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. 2022 Oct 21;119(42):716–723. doi: 10.3238/arztebl.m2022.0277

The Treatment of Coronary Artery Disease

Current Status Six Decades After the First Bypass Operation

Torsten Doenst 1,*, Holger Thiele 2, Jörg Haasenritter 3, Thorsten Wahlers 4, Steffen Massberg 5,6, Axel Haverich 7
PMCID: PMC9835700  PMID: 35912444

Abstract

Background

The first coronary artery bypass operation (CABG) was performed on May 2, 1960. The first percutaneous coronary intervention (PCI) was performed almost 20 years later. Since then, the invasive treatment of coronary artery disease (CAD) has moved into the spotlight of cardiac medical care.

Methods

We summarize the current status of medical and invasive CAD treatment through a selective review of the literature.

Results

More than 800 000 patients currently undergo invasive diagnostic and therapeutic procedures for CAD in Germany each year. The number of coronary artery bypass grafting (CABG) procedures rose to 65 000/year by the turn of the millennium and has been declining since then. In contrast, the number of PCIs in Germany rose to approximately 350 000/year by 2017, and a beginning decline is being observed at present. This development occurred even though, for elective patients, a survival advantage from an invasive procedure compared to medical therapy has been shown in direct comparison only for CABG.

Conclusion

Conservative treatment is always the baseline treatment and has undergone major advances in the last few decades. Moreover, non-invasive coronary evaluation with computed tomography, as well as non-invasive cardiac stress imaging studies, are increasingly replacing primary invasive coronary evaluations. In this review, we illustrate a mechanistic concept of the appropriate use of CABG and PCI that can improve patient care, while underscoring the importance of interdisciplinary and intersectoral collaboration.

cme plus

This article has been certified by the North Rhine Academy for Continuing Medical Education. Participation in the CME certification program is possible only over the internet: cme.aerztebatt.de. The deadline for submission is 20.10.2023.

There are basically three therapeutic principles for treating coronary artery disease (CAD). Conservative therapy is aimed at treating symptoms, preventing disease progression, and preventing adverse events, especially myocardial infarction. The conservative approach can be complemented by invasive therapy using either percutaneous coronary intervention (PCI) or heart bypass surgery, also known as coronary artery bypass grafting (CABG).

History of invasive treatment of CAD

The first successful heart bypass operation was performed on a New York taxi driver by Robert Goetz on May 2, 1960, using an anastomosis system. The first hand-sewn anastomosis was then performed in 1962 by David Sabiston (1). History books attribute the first bypass operation to the Russian surgeon Vasilii Kolesov because he had published his report earlier than Sabiston, having performed the procedure on February 25, 1964 (1). The subsequent development of the heart-lung machine and cardioplegia for safe cardiac arrest then allowed the rapid advancement of the field (1). In Germany alone there was a ten-fold increase in heart operations to 100 000 per year between 1980 and 2000.

The first coronary angioplasty was undertaken in 1977 by the German cardiologist Andreas Grüntzig in Zurich (2). This event triggered an even more rapid development than that of cardiac surgery, leading to modern percutaneous coronary intervention (PCI) via the placement of the well-known vascular stents (initially bare-metal stents, later drug-eluting stents). PCI is now being performed more than 300 000 times a year in Germany (3).

The life-saving effect of invasive therapy in acute coronary syndrome, and specifically myocardial infarction, has been demonstrated in multiple randomized trials (4). A meta-analysis conducted in the 1990s demonstrated a survival benefit for bypass surgery over medical management alone in the treatment of chronic coronary syndrome, previously known as stable angina pectoris (5). Similar comparisons found no additional survival benefit for PCI (6, 7). It is debatable whether there is a potential effect of PCI for the endpoint “cardiac mortality” (8) (see below). With medical therapy improving, a life-prolonging effect for CABG is currently once again being called into question (9). Current studies are characterized by comparisons of the intervention with surgery in patients with mostly complex disease, in whom sometimes mixed results are repeatedly found. The following article reports the evidence and illustrates a mechanistic concept which can potentially resolve any remaining obscurities.

