Frequency of Angina Pectoris After Percutaneous Coronary Intervention and the Effect of Metallic Stent Type

Although metallic coronary stents significantly reduce angina pectoris compared with optimal medical therapy, angina after percutaneous coronary intervention (PCI) remains frequent. We, therefore, sought to compare the incidence of any angina during the 1 year after PCI among the spectrum of commercially available metallic stents. Metallic stent type was classified as bare metal stent, Cypher, Taxus Express, Xience V, Promus Element, and Resolute. The primary end point was patient-reported angina within 1 year of PCI. Multivariable logistic regression was performed to assess the independent association of stent type with any angina at 1 year. Overall, 8,804 patients were queried in regard to angina symptoms; 32.3% experienced angina at some point in the first year after PCI. Major adverse cardiovascular events, a composite of all-cause mortality, target vessel revascularization, and Q-wave myocardial infarction, increased with angina severity: 6.8% for patients without angina, 10.0% for patients with class 1 or 2 angina, and 19.7% for patients with class 3 or 4 angina (p <0.001 for trend). After multivariable adjustment, there was no significant association between stent type and angina at 1 year after PCI. Baseline Canadian Cardiovascular Society class 3 or 4 angina, history of coronary artery bypass grafting, and history of PCI were associated with a higher likelihood of angina at 1 year; increasing age, male gender, presentation with acute coronary syndrome, and higher stented length were associated with less angina. In conclusion, metallic stent type is not associated with the occurrence of angina at up to 1 year after PCI.

Metallic coronary stents, in comparison with optimal medical therapy, decrease the incidence and severity of angina pectoris. Angina, however, is remarkably frequent after percutaneous coronary intervention (PCI); in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, 34% of patients had experienced significant angina at some point in the year after PCI with bare metal stents (BMS). Despite its status as a patient-reported end point, anginal symptoms in patients with coronary artery disease (CAD) are also significantly associated with adverse cardiac events and mortality; indeed, this even applies to patients without demonstrable ischemia. Furthermore, patients with angina have increased health care costs and are at higher risk for rehospitalization than those without angina. Angina after PCI is at least in part driven by restenosis and progression of disease in other vessels, but such a high frequency of angina suggests that other factors may play a role. One such factor may be the metallic stent itself, which straightens the natural curvature of an epicardial coronary vessel and may lead to changes in vessel geometry, shear stress, and hemodynamics. Given that stents vary significantly in regard to design, drug elution, and architecture, the incidence of angina after PCI with different stents might vary as well. Angina after PCI, however, is inconsistently reported in clinical trials, and literature comparing angina outcomes among different types of stents is scant. We, therefore, sought to compare the incidence of any angina during the 12 months after PCI with BMS, first-generation drug-eluting stents (DES), and second-generation DES.


Clinical, procedural, and follow-up data for patients who underwent PCI with a commercially available stent at the Washington Hospital Center was prospectively entered into a database and retrospectively analyzed. This study included patients who underwent PCI from April 2003 to July 2014. Indications for PCI included stable angina, unstable angina, and acute myocardial infarction (MI). Patients were queried by telephone or in-person at 1 month, 6 months, and 1 year regarding symptoms of angina pectoris; if they reported angina, they were categorized as Canadian Cardiovascular Society (CCS) classes 1 through 4. Patients without information available regarding angina symptoms were excluded. In addition, anginal events within 7 days of PCI were excluded. Metallic stent type was classified as: BMS, Cypher (sirolimus eluting), Taxus Express (paclitaxel eluting), Xience V (everolimus eluting), Promus Element (everolimus eluting), and Resolute (zotarolimus eluting). Stent types were then combined into first-generation (Cypher and Taxus) and second-generation (Xience, Promus, and Resolute) groups for purposes of comparison.

All patients received aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) before or during the procedure. Anticoagulation regimens were chosen at the operator’s discretion and included unfractionated heparin targeted to achieve an activated clotting time of 200 to 300 seconds, with or without a glycoprotein IIb/IIIa inhibitor, or bivalirudin 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure. After the procedure, aspirin was prescribed indefinitely, and a P2Y12 inhibitor was recommended for a minimum of 1 month in patients receiving BMS and 12 months in those receiving DES.

The Institutional Review Board at the Washington Hospital Center and MedStar Cardiovascular Research Network (Washington, District of Columbia) approved this study. A dedicated data co-ordinating center performed all data management and analyses. Prespecified clinical and laboratory data during hospitalization periods were obtained from hospital charts reviewed by independent research personnel blinded to the objectives of the study. All patients routinely underwent pre- and post-PCI 12-lead electrocardiography to detect procedure-related ischemic changes and/or the presence of new pathologic Q waves. Blood samples at 6 and 24 h pre- and post-PCI were drawn to assess the creatine kinase-MB biomarker. If the creatine kinase-MB was elevated above the reference range (4 mg/dl), measurements were repeated every 8 hours until it returned to below the reference range. Clinical follow-up at 30 days, 6 months, and 1 year was conducted by telephone contact or office visits. In addition to angina, the occurrence of major clinical events at 1 year was recorded; this included all-cause mortality, Q-wave MI, target vessel revascularization (TVR), and stent thrombosis.

