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Two years since the SWEDEPAD trial was halted over safety concerns with paclitaxel-coated devices in peripheral artery disease (PAD), an interim analysis of the resumed trial showed no association between these devices and mortality.

All-cause mortality during an average 2.49 years and up to 4 years of follow-up occurred in 25.5% of people receiving drug-coated balloons and stents and 24.6% of controls receiving uncoated alternatives (HR 1.06, 95% CI 0.92-1.22), according to Mårten Falkenberg, MD, PhD, of Sweden's Gothenburg University, and colleagues.

Excess deaths weren't seen either in those with chronic limb-threatening ischemia (33.4% vs 33.1%) or with intermittent claudication (10.9% vs 9.4%), Falkenberg's group reported in an interim analysis published online in the New England Journal of Medicine.

"The SWEDEPAD trial was not primarily intended for analysis of total mortality," they cautioned. "The main purpose was to determine whether drug-coating technology ultimately improves the lives of patients with symptomatic PAD by preventing amputations and improving health-related quality of life."

"The rationale for publishing these total mortality data ahead of completion of the trial is twofold. First, we sought to reduce patients' and physicians' concerns regarding the safety of paclitaxel-coated devices, and second, we considered the data to be important to support completion of ongoing trials investigating the efficacy of such devices in PAD," according to the SWEDEPAD group.

Safety concerns of paclitaxel-coated stents and balloons in PAD had been sparked by a suggesting an increase of long-term mortality risk. Days later, the SWEDEPAD and trials of drug-coated devices were halted as a precaution.

What ensued was a "scientific and clinical deadlock," in the words of Falkenberg and colleagues. Various groups, including the Vascular Interventional Advances physician group, reaffirmed the safety concern in their own analyses. This was backed by the FDA, which advised clinicians to consider alternative PAD treatments for their patients.

Yet the growing evidence seemed to point toward the lack of a late mortality signal. Moreover, critics of the 2018 meta-analysis have noted the lack of a plausible mechanism by which paclitaxel use in endovascular interventions would result in mortality, as well as the potential biases in many of the trials originally included in that report.

In 2019, both SWEDEPAD and BASIL-3 resumed enrollment.

investigators recruited adults with symptomatic PAD for random assignment to paclitaxel-coated and uncoated device groups. The interim analysis included the 2,289 patients who were already enrolled when the trial was paused on Dec. 10, 2018. Patients were followed for up to 4 years.

Study participants belonged to one of two cohorts: those with chronic limb-threatening ischemia (mean age 76.8 years, 55.1% men) and peers with intermittent claudication (76.8 years, 54.3% men). Those groups were randomized separately to drug-coated and uncoated device groups.

In total, there are 3,733 people planned for the final efficacy assessment of the trial, according to the investigators. There are separate primary efficacy endpoints for each cohort.

The open-label design of SWEDEPAD could be a source of bias, Falkenberg's team cautioned. The group added that the definitiveness of the mortality results in patients with intermittent claudication was limited by the small number of deaths in that cohort.

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