IDEAL-LM (Improved Drug Eluting Stent for All-Comers Left Main) Trial

A prospective, randomized, multicenter study conducted for comparing a biodegradable polymer everolimus-eluting stent (BP-EES) followed by four months of dual antiplatelet therapy (DAPT) and a conventional durable polymer everolimus-eluting stent (DP-EES) followed by 12 months of DAPT in patients undergoing percutaneous coronary intervention (PCI) for unprotected left main coronary artery disease. 818 patients were included in the study and randomized to 1: 1. The primary endpoints were death due to all causes myocardial infarction and target vessel revascularization. At the end of the 2-year follow-up, non-inferiority for MACE was observed in 14.6% in BP-EES group and 11.4% in DP-EES group. No statistical difference was observed between the two groups in terms of ischemic events including stent thrombosis. However, no lower bleeding events were observed in the short-term DAPT group (2.7 percent for DP-EES versus 0.5 percent for DP-EES, p = 0.02).

COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) Trial

A randomized, parallel-controlled, open-label multicenter trial evaluating transcatheter mitral valve repair with the MitraClip device in patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation (MR) who remained symptomatic despite maximally-tolerated medical therapy (MMT). A total of 614 subjects were enrolled and randomized at 78 centers. Patients were 1:1 randomized into two groups: MMT and MMT + Mitraclip. Patients randomized to MMT were not allowed to switch to MitraClip before 24 months, but crossover was allowed after 24 months. The aim of the study was to evaluate the 3-year clinical outcome of mitraclip treatment for MMT, including patients who were cross-linked to the mitraclip group. At the end of 3 years, hospitalization due to heart failure was 220 in the MMT + Mitraclip arm and 378 in the MMT group (HR [95% CI] = 0.49 [0.37, 0.63], P = 0.00006). At the end of 3 years, all-cause mortality was 42.8% in the MMT + Mitraclip group (including cross-over) and 55.5% in the MMT group (HR [95% CI] = 0.67 [0.52, 0.85] P = 0.001).

PARTNER 2A (5-Year Outcomes From a Randomized Trial of Transcatheter vs. Surgical Aortic Valve Replacement in Intermediate-Risk Patients With Severe Aortic Stenosis)

The goal of this study was to compare the key clinical outcomes, bioprosthetic valve function, and quality-of-life measures in patients with severe aortic stenosis (AS) and intermediate surgical risk who underwent for Transcatheter aortic valve replacement (TAVR) versus surgery aortic valve replacement (SAVR) at five years. A total of 2032 subjects were enrolled and randomized at 57 centers. At five years, event rates for the primary endpoint of death or disabling stroke were 47.9% after TAVR and 43.4% after SAVR (HR: 1.09; 95% CI: 0.95 to 1.25; P=0.21). In the transfemoral cohort, there also was no difference at five years (44.5% TAVR versus 42.0% SAVR; HR: 1.02; 95% CI: 0.87 to 1.20; P=0.80).

However, in the transthoracic cohort, the rate of death or disabling stroke was significantly higher after TAVR (59.3% versus 48.3%; HR: 1.32; 95% CI: 1.02 to 1.71; P=0.03). In addition, early improvements in functional status and quality of life were maintained through five years for both TAVR and SAVR patients.

EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) Trial

The aim of the EXCEL study was to evaluate the effect of percutaneous coronary intervention (PCI) with second generation drug-eluting stent (DES)s on 5-year outcomes compared to CABG in patients with unprotected left main coronary (LMCA) lesions. 1905 patients with SYNTAX score <32 were randomized into PCI group (PCI with everolimus-eluting Xience stents) (948 patients) and CABG group (957 patients). During 5-year follow-up, primary combined endpoint (death, stroke, and MI) was 22% in the PCI group and 19.2% in the CABG group (p = 0.13). When the results were examined by dividing into three temporal-intervals, for the first 30-days, primary combined events was higher in the CABG group (4.9% vs. 8%, p = 0.008); for 30 days to 1 year, the event rates were similar between PCI and CABG groups (3.8% vs. 4.1%); for 1 to 5 years, the incidence of event rate was higher in PCI groups (15.1% vs 9.7%, HR 1.61; 95% CI 1.23-2.12). Secondary combined outcomes (death, stroke, MI, ischemia driven revascularization) were occured 31.2% in PCI group and 24.9% in CABG group (p = 0.002). Examining the events one by one; all-cause mortality was higher in the PCI group (13.0% vs 9.9%). There was no significant difference between PCI and CABG groups in terms of rates of cardiovascular mortality (5.0% to 4.5%), myocardial infarction (10.6% vs 9.1%) and stroke (2.9% vs 3.7%). Ischemia-driven revascularization was higher in the PCI group (10% compared to 16.9%). All cerebrovascular events (3.3% vs. 5.2%) and thrombotic events (stent thrombosis or symptomatic graft stenosis /occlusion) (1.6% vs. 6.5%) were higher in the CABG group. In conclusion, in unprotected LMCA lesions, PCI with second-generation DES was found to be non-inferior to CABG in terms of clinical outcomes at 5-year follow-up.

Onyx-One (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy (DAPT) for High-Bleeding Risk Patients) Trial

The aim of Onyx-One study was to compare the safety and efficacy of Resolute Onyx (durable polymer-based zotarolimus-eluting stent) DES with BioFreedom (polymer-free-biolimus-drug coated stent) DCS in patients with high bleeding risk who underwent PCI and received 1-month dual antiplatelet therapy. Patients (mean age: 74 years) were randomized into two groups as Resolute Onyx DES (n = 1,003 patients) and BioFreedom DCS (n = 993 patients), and received 1-month DAPT followed by single antiplatelet therapy for 1 year. Alternative stent crossover rates were quite frequent in the Biofreedom arm (2 versus 40, p <0.001). Resolute Onyx DES was noninferior for primary safety outcomes (cardiac death, MI, stent thrombosis) compared to Biofreedom DCS (17.1% vs. 16.9% (p for noninferiority = 0.011, p for superiority = 0.84).

Secondary outcome (1-year target lesion failure) rates were 18% for Resolute Onyx DES and 17.9% for Biofreedom. Comparing Resolute Onyx DES with Biofreedom DCS, rates of myocardial infarction (13.5% vs. 15.5% p = 0.50), cardiac death (4.6% vs. 3.9% p = 0.40) and stent thrombosis (2.2% vs. 1.5% p = 0.21) were similar. During 1-year follow-up, the rate of spontaneous MI was significantly higher in the Biofreedom arm (7.1% vs 4.6%; P = 0.02). Bleeding endpoint (Bleeding Academic Research Consortium 2-5 bleeding rates) was similar between Resolute Onyx and Biofreedom (15.1% vs. 13.7% (p = 0.4). In conclusion, Resolute Onyx DES was noninferior for BioFreedom DCS in terms of safety and efficacy at 1-year follow-up.

TWILIGHT (Ticagrelor with or without Aspirin in High-Risk Patients after PCI) Trial

In the TWILIGHT study; short-term dual antiplatelet therapy following by ticagrelor monotherapy was compared with 12-month DAPT treatment for safety and efficacy in patients with high risk for ischemia or bleeding and who were underwent PCI with drug eluting stents. Patients who received DAPT for 3 months after PCI, were divided into two arms as ticagrelor and ticagrelor + aspirin and followed up for 12 months. Bleeding as primary endpoint was occurred 4% in ticagrelor arm and 7.2% in ticagrelor + aspirin arm. The rate of secondary combined outcome (all-cause death, MI and stroke) was 3.9% in both groups (p <0.001 for non-inferiority). Stent thrombosis was observed in 0.4% of ticagrelor arm and 0.6% in ticagrelor + aspirin arm (p <0.05). In conclusion, compared to 12-month DAPT treatment, 3 months DAPT treatment followed by ticagrelor monotherapy resulted in lower rate of bleeding events and was found to be non-inferior for ischemic events.