Session 3: BBRAUN - DCB’s Journey: From local innovation to global therapy – Bruno Scheller

History of Drug-Coated Balloons in Interventional Cardiology

Introduction to Key Figures and Concepts

• The talk begins with a historical overview, introducing Professor Beck, who was pivotal in the development of contrast media.

• Professor Beck's research included the creation of gadolinium and its application in local drug delivery using contrast media.

Initial Experiments and Findings

• Early experiments combined paclitaxel with contrast medium, showing that short incubation could inhibit vascular smooth muscle cell growth.

• In an experimental model for porcine wrist stenosis, controlled oversizing led to neointimal proliferation; adding paclitaxel reduced this formation significantly.

Development of Coated Balloons

• The challenge arose in controlling drug dosage during injections, leading to the idea of coating balloons with drugs.

• Initial skepticism from Professor Beck did not deter experimentation; prototypes were created that showed varying effects on neointimal proliferation based on formulation.

Clinical Trials and Landmark Findings

• A small trial (POCUT IS1) was conducted in 2002–2003 focusing on bare metal stent stenosis treatment using either uncoated or paclitaxel-coated balloons.

• Results demonstrated a significant reduction in late lumen loss from 74% to nearly zero at six months, marking a breakthrough in interventional cardiology.

Industry Collaboration and Further Research

• Lack of funding led to collaboration with industry partners like Dr. Boxberger, resulting in support for further trials involving drug-coated balloons (DCBs).

• Smaller trials were initiated to explore various indications for DCB use, revealing that many lesions could be treated effectively without additional stenting.

Evolving Treatment Strategies

• The Pepcat 1 trial highlighted that approximately 80% of lesions could be treated solely with DCB, challenging previous assumptions about stenting necessity.

• This led to recommendations for lesion preparation before deciding between DCB or stent treatment—an approach initially seen as merely procedural but later recognized for improving outcomes.

Long-term Outcomes and Insights

• Subsequent findings indicated improvements over time regarding lumen size post-treatment—a notable shift compared to traditional stenting methods which typically resulted in lumen loss.

Coronary Artery Interventions and Drug-Coated Balloons

Overview of Drug-Coated Balloons (DCB) in Coronary Arteries

• The study focused on coronary arteries less than 3 mm in diameter, comparing outcomes between DCB and stent implantation over three years, revealing similar results.

• The Sequent Please balloon was used as a control group in trials comparing DCB with other treatments, demonstrating its significance in the research landscape.

• Higher dissection rates were observed with certain coatings; however, this led to reduced late lumen loss compared to the Corolimus-coated balloon.

Investigating Different Drug Formulations

• A preclinical program explored various formulations of Cerolimus, finding that crystalline coatings allowed for longer drug persistence within vessel walls.

• Clinical trials indicated that both Paclitaxel and Corolimus-coated balloons had similar late lumen loss distributions at six months for instant stenosis cases.

Safety Analysis of DCB Treatments

• A safety debate arose from Katzanos' meta-analysis regarding peripheral arteries; subsequent discussions led to a dedicated meta-analysis for coronary arteries.

• Findings showed no significant safety signals for Paclitaxel-coated balloons in coronary applications, indicating lower rates of acute myocardial infarction within the first year.

Trends in DCB Usage

• Japan's use of DCB has increased significantly, with a current ratio of 1.4 stents to DCB usage; overall trends show rapid adoption across Asia and Europe.