Key Points
- Drug-eluting stents are the standard of care for percutaneous coronary intervention of de novo coronary lesions but nevertheless have a risk of stent thrombosis and in-stent restenosis. Drug coated balloons may offer an alternative treatment strategy.
- REC-CAGEFREE I was an open label, randomized non-inferiority trial comparing drug-coated balloon angioplasty with drug eluting stent among 2272 patients with acute and chronic coronary syndromes and de novo coronary lesions.
- Over 24 months of follow-up, the composite endpoint of cardiac death, target lesion myocardial infarction, and clinically and physiologically indicated target vessel revascularization occurred in 6.4% of patients in the drug-coated balloon angioplasty arm and 3.4% in the drug-eluting stent arm failing to meet the criterion for non-inferiority.
Currently, drug eluting stents are favored over plain old balloon angioplasty for the purposes of percutaneous coronary intervention due to lower rates of repeat revascularization. Nevertheless, they are limited by chronic inflammation which can result in stent thrombosis and a 2% annual rate of in-stent restenosis. Drug-coated angioplasty is a contemporary novel treatment method for obstructive coronary artery disease which enables the delivery of anti-proliferative medications into the arterial wall. Their potential role in treating de novo coronary lesions irrespective of diameter size is not well studied.
REC-CAGEFREE I was a randomized, open-label, non -inferiority trial which randomized 2272 patients from 43 medical centers in China with acute or chronic coronary syndrome to receive drug-coated balloon angioplasty versus primary stenting for the treatment of de novo lesions. Patients randomized to the drug coated balloon arm received paclitaxel-coated balloon angioplasty with bailout second-generation sirolimus-eluting stent if angioplasty was unsuccessful. Patients randomized to primary stenting received a second-generation sirolimus-eluting stent. The primary endpoint was a Device oriented Composite Endpoint (DoCE) which is a composite endpoint of cardiac death, target vessel myocardial infarction, and clinically or physiologically indicated target vessel revascularization at 24 months. The trial excluded individuals with prior intracranial hemorrhage, atrial fibrillation on anticoagulation, prior coronary artery bypass grafting, cardiogenic shock, persons with specific allergies (such as aspirin and contrast), and those with a life expectancy of less than 2 years.
The median age at the time of randomization was 62 years (interquartile range 54–69 years). Approximately 31% of the study participants were female and 27% had diabetes. All patients were of Chinese ethnicity. The majority of participants had acute coronary syndrome; 45% had chronic coronary syndrome. The median follow-up time was 734 days (interquartile range 731–739 days). At 24 months, the composite endpoint occurred in 72 (6.4%) of the 1133 patients treated with drug coated balloon angioplasty and 38 (3.4%) of 1139 who were treated with primary drug eluting stenting. This corresponded to a risk difference of 3.04% (upper boundary of the one-sided 95% CI 4·52) in the cumulative event rate which was above the prespecified threshold for non-inferiority (Pnon-inferiority = 0.65). There were higher rates of clinically and physiologically indicated target lesion revascularization among patients treated with drug coated balloon angioplasty (3.1% vs 1.2%, P=0.002). Of the 1133 patients treated with drug coated balloon angioplasty, 106 (9.4%) required rescue stenting after unsatisfactory balloon angioplasty. Periprocedural MIs occurred at similar rates in both treatment groups (0.9% vs 0.8%). There was heterogeneity in the study results based on size of the target lesion (Pinteraction=0.02). Among patients with small target vessel size (<3.0 mm), treatment with drug-coated balloon angioplasty was associated with similar DoCE compared to those treated with drug eluting stents.
The study investigators concluded that drug eluting stent implantation “should remain the preferred treatment strategy” for treatment of de novo acute and chronic coronary syndromes, especially for non-small vessel disease.