Paclitaxel-Coated Balloons (PCB) and Paclitaxel-Eluting Stents (PES) for the Treatment of Peripheral Arterial Disease (PAD) and the Potential Risk of Long-Term All-Cause Mortality

Starting date:: May 6, 2019
Posting date:: May 6, 2019
Type of communication:: Dear Healthcare Professional Letter
Subcategory:: Medical Device
Source of recall:: Health Canada
Issue:: Important Safety Information
Audience:: Healthcare Professionals
Identification number:: RA-69848

Last updated: 2019-05-06

Audiences

Healthcare professionals in hospitals, including hospital chiefs of medical staff, department of vascular surgery, interventional radiologists, and other relevant departments

Key messages

A study published in the Journal of the American Heart Association has identified a possible increased risk of death after the use of paclitaxel coated balloons (PCB) and paclitaxel-eluting stents (PES) to treat peripheral arterial disease (PAD).^Footnote 1 The reason for this possible increased risk of death is not yet known.
Health Canada is currently evaluating recently-published information on this risk. As a precautionary measure, healthcare professionals are advised to:
- Continue surveillance of patients who have been treated with paclitaxel-containing devices for treatment of PAD according to current standards of care.
- Weigh the risks and benefits for each patient when considering the use of PCB and PES in patients with PAD.
- Consider alternative treatment options rather than PCB and PES until additional analysis of the safety concern has been done.
- Consider limiting the use of PCB and PES to patients with critical limb ischemia (CLI).
- Inform patients of the possible additional risks associated with the use of paclitaxel-containing devices.
Health Canada has also requested that manufacturers update the labelling of paclitaxel-containing devices to include details about this potential risk.

Issue

A potential increased risk of long-term, all-cause mortality (at 2 years to 5 years) after the use of PCB and PES for the treatment of PAD was identified in a meta-analysis, which was published in the Journal of the American Heart Association (JAHA) in December 2018.^Footnote 1 The reason for the potential increased risk of death is not yet known. Health Canada is currently evaluating this safety concern to determine if there is an increased long-term mortality risk associated with paclitaxel‐containing devices used for PAD treatment.

Products affected
Medical Device Name	Manufacturer	Device Licence Number
* Device no longer licensed in Canada as of October 2018 **Other paclitaxel-containing devices are licensed for treatment of different^Footnote 1
Paclitaxel-containing devices used to treat PAD
LUTONIX 035 DRUG COATED BALLOON PTA CATHETER	Lutonix Inc.	96031
IN.PACT ADMIRAL PACLITAXEL-COATED PTA BALLOON CATHETER	Medtronic Inc.	98019
LUTONIX 014 DRUG COATED PTA DILATATION CATHETER	Lutonix Inc.	91277
RANGER OTW PACLITAXEL-COATED PTA BALLOON CATHETER	Hemoteq AG	97627
RANGER SL OTW PACLITAXEL-COATED PTA BALLOON CATHETER	Hemoteq AG	97627
IVASCULAR LUMINOR 14M, PACLITAXEL ELUTING PTA BALLOON DILATATION CATHETER	Life Vascular Devices Biotech S.L.	97387
ZILVER PTX DRUG-ELUTING PERIPHERAL STENT (6FR)	Cook Ireland LTD.	90774
ZILVER PTX DRUG-ELUTING PERIPHERAL STENT (7FR) *	Cook, Inc.	90773
Other paclitaxel-containing devices **
PANTERA LUX PACLITAXEL RELEASING PTCA BALLOON CATHETER	Biotronik AG	95407
OPTILUME URETHRAL DRUG COATED BALLOON CATHETER	Urotronic Inc.	101026
LUTONIX 035 DRUG COATED BALLOON PTA CATHETER	Lutonix Inc.	100575

Background information

PCB and PES are intended to treat de novo or restenotic lesions in the leg, including the superficial femoral and femoropopliteal arteries to mechanically open obstructed vessels. The release of paclitaxel from these devices is intended to reduce restenosis in the artery that can reduce blood flow. Paclitaxel-containing devices have also been licensed for the treatment of coronary artery disease, stenotic lesions in dysfunctional arteriovenous dialysis fistulae, and other diseases.