Evidence of current therapeutic procedures

Conservative management

Conservative treatment of CAD aims to halt the progression of atherosclerosis, reduce symptoms, and prevent atherothrombotic events (10). This involves combining lifestyle-altering measures, such as exercise and diet, with medical therapy. Medical therapy is the cornerstone of CAD treatment (3). It usually comprises a combination of anti-ischemic drugs – primarily beta-blockers or calcium-channel inhibitors, as well as nitrates – and those which prevent atherothrombotic events and control cardiovascular risk factors. The latter primarily include antiplatelet therapy using, for example, acetylsalicylic acid (ASA) or clopidogrel, statin therapy, lipid-lowering agents, and the administration of renin-angiotensin-aldosterone system (RAAS) inhibitors. The final choice of medication must be tailored to the individual patient.

Antithrombotic and cholesterol-lowering forms of therapy are associated with significant survival benefits (10). A relative reduction of total mortality by 13% in patients with underlying cardiovascular disease has been reported for statins, and a relative risk reduction of 10% per year in patients after myocardial infarction, stroke, or transient ischemic attack has been reported for ASA (11). This effect is also evident in patients who have undergone CABG (12, 13). Medical therapy works as a complement to bypass surgery and is considered the central pillar in the management of CABG patients. This association emphasizes the need for intersectoral collaboration among surgeons, cardiologists, and primary care physicians. The same is also true for PCI where dual platelet inhibition is essential on a temporary basis to prevent stent thrombosis.

Anti-ischemic treatment primarily targets symptom control and improvement of quality of life. The proportion of patients for whom medical therapy does not produce adequate symptom control can only be guessed. Data from clinical and observational studies show that most patients with chronic CAD have no, or only few, and irregular symptoms (14).

In the ISCHEMIA trial, 21% of the patients in the conservative study arm received additional invasive treatment over the course of the study (9). The reason for this in many cases was probably persistent symptoms. However, patients with unacceptable angina were not included in the ISCHEMIA trial despite medical therapy.

The use of CABG and PCI can also contribute towards symptom relief and, potentially, to an improvement in prognosis in patients with clinically relevant CAD (3). However, given their potential for harm, some evidence of benefit should first be demonstrated.

PCI

The guidelines recommend that PCI be individualized for patients with chronic CAD to take into account clinical condition, stenosis severities, and the various methods used to confirm ischemia (3). With regard to the latter, increasing importance is being placed on measuring fractional flow reserve (FFR) using parameters such as instantaneous wave-free ratio (iFR) or resting full cycle ratio (RFR). These procedures determine the hemodynamic relevance of a stenosis. Performing PCI for non-flow limiting stenoses with an FFR of more than 0.8 may even have an adverse effect for patients with chronic CAD (15). The primary aim of a PCI is therefore to eliminate clinically relevant mechanical restrictions to flow.

Available evidence has consistently confirmed the therapeutic effect of PCI on symptoms (3, 4). However, any prognostic benefit of PCI in chronic CAD is currently a topic of debate. Recent meta-analyses looking exclusively at randomized controlled trials (RCTs) in patients with chronic CAD show no effect on cardiovascular death, overall mortality, or myocardial infarction (Graphs 1a, 1b) (6, 7, 9, 16). Another meta-analysis that combined acute and chronic coronary syndrome with PCI and CABG did find an effect of invasive therapy on the endpoint “cardiac mortality”, but this article is controversial (8, 17). However, this study did find an association between cardiac mortality and myocardial infarction, which seems relevant from a mechanistic point of view (see below).

