DÄ internationalArchive15/2009Different Treatment Options in Chronic Coronary Artery Disease

Review article

Different Treatment Options in Chronic Coronary Artery Disease

When Is It the Time for Medical Treatment, Percutaneous Coronary Intervention or Aortocoronary Bypass Surgery?

Dtsch Arztebl Int 2009; 106(15): 253-61. DOI: 10.3238/arztebl.2009.0253

Ruß, M; Cremer, J; Krian, A; Meinertz, T; Werdan, K; Zerkowski, H

Background: 3% to 4% of the population suffers from chronic coronary artery disease (CAD). Primary care physicians, internists, cardiologists, and cardiac surgeons are involved in their long-term care. This article presents a complementary care pathway that integrates two apparently competing treatment options, aortocoronary bypass surgery (ACB) and percutaneous coronary intervention (PCI). Together with lifestyle changes and medical therapy, these treatments reduce morbidity and mortality and improve quality of life.
Methods: This article was written by cardiac surgeons and cardiologists on the basis of the current treatment guidelines for coronary artery disease, a selective review of the literature (randomized, controlled trials and registry data), and a process of interdisciplinary consensus building.
Results and conclusions: Lifestyle changes can reduce cardiovascular risk factors, improve quality of life, and lower cardiovascular morbidity and mortality. They provide additional benefit over and above medical therapy and/or revascularization procedures and should be strongly recommended to all patients. Revascularization is not indicated for patients who are asymptomatic on medical therapy or who have only a small area of myocardial ischemia. With either PCI or ACB, the symptoms of angina pectoris can be markedly improved, or even eliminated. Both of these revascularization procedures should be accompanied by optimized medical treatment. Revascularization is indicated when the area of myocardial ischemia is large, whether or not symptomatic angina is present. ACB is the treatment of choice for 3-vessel disease and/or left main stenosis. For all other constellations of coronary findings, ACB and PCI are equally good therapeutic options. The treating physician should take the patient's expectations into account and present the short- and long-term benefits and drawbacks of each proposed treatment to the patient so that an informed decision can be made.
Dtsch Arztebl Int 2009; 106(15): 253–61
DOI: 10.3238/arztebl.2009.0253
Key words: coronary heart disease, chronic disease, cardiac surgery, bypass surgery, ischemia
LNSLNS Approximately 3% to 4% of the population suffers from chronic coronary artery disease (CAD) (1). The long-term care of these patients involves primary care physicians, internists, cardiologists, and cardiac surgeons. Up to a few years ago, chronic CAD, principally manifested by stable angina pectoris, was thought to be a steadily progressing process culminating in myocardial infarction. Now that the pathogenesis of the acute coronary syndrome has been clarified, however—with rupture or erosion of a vulnerable plaque as the triggering event—it seems that stable CAD and acute coronary syndrome (ACS) are different manifestations of coronary atherosclerosis with differing prognoses. Thus, each requires its own treatment strategy: in ACS the most important measures are swift diagnosis and revascularization (2), while in stable CAD the choice has to be made between revascularization (percutaneous coronary intervention or aortocoronary bypass surgery) and exclusively medical treatment.

The goal of this review is to demonstrate how the apparently competing surgical options—aortocoronary bypass (ACB) and percutaneous coronary intervention (PCI)—can be sensibly integrated into a complementary treatment plan. Together with lifestyle modification and medical treatment, in this way the patients' quality of life can be improved and morbidity and mortality lowered.

Methods
This review was performed jointly by cardiac surgeons and cardiologists. It is based on the current management guidelines for CAD, a review of the literature with continuous searching of the Medline database (PubMed) (randomized controlled trials and registry data), and a process of interdisciplinary consensus building.

The authors drew upon the German interdisciplinary National Disease Management Guideline "Chronische Koronare Herzkrankheit" (Chronic Coronary Artery Disease), an exemplary guideline that has achieved broad consensus among the various disciplines involved (3). It was decided not just to analyze the results of randomized controlled trials but to include the complementary data from large registries.

Results and discussion
Treatment goals
The targets of treatment of chronic CAD (box 1 gif ppt) are on one hand improvement of the prognosis, on the other an increased quality of life for the patients, with a minimum of procedural complications. All those participating in treatment should follow the guideline recommendations or base their actions on the best available evidence.

