In the final analysis, this study suggests hospitalists remain alert to possible problems that might develop during the vulnerable first few days following discharge. It reminds us to advise patients how to receive prompt and knowledgeable medical advice from someone familiar with their hospital care prior to their first scheduled follow-up.
Based on the reported rate of new or worsening symptoms, should a post-discharge clinic be part of hospitalists’ scope of practice, at least for selected patients? Can subsets of patients who would benefit most from such intervention be identified? These and many more questions are raised by this study. We look forward to further research into the best process for ensuring optimal outcomes in the immediate post-discharge period.
Rosiglitazone’s Effect on MI Risk in Diabetes Patients
Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007 June 14;356(24):2457-2471.
Cardiovascular causes account for more than 65% of deaths in diabetic patients. Rosiglitazone—a thiazolidinedione-class drug—has been broadly used in diabetes, but its effect on cardiovascular morbidity and mortality has not been conclusively determined. The authors initiated this meta-analysis to determine the effect of rosiglitazone on the risk of myocardial infarction (MI) and death from cardiovascular causes in diabetics.
The meta-analysis included 42 trials from three data sources. Forty trials were obtained from the Food and Drug Administration (FDA) Web site and the GlaxoSmithKline clinical trials registry. The third data source comprised two recent large, well-known trials: the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) and the A Diabetes Outcome Prevention Trial (ADOPT).1-2 The authors’ inclusion criteria were a study with a duration of more than 24 weeks, the use of a randomized control group not receiving rosiglitazone (placebo or comparator drug), and the availability of outcome data for MI and death from cardiovascular causes.
The studies included 15,560 patients randomly assigned to regimens that included rosiglitazone and 12,283 patients to comparator groups that did not include rosiglitazone.
The authors reviewed the data summaries of the 42 trials and tabulated adverse events (not reported as outcomes) of MI and death from cardiovascular causes. Hazard ratios could not be calculated since time-to-event data were lacking. Summary data also precluded the ability to determine whether the same patient suffered both an MI and death from cardiovascular causes.
Results of the authors’ statistical analyses included odds ratios and 95% confidence intervals to assess the risk associated with the rosiglitazone group as well as the subgroups of metformin, sulfonylurea, insulin, and placebo versus rosiglitazone.
The authors tabulated 86 MIs and 39 unadjudicated deaths from cardiovascular causes in the rosiglitazone group, and 72 MIs plus 22 deaths from cardiovascular causes in the control group.
The main conclusion was that rosiglitazone was associated with a statistically significant increase in the risk of MI (odds ratio 1.43, 95% confidence interval 1.03 to 1.98, p=0.03), but was not associated with a statistically significant increase in the risk of death from cardiovascular causes (odds ratio 1.64, 95% confidence interval 0.98 to 2.74, p=0.06).
Additionally, there were no statistical differences between rosiglitazone versus placebo or the individual antidiabetics in the subanalyses.
The authors have recognized the following major limitations in this meta-analysis:
- The low rate of MI is 0.55% (86 of 15,560 cases) in the rosiglitazone group and 0.59% (72 of 12,283 cases) in the control group. The odds ratio of 1.43 was statistically significant in the rosiglitazone group, although the event rate was higher in the control group. The risk of cardiovascular death was not significant, though a trend toward a higher death rate is noted;
- The lack of source data did not allow the use of time event analysis including hazard ratios;
- The definition of MI was unavailable; and
- MI and cardiovascular events were recorded in the trials as adverse events, not outcomes. Therefore, deaths from the latter were unadjudicated.