PCI is the most appropriate therapy for the treatment of acute myocardial infarction, mainly because of its speed of application. It is associated with both symptom relief and extension of life expectancy (4). The guidelines recommend treatment of functionally relevant stenosis by PCI in patients with chronic CAD (15, 18). This reduces, in the first instance, exercise-induced ischemia and, consequently, symptoms (9, 19). More recent developments include techniques such as lithotripsy, methods for recanalization of chronic total occlusion (CTO), intracoronary imaging using intravascular ultrasound (IVUS), optical coherence tomography (OCT), robotic-assisted PCI, and software-based FFR measurements without guidewires. Ultra-thin drug-eluting stents are also used. Bioresorbable stents are also being further investigated for special applications – despite their initially unconvincing results (20, 21).

CABG

The guidelines recommend the use of CABG as primary therapy of anatomically complex CAD; it is considered virtually equivalent to PCI in patients with less anatomical complexity (4). In acute coronary syndrome, bypass surgery is a treatment option when primary PCI cannot be performed or complications occur (4).

The assumption of a survival benefit from CABG in chronic CAD dates back to a meta-analysis from the 1990s (5). Modern medical therapy is once again challenging this effect (9, 22). A more recent study showed a survival benefit for CABG over guideline-directed medical therapy in patients with ventricular dysfunction (23) (Figure 2a). Overall, patients lived on average 1.5 years longer over ten years after CABG than with medication alone. A comparison with PCI in this respect is not yet available.

Figure 2.

Figure 2

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a) Mortality up to 10 years with medical therapy or after bypass surgery in patients with clinically relevant CAD and reduced ejection fraction (≤35%), taken from the STICH study (23)

b) Mortality up to 5 years after PCI or bypass surgery (CABG) from a meta-analysis of 11 randomized trials involving patients with multivessel disease, based on individual patient data (24)

c) Mortality and spontaneous myocardial infarctions 5 years after PCI or bypass surgery (CABG) from a meta-analysis of 4 randomized studies involving patients with left main coronary artery stenosis based on individual patient data (25) HR, hazard ratio; CAD, coronary artery disease; CI, confidence interval; PCI, percutaneous coronary intervention

Comparisons of CABG versus PCI were designed for non-inferiority of PCI to CABG and examined combined endpoints mostly for case number reasons. A meta-analysis based on individual patient data recently demonstrated a statistically significant survival benefit for CABG in patients with chronic multivessel CAD (24) (Figure 2b). In this study, mortality at five years was 2% lower than PCI with a relative risk reduction of 20%.

A technically comparable meta-analysis of PCI versus CABG in left main coronary artery stenosis with individual patient data from four randomized trials (EXCEL, BEST, PRECOMBAT, SYNTAX) found equal five-year survival rates but significantly fewer spontaneous myocardial infarctions after CABG (Figure 2c) (25).

CABG therefore appears particularly beneficial when the anatomic complexity of CAD and/or patient comorbidities are high (26). SYNTAX was the first study to compare PCI using drug-eluting stents (Taxus®) with CABG in patients with three-vessel disease. The use of PCI failed to achieve the goal of non-inferiority to CABG for the endpoints of “death”, “stroke”, “cardiovascular event”, and “revascularization” after one year. However, in subanalyses that subdivided the anatomic complexity of CAD using the so-called SYNTAX score, PCI and CABG were shown to be equivalent when the SYNTAX score was low.

In the FAME-3 trial, 1500 elective patients with three-vessel CAD from 48 centers recently received either CABG or PCI with FFR-guided zotarolimus-eluting stents (27). Despite employing the most advanced methods, the use of PCI again failed to meet the claim of non-inferiority to CABG for the same combined one-year endpoint as used in the SYNTAX trial (27). Once again, the particular advantage of CABG in anatomically complex CAD and the equivalence of PCI in less pronounced complexity were demonstrated. Interestingly, the patients suffered only about half the adverse events as compared with the SYNTAX trial despite identical risk profiles. The study therefore highlights the progress achieved by not only PCI but also CABG. These results thus demonstrate the potential of modern bypass surgery.

