Stelara (Ustekinumab) Safety

F Poizeau et al. JAMA Dermatol. Published online September 9, 2020. doi:10.1001/jamadermatol.2020.2977. Association Between Early Severe Cardiovascular Events and the Initiation of Treatment With the Anti–Interleukin 12/23p40 Antibody Ustekinumab

Methods: “This case-time-control study used data from the French national health insurance database, covering 66 million individuals, on all patients exposed to ustekinumab between April 1, 2010, and December 31, 2016, classified according to their cardiovascular risk level (high- and low-risk strata). The risk period was the 6 months before the SCE, defined as acute coronary syndrome or stroke, and the reference period was the 6 months before the risk period. Statistical analysis was performed from September 20, 2017, to July 6, 2018.”

Key findings:

  • Of the 9290 patients exposed to ustekinumab (4847 men [52%]; mean [SD] age, 43 [14] years), 179 experienced SCEs (65 cases of acute coronary syndrome, 68 cases of unstable angina, and 46 cases of stroke).
  • Among patients with a high cardiovascular risk, a statisically significant association between initiaton of ustekinumab treatment and SCE occurrence was identified (odds ratio, 4.17; 95% CI, 1.19-14.59).
  • Conversely, no statistically significant association was found among patients with a low cardiovascular risk (odds ratio, 0.30; 95% CI, 0.03-3.13).

My take: This study suggests that the initiation of ustekinumab treatment may trigger SCEs among patients at high cardiovascular risk; however, the study conclusions are limited as this was an observational study (not a randomized trial).

How Hepatitis C Therapy Affects Cardiovascular Outcomes

Briefly noted: A recent retrospective study (AA Butt et al. Gastroenterol 2019; 156: 987-96) utilized a Veterans HCV database (n=242,680) and determined that HCV therapy improved cardiovascular outcomes.

Key finding: Treatment with a direct-acting antiviral regimen lowered the risk of cardiovascular events by more than 40% (hazard ratio of 0.57) compared to no treatment.

This finding is limited based on the reliance of a retrospective study and not being able to control for factors that may have led some patients to not receive treatment.

Related blog posts:

How Soccer Can Be Bad for Your Health

When people complain that “everything is bad for your health,” they just might be right.  After yesterday’s soccer match, the NEJM posted a link to a 2008 article (N Engl J Med 2008; 358:475-483).  Here’s part of the abstract:

Methods: Cardiovascular events occurring in patients in the greater Munich area were prospectively assessed by emergency physicians during the World Cup. We compared those events with events that occurred during the control period: May 1 to June 8 and July 10 to July 31, 2006, and May 1 to July 31 in 2003 and 2005.

Results: Acute cardiovascular events were assessed in 4279 patients. On days of matches involving the German team, the incidence of cardiac emergencies was 2.66 times that during the control period…On those days, the highest average incidence of events was observed during the first 2 hours after the beginning of each match.

Conclusions: Viewing a stressful soccer match more than doubles the risk of an acute cardiovascular event.

Take-home point: Some people are not lying when they say they live and die with their favorite team.

n-3 Fatty Acids and Cardiovascular Outcomes

A recent study has cast doubt on the benefit of n-3 fatty acids for preventing cardiovascular complications in patients with type 2 diabetes (NEJM 2012; 367: 309-18).

While previous studies have indicated that persons who consume fish regularly or take supplements with n-3 fatty acids have a reduced risk of cardiovascular events, there are many potential confounding variables.  This “ORIGIN” study (Outcome Reduction with an Initial Glargine Intervention) which had 12,611 patients undergo randomization looked at a high risk group (type 2 diabetes patients) but did not find any change in cardiovascular events, including death over a median followup of 6.2 years.  The treatment group received 1 gram of n-3 fatty acids which did result in a lower triglyceride level (by 14.5 mg/dL).

How do the authors explain the results of this negative study in comparison to previous reports?

  • Two of the largest trials had recruited patients with recent myocardial infarction –these patients may have been more likely to benefit
  • In ORIGIN study, more concomitant cardioprotective therapies were being used which could have reduced the potential benefit of n-3 fatty acids
  • Other study populations may have had a lower dietary intake of n-3 and therefore benefitted more from supplementation

While the results of this study may reduce the enthusiasm for n-3 fatty acids, several additional large studies (ASCEND/NCT00135226, VITAL/NCT01169259) are underway which should give additional information on this topic, including in participants at lower risk for cardiovascular events. In addition, the authors conclude that while their findings do not show a reduction in cardiovascular events, they state that dietary recommendations of increased fish consumption should not change; increased fish consumption not only increases n-3 fatty acids but results in lower intakes of red meats which may be harmful.

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TODAY is worrisome for a lot of tomorrows

Who needs aspirin?

Cardiovascular disease for the entire family

Treating diabetes with surgery