T he invention of balloon angioplasty as a percutaneous treatment for obstructive coronary disease by Andreas Gruntzig in 1977 was a huge leap forward in cardiovascular medicine and undoubtedly will always be remembered as a revolution in the field of revascularization. However, this technique was plagued by multiple problems, including the risk of acute vessel closure secondary to occlusive coronary dissection, sometimes necessitating emergency coronary artery bypass surgery. 1-3 Although late luminal enlargement and vascular remodeling could take place, more often restenosis 4 -8 would occur instead. The restenosis would essentially be caused by constrictive remodeling 9 -13 and, to a lesser extent, by elastic recoil 14 or the neointimal hyperplastic healing response. [15][16][17] The advent of bare metal stenting (BMS) and the landmark Belgian-Netherlands Stent Study (BENESTENT) and Stent Restenosis Study (STRESS) trials have established BMS as the second revolution in interventional cardiology. 18,19 This technology provided a solution to acute vessel occlusion by sealing the dissection flaps and preventing recoil. The rate of subacute occlusion was reduced to 1.5%, making emergency bypass surgery a rare occurrence. Restenosis rates were further reduced from 32% to 22% at 7 months, but this rate was still high, and neointimal hyperplasia inside the stent was even more prominent than with angioplasty, necessitating repeat treatment in numerous patients. 18 Because the vessel was now caged with metal, late luminal enlargement and advantageous vascular remodeling could no longer occur. Another problem, namely late stent thrombosis (ST), was also first described. 20 To solve the problem of in-stent restenosis, after the historic failure of brachytherapy to resolve this problem, 21,22 drug-eluting stents (DES) were introduced. The first 45 patients implanted with the sirolimuseluting Bx velocity stent (Cordis, Johnson & Johnson, Warren, NJ) were found to have negligible neointimal hyperplasia at follow-up. 23,24 This was confirmed in the randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization (RAVEL) study. 25,26 The introduction of DES was thus dubbed the third revolution in interventional cardiology. Both large-scale randomized trials and all-comer registries showed excellent results in terms of the need for repeat revascularization. However, the early enthusiasm has been tempered in recent years after widespread concerns about the increased risk of late and very late ST. [27][28][29][30][31] Registries of all comers treated with DES showed late ST rates of 0.53%/y, with a continued increase to 3% over 4 years. 32,33 In the Arterial Revascularization Therapies Study II (ARTS II) trial, which enrolled patients with complex multivessel disease, the rate of combined definite, probable, and possible ST was as high as 9.4% at 5 years, accounting for 32% of major adverse cardiovascular events (MACEs). 34 In addition, postmortem pathological specimens of DES revealed sig...