However, the decisive factor for efficacy is patency of the applied bypass grafts, which can be increased by full-arterial grafting if appropriate expertise is available (28). “No-touch” harvesting techniques (gentle harvesting of the vein to include a pedicle of surrounding fat tissue) can also achieve improved patency rates for venous grafts (29). This improvement could conceivably be explained by the preservation of the adventitia and possibly the vasa vasorum (30). Concerns about stroke can be addressed with a combination of aortic “no-touch” and “off-pump” techniques (31), in which the aorta is not manipulated. Finally, some surgeons are also capable of placing multiple bypass grafts using a left-sided mini-thoracotomy (32). The extent to which bypass surgery can be safely planned and performed using non-invasive imaging such as coronary computed tomography is currently under investigation (33).

Mechanism-oriented approach to reconcile discrepancies

Applying a mechanistic view on the available data reveals a pattern that may explain conflicting study results. Because the use of both CABG and PCI is recommended primarily in patients who remain symptomatic despite receiving guideline-directed medical therapy, grouping the two invasive procedures under the term “revascularization” is possibly understandable. However, this is not a useful approach because it inadequately describes the underlying mechanisms of treatment.

An analysis of comparative studies suggested the concept of surgical collateralization as a mechanism for the life-prolonging effect of CABG versus PCI and medical therapy (34, 35). However, the term revascularization does not reflect the effect of collateralization. The vast majority of spontaneous myocardial infarctions results from non-flow limiting CAD lesions (Figure 3a). PCI in chronic CAD has as its main therapeutic goal the treatment of flow-limiting lesions, while CABG, on the other hand, bypasses all lesions and therefore usually inserts distal to any future infarct-causing lesions (36). Performing CABG therefore provides the greatest protection against spontaneous myocardial infarction (surgical collateralization, Figure 3b, [35]), especially when the atherosclerotic plaque burden and thus the risk of infarction are high. When comparative studies of the use of PCI versus that of CABG are analyzed, a survival benefit in favor of CABG is always found when the CABG group has fewer concomitant non-fatal myocardial infarctions (figure 4) (37). Because myocardial infarction is a life-threatening event – current mortality ranges between 10% and 30% (38) – it is understandable why, over the long-term, the use of CABG is associated with fewer infarctions and lower mortality rates in randomized trials in the presence of anatomically complex CAD. This consideration may also explain the repeatedly superior performance of bypass surgery in high-risk patients, for example, in those with chronic kidney disease or diabetes [24, 31, 34, 39], because these patients also usually have a very high risk of myocardial infarction. The often increased risks of surgery do not seem to diminish this beneficial effect.

Figure 3.

Figure 3

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Infarct prevention: main difference between CABG and PCI in chronic CAD

a) Distribution of the frequency of myocardial infarction according to stenosis severity of the infarct vessel (modified from [34])

b) Schematic illustration of the principle of surgical collateralization (modified from [35])

CABG, coronary artery bypass grafting; CAD, coronary artery disease; PCI, percutaneous coronary intervention

Figure 4.

Figure 4

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Central illustration taken from a meta-analysis of mortality in PCI versus CABG comparative studies without (upper group) or with (middle group) a significant difference in spontaneous myocardial infarction rate. CABG, coronary artery bypass grafting; CI, confidence interval; PCI, percutaneous coronary intervention; SMI, spontaneous myocardial infarction From (37), reprinted with the kind permission of Elsevier.

However, the term “revascularization” is also imprecise for symptom-based treatment of clinically relevant obstruction to blood flow. When looking at the mechanisms of action of PCI and CABG (figure 5), three types emerge, each of which is utilized to a different extent but has different treatment effects (39).

Figure 5.

Figure 5

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Summary of the possible mechanisms and therapeutic effects of PCI and bypass surgery as therapeutic principles for CAD (modified from [39]).

* some studies doubt the existence of chronic ischemia (39, 40)

ACS, acute coronary syndrome; CCS, chronic coronary syndrome; CAD, coronary artery disease, MI, myocardial infarction; PCI, percutaneous coronary intervention

Reperfusion

This involves the use of PCