Influence of Frequency of Stenting on Acute and One-Year Follow-up Results

Stents were introduced as a bail-out therapy for threatened abrupt closure1–5 following plain balloon coronary angioplasty. They were subsequently demonstrated to lower the restenosis rates in selected patient populations.6–8 The smooth appearance of the vessel after stenting has seduced the interventionist. The stenting rates are reported to be approximately 70%9 and move toward 100%. Stenting, albeit an essential and effective tool, has downsides such as stent thrombosis (still a concern in spite of newer antiplatelet drugs) and intricate in-stent restenosis. The long and diffuse variety of in-stent restenosis has been the bane of stenting, with only partial reprieve provided with the use of costly intracoronary radiation.10 Even the promising drug-eluting stents will not eliminate this problem. Increased stent use has resulted in higher coronary angioplasty costs.11 This will be further compounded with the ever-growing use of stents. There are other problem areas and limitations of stent use, such as the increased loss of sidebranches in bifurcating lesions and compromised results in small vessels and diffuse coronary arteries.12 The no-flow phenomenon has increased in the wake of the universal adoption of stenting and has engendered the call for time and money-consuming protection devices. The major purpose of this study was to investigate whether a higher frequency of stenting afforded benefits in unselected populations. Methods Study population. Retrospective data of a total of 322 consecutive patients undergoing coronary angioplasty at our center by the 2 experienced operators were obtained from the hospital data bank. Patients undergoing intervention for acute myocardial infarction were excluded from the analysis. Baseline characteristics, post-intervention markers of ischemia (CK, CK-MB and troponin T) and in-hospital major cardiac events (MACE) were tabulated. Follow-up data on MACE were obtained from other hospitals, our outpatient clinic, the referring physicians, and from the patients or their relatives, and was complete as per our records. Definitions. CK values at least 3 times the baseline value with at least 1 additional criterion (elevated CK-MB, typical pain or new Q-waves) were considered proof of periprocedural myocardial infarction. Coronary artery disease was considered significant if the stenoses were visually estimated at > 50%. Stent-like result after coronary angioplasty was defined as Statistics. Baseline characteristics were presented in means and standard deviations (SD) or frequencies (%). Comparisons between groups and categorical variables were performed with the Chi-square test (or Fisher’s exact test if there were fewer than 5 expected observations). For comparisons of continuous variables, paired or unpaired t-tests were used. Two-sided p-values of 0.05 and less are reported. Results Of the 322 consecutive patients, a total of 212 were treated by the most generous stent user (operator 1: 71% stenting) and 110 by the most frugal stent user (operator 2: 49% stenting). Both operators were highly experienced and skilled, with several thousand angioplasties on their account. Baseline characteristics including age, sex, hypertension, diabetes mellitus, multivessel angioplasty and use of glycoprotein IIb/IIIa inhibitors were comparable in the 2 groups. Total stent length (16 ± 6 mm versus 15 ± 5 mm), stents per patient (1.4 ± 0.7 versus 1.4 ± 0.70) and stent diameter (3.1 ± 0.5 mm versus 3.1 ± 0.5 mm) were also comparable (Table 1). In-hospital outcomes: Markers of ischemia. No statistically significant difference was observed in the 2 groups regarding post-intervention acute markers of ischemia: CK (418 ± 744 versus 427 ± 1250; p = 0.33), CK-MB (105 ± 159 versus 239 ± 263; p = 0.07) and troponin T (149 ± 326 versus 282 ± 380; p = 0.3). In-hospital outcomes: MACE. In-hospital major cardiovascular events were no different in either group [4/212 (2%) versus 2/110 (1.8%); p = 0.51)] (Table 2) with 1 patient in each group needing a repeat TLR for stent thrombosis. No patient in either group needed an emergency bypass operation and there was no mortality (Table 2). The remaining events in both groups were enzymatic infarcts, which were attributed to sidebranch occlusion (jailing by stents) or distal embolizations. Follow-up MACE. One-year follow-up data were obtained in all patients. There was no statistically significant difference regarding MACE [44/212 (21%) versus 20/110 (18%); p = 0.58] (Table 3) between the 2 groups, with 11 deaths (5%) and 4 deaths (4%) at 1 year in the respective groups (p = 0.73). Repeat PTCA (16% versus 10%; p = 0.2) and coronary artery bypass graft surgery (2% versus 3%; p = 1.00) (Table 3) at 12 months were also comparable, but clearly not in favor of the higher stenting rate. Subgroup analysis of follow-up MACE in diabetics (8/34 versus 3/20; p = 0.51) (Table 4) in patients with single-vessel angioplasty (14/155 versus 2/88; p = 0.8) and multivessel angioplasty (31/47 versus 18/22; p = 0.29) (Table 5) failed to demonstrate any significant statistical difference between the respective groups. MACE were similar, irrespective of vessel size, in each group (Table 6). Discussion The asset of coronary stents to the armamentarium of percutaneous coronary intervention can hardly be overemphasized. Stents have reduced the incidence of acute complications and need for emergency surgery in poor results after balloon angioplasty. They also reduced restenosis in selected patients.3,4,11,13–19 This has led to a proliferation of stent use, with studies recommending elective over selective stenting.20,21 However, stents have limitations. The acute increase in lumen dimensions is partially offset by enhanced neointimal proliferation leading to in-stent restenosis, which is more difficult to treat than unstented restenosis, and has a high rate of recurrence.22–25 Results in small vessels have been varied, with no real long-term benefit demonstrated over plain balloon angioplasty except in focal STRESS study-type lesions.12,26,27 Stents in bifurcating lesions carry an increased risk of sidebranch occlusion, reported at 8–29%.28 This is one of the major causes of periprocedural enzyme elevation and myocardial infarction, with at least one-third of cases of enzyme rise attributed to it.29–31 In-stent restenosis may be partially prevented with the use of intracoronary radiation,10 but this has its own limitations and is expensive. The issue of restenosis may be alleviated with the promising results of drug-eluting stents, e.g., sirolimus; however, these results need to be substantiated for all comers. As for now, stent use should be judicious. It has been reported that balloon angioplasty obtaining stent-like results achieved similar results compared to elective stenting.32,33 Ten-year results regarding TLR were significantly lower for patients with stent-like results (23% versus 32%; p = 0.003).34 In addition, a study demonstrates the beneficial results of stents in highly selected populations, with exclusion of more than 80% of cases not fulfilling STRESS-like criteria.35 In such cases, the 1-year MACE rate was two-fold higher in ineligible patients compared with eligible patients.35 On the basis of these results, the concept of provisional stenting for selected cases was suggested.36 This strategy appears more cost effective. The retrospective analysis of our patients comparing the most generous with the most frugal stent user demonstrated no statistical difference as regards periprocedural enzyme release or MACE up to 1-year follow-up. The results of our analysis are in agreement with the results of the analysis of 2 major clinical trials,37,38 in which the aggressive balloon angioplasty arm demonstrated a 6-month TLR of 17% with crossover stent rate of approximately 14%. Similar results were also reported from the BENESTENT-I trial for the stent-like result group, with a 1-year event-free survival rate of 77%.39 Our results are not in agreement with those reported by Hannal et al.40 In these patients, the 2-year bypass surgery rate (11% for provisional stenting versus 7% for elective stenting) and repeat angioplasty rate (19% versus 14%) were in favor of stenting. However, this amounts to only a 5% benefit. This means that to benefit 1 patient, twenty patients need to be stented (cost, approximately $20,000). It is of note that the benefit does not consist of survival or prevention of infarction, but mainly in sparing a repeat intervention, which can be performed at a lesser price. Moreover, these results cannot be generalized for small vessels and vessels with diffuse disease. With the availability of potent platelet glycoprotein IIb/IIIa inhibitors as protective shields, attempts at aggressive balloon angioplasty to obtain stent-like results have become safer, to the end of a larger lumen without increased risk of abrupt vessel closure. The only downside is that one might have to wait for a few minutes16,41 to assess the dilated segment for recoil or threatened closure. In our opinion, aggressive balloon angioplasty with the selective use of stenting for complications or suboptimal balloon results may be a more effective strategy and stenting should remain an adjunct to balloon angioplasty rather than becoming a sine qua non. Study limitations. First, there is the retrospective design; second, there was no subanalysis of the stent versus no stent subgroups; third, patients with acute myocardial infarctions were excluded; fourth, restenosis rates were not assessed angiographically; and fifth, there may have been some underreporting of events (however, these should affect both groups equally). Conclusion. The fact that in the pre-stent era about 70% of angioplasty patients did not suffer an acute event or restenosis dictates that stents will be beneficial for about 25% of patients at the maximum (30% of patients with problems after balloon angioplasty minus about 5% of patients with problems after stenting). Since it is impossible to predict all patients likely to benefit from stenting, some overstenting is in order; however, 100% stenting is clearly not justified. This study shows that increasing the stenting rate from about 50% to 70% of patients does not beneficially influence in-hospital and 1-year follow-up events.

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