https://orcid.org/0000-0001-9456-9852
Figures
Abstract
Background
Patients with peripheral arterial disease (PAD) have known to a high risk of cardiac mortality. However, the effectiveness of the routine evaluation of coronary arteries such as routine coronary angiography (CAG) in PAD patients receiving percutaneous transluminal angioplasty (PTA) is unclear.
Methods
A total of 765 consecutive PAD patients underwent successful PTA and 674 patients (88.1%) underwent routine CAG. Coronary artery disease (CAD) was defined as angiographic stenosis ≥70%. Patients were divided into three groups; 1) routine CAG and a presence of CAD (n = 413 patients), 2) routine CAG and no CAD group (n = 261 patients), and 3) no CAG group (n = 91 patients). To adjust for any potential confounders that could cause bias, multivariable Cox-proportional hazards regression and propensity score matching (PSM) analysis was performed. Clinical outcomes were evaluated by Kaplan-Meier curved analysis at 5-year follow-up.
Results
In this study, the 5-year survival rate of patients with PAD who underwent PTA was 88.5%. Survival rates were similar among the CAD group, the no CAD group, and the no CAG group, respectively (87.7% vs. 90.4% vs. 86.8% P = 0.241). After PSM analysis between the CAD group and the no CAD group, during the 5-year clinical follow-up, there were no differences in the incidence of death, myocardial infarction, strokes, peripheral revascularization, or target extremity surgeries between the two groups except for repeat PCI, which was higher in the CAD group than the non-CAD group (9.3% vs. 0.8%, P<0.001).
Conclusion
PAD patients with CAD were expected to have very poor long-term survival, but they are shown no different long-term prognosis such as mortality compared to PAD patients without CAD. These PAD patients with CAD had received PCI and/or optimal medication treatment after the CAG. Therefore a strategy of routine CAG and subsequent PCI, if required, appears to be a reasonable strategy for mortality risk reduction of PAD patients. Our results highlight the importance for evaluation for CAD in patients with PAD.
Citation: Choi BG, Hong J-Y, Rha S-W, Choi CU, Lee MS (2021) Long-term outcomes of peripheral arterial disease patients with significant coronary artery disease undergoing percutaneous coronary intervention. PLoS ONE 16(5): e0251542. https://doi.org/10.1371/journal.pone.0251542
Editor: Xianwu Cheng, Nagoya University, JAPAN
Received: July 29, 2019; Accepted: April 28, 2021; Published: May 19, 2021
Copyright: © 2021 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper.
Funding: This work was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (Project Number: 9991006707, KMDF_PR_20200901_0034).
Competing interests: The authors have declared that no competing interests exist.
Introduction
Peripheral arterial disease (PAD) reduces the quality of life and is associated with poor long-term clinical prognosis [1,2]. Also, coronary artery disease (CAD) is a leading cause of death in many geographies of the world [3]. It shares many risk factors with PAD including age, smoking, diabetes, and chronic kidney disease [2–4]. Because atherosclerosis is a systemic process that can affect multiple vascular territories, patients with either PAD or CAD commonly have the other condition [1,2,5,6]. The severe CAD has been observed in 54% to 69% of patients with PAD [7–10]. Patients with PAD have particularly a high mortality rate from cardiovascular events [6,11–13]. Thus, patients with both PAD and CAD are expected to have a particularly poor long-term prognosis.
Percutaneous transluminal angioplasty (PTA) is commonly used to improve claudication of the extremities and treat critical limb ischemia [7,14]. The use of cardio-protective drugs such as antiplatelet therapy, statin, and angiotensin-converting enzyme inhibitors in PAD helps to improve survival, but the introduction of these guidelines is more than a decade behind CAD [15]. Therefore, evaluating the presence of CAD, which can lead to coronary revascularization and optimal medical treatment, can improve both short- and long-term surviaval in patients receiving PTA [8,16,17]. However, the effective of routine evaluation of coronary arteries in patients receiving PTA is unclear [11,18]. In the present study, we evaluated the long-term clinical outcomes of the strategy of routine coronary angiography (CAG) and subsequent percutaneous coronary intervention (PCI) in patients with PAD who underwent PTA.
