risk individuals with hyperlipidemia, based on the information nicely summarized in this recent overview.
Purpose of study: To carry out a meta-analysis and systematic review of the effects of fibrate therapy on the development of various CVD related outcomes.
Location of study: Sydney, Australia
Study design: Meta analysis
Results: The authors carried out a systematic search of the published literature between 1950 and 2010 for purposes of identifying any published RCTs that had examined the effects of fibrate therapy on various CVD outcomes. As a result of the authors' exhaustive search, a total of 18 RCTs were identified which satisfied the investigators pre-defined inclusion criteria.
These wide ranging trials included less than 100 to more than 10,000 participants. A total of 45,058 patients were included in the 18 trials identified in whom the annual major CVD event rates ranged from 1.2% to 3.3% while the annual frequency of all coronary events ranged from 0.4% to 5.2%. The characteristics of men and women enrolled in these trials varied widely as did their levels of serum cholesterol and additional comorbidities. The average age of study participants ranged from 46 to 68 years, only men were included in eight trials, secondary prevention was the goal in 11 published studies, primary prevention of CVD was the principal objective of four trials, and the remainder of the trials included patients with and without a history of CVD such that efforts of primary and secondary prevention could be examined in these latter studies.
Across the studies reviewed, fibrate therapy was associated with a 10% reduction in the risk of major CVD events compared to individuals who were treated with placebo. In examining the relation between fibrate therapy and coronary events, fibrate therapy was associated with a 13% reduced risk of coronary events.
In examining the association between fibrate therapy and specific CVD endpoints, there was no evidence that fibrate therapy was associated with a reduced risk of stroke (-3%: 95% CI - 1.6 to +9%), CVD mortality (+3% (-7% to +12%), sudden cardiac death (+11%; -6% to 26%), or nonvascular related mortality (-10% (-21% to +1%). Fibrate therapy was also not significantly associated with all-cause mortality (0% (-8% to +7%) but it was associated with a reduced risk of albuminuria progression or diabetic retinopathy in a limited number of trials that examined these latter endpoints.
Several adverse outcomes were not significantly associated with the use of fibrate therapy in these published trials, although increases in serum creatinine concentrations were observed in association with the use of fibrate therapy, suggesting possible caution in the use of this medication in patients with chronic kidney disease, or at increased risk for chronic kidney disease.
Title: Effects of fibrates on cardiovascular outcomes: A systematic review and meta-analysis
Authors: M Jun, C Foote, J Lu, B Neal, et al.
Reference: Lancet 2010; 375(9729): 1875-84
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2960656-3/abstract
Reviewer: Robert Goldberg, PhD, Contributing editor, ProCor; Professor of Medicine and Epidemiology, Division of Cardiovascular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Reviewer comments: Fibrate therapy has been used for the management of persons with elevated serum lipid levels for several decades. While statin therapy is presently the primary medication choice for lowering serum lipids in both healthy individuals and in those with underlying cardiovascular disease (CVD), fibrate therapy has been shown to be effective in raising serum HDL cholesterol levels, lowering serum concentrations of triglycerides, and possibly reducing LDL cholesterol levels. The prior literature which has examined the effectiveness of fibrate therapy on CVD related outcomes has been mixed as some studies have shown a benefit of fibrate therapy, whereas others have not, on the development of CVD.
The results of the present summary overview suggest that fibrates can reduce the risk of major CVD events, with one of the primary mechanisms thought to be through the prevention of CHD. These medications may also have fewer side effects than other lipid lowering therapies, including statins, and appear to be safe and well tolerated by patients taking this medication. While statins have been shown to have a multiplicity of beneficial effects, and are very effective in reducing serum lipid levels, consideration should also be given to the use of fibrates in at risk individuals with hyperlipidemia, based on the information nicely summarized in this recent overview.
Purpose of study: To carry out a meta-analysis and systematic review of the effects of fibrate therapy on the development of various CVD related outcomes.
Location of study: Sydney, Australia
Study design: Meta analysis
Results: The authors carried out a systematic search of the published literature between 1950 and 2010 for purposes of identifying any published RCTs that had examined the effects of fibrate therapy on various CVD outcomes. As a result of the authors' exhaustive search, a total of 18 RCTs were identified which satisfied the investigators pre-defined inclusion criteria.
These wide ranging trials included less than 100 to more than 10,000 participants. A total of 45,058 patients were included in the 18 trials identified in whom the annual major CVD event rates ranged from 1.2% to 3.3% while the annual frequency of all coronary events ranged from 0.4% to 5.2%. The characteristics of men and women enrolled in these trials varied widely as did their levels of serum cholesterol and additional comorbidities. The average age of study participants ranged from 46 to 68 years, only men were included in eight trials, secondary prevention was the goal in 11 published studies, primary prevention of CVD was the principal objective of four trials, and the remainder of the trials included patients with and without a history of CVD such that efforts of primary and secondary prevention could be examined in these latter studies.
Across the studies reviewed, fibrate therapy was associated with a 10% reduction in the risk of major CVD events compared to individuals who were treated with placebo. In examining the relation between fibrate therapy and coronary events, fibrate therapy was associated with a 13% reduced risk of coronary events.
In examining the association between fibrate therapy and specific CVD endpoints, there was no evidence that fibrate therapy was associated with a reduced risk of stroke (-3%: 95% CI - 1.6 to +9%), CVD mortality (+3% (-7% to +12%), sudden cardiac death (+11%; -6% to 26%), or nonvascular related mortality (-10% (-21% to +1%). Fibrate therapy was also not significantly associated with all-cause mortality (0% (-8% to +7%) but it was associated with a reduced risk of albuminuria progression or diabetic retinopathy in a limited number of trials that examined these latter endpoints.
Several adverse outcomes were not significantly associated with the use of fibrate therapy in these published trials, although increases in serum creatinine concentrations were observed in association with the use of fibrate therapy, suggesting possible caution in the use of this medication in patients with chronic kidney disease, or at increased risk for chronic kidney disease.
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