Lifestyle modification and medical treatment
The cornerstones of the treatment plan for stable CAD are on one hand healthy living (lifestyle modification) and on the other full exploitation of the medical treatment options (box 2 gif ppt). The results that can be achieved are comparable to those of PCI, and not only in patients with a lower coronary risk constellation (4) or in those more highly motivated to exercise (5). Also in patients with coronary three-vessel disease and proximal stenosis of the left anterior descending artery (LAD) (6, e1), medical conservative treatment matches primary revascularization by means of PCI for the criterion "mortality." Even for the goal "improvement in quality of life," the difference is only slight. However, both patient and physician face challenges if the "conservative" treatment goals (as in the COURAGE study) (box 2) (6) are to be achieved.

Revascularization goal: elimination of myocardial ischemia
The indication for interventional (box 3 gif ppt) or surgical (box 4 gif ppt) coronary revascularization is usually determined on the basis of the morphology as revealed by angiography. However, revascularization yields convincing results primarily when management focuses not only on symptomatic reduction of angina but also on objective elimination of the ischemic zone (7). The latter can be demonstrated in a stress test by, for example, electrocardiography (ECG), echocardiography, magnetic resonance imaging (MRI), myocardial scintigraphy, or positron emission tomography (PET).

Revascularization by PCI and ACB is superior to solely medical treatment for moderate to severe myocardial ischemia, when more than 10% of the myocardium is ischemic, but revascularization has no advantage when less than 10% of the myocardium is involved (figure gif ppt) (8). The greater the extent of myocardial ischemia in a patient with chronic CAD, the higher the risk of myocardial infarction or a fatal heart attack. Hence revascularization should be preferred in extensive myocardial ischemia, because it reduces the ischemia more effectively than the currently available medical treatment options. It remains to be shown whether new pharmacological approaches (ivabradine [e2], ranolazine, new antithrombotics) can improve the medical conservative treatment of ischemia.

Today, the standard means of demonstrating myocardial ischemia is either by stress ECG or by imaging (echocardiography, scintigraphy, or MRI) under conditions of physical or pharmacological stress. Measurement of the fractional flow reserve (FFR) with a pressure wire (i.e., measurement of trans-stenotic intracoronary pressure gradient before and after maximal vessel dilation) permits estimation of the functional significance of a coronary stenosis (9) during cardiac catheterization.

Knowing the significance of myocardial ischemia, invasive coronary diagnosis is indicated when ischemia has been sufficiently demonstrated by noninvasive means and the patient would be in agreement with revascularization if extensive myocardial ischemia were found. In routine practice, however—at least in the USA—the demonstration of ischemia is frequently not performed (e3).

ACB or PCI? What do the guidelines say?
Whatever procedure is used to treat stable angina pectoris—conservative medical, PCI, ACB—the management must be oriented on the treatment goals (box 1). With an annual incidence of myocardial infarction of 3% to 3.5% and overall 5-year mortality of 8%, the treatment goals include not only reduction of disease-related mortality but also, above all, reduction of cardiovascular morbidity (major adverse cardiovascular events [MACE], e.g., re-PCI, re-ACB, cardiovascular related death, nonfatal myocardial infarction, hospitalization for cardiac insufficiency, stroke) and improvement of the patients' quality of life.

Depending on the treatment goal, the treating physician's discussion of the advantages and disadvantages of PCI and ACB (table 1 gif ppt) with his/her patient can lead to different conclusions.

The National Disease Management Guideline "Chronische Koronare Herzkrankheit" (Chronic Coronary Artery Disease) (www.versorgungsleitlinien.de) (3) states that PCI or ACB are indicated in patients in whom stable angina pectoris (CCS class III and IV) persists after medical treatment according to the guideline ("angina indication") or in whom noninvasive diagnostic measures have satisfactorily demonstrated ischemia ("ischemia indication"). The recommendations regarding revascularization are presented in table 2 (gif ppt).

Comparison of ACB and PCI—impact on cardiovascular mortality
Finding: coronary multi-vessel disease
ACB is the method of choice for coronary three-vessel disease (see the legend accompanying table 2), particularly in patients with restricted pump function.

