Pioglitazone does not increase cardiovascular events (PROactive)
Clinical Question
What is the effect of pioglitazone (Actos) on the likelihood of cardiovascular events in patients with diabetes at high risk?
Bottom Line
Pioglitazone (Actos), unlike its chemical cousin rosiglitazone (Avandia), does not seem to increase the likelihood of cardiovascular events (N Engl J Med. 2007;356:2457-2471). The researchers conducting this study stretched -- and broke -- the scientific method when claiming benefit, but any claims of benefit are specious. (LOE = 1a-)
Reference
Wilcox R, Kupger S, Erdmann E, for the PROactive study investigators. Effects of pioglitazone on major adverse cardiovascular events in high-risk patients with type 2 diabetes: Results from PROspective pioglitAzone Clinical Trial in macro Vascular Events (PROactive 10). Am Heart J 2008;155:712-7. [PMID:18371481]
Study Design
Randomized controlled trial (double-blinded)
Funding
Industry
Allocation
Concealed
Setting
Outpatient (specialty)
Synopsis
To study the effect of pioglitazone on cardiovascular events, these European researchers enrolled 5,238 high-risk patients with diabetes for an average 9.5 years. Most of the patients (75%) had hypertension, half had myocardial infarction in their history, and 19% had experienced a stroke. In additional to their aggressive treatment for all of these risk factors, patients were radomized (allocation concealed) to receive either placebo or pioglitazone, force-titrated to 45 mg/day, for 3 years. Over this time period, approximately 11% of patients experienced at least one of the three events that made up the composite outcome evaluated in this report: cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The researchers report a statistically significant difference between treatment and placebo, though their statistical analysis was suspect and likely improper. Despite having several analyses, they did not adjust the p-value for multiple comparisons. Also, none of the outcomes, when assessed individually, were statistically lower in the treated group. For a composite outcome to be considered valid, at least one of the individual outcomes should be statistically significant. An even greater threat to the validity of this study is that the overall goal of the PROactive study was to evaluate the effect of pioglitazone on a different composite outcome, all-cause mortality, nonfatal myocardial infarction, stroke, acute coronary syndrome, endovascular or surgical intervention in the coronary or leg arteries, and amputation above the ankle. There was no difference with therapy on this outcome (Lancet 2005;366:1279-89). Researchers cannot slice-and-dice their data so that they find a significant difference.
Citation
Barry, Henry, et al., editors. "Pioglitazone Does Not Increase Cardiovascular Events (PROactive)." EE+ POEM Archive, John Wiley & Sons, 2024. Evidence Central, evidence.unboundmedicine.com/evidence/view/infoPOEMs/426079/all/Pioglitazone_does_not_increase_cardiovascular_events__PROactive_.
Pioglitazone does not increase cardiovascular events (PROactive). In: Barry HH, Ebell MHM, Shaughnessy AFA, et al, eds. EE+ POEM Archive. John Wiley & Sons; 2024. https://evidence.unboundmedicine.com/evidence/view/infoPOEMs/426079/all/Pioglitazone_does_not_increase_cardiovascular_events__PROactive_. Accessed November 3, 2024.
Pioglitazone does not increase cardiovascular events (PROactive). (2024). In Barry, H., Ebell, M. H., Shaughnessy, A. F., & Slawson, D. C. (Eds.), EE+ POEM Archive. John Wiley & Sons. https://evidence.unboundmedicine.com/evidence/view/infoPOEMs/426079/all/Pioglitazone_does_not_increase_cardiovascular_events__PROactive_
Pioglitazone Does Not Increase Cardiovascular Events (PROactive) [Internet]. In: Barry HH, Ebell MHM, Shaughnessy AFA, Slawson DCD, editors. EE+ POEM Archive. John Wiley & Sons; 2024. [cited 2024 November 03]. Available from: https://evidence.unboundmedicine.com/evidence/view/infoPOEMs/426079/all/Pioglitazone_does_not_increase_cardiovascular_events__PROactive_.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC
T1 - Pioglitazone does not increase cardiovascular events (PROactive)
ID - 426079
ED - Barry,Henry,
ED - Ebell,Mark H,
ED - Shaughnessy,Allen F,
ED - Slawson,David C,
BT - EE+ POEM Archive
UR - https://evidence.unboundmedicine.com/evidence/view/infoPOEMs/426079/all/Pioglitazone_does_not_increase_cardiovascular_events__PROactive_
PB - John Wiley & Sons
DB - Evidence Central
DP - Unbound Medicine
ER -