Methods
We obtained data from PTA registry of Korea University Guro Hospital (KUGH), Seoul, South Korea. This registry has been described in detail in previous studies [8,19,20]. In brief, this is a single-center, prospective, all-comers registry which started in 2006 and was designed to reflect “real world” practice. Data are collected by trained study-coordinators using standardized case report forms.
Ethical approval
Participants or their legal guardians were given a thorough literal and verbal explanation of the study procedures before asking for written consent to participate in the study. The study protocol was approved by the Medical Device Institutional Review Board (MD-IRB) of KUGH (IRB protocol #MD12018).
Data source and population
A total of 765 consecutive PAD patients underwent successful PTA and 674 patients underwent routine CAG. For the remaining 91 patients who did not receive the CAG, but the cardiac function was evaluated non-invasively by the cardiologist. CAD was defined as angiographic stenosis ≥70% in the main epicardial coronary vessels. Patients were divided into three groups; 1) routine CAG and a presence of CAD (the CAD group: 413 patients), 2) routine CAG without CAD (the no CAD group: 261 patients), and 3) no CAG group (91 patients).
Percutaneous transluminal angioplasty
Standard techniques were used for PTA. For below-the-knee lesions, a 5 Fr Heartrail guiding catheter (Terumo) was used, and a 0.014˝ guidewire was used to traverse the lesions. If intraluminal wiring failed, sub-intimal angioplasty or retrograde approach was performed. After guidewire crossing, prolonged balloon inflation with a balloon ranging in size from 1.5–3.0 mm was used for infra-popliteal vessels and 4–7 mm for femoro-popliteal vessels. Provisional stenting was performed using self-expanding nitinol stents (Xpert, Abbott Vascular, or Maris Deep; Medtronic-Invatec) if balloon angioplasty results were suboptimal. For the ilio-femoral lesion, 6 or 7 F guiding sheath was placed and true lumen angioplasty was attempted to treat chronic total occlusion (CTO) of the superficial femoral artery (SFA) and iliac artery using dedicated 0.018˝ CTO wires. If the intraluminal approach was unsuccessful, subintimal angioplasty using 0.035˝ soft Terumo wire (1.5 J curve) with a 5 Fr angiocatheter support was performed for longer CTO lesions with prolonged balloon inflation with adequate size. If balloon angioplasty results were favorable, PTA with drug-coated balloons (DCB) was performed. If the balloon angioplasty result was suboptimal, provisional stenting with self-expanding nitinol stents or drug-eluting stents was performed. Wiring of the true lumen was performed for shorter CTO lesions. Re-entry with CTO wires or a re-entry device (Outback catheter, Cordis) was used if the subintimal wiring failed to re-enter the distal true lumen for femoropopliteal CTO lesions. A retrograde approach from the distal SFA, popliteal, or infra-popliteal arteries was used in selected cases.
Study definitions [21,22]
PAD was defined as ischemic pain at rest, an ulcer, or gangrene in one or both legs attributed to objectively proven arterial occlusive disease. The main epicardial coronary arteries were defined as having a reference vessel diameter of >2.5 mm at left main-, left anterior descending-, left circumflex-, right coronary-, and the ramus artery. Major adverse cardiovascular and cerebrovascular events (MACCE) were defined as the composite of total death, myocardial infarction (MI), stroke, and revascularization including PCI and coronary artery bypass graft (CABG). Target lesion revascularization (TLR) was defined as ischemia-induced PTA of the target lesion due to restenosis or re-occlusion within the balloon angioplasty site, stent, or in the adjacent 5 mm of the distal or proximal segment. Target extremity revascularization (TER) was defined as clinically-driven PTA of the target lesion or any segment of the same limb containing the target lesion. Major adverse limb events (MALE) were defined as the composite of TER and target extremity surgery.
