SCAI Issues Statement on the Association of Paclitaxel Devices and Mortality


January 25, 2019—The Society for Cardiovascular Angiography and Interventions (SCAI) has issued a statement on the recent study of the association between paclitaxel-eluting devices and mortality.

On December 6, Konstantinos Katsanos, MD, et al published a systematic review and meta‐analysis of randomized controlled trials (RCTs) evaluating the use of paclitaxel‐coated/eluting balloons and stents in the femoral and/or popliteal arteries. The investigators concluded that there is an increased risk of death after application of these devices in this anatomy. The study is available online in Journal of the American Heart Association.

As noted by SCAI, the study evaluated 28 RCTs that included 12 different devices for the treatment of femoropopliteal disease. Findings from the Katsanos study include:

  • At 1 year with 4,432 patients, there was no difference between the paclitaxel-eluting arm and the control arm for all-cause mortality (2.3% vs 2.3%; risk ratio [RR], 1.06; 95% confidence interval [CI], 0.72–1.61).
  • At 2 years with 2,316 patients in 12 studies, there was a sharp increase in all-cause mortality with paclitaxel-eluting devices compared to control (7.2% vs 3.8%; RR, 1.68; 95% CI, 1.15–2.47).
  • At 5 years with 863 patients in three studies, there was a persistently higher risk of all-cause mortality for paclitaxel-eluting devices compared to control (14.7% vs 8.1%; RR, 1.93; 95% CI, 1.27–2.93).
  • Risk was fairly stable in various sensitivity analyses: drug-eluting stents versus drug-coated balloons (DCBs). Trials with a higher dose of paclitaxel had a higher risk ratio (highest with a 3.5-mg dose). This dose response was confirmed on meta-regression with 0.4% increased risk for every paclitaxel mg–year.

Experts from the SCAI Vascular Disease Council have reviewed this meta-analysis and have concluded that the methods are appropriate and within constraints of trial-level meta-analysis. However, SCAI noted that the associations are hypothesis generating and require further investigation with patient-level data.

SCAI noted the following limitations of this study:

  • 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 reported data beyond 1 year and only 3% at 5 years.
  • The equation to assess the paclitaxel dose/time relationship may have overestimated drug exposure and its effect over time.

Following publication of the study, the FDA issued a letter to alert physicians of these findings. The FDA instructed health care providers to report any adverse events or suspected adverse events with paclitaxel-eluting devices through the MedWatch program.

On January 22, investigators from several device trials presented new patient-level data at LINC 2019, the Leipzig Interventional Course in Leipzig, Germany. Data from these trials show comparable mortality rates among patients treated with paclitaxel-coated or paclitaxel-eluting devices compared to angioplasty or bare-metal stents.

The presentations at LINC included the following data:

  • At 5 years, a pooled analysis of 1,980 patients from the IN.PACT DCB program (Medtronic) demonstrated that there was no statistically significant difference in all-cause mortality between the DCB and the control arms (9.3% vs 11.2%; P= .399).
  • At 3 years, randomized trial data from 105 patients in the RANGER-SFA (Boston Scientific Corporation) showed no significant difference in all-cause mortality between DCB and control (13.8% vs 10.7%).
  • At 5 years, data from 479 patients enrolled in the Zilver PTX randomized trial showed no statistically significant difference in all-cause mortality between patients treated with Zilver PTX (Boston Scientific Corporation) and the control group (18.7% vs 17.6%; P= .53).
  • A 3-year pooled analysis of 2,521 patients from RCTs and non-RCTs from the Stellarex DCB program (Philips) (DCB = 2,351; control, 170) showed no statistically significant difference in all-cause mortality between the Stellarex and the control groups (7.9% vs 9.9%; P= .78).
  • At 5-years, data from 1,189 patients in the LEVANT 2 trial within the Lutonix DCB program (BD Interventional) showed no statistically significant difference in all-cause mortality between DCB and the control group (14.1% vs 10.6%; P= .22).

SCAI noted that additional details from these meta-analyses will 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.

In the announcement, SCAI President David A. Cox, MD, commented, “At present, SCAI concurs with FDA that the benefits of paclitaxel devices continue to outweigh any potential risks. However, we strongly encourage our members to discuss the findings of the meta-analysis with their patients and to report any safety concerns to FDA.”


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