Long-Term Clinical Outcome of Early Generation Versus New-Generation Drug-Eluting Stents in 481 Patients Undergoing Rotational Atherectomy: A Retrospective Analysis

For all cases, RA was performed using the CE-marked Rotablator device (Boston Scientific Scimed Inc., Maple Grove, MN, USA). The burr size was selected aiming at a burr/vessel ratio of 0.5 (max. 0.7 if needed). Rotational speed ranged between 140,000 and 180,000 rotations per minute (rpm). To prevent slow-flow, a continuous intracoronary infusion of unfractioned heparin (UFH), nitroglycerine and verapamil was used during RA. Prior to RA, patients were treated with 325–500 mg aspirin intravenously and an oral loading dose of a P2Y12 inhibitor (Clopidogrel, Prasugrel or Ticagrelor). In addition, patients were administrated a periprocedural anticoagulation with either UFH intra-arterially or bivalirudin. The use of glycoprotein IIb/IIIa inhibitors was at the operator’s discretion. Technical details of RA at our institution have been reported in previous publications [8].

RA was defined as elective in the absence of any previous attempt to cross the lesion with a balloon or a stent. Angiographic success was defined as a final residual stenosis < 30% and grade 3 thrombolysis in myocardial infarction (TIMI) flow. During hospitalization, occurrence of any adverse event and any additional coronary intervention were registered. Periprocedural myocardial infarction following PCI was defined as CK-MB elevation > 3 times the upper range limit of normal at 48 h after the procedure. Major adverse cardiac events (MACE) were defined as all cause death, spontaneous myocardial infarction (MI) and target vessel revascularization (TVR). Death was classified as either cardiac or non-cardiac, and death of unknown cause was adjudicated as cardiac death. Stent thrombosis and myocardial infarction (MI) were defined according to the Academic Research Consortium [15]. TVR was defined as any repeat PCI or surgical bypass of the target vessel. Finally, target lesion revascularization was defined as any repeat revascularization either with PCI or coronary artery bypass graft (CABG) for restenosis or other complication inside the stent implanted during the index procedure or within 5 mm proximal or distal to the stent.

Survival times for the two groups were also compared using Cox proportional hazard model. Multivariable method was used to allow for differences in profile between the EG and NG-DES groups. The following covariates were considered: age, gender, diabetes mellitus, hypertension, dyslipidemia, current smoking, family history of coronary artery disease, previous MI, previous PCI, previous CABG, left ventricular ejection fraction, glomerular filtration rate (GFR) < 30 ml/min, lesion type B2/C, chronic total occlusions (CTO), multivessel coronary disease, culprit lesion in the left main (LMT) coronary artery and acute coronary syndrome (ACS). Covariates to be used in multivariable models were found in two stages, first omitting variables with p value > 0.1 in a model just including the variable and group and then carrying out a backward elimination procedure with the remaining variables. In the backward elimination procedure, non-significant variables were dropped one-by-one until only significant variables remained in the model. All reported p values were two-sided, and p values < 0.05 were considered statistically significant. Statistical analysis was performed using Stata SE 14 (StataCorp LP, College Station, TX, USA) and SAS version 9.4 (SAS Institute Software GmbH, Vienna, Austria) statistical software.

Baseline clinical characteristics are reported in Table 1. The mean age of the study population was 72 ± 8 years and 353 patients (73.3%) were males. Left ventricular ejection fraction (LV-EF) was reduced in 29.2% of the patients. 24.7% of RA was performed in patients presenting with an acute coronary syndrome. EG-DES and NG-DES patients were not significantly different in the latter aspects. However, significantly more patients in the EG-DES group had dyslipidemia (75.6% vs. 61.1%; p = 0.001), a family history of premature coronary artery disease (26.3% vs. 16.8%; p = 0.014) or MI (25.7% vs. 16.4%; p = 0.014), while in the NG-DES group diabetes mellitus (31.9% vs. 40.9%; p = 0.04) and multivessel coronary artery disease (82.5% vs. 90.9%; p = 0.008) were more frequent.