A recent meta-analysis of randomized controlled trials published in the Journal of the American Heart Association (JAHA) in December 2018 identified an increase in all-cause mortality at two years in PAD patients treated with PCB and PES compared to patients treated with non-coated balloons or bare metal stents.^Footnote 1 This increase persisted for five years. The reason for the potential increased risk of death is not yet known.

This issue was discussed at the March 1, 2019, meeting of Health Canada’s Scientific Advisory Committee on Medical Devices Used in the Cardiovascular System (SAC-MDUCS), which is made up of medical experts.^Footnote 2 The committee felt the benefits of the use of devices containing paclitaxel continue to outweigh the potential increased risk for patients with CLI. However, the potential impact of this issue remains unclear in patients treated for claudication.

Health Canada is currently evaluating the recently published meta-analysis and other information to assess the risk/benefit profile of paclitaxel-containing devices indicated for PAD treatment. As an interim measure, while Health Canada and other global stakeholders continue to assess data, the department has requested additional information from manufacturers for PCB and PES licensed in Canada. Health Canada has also requested that manufacturers update the labelling of paclitaxel-containing devices to include details about this potential risk.

Who is affected

Information for consumers

Paclitaxel-coated balloons are devices inserted into narrowed or blocked blood vessels to restore blood flow. After the balloon is removed, a drug called paclitaxel remains on the blood vessel to prevent scar tissue formation and recurrence of the vessel blockage. Paclitaxel-eluting stents are devices placed to hold a blood vessel open and slowly release the drug to prevent scar tissue and blockage. The drug from paclitaxel-coated balloons and in paclitaxel-eluting stents is released over days to months.

A recently-published study showed a higher risk of death in the long term in patients treated with paclitaxel-containing devices in blood vessels in the leg compared to patients treated with balloons and stents that do not contain the drug. The reason for the potential increased risk of death is not known at this time.

Patients who have been treated with paclitaxel-containing devices should continue to consult their health care provider for regular follow-up. Patients who are potentially going to be treated with these devices should discuss all known risks with their health care provider.

Information for healthcare professionals

Until additional information is available, healthcare professionals are advised to:

Continue surveillance of patients who have been treated for PAD with PCB and PES according to current standards of care.
Determine whether the benefits of using these devices outweigh the risks for each patient.
Consider limiting the use of PCB and PES indicated for the treatment of PAD to CLI patients.
Make the patient aware of the potential additional risks associated with these products.

Action taken by Health Canada

Health Canada discussed this potential safety issue at the recent SAC-MDUCS meeting.² Additional information was requested from the Canadian PCB and PES manufacturers in order to further assess the potential risk. Health Canada continues to actively engage with the manufacturers, clinicians, and other international regulatory agencies to better understand the safety issue. This important safety information is being communicated to Canadians via the Recalls and Safety Alerts Database on the Healthy Canadians website. This communication will be further distributed through the MedEffect™ e-Notice email notification system as well as social media channels including LinkedIn and Twitter.

Health Canada will also continue to monitor safety information involving PCB and PES, as it does for all health products on the Canadian market, to better understand this potential risk and identify and assess other potential harms. Appropriate and timely action will be taken if and when any new health risks are identified.

Report health or safety concerns

Health Canada’s ability to monitor the safety of marketed health products depends on healthcare providers and consumers reporting adverse reactions and medical device incidents. Any cases of death or serious or unexpected side effects in patients receiving PCB and PES should be reported to the device manufacturer or Health Canada.

Any suspected adverse incident can be reported to:

Regulatory Operations and Enforcement Branch
HEALTH CANADA
Address Locator: 2003D
Ottawa, Ontario K1A 0K9
Telephone: Regulatory Operations and Regions Branch Hotline: 1-800-267-9675

The Health Product Complaint Form (FRM-0317) can be found on the Health Canada Web site.

For other health product inquiries related to this communication, contact Health Canada at:

Marketed Health Products Directorate (MHPD)
E-mail: mhpd-dpsc@canada.ca
Telephone: 613-954-6522
Fax: 613-952-7738

MEDDESKTOP

Monday, May 06, 2019

Paclitaxel-Coated Balloons, Paclitaxel-Eluting Stents used for the Treatment of Peripheral Arterial Disease Brings a Potential Risk of Long-Term All-Cause Mortality