The most recent meta-analysis, published in 2007 (10), embraced 23 studies and a total of 10 000 patients (only one study with a drug-eluting stent). It showed only a small difference in 5-year survival rate between ACB (90.7%) and PCI (89.7%). Procedural strokes were significantly more common after ACB (1.2%) than after PCI (0.6%). With regard to the treatment goal of freedom from angina pectoris after 5 years, ACB (84%) was more successful than PCI (79%) (p<0.001). The rate of repeat revascularization within 5 years was 46.1% after coronary angioplasty without a stent and 40.1% after stent implantation, but only 9.8% in patients treated with ACB (p<0.001). Patients with marked coronary findings seemed to have a lower risk of mortality with ACB, while PCI appeared more favorable in this respect for patients with less severe findings (10).

New York registry data on 17 000 patients with coronary multi-vessel disease compared the results of ACB and implantation of a drug-eluting stent (DES), thus complementing early data comparing ACB and a non-drug-coated ("bare metal") stent (11):

After risk adjustment, ACB patients had a 20% lower (hazard ratio [HR] 0.80) 18-month mortality (survival rate 94.0% vs. 92.7%, p=0.03). The combination of death and myocardial infarction was 25% lower (HR 0.75) and the rate of survival without myocardial infarction was higher in the ACB group (92.1%) than in the DES group (89.7%). More favorable results for ACB were also found in the subgroup of patients with coronary two-vessel disease (death: HR 0.71; survival rate 96.0% vs. 94.6%, p<0.003; death and myocardial infarction: HR 0.71; survival without myocardial infarction: 94.5% vs. 92.5%, p<0.0001). Moreover, ACB patients less often have to undergo repeat revascularization.

In summary, registry analyses show that even when a DES is implanted, ACB achieves a higher survival rate than treatment by PCI in three-vessel disease. Moreover, ACB patients less frequently require repeat revascularization and suffer less disease-related impairment of quality of life.

In patients with previous interventional treatment, it must be established in each individual case to what extent antithrombocytic or anticoagulation treatment should be continued right up to the time of operation. Recent findings indicate that PCI-pretreated patients with multi-vessel disease may have a higher surgical risk (e4), and this must be considered when choosing the primary strategy. In patients in whom a stent was implanted uncritically problems may be encountered finding a favorable site for a bypass anastomosis. In other words: extensive PCI treatments can eliminate surgical options.

Finding: left main stenosis
The superiority of ACB over medical treatment for left main stenosis has been demonstrated in subgroup analyses of large randomized studies, e.g., the Coronary Artery Surgery Study (CASS) (12). There is a lack of such studies, however, enabling comparison of ACB and PCI. Early observational studies of PCI treatment for left main stenosis showed that good acute success rates were accompanied by a high rate of severe complications; however, these studies included a high proportion of patients treated for acute myocardial infarction, cardiogenic shock, and/or multimorbidity. The results achieved with DES in elective patients with left main stenosis have been quite encouraging (e5), and recent registry studies (13, 14) based on a propensity score have also revealed only slight differences from ACB. Nevertheless, the recurrence rates remain high in bifurcation stenoses, and stent thromboses are still particularly dangerous.

In view of the available data, ACB is the primary treatment procedure for stenosis of the "unprotected" main stem of the left coronary artery (i.e., neither the LAD nor the LCX [left circumflex artery] is bypassed). PCI is reserved for individual cases in which the stenosis and vessel situation is favorable, e.g., collaterals, or in which surgery would be problematic.

Finding: coronary single-vessel disease with severe proximal LAD stenosis
Proximal LAD stenoses and their revascularization are of particular significance for the prognosis, because the area of the left ventricle supplied by the LAD is often larger than that supplied by the LCX and the right coronary artery together.

On the basis of this experience ACB and PCI (implantation of a bare metal stent) were compared in patients with isolated severe proximal LAD stenosis. In the Medicine, Angioplasty, or Surgery Study (MASS) (15), the internal thoracic bypass was inserted conventionally, while in two other studies (16, 17) a minimally invasive technique was used to insert the internal thoracic bypass. The mortality was low overall, and the studies found no difference between ACB and PCI or between MIDCAB (minimally invasive direct coronary artery bypass) and PCI.

Following surgical revascularization angina pectoris also occurs less frequently in single-vessel disease, so there is less need for repeat revascularization. Bypass surgery, preferably MIDCAB, is therefore the procedure of choice after unsuccessful PCI or re-stenosis of proximal LAD stenoses (e2).