Statistical analysis
Differences in continuous variables, among the three groups, were evaluated by ANOVA or Kruskal-Wallis, and post-hoc analysis between the two groups were evaluated by Hochberg or Dunnett-T3 test. Differences in continuous variables between the two groups were evaluated using the unpaired t-test or Mann-Whitney rank test. Data are expressed as means ± standard deviations. For discrete variables, differences are expressed as counts and percentages and were analyzed with the χ2 test or Fisher’s exact test. Multivariable Cox-proportional hazards regression, which includes baseline-confounding factors, was used for assessing independent impact factors. To adjust for any potential confounders, propensity score matching (PSM) analysis was performed using a logistic regression model. Matching was performed with a 1:1 matching protocol using the nearest neighbor matching algorithm with a caliper width less than 0.01 the standard deviation of the propensity score. Clinical outcomes that occurred over a period of 5-year were analyzed by Kaplan-Meier analysis, and differences between groups were compared with the log-rank test before and after PSM. For all analyses, a two-sided p < 0.05 was considered statistically significant. All data were analyzed using SPSS (version 20.0, SPSS-PC, Inc. Chicago, Illinois).
Study endpoints
Primary endpoints were MACCE as the composite of total death, MI, stroke, revascularization such as PCI and CABG at 5-year follow-up. Secondary endpoints were TLR, TER, and target extremity surgery after PTA at 5-year clinical follow-up. Patients were followed up at one month and then every 6 months after the PTA procedure as well as whenever cardiovascular ischemic symptoms occurred. Follow-up was performed with face-to-face interviews at the regular outpatient clinic, medical chart reviews, and/or telephone contact.
Results
A total of 765 consecutive PAD patients underwent successful PTA and 674 patients subsequently underwent a routine CAG. The baselines clinical characteristics were similar between the CAG group (the CAD group and the no CAD group) and the no CAG group. In the CAG group, a total of 61.2% patients (413/674) were diagnosed with severe CAD in the main epicardial coronary arteries. Among the patients with CAD, 15.0% (62/413) and 59.0% (244/413) had left main disease and multi-vessel disease, respectively. Among the CAD patients, 71.6% (296/413) treated CAD lesions by PCI and/or CABG, during or after the PTA admission period based upon the physician’s discretion. The CAD group had more elderly patients, diabetics, and higher levels of creatinine than patients in the no CAD group (Table 1). The no CAD group had a higher prevalence of Buerger’s disease and were more likely to be current smokers and alcohol drinkers than the CAD group. The CAD group had a higher prevalence of femoral lesions (49.9% vs. 40.8%, p = 0.011) (Table 2).
Procedural and in-hospital complications after PTA were similar among the three groups (Table 3). The CAD group received more clopidogrel, sarpogrelate, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers (ARB), β-blocker than the non-CAD, and no-CAG group (Table 3).
In this study, the 5-year survival rate of patients with PAD who underwent PTA was 88.5%. Survival rates were similar among the CAD group, the no CAD group and the no CAG group up to 5-year of clinical follow-up, respectively (87.7% vs. 90.4% vs. 86.8% P = 0.241) (Table 4, Fig 1). There was a trend toward a higher incidence of cardiac death in the no CAG group (3.0% vs. 0.8% vs. 3.6%, P = 0.066) than the CAD group and the no CAD group. Coronary revascularization was higher in the CAD group (9.4% vs. 0.8% vs. 4.9% P = 0.005). There was no difference between the two groups in PTA-related events such as peripheral revascularization or target extremity surgery (Table 4).
Figure A,C,E, and G show an Un-adjusted hazard ratio by Cox-proportional hazards regression analysis. Figure B,D,F, and H show an adjusted hazard ratio by Cox-proportional hazards regression analysis. Adjusted confounders are Wound, Sex, Age, Hypertension, Diabetes mellitus, Chronic Renal Insufficiency, Current of smoking, treated limb side, and treated lesion (femoral, Popliteal, and Below the knee artery). MACCE, major adverse cerebrovascular and cardiac events; CI, confidence interval; CAD, coronary artery disease; CAG, coronary angiogram.
PSM analysis between the CAD group and the non-CAD group yielded two matched groups (160 pairs, n = 320) with balanced baseline characteristics (Tables 1–3). There were no differences in MI, strokes, peripheral revascularization, or target extremity surgeries between the two groups over the 5-year clinical follow-up period except for non-cardiac death and coronary revascularization. The non-cardiac death was higher in the non-CAD group (5.1% vs. 12.0%, P<0.001) but the coronary revascularization was higher in the CAD group (8.5% vs. 0.0%, P<0.001) (Table 4).
