No Mortality Signal With Paclitaxel Balloons in Coronary PCI

Batya Swift Yasgur MA, LSW

March 06, 2020

Paclitaxel drug-coated balloons (DCB) are not associated with increased mortality, compared with non-DCB devices, and may even confer additional survival benefits when used in coronary revascularization, a new meta-analysis shows.

Investigators analyzed 26 randomized controlled trials, including more than 4500 patients, which compared DCBs with non-DCB devices and found no difference in all-cause mortality rates at 1 year and 2 years.

After 3 years of follow-up, all-cause mortality and cardiac mortality were significantly lower in the DCB group than in the control treatment group.

"When using coronary DCB coated with paclitaxel, not only is there no signal for increased mortality, but there are even indications of improved long-term survival," lead author Bruno Scheller, MD, professor of clinical and experimental interventional cardiology, Saarland University, Homburg/Saar, Germany, told theheart.org | Medscape Cardiology.

The study was published online March 2 in the Journal of the American College of Cardiology.

Urgent Need

"In recent years, DCB had almost become standard of care in the treatment of peripheral arterial occlusive disease [PAD] in the superficial femoral artery," Scheller said.

After publication of a meta-analysis by Katsanos et al suggesting increased mortality from DCB when used for he treatment of PAD, "the safety of DCB was questioned in principle, with the consequence that countless PAD patients no longer receive adequate treatment," he said.

Scheller reported that he and other principle investigators of studies focusing on the use of DCB in coronary arteries had been asked by the German Institute for Drugs and Medical Devices to comment on the safety of these devices because the agency "argued with the publication of Katsanos, although no coronary studies had been investigated in this paper."

"It was clear to all of us that Katsanos' results were questionable and certainly had nothing to do with clinical evidence in the coronary arteries," Scheller said.

For this reason, "in early summer 2019, there was an urgent need to evaluate the coronary studies regarding survival," so as "to answer the question of a possible influence of local coronary paclitaxel administration on survival with all available randomized studies and indications," he said.

Scheller emphasized that "the quality of the raw data was crucial for us."

He and his coauthors were "able to guarantee this, on the one hand, by having the principle investigators of many of the studies directly involved and, on the other hand, by means of a permanent internal quality control with an independently acting team."

Randomized Trials

The meta-analysis looked at 26 RCTs published between 2006 and 2019 (with 4590 patients, of whom 2322 were randomized to DCBs only and 2268 to alternative treatments).

Studies were required to be randomized and to compare percutaneous coronary intervention (PCI) without stent implantation and implantation of bare-metal stents (BMS) and/or drug-eluting stents (DES) or plain old balloon angioplasty (BOBA).

The analysis included patients with acute coronary syndrome (ACS), stable angina pectoris, treatment of in-stent restenosis, and small vessel disease. It also included patients with coronary in-stent restenosis, as well as those with de novo lesions.

The primary outcome was the difference in all-cause mortality between patients treated with DCB and those treated with non-DCB devices.

There was no significant difference in all-cause mortality between DCB and non-DCB devices observed at 6 to 12-month follow-up, and DCB treatment was actually associated with a numerically lower mortality risk (45 vs 63 events; risk ratio [RR], 0.74; 95% CI, 0.51 - 1.08; P = .116).

Likewise, at 2-year follow-up (eight RCTs; 1477 patients) the risk for mortality between the two groups was similar (RR, 0.84; 95% CI, 0.51 - 1.37; P = .478).

The results at 3-year follow-up (nine RCTs; 1775 patients) were even more supportive of the safety of DCB. At that juncture, all-cause mortality was significantly lower in the DCB than in the control treatment groups (RR, 0.73; 95% CI, 0.53 - 1.00; P = .047), with a number needed-to-treat of 36 to prevent one death.

The researchers looked separately at cardiac mortality and found that it was similarly comparable after 1-year follow-up (RR, 0.88; 95% CI, 0.55 - 1.40; P = .582) and 2-year follow-up (RR, 0.58; 95% CI, 0.29 - 1.19; P = .140), respectively.

After 3 years, there was significantly better cardiac survival in patients receiving DCB than in control subjects (RR, 0.53; 95% CI, 0.33 - 0.85; P = .009).

Moreover, "target lesion revascularization rates were not different between DCB and alternative treatments at all time points," they report.

Commenting on the apparent differences between the findings of Katsanos et al regarding safety concerns in DCBs for PAD and the current encouraging safety findings, Scheller said that he "disagrees that there are differences in the safety of coronary and peripheral DCB."

Scheller called the findings of Katsanos et al "questionable, due to selection bias and counting for wrong numbers."

"From today's perspective, the neglect of hard end points such as death in peripheral studies must be viewed very critically," he said. "The consequence of this will be that higher quality standards will have to apply to peripheral studies in the future."

By contrast, "in the coronary studies, high standards were applied from the beginning, also for secondary end points."

Additionally, "there may be differences in secondary prevention among patients in the coronary and peripheral studies. In the peripheral studies, it could be shown that factors such as patient compliance for follow-up visits have an influence on survival," Sheller stated.

Consistent and Very Robust

Commenting on the study for theheart.org | Medscape Cardiology, Fernando Alfonso, MD, PhD, head of the Cardiac Department, La Princesa University Hospital, Madrid, Spain, called it a "uniquely large meta-analysis including all RCTs available in the coronary space" that was "very well conducted, from a methodological standpoint."

Alfonso, who is also the coauthor of an accompanying editorial and was not involved with the study, said the "results were always consistent and very robust."

In particular, one contribution of the meta-analysis was that they included the use of DCB for patients with in-stent restenosis and also for patients with de novo lesions, he observed.

The analysis has an important take-home message, Alfonso said.

"DCB are very safe when used in the coronary territory, with no sign of mortality risk or vessel thrombosis risk. In fact, in this study, a strong trend was found regarding safety when DCB were compared with different alternative therapeutic strategies."

Scheller added that, based on the findings of the meta-analysis, "the concept of 'leaving nothing behind' only with DCB thus appears very attractive and represents more than a niche indication."

Further, "the results — like many other data from the peripheral studies — question the findings of Katsanos," he noted. "A restriction of devices coated with paclitaxel to 'high' restenosis risk seems ethically questionable."

No source of study funding listed. Scheller is a shareholder of InnoRa GmbH and has been named as a coinventor on patent applications submitted by Charité University Hospital . The other authors disclosures are listed on the original paper. Alfonso reports no relevant financial relationships. His coauthors' disclosures are listed on the original editorial.

J Am Coll Cardiol. Published online March 2, 2020. Article, Editorial

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