Lesion characteristics and procedural details are presented in Table 2. In general, the NG-DES cohort had more complex lesions and more complex procedures. In the NG-DES group 39 lesions were located in LMT whereas only 22 lesions involving the LMT were treated in the EG-DES group (p < 0.001). Furthermore, the number of CTO in the NG-DES group was significantly higher (3.5 vs. 8.5%; p = 0.016). Patients who received NG-DES after RA had a significantly higher rate of multiple stent implantation (48.6 vs. 63.1%; p = 0.001) as well as a longer median stent length (30.5, IQR 20–40 mm vs. 38, IQR 22–53 mm; p < 0.001). High angiographic success rates were achieved in both groups (97.2 vs. 96.9%; p = 0.82). Iatrogenic coronary perforation occurred in only one case in the EG-DES but was reported in seven patients in the NG-DES group (p = 0.012). Other procedural complications were rare and similar between the groups.

In-hospital death occurred in 1.1 and 1.4% of the patients in the EG-DES and NG-DES group, respectively (p = 0.77). All deaths were due to cardiovascular cause. Thirty-two patients developed MI during hospitalization (6.6%), of which three were Q-wave MI. Overall, the incidence of peri-procedural MI was higher in the group of patients who received NG-DES after RA (8.9%) compared to the patients who were treated with EG-DES (4.8%) even though statistical significance was not reached (p = 0.07). In-hospital TVR (0.8% vs. 0.5%, p = 0.57) and TLR (0.4% vs. 0.5%, p = 0.69) were not significantly different between EG-DES and NG-DES groups.

Long-term clinical follow-up was available in 457 patients with a median follow-up period of 32 months (IQR 23–60) in the EG-DES group and 17 months in the NG-DES population (IQR 12–31) (Fig. 1). There was no significant difference between the groups for the estimated rate of MI (4.9% vs. 4.1%, log rank p = 0.89) and TVR (17.6% vs. 12.9%, log-rank p = 0.19) at 2 years, with a trend towards a lower rate of TLR (12.7% vs. 7.9%, log-rank p = 0.13) in the NG-DES group. All-cause mortality was numerically higher in the EG-DES group (13.5% vs. 8.2%, log-rank p = 0.13) due to a significantly higher incidence of death from non-cardiovascular causes (8.2% vs. 1.5%, log rank p = 0.05). Cardiovascular mortality was not significantly different (5.8% vs. 6.8%, log-rank p = 0.64). However, the Kaplan–Meier estimated rate of MACE showed a significant reduction in the EG-DES group (31.1% vs. 21.1%, log-rank p = 0.04) (Fig. 1). By multivariable analysis, the use of new-generation DES was independently associated with a lower incidence of all cause mortality (HR 0.49; 95% CI 0.26–0.92; p = 0.03), and the superiority of NG-DES for reducing MACE rate was confirmed (HR 0.65; 95% CI 0.42–0.98; p = 0.04) (Fig. 2). Cardiovascular mortality was not statistically different between the two groups (HR 0.82; 95% CI 0.37–1.85) as well as the incidence of definite and probable stent thrombosis (0.9% in the EG-DES and 2.4% in NG-DES group, log-rank p = 0.13, adjusted HR 3.33; 95% CI 0.64–17.28; p = 0.15).

Some limitations of the current study need to be mentioned. First, the analysis was conducted in a single-center, retrospective and non-randomized study and therefore has all the limitations of an observational study. Second, both study groups were not uniform in the components of the stents, but represent common patterns of both DES generations. Third, the groups were treated at different time periods and thus operator experience might have influenced the results. Fourth, many differences were observed between the groups in their clinical and angiographic baseline characteristics. Furthermore, some important parameters that could influence outcome such as the use of intravascular imaging and duration of dual anti-platelet therapy were not collected and analyzed in the registry. Additionally, the clinical implication of this study is limited with the fact that currently almost all patients are treated with NG-DES. Finally, the difference observed in all cause morality could be the result of a degree of unmeasured confounding in this study. Although meticulous statistical methods have been used to adjust for baseline differences, unmeasured confounders can never be excluded. Nevertheless, the analyzed data is from one of the largest cohort of patients treated with RA and a high rate of long-term clinical follow-up was achieved.