Comparison of ACB and PCI—impact on angina pectoris and MACE rates
Both ACB and PCI reduce the symptoms of angina pectoris more effectively then medical treatment. Bypass surgery leads to very good medium- and long-term amelioration of angina pectoris. Renewed revascularization—repeated bypass surgery or PCI—is seldom necessary. In this regard surgical revascularization performs significantly better than PCI. This is due particularly to the problem of re-stenosis after percutaneous transluminal coronary angioplasty (PTCA; i.e., only balloon dilatation, no stent implantation) or PCI. The introduction of uncoated and drug-coated stents reduced the necessity for repeat revascularization after 1 to 3 years from 30% to 15–20% and to 5–10%, respectively (e13). In the case of drug-coated stents, however, this came at the price of a slightly higher rate of late stent thromboses.

It is positive that in the case of an in-stent re-stenosis following PCI a single re-intervention usually suffices to achieve a stable long-term result (e6). All comparative studies convincingly demonstrate that the higher MACE rate of PTCA/PCI can be overwhelmingly attributed to the higher rate of re-intervention; the differences were at most slight for the other MACE criteria, e.g., death from cardiac causes, nonfatal myocardial infarction, or hospitalization for cardiac insufficiency.

Coronary revascularization in the elderly
In contrast to the widely held belief, revascularization—both interventional and surgical—represents a reasonable treatment option in older people (>75 years) with CAD (table 2). Surprisingly, registry studies showed higher 4-year survival rates in elderly patients treated with ACB or PCI than in those who received only medical treatment. The success of therapy was more pronounced for bypass surgery than for PCI (18). Above all, however, even at advanced age revascularization leads to a clear reduction in symptom severity without an accompanying increase in 1- and 4-year mortality (19, 20). On the other hand, in about 40% of elderly patients purely medical treatment does not control the symptoms adequately and revascularization becomes necessary (e7).

Of course, the decision regarding revascularization in the elderly will be influenced by the increased risk attendant upon intervention and the existence of any comorbidity. In the pre-stent era PTCA involved a 2 to 4 times greater periprocedural risk than in younger patients, but the difference has been greatly narrowed by stent implantation with optimized accompanying medical treatment. Comorbid conditions such as renal insufficiency or chronic obstructive pulmonary disease favor PCI over ACB.

Coronary revascularization in patients with chronic renal insufficiency and diabetes mellitus
Not only terminal renal insufficiency represents a hazard. Even moderate chronic renal insufficiency, with a glomerular filtration rate (GFR) of 59 to 30 mL/min, raises the relative risk of morbidity and mortality for ACB (e8):

- Perioperative mortality 1.55-fold
- Stroke 1.47-fold
- Prolonged ventilation 1.49-fold
- Deep sternal infection 1.25-fold
- Re-operation 1.3-fold
- Longer hospital stay (>14 days) 1.54-fold
- New dialysis requirement 4.65-fold.

PCI also involves an increased risk of morbidity and mortality in patients with renal insufficiency (21), so that neither form of revascularization is currently recommended over the other. On the basis of these figures, great caution should be exercised when deciding whether revascularization is indicated, particularly if the principal aim is to ameliorate the symptoms.

Diabetes mellitus worsens the prognosis with regard to mortality and morbidity, both for surgical and for interventional revascularization. Subgroup analyses in a few studies (e.g. the BARI study) have found an advantage for surgical revascularization, but this effect has not been shown consistently in other studies. The FREEDOM Study can be expected to clarify this point (e9).

Acknowledgement
The authors thank the president of the German Cardiac Society (DGK) and the German Society for Thoracic, Cardiac, and Vascular Surgery (DGTHG) for initiating this consensus paper. They thank Prof. Friedhelm Beyersdorf, Freiburg; Prof. Martin Borggrefe, Mannheim, Prof. Hans-Reiner Figulla, Jena, Prof. Hermann Reichenspurner, Hamburg, and Prof. Christian Hamm, Bad Nauheim, for fruitful discussions during preparation of the manuscript.

Conflict of interest statement
Professor Werdan has received financial support for research projects and honoraria from Servier for his work on the Advisory Board and as consultant. The remaining authors declare that no conflict of interest exists according to the guidelines of the International Committee of Medical Journal Editors.

Manuscript received on 20 November 2008, revised version accepted on
4 February 2009.

Translated from the original German by David Roseveare.