The primary end point was the occurrence of any angina during the 1 year after PCI; this included CCS class 1 to 4 angina, at any time point during follow-up. Secondary end points included all-cause mortality, Q-wave MI, TVR, and stent thrombosis; major adverse cardiac events were defined as the composite of these end points. Q-wave MI was defined as the appearance of new pathologic Q waves in the coronary distribution of the treated artery with an increase of creatine kinase-MB to ≥2 times the reference values. TVR was defined as revascularization occurring in any area along the previously treated vessel. Acute coronary syndrome (ACS) was defined as presentation with non–ST-elevation MI or ST-elevation MI. Major bleeding was quantified according to the Thrombolysis In Myocardial Infarction Study Group definition and consisted of intracranial hemorrhage or clinically overt bleeding with a decrease in hemoglobin of ≥5 g/dL or hematocrit of ≥15%.

Continuous variables are presented as mean ± SD; categorical variables are presented as percentages. Differences in continuous variables between groups were compared using Student’s t test. Categorical variables were compared using the chi-square or Fisher’s exact test when appropriate. Means for different groups were compared with an analysis of variance. A p value <0.05 was considered statistically significant. Kaplan-Meier analysis was used to analyze the association of stent type with the cumulative incidence of angina at 1 year. The primary outcome of any angina at 1 year was then compared among different metallic stent types using univariable logistic regression. To test the independent association of stent type and occurrence of angina after PCI, we constructed a multivariable logistic regression model. Covariables for the model were selected based on significant univariable p values and overall clinical relevance. Covariables in the model, in addition to stent type, included age (per 10 years), gender, presentation with ACS, current smoking, and a history of PCI, coronary artery bypass grafting (CABG), chronic renal insufficiency, diabetes mellitus, stented length (per 5 mm), and CCS class 3 or 4 angina at baseline. Covariables in the model are expressed as odds ratios with 95% confidence intervals. Statistical analyses were performed using SAS, version 9.1 (SAS Institute, Cary, North Carolina).


Overall, 8,804 patients underwent PCI with a metallic stent and had information available regarding angina symptoms during the first year after PCI. In regard to stent type, 19.2% received a BMS, 50.4% a first-generation DES, and 30.5% a second-generation DES. Certain co-morbidities were more common in patients receiving BMS, including older age, chronic renal insufficiency, congestive heart failure, and current smoking ( Table 1 ). Patients receiving BMS were also more likely to present with an ACS, cardiogenic shock, and baseline CCS class 3 or 4 angina. In regard to procedural characteristics, patients with BMS had shorter stented length (16.1 ± 5.9 mm) than either first- (20.0 ± 6.7 mm) or second-generation DES (18.2 ± 6.0 mm, p <0.001; Table 2 ). Glycoprotein IIb/IIIa inhibitor use decreased over time, as evidenced by more frequent use with BMS (7.6%) and first-generation DES (7.9%) than with second-generation DES (3.6%); heparin use, however, was relatively consistent across the stent types. Clopidogrel was almost exclusively used in the second-generation DES group (99.4%), whereas the use of ticagrelor and prasugrel was most common with second-generation DES (13.4% and 4.4%, respectively.)

Table 1

Baseline characteristics by stent type

Variable Bare metal
DES (n=4523)
DES (n=2713)
p value
Age (SD) 67.8 ± 12.9 64.9 ± 12.2 64.6 ± 11.0 <0.001
Male 1129 (64.6%) 2950 (65.2%) 1858 (68.5%) 0.006
White 1050 (60.1%) 3141 (69.4%) 1703 (62.7%) <0.001
Black 589 (33.7%) 1035 (22.9%) 859 (31.6%) <0.001
Asian 37 (2.1%) 200 (4.4%) 49 (1.8%) <0.001
Hispanic 22 (1.3%) 34 (0.8%) 26 (1.0%) 0.16
Acute coronary syndrome 585 (33.5%) 488 (10.8%) 449 (16.6%) <0.001
Cardiogenic shock on presentation 70 (4.0%) 89 (2.0%) 18 (0.7%) <0.001
CCS 3 or 4 baseline angina 950 (54.9%) 2281 (53.2%) 1124 (41.7%) <0.001
Previous PCI 337 (19.8%) 1250 (28.9%) 732 (27.3%) <0.001
Previous CABG 299(17.2%) 815 (18.1%) 512 (18.9%) 0.35
Diabetes mellitus 580 (33.3%) 1543 (34.5%) 1003 (37.1%) 0.02
Hypertension 1500 (86.0%) 3832 (84.8%) 2334 (86.0%) 0.28
Hyperlipidemia 1423 (81.5%) 3984 (88.5%) 2287 (84.3%) <0.001
Congestive heart failure 297 (17.1%) 571 (13.3%) 290 (10.7%) <0.001
Chronic renal insufficiency 354 (20.3%) 564 (12.5%) 390 (14.4%) <0.001
Peripheral vascular disease 258 (14.8%) 635 (14.1%) 382 (14.1%) 0.77
Current smoker 453 (25.9%) 873 (19.3%) 627 (23.1%) <0.001

CABG = coronary artery bypass grafting; CCS = Canadian Cardiovascular Society; PCI = percutaneous coronary intervention.

Table 2

Procedural characteristics (lesion based)

Variable Bare metal stent
stent (n=4525)
stent (n=2715)
p value
Intervention Vessel
Right 828 (38.3%) 2155 (31.1%) 1116 (30.8%) <0.001
Left main 33 (1.5%) 118 (1.7%) 82 (2.3%) 0.07
Left anterior descending 671 (31.0%) 2791 (40.3%) 1391 (38.3%) <0.001
Left circumflex 458 (21.2%) 1496 (21.6%) 879 (24.2%) 0.004
Saphenous vein graft 166 (7.7%) 335 (4.8%) 154 (4.2%) <0.001
Procedural success 1706 (97.6%) 4506 (99.6%) 2703 (99.6%) <0.001
Intravascular ultrasound 874 (40.4%) 4446 (64.6%) 2065 (56.8%) <0.001
Stented length (mm) 16.1 ± 5.9 20.0 ± 6.7 18.2 ± 6.0 <0.001
Vessels >50% stenosis 1.75 ± 0.82 1.82 ± 0.86 1.64 ± 0.78 <0.001
Lesions dilated 1.23 ± 0.58 1.50 ± 0.83 1.32 ± 0.63 <0.001
Heparin 246 (14.1%) 584 (12.9%) 368 (13.6%) 0.44
Bivalirudin 1448 (82.8%) 3515 (77.7%) 2402 (88.5%) <0.001
Glycoprotein IIb/IIIa inhibitor 133 (7.6%) 354 (7.9%) 97 (3.6%) <0.001
Clopidogrel 1602 (93.1%) 4442 (99.4%) 1185 (82.1%) <0.001
Prasugrel 88 (5.1%) 13 (0.3%) 193 (13.4%) <0.001
Ticagrelor 28 (1.6%) 0 64 (4.4%) <0.001

The incidence of any angina in the first year after PCI was quite common at 32.3%. In regard to individual stents, the incidence of any angina at 1 year was numerically highest for Xience at 36.9%, followed by BMS (34.2%), Taxus (30.2%), Cypher (29.6%), Resolute (27.3%), and Promus (25.9%). In regard to the unadjusted time-to-event Kaplan-Meier analysis, the cumulative incidence of angina at 1 year was highest for Cypher, approaching 50% ( Figure 1 ). The occurrence of major adverse cardiac events at 1 year was highest among patients who reported class 3 or 4 angina and lowest among those without angina after PCI ( Table 3 ). This difference was because of higher rates of TVR and Q-wave MI in the patients with angina; there was no statistically significant difference in the rates of all-cause mortality between patients with angina and those without. There also appeared to be a higher rate of stent thrombosis in patients with class 3 or 4 angina (2.0%), compared with those with class 1 or 2 angina (0.4%) or no angina (0.3%; p <0.001 for trend). In regards to individual stent type, unadjusted rates of TVR at 1 year were highest in patients receiving BMS, at 8.2%. Among patients receiving DES, TVR at 1 year was highest with Cypher at 7.9%, followed by Taxus at 6.0%, Xience at 5.5%, Promus at 4.2%, and Resolute at 4.0%.

Figure 1

Cumulative incidence of any angina at 1 year by stent type.

Table 3

Major adverse cardiac events at 1 year by worst angina severity (unadjusted)

Variable CCS Class 0 CCS Class 1
or 2
CCS Class 3
or 4
p value
All-cause mortality 3.1% 2.0% 2.3% 0.07
Q-wave myocardial infarction 0.2% 0.3% 1.2% <0.001
Target vessel revascularization 3.9% 8.0% 17.8% <0.001
Target lesion revascularization 2.6% 5.3% 11.4% <0.001
Stent thrombosis 0.3% 0.4% 2.0% <0.001
Major adverse cardiac events 6.8% 10.0% 19.7% <0.001

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Nov 27, 2016 | Posted by in CARDIOLOGY | Comments Off on Frequency of Angina Pectoris After Percutaneous Coronary Intervention and the Effect of Metallic Stent Type

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