Study design: Meta-analysis.
Setting: All clinical trials (published and unpublished) involving rosiglitazone.
Synopsis: The authors reviewed data from all randomized trials of rosiglitazone versus placebo or other drugs for at least 24 weeks. From the 42 included trials (including more than 28,000 patients) researchers found a statistically significant increased risk of the odds of AMI (odds ratio 1.43, confidence interval 1.03-1.98) in the rosiglitazone group, and a non-significant risk of death from any cardiovascular cause (odds ratio 1.64, confidence interval 0.98-2.74) and all-cause mortality (odds ratio 1.18, confidence interval 0.89-1.55). The meta-analysis was criticized due to the small number of events (fewer than 100 acute AMIs in each group) and lack of patient-level data, but one expert wrote that “in view of the potential cardiovascular risks and in the absence of evidence of other health advantages … the rationale for prescribing rosiglitazone at this time is unclear.”
The study raised larger concerns regarding Food and Drug Administration drug approvals, because the drug was approved due to its effect on lowering blood sugar levels (a surrogate outcome) without enough scrutiny of other patient outcomes.
Bottom line: Rosiglitazone is associated with increased risk of AMI. Alternative oral agents should be considered first for blood sugar control in diabetics.
Citation: Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007 Jun;356(24):2457-2471.
Editorial: Psaty BM, Furberg CD. Rosiglitazone and cardiovascular risk. N Engl J Med. 2007 Jun;356(24):2522-2524.
Is Rosiglitazone Associated with Adverse Cardiovascular Outcomes in Interim Analysis?
Background: In response to a meta-analysis, an interim analysis of an ongoing open-label manufacturer-sponsored trial was undertaken to determine the cardiovascular risks of rosiglitazone.
Study design: Unplanned interim analysis of a randomized, multicenter, open-label, non-inferiority trial.
Subjects: Outpatient, inadequately controlled type 2 diabetics.
Synopsis: This was an unplanned interim analysis of an open-label manufacturer-sponsored trial. There were 4,447 inadequately controlled type 2 diabetics on either metformin or sulfonylurea. The patients were randomized to receive both drugs (controls) or add-on rosiglitazone. After a mean follow up of 3.75 years, there was no statistically significant difference between the groups in the primary end point (hospitalization or death from cardiovascular causes), or other end points (MI and death from cardiovascular causes or any cause). However, rosiglitazone was associated with an increased risk of heart failure (hazard ratio 2.15, confidence interval 1.30-3.57). Because this was an unplanned interim analysis for a trial expected to continue for six years, experts caution that the results are inconclusive due to low statistical significance and small event rates.
Bottom line: Rosiglitazone is associated with an increased risk of heart failure, but the risks of hospitalization, death, and acute MI remain unclear.
Citation: Home PD, Phil D, Pockock SJ, et al. Rosiglitazone evaluated for cardiovascular outcomes—an interim analysis. N Engl J Med. 2007 Jul;357(1):28-38.
How Often do Discharged Patients with Unresolved Medical Issues Require Outpatient Workups?
Background: Patients are often discharged from the hospital with incomplete workups, but it is unknown how often and what factors affect the completion of the intended workup.
Study design: Retrospective cohort.
Setting: Single institution teaching hospital.
Synopsis: The authors evaluated the inpatient and outpatient medical records of all patients discharged from the medicine or geriatric service over 18 months. Of almost 700 discharges, 28% of the patients had outpatient workups recommended (48% diagnostic procedures, 35% referrals, and 17% lab tests) by the discharging physician. Completion of the workup did not occur 36% of the time, and the likelihood of non-completion increased with time to the first follow-up appointment and lack of availability of the discharge summary.