Corresponding author
Prof. Dr. med. Karl Werdan, Dr. med. Martin Ruß
Universitätsklinik und Poliklinik für Innere Medizin III
Universitätsklinikum der Martin-Luther-Universität Halle-Wittenberg
Ernst-Grube-Str. 40
06120 Halle (Saale), Germany
karl.werdan@medizin.uni-halle.de, martin.russ@medizin.uni-halle.de
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Klinik und Poliklinik für Innere Medizin III, Universitätsklinikum Halle/Saale der Martin-Luther-Universität Halle-Wittenberg: Dr. med. Ruß, Prof. Dr. med. Werdan
Klinik für Herz- und Gefäßchirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel: Prof. Dr. med. Cremer
Klinik für Thorax- und Vaskularchirurgie, Evangelisches und Johanniter-Klinikum Niederrhein, Duisburg: Prof. Dr. med. Krian
Universitäres Herzzentrum, Hamburg-Eppendorf: Prof. Dr. med. Meinertz
Genolier Swiss Medical Network, Genolier (VD), Schweiz: Prof. Dr. med. Zerkowski
 1. Bruckenberger E: 20. Herzbericht 2007. www.herzbericht.de; www. bruckenberger.de
 2. Keeley EC, Boura JA, Grines CL: Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003; 361: 13–20.
 3. BÄK, KBV, AWMF (Hrsg.): Nationale VersorgungsLeitlinie Chronische KHK. Köln: Deutscher Ärzte-Verlag 2007/2008; www.versorgungsleitlinien.de/themen/khk/pdf/nvl_khk_lang.pdf
 4. Pitt B et al.: Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. N Engl J Med 1999; 341: 70–6.
 5. Hambrecht R et al.: Percutaneous coronary angioplasty compared with exercise training in patients with stable coronary artery disease: a randomized trial. Circulation 2004; 109: 1371–8.
 6. Boden WE et al.: Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007; 356: 1503–16.
 7. Davies RF et al.: Asymptomatic cardiac ischemia pilot (ACIP) study two-year follow-up: outcomes of patients randomized to initial strategies of medical therapy versus revascularization. Circulation 1997; 95: 2037–43.
 8. Hachamovitch R et al.: Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography. Circulation 2003; 107: 2900–7.
 9. Tonino PA et al.: Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009; 360: 213–24.
10. Bravata DM et al.: Systematic Review: The comparative effectiveness of percutaneous coronary interventions and coronary artery bypass surgery. Ann Intern Med 2007; 147: 703–16.
11. Hannan EL et al.: Long-term outcomes of coronary-artery bypass grafting versus stent implantation. N Engl J Med 2005; 352: 2174–83.
12. Caracciolo EA et al.: Comparison of surgical and medical group survival in patients with left main equivalent coronary artery disease: long-term CASS experience. Circulation 1995; 91: 2335–44.
13. Brener SJ et al.: Comparison of percutaneous versus surgical revascularization of severe unprotected left main coronary stenosis in matched patients. Am J Cardiol 2008; 101: 169–72.
14. Seung KB et al.: Stents versus coronary-artery bypass grafting for left main coronary artery disease. N Engl J Med 2008; 358: 1781–92.
15. Hueb WA et al.: Five-year follow-up of the Medicine, Angioplasty, or Surgery Study (MASS): A prospective, randomized trial of medical therapy, balloon angioplasty, or bypass surgery for single proximal left anterior descending coronary artery stenosis. Circulation 1999; 100: II107–13.
16. Reeves BC et al.: A multi-centre randomised controlled trial of minimally invasive direct coronary bypass grafting versus percutaneous transluminal coronary angioplasty with stenting for proximal stenosis of the left anterior descending coronary artery. Health Technol Assess 2004; 8: 1–43.
17. Thiele H, Oettel S, Jacobs S et al.: Comparison of bare-metal stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery: a 5-year follow-up. Circulation 2005; 112: 3445–50.
18. Graham MM et al.: Survival after coronary revascularization in the elderly. Circulation 2002; 105: 2378–84.
19. Kaiser C et al.: Risks and benefits of optimised medical and revascularisation therapy in elderly patients with angina – on-treatment analysis of the TIME trial. Eur Heart J 2004; 25: 1036–42.
20. Pfisterer M et al.: Outcome of elderly patients with chronic symptomatic coronary artery disease with an invasive vs optimized medical treatment strategy: one-year results of the randomized TIME trial. JAMA 2003; 289: 1117–23.
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