Discussion
The main finding of this study is that routine CAG and subsequent PCI for significant CAD in symptomatic PAD patients undergoing PTA is safe and resulted in similar long-term survival as compared with the symptomatic PAD patients who undergoing PTA and who did not have CAD. Not surprisingly, repeat PCI was performed more frequently in PAD patients with CAD at long-term follow-up.
The summarize of this study is that PAD patients with CAD were expected to have very poor long-term survival, but they are shown no different long-term prognosis such as mortality compared to PAD patients without CAD. These PAD patients with CAD had received PCI and/or optimal medication treatment after the CAG. Considering the high mortality rate of patients with PAD [15], the imaging evaluation of the coronary arteries such as the CAG in PAD patients is important for improving their long-term survival.
PTA is commonly performed to treat PAD patients such as critical limb ischemia (CLI). Both PAD and CAD are known to be associated with a poor quality of life and a poor prognosis [1,2,5,7]. These diseases share most risk factors, and are often comorbid. The best treatment option for these patients may be lifestyle modification and early prevention through global risk reduction [4,14,16,17]. In addition, evaluation of coronary arteries along with subsequent optimal treatment of PAD patients undergoing PTA may improve survival [6,8,11,13,18]. However, an effects on a routine evaluation of the coronary artery such as routine CAG and echocardiography has been controversial in patients undergoing PTA in terms of cost effectiveness. The majority of CAD patients who received PCI in our study received elective PCI. The COURAGE Trial shown that PCI may not have the advantage in stable CAD patients [23]. Also, some clinician can think of it, regardless of symptoms, doing PCI based on CAG results can be an excessive treatment. However, a large number of patients receiving PTA are CLI patients such as wounds and diabetic foot ulcer. Two-thirds of our study population is CLI. Most CLI patients may have limited activity, making it difficult to clearly assess coronary function and associated with less ischemic symptoms. Higher prevalence of advanced PAD patients also associated with higher incidence of silent myocardial ischemia. Our research results provide insight into the long-term clinical effects of active PCI for CAD patients according to routine evaluation of coronary artery and treatment decisions by clinician in PAD patients undergoing PTA. In real world clinical practice, physicians who are performing endovascular intervention commonly only focusing on the extremity target lesion intervention without concerning of CAD evaluation and management [15]. Also, the use of cardio-protective drugs such as antiplatelet therapy, statin, and ACE inhibitors in PAD helps to improve survival, but the introduction of these guidelines is more than a decade behind CAD [15]. Thus, main intention of this report is to provoke all the endovascular intervention specialties should check patient’s co-existing significant CAD and to have an idea to safely manage the CAD together to prevent future cardiovascular events. Routine CAD checkup is not commonly widely accepted in daily clinical practice, especially in terms of cost-effectiveness but this should be changed according to our novel data.
Generally, severe CAD is reported in 54% to 69% of patients with CLI [7–10]. In the present study, 61.2% of patients with PAD were diagnosed with severe CAD. Left main disease and multi-vessel disease were observed at frequencies of 15% and 59%, respectively, in the CAD patients, which portend poor prognosis if left undiagnosed and untreated. Therefore, prompt diagnosis of life-threatening CAD and appropriate revascularization may improve clinical outcomes. Similary, Faglia et al., reported that attention to CAD at the time of admission for treatment of CLI improves the survival of patients with diabetes [11].
Aforementioned in introduction part, patients with PAD have particularly a high mortality rate from cardiovascular events [6,15]. Mortality rates of up to 20% within 6 months from diagnosis and in excess of 50% at 5 years have been reported for CLI [15]. On the other hand, in our study, the mortality rates of PTA patients were significantly lower than the previous studies. The present observation of long-term clinical results of 5-years in patients undergoing PTA, mortality rates were similar among the CAD group, the non-CAD group and the no-CAG group, respectively (12.3% vs. 9.6 vs. 13.2%). This means that the imaging evaluation of the coronary arteries in PAD patients is important for improving their long-term survival and prevent of MI.
