Experts from the Society for Cardiovascular Angiography and Interventions (SCAI) have reviewed the recent meta-analysis by Katsanos and colleagues and have concluded that the methods are appropriate and within constraints of trial-level meta-analysis. However, the society statement says “it is important to note that SCAI believes the associations are hypothesis-generating and require further investigation with patient-level data.”
The Katsanos meta-analysis, published in the Journal of the American Heart Association (JAHA), revealed an increase in long-term mortality with paclitaxel-coated balloons and paclitaxel-eluting stents. The study evaluated 28 randomised controlled trials across 12 devices for the treatment of femoropopliteal disease.
The SCAI statement summarises the findings of the Katsanos meta-analysis, before highlighting some limitations of the study. It identifies the following limitations:
- There is no mechanistic explanation for the study findings.
- A post-hoc analysis did not include patient-level data to adjust for clinical and angiographic differences between those who died and those who did not.
- There is evidence of discrepancy in some of the reported numbers.
- The study findings could be by chance—a type-1 error due to multiple testing.
- Less than 50% of the trials report data beyond one year and only 3% at five years.
- The equation to assess the paclitaxel dose/time relationship may have overestimated drug exposure and its effect over time.
Recently, the US Food and Drug Administration (FDA) issued a letter to alert physicians to the meta-analysis findings. The agency has asserted that the benefits of paclitaxel-coated devices outweigh the risks when used as indicated. However, the SCAI point out that the FDA urged healthcare providers to report any adverse events or suspected adverse events with paclitaxel-eluting devices through its MedWatch programme.
The SCAI indicate several recent, large trials with patient-level data presented by investigators at the Leipzig Interventional Course (LINC; 22-25 January 2019, Leipzig, Germany). Data from these trials show comparable mortality rates among patients treated with paclitaxel-coated or -eluting devices compared to plain angioplasty or bare metal stents.
- Firstly, the Medtronic IN.PACT drug-coated balloon (DCB) programme. This involved a pooled analysis of 1,980 patients and demonstrated that at five years, there was no statistically significant difference in all-cause mortality between the DCB and the control arm (9.3% vs. 11.2% respectively, p=0.399).
- Secondly, the SCAI statement points to the RANGER SFA randomised trial three-year data from 105 patients. This showed no significant difference in all-cause mortality between DCB and control (13.8% vs. 10.7%, respectively).
- Five-year data from 479 patients enrolled in the ZILVER PTX randomised trial showed no statistically significant difference in all-cause mortality between ZILVER PTX and the control group (18.7% vs. 17.6% respectively, p=0.53).
- A three-year pooled analysis of 2,521 patients from RCTs and non-RCTs from the Stellarex DCB programme (2,351 DCB and 170 controls), showed no statistically significant difference in all-cause mortality between Stellarex and the control groups (7.9% vs. 9.9% respectively, p=0.78).
- Five-year data from 1,189 patients in the Levant 2 Trial within the LUTONIX DCB programme showed no statistically significant difference in all-cause mortality between DCB and the control group (14.1% vs. 10.6% respectively, p=0.22).
The SCAI concludes: “We expect further details from these meta-analyses to be examined in peer reviewed journals in the near future. Additional patient-level analyses are underway by [the] FDA, independent physicians, and industry, and SCAI is closely monitoring this evolving situation.”
“At present, SCAI concurs with [the] FDA that the benefits of paclitaxel devices continue to outweigh any potential risks,” says SCAI president, David Cox. “However, we strongly encourage our members to discuss the findings of the meta-analysis with their patients and to report any safety concerns to [the] FDA.”