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Thiazolidinedione Drugs and Cardiovascular Risks: A Science Advisory From the American Heart Association and American College of Cardiology Foundation
Perspective: The following are 10 points to remember about this science advisory.
1. The thiazolidinedione class of drugs, ligands of the
peroxisome-proliferator–activated receptor-γ, which is intricately
involved in insulin signaling, were the first drugs developed that
directly targeted insulin resistance.
2. Two thiazolidinediones are currently available in the United States, rosiglitazone (Avandia) and pioglitazone (Actos).
3. To date, there has been only one randomized clinical trial
prospectively designed to assess the effect of rosiglitazone on
cardiovascular outcomes, the Rosiglitazone Evaluated for Cardiac
Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial.
4. The majority of evidence regarding the cardiovascular effects of
rosiglitazone is derived from meta-analyses of randomized clinical
trials that evaluated the effects of rosiglitazone on glycemic control.
5. An association between rosiglitazone and ischemic heart disease
(IHD) outcomes has not yet been firmly established. Additional
prospective clinical trials designed for the specific purpose of
establishing the cardiovascular benefit or risk of rosiglitazone would
be the best way to resolve the uncertainties regarding the safety of
rosiglitazone.
6. However, sufficient evidence has emerged to raise concerns about a
potential adverse effect of rosiglitazone. The Food and Drug
Administration’s decision on November 14, 2007, to allow rosiglitazone
to remain on the market with an additional boxed warning about the risk
of IHD events further reflects these uncertainties.
7. The majority of published studies do not suggest an increased hazard
for IHD events in pioglitazone-treated patients. Accordingly, there is
no boxed warning on the risk of IHD for pioglitazone.
8. On the basis of all available evidence, thiazolidinediones should
not be used with an expectation of benefit with respect to IHD events,
and should be used with the understanding that they might increase the
risk of heart failure.
9. More data are urgently needed to clarify the effects of all existing
and future glucose-lowering agents, including thiazolidinediones, on
IHD events.
10. The ongoing Thiazolidinedione Intervention With Vitamin D
Evaluation (TIDE) study will test the cardiovascular effects of
rosiglitazone or pioglitazone when used as part of standard of care
compared to similar standard of care without rosiglitazone or
pioglitazone in patients with type 2 diabetes who have a history of or
are at risk for cardiovascular disease.
1. The thiazolidinedione class of drugs, ligands of the
peroxisome-proliferator–activated receptor-γ, which is intricately
involved in insulin signaling, were the first drugs developed that
directly targeted insulin resistance.
2. Two thiazolidinediones are currently available in the United States, rosiglitazone (Avandia) and pioglitazone (Actos).
3. To date, there has been only one randomized clinical trial
prospectively designed to assess the effect of rosiglitazone on
cardiovascular outcomes, the Rosiglitazone Evaluated for Cardiac
Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial.
4. The majority of evidence regarding the cardiovascular effects of
rosiglitazone is derived from meta-analyses of randomized clinical
trials that evaluated the effects of rosiglitazone on glycemic control.
5. An association between rosiglitazone and ischemic heart disease
(IHD) outcomes has not yet been firmly established. Additional
prospective clinical trials designed for the specific purpose of
establishing the cardiovascular benefit or risk of rosiglitazone would
be the best way to resolve the uncertainties regarding the safety of
rosiglitazone.
6. However, sufficient evidence has emerged to raise concerns about a
potential adverse effect of rosiglitazone. The Food and Drug
Administration’s decision on November 14, 2007, to allow rosiglitazone
to remain on the market with an additional boxed warning about the risk
of IHD events further reflects these uncertainties.
7. The majority of published studies do not suggest an increased hazard
for IHD events in pioglitazone-treated patients. Accordingly, there is
no boxed warning on the risk of IHD for pioglitazone.
8. On the basis of all available evidence, thiazolidinediones should
not be used with an expectation of benefit with respect to IHD events,
and should be used with the understanding that they might increase the
risk of heart failure.
9. More data are urgently needed to clarify the effects of all existing
and future glucose-lowering agents, including thiazolidinediones, on
IHD events.
10. The ongoing Thiazolidinedione Intervention With Vitamin D
Evaluation (TIDE) study will test the cardiovascular effects of
rosiglitazone or pioglitazone when used as part of standard of care
compared to similar standard of care without rosiglitazone or
pioglitazone in patients with type 2 diabetes who have a history of or
are at risk for cardiovascular disease.
Full text at JACC