After PSM analysis, coronary revascularization remained higher in the CAD group than the non-CAD group, highlighting the fact that repeat coronary revascularization remains a problem in CAD patients. Also, regardless of the baseline risk adjustment, there was no difference between the two groups in PTA-related events such as peripheral revascularization or target extremity surgery. The strategy for CAD evaluation and treatment in PTA patients seems to be a safe and effective strategy not only for better short-term outcomes but also durable long-term outcomes. Similar to our research, Chen and colleagues have registered the multi-center randomized controlled trial (NCT02169258) “Routine Coronary Catheterization in Low Extremity Artery Disease Undergoing Percutaneous Transluminal Angioplasty (PIROUETTE-PTA)” at ClinicalTrials.gov [18]. Estimated enrollment is 700 participants and the primary endpoint of the study was composite major adverse cardiac events at the 1-year follow-up.
There are some limitations to our study. First, the results of our study were derived indirectly by comparison with the survival rates of other studies. In general, the 5-year survival rate of PAD patients is around 50% [15], and the survival rate of our study subjects, 88.5%, was very high. The no CAG group without cardiac function evaluation should be allocated to verify the effectiveness of routine CAG in PAD patients, but this is a problem that may be against research ethics. In this study, PTA was performed by an interventionist based on cardiology, the cardiac function of all subjects was evaluated non-invasively and/or invasively by the cardiologist. Therefore, the no CAG group in this study should not be confused with the patients that did not perform cardiac function evaluation. Second, we analyzed data retrospectively, and PSM analysis was performed to minimize confounding factors, which could have affected our results. The registry was designed as an all-comers prospective registry from 2006. However, we could not adjust for all limiting factors not shown in medical records or collected through telephone contact. Third, in the PSM analysis, a total of 320 patients from 160 pairs in both groups were analyzed. This sample size may be insufficient to produce results. Our study is a registered observational study and may be a limitation of analysis. As Chen and colleagues’ research results come out, the results will be updated a bit (18).
In conclusion, a strategy of routine CAG and subsequent PCI, if required, appears to be a reasonable strategy for significant PAD patients undergoing PTA. Our results highlight the importance of CAD evaluation in patients with PAD. A result of randomized trial is needed to assess the efficacy and safety of this treatment strategy for PAD patients finally [18].
References
- 1. Ouriel K (2001) Detection of peripheral arterial disease in primary care. JAMA 286: 1380–1381. pmid:11560546
- 2. Regensteiner JG, Hiatt WR, Coll JR, Criqui MH, Treat-Jacobson D, et al. (2008) The impact of peripheral arterial disease on health-related quality of life in the Peripheral Arterial Disease Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) Program. Vasc Med 13: 15–24. pmid:18372434
- 3. Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, et al. (2017) Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. J Am Coll Cardiol 70: 1–25. pmid:28527533
- 4. Selvin E, Erlinger TP (2004) Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999–2000. Circulation 110: 738–743. pmid:15262830
- 5. Hussein AA, Uno K, Wolski K, Kapadia S, Schoenhagen P, et al. (2011) Peripheral arterial disease and progression of coronary atherosclerosis. J Am Coll Cardiol 57: 1220–1225. pmid:21371639
- 6. Jeremias A, Gruberg L, Patel J, Connors G, Brown DL (2010) Effect of peripheral arterial disease on in-hospital outcomes after primary percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 105: 1268–1271. pmid:20403477
- 7. Faglia E, Dalla Paola L, Clerici G, Clerissi J, Graziani L, et al. (2005) Peripheral angioplasty as the first-choice revascularization procedure in diabetic patients with critical limb ischemia: prospective study of 993 consecutive patients hospitalized and followed between 1999 and 2003. Eur J Vasc Endovasc Surg 29: 620–627. pmid:15878541
- 8. Lee MS, Rha SW, Han SK, Choi BG, Choi SY, et al. (2015) Clinical outcomes of patients with critical limb ischemia who undergo routine coronary angiography and subsequent percutaneous coronary intervention. J Invasive Cardiol 27: 213–217. pmid:25840405
- 9. Nishijima A, Yamamoto N, Yoshida R, Hozawa K, Yanagibayashi S, et al. (2017) Coronary Artery Disease in Patients with Critical Limb Ischemia Undergoing Major Amputation or Not. Plast Reconstr Surg Glob Open 5: e1377. pmid:28740785
- 10. Ryu HM, Kim JS, Ko YG, Hong MK, Jang Y, et al. (2012) Clinical outcomes of infrapopliteal angioplasty in patients with critical limb ischemia. Korean Circ J 42: 259–265. pmid:22563339
- 11. Faglia E, Clerici G, Caminiti M, Quarantiello A, Curci V, et al. (2008) Advantages of myocardial revascularization after admission for critical limb ischemia in diabetic patients with coronary artery disease: data of a cohort of 564 consecutive patients. J Cardiovasc Med (Hagerstown) 9: 1030–1036. pmid:18799966
- 12. Parikh SV, Saya S, Divanji P, Banerjee S, Selzer F, et al. (2011) Risk of death and myocardial infarction in patients with peripheral arterial disease undergoing percutaneous coronary intervention (from the National Heart, Lung and Blood Institute Dynamic Registry). Am J Cardiol 107: 959–964. pmid:21256469
- 13. O’Rourke DJ, Quinton HB, Piper W, Hernandez F, Morton J, et al. (2004) Survival in patients with peripheral vascular disease after percutaneous coronary intervention and coronary artery bypass graft surgery. Ann Thorac Surg 78: 466–470; discussion 470. pmid:15276497
- 14. Pentecost MJ, Criqui MH, Dorros G, Goldstone J, Johnston KW, et al. (1994) Guidelines for peripheral percutaneous transluminal angioplasty of the abdominal aorta and lower extremity vessels. A statement for health professionals from a special writing group of the Councils on Cardiovascular Radiology, Arteriosclerosis, Cardio-Thoracic and Vascular Surgery, Clinical Cardiology, and Epidemiology and Prevention, the American Heart Association. Circulation 89: 511–531. pmid:8281692
- 15. Teraa M, Conte MS, Moll FL, Verhaar MC (2016) Critical Limb Ischemia: Current Trends and Future Directions. J Am Heart Assoc 5. pmid:26908409
- 16. Iqbal J, Zhang YJ, Holmes DR, Morice MC, Mack MJ, et al. (2015) Optimal medical therapy improves clinical outcomes in patients undergoing revascularization with percutaneous coronary intervention or coronary artery bypass grafting: insights from the Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) trial at the 5-year follow-up. Circulation 131: 1269–1277. pmid:25847979
- 17. Stone KE, Chiquette E, Chilton RJ (2007) Diabetic endovascular disease: role of coronary artery revascularization. Am J Cardiol 99: 105B–112B. pmid:17307063
- 18. Chen IC, Lee CH, Chao TH, Tseng WK, Lin TH, et al. (2016) Impact of routine coronary catheterization in low extremity artery disease undergoing percutaneous transluminal angioplasty: study protocol for a multi-center randomized controlled trial. Trials 17. pmid:26927298
- 19. Lee MS, Rha S-W, Han SK, Choi BG, Choi SY, et al. (2015) Gender Differences in Endovascular Revascularization for Peripheral Arterial Disease. Vascular Disease Management 12: 117–125.
- 20. Lee MS, Rha SW, Han SK, Choi BG, Choi SY, et al. (2015) Comparison of diabetic and non-diabetic patients undergoing endovascular revascularization for peripheral arterial disease. J Invasive Cardiol 27: 167–171. pmid:25740971
- 21. Diehm N, Baumgartner I, Jaff M, Do DD, Minar E, et al. (2007) A call for uniform reporting standards in studies assessing endovascular treatment for chronic ischaemia of lower limb arteries. Eur Heart J 28: 798–805. pmid:17317699
- 22. Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, et al. (2007) Clinical end points in coronary stent trials. Circulation 115: 2344–2351. pmid:17470709
- 23. Boden WE, O’Rourke RA, Teo KK, Hartigan PM, Maron DJ, et al. (2007) Optimal medical therapy with or without PCI for stable coronary disease. New England Journal of Medicine 356: 1503–1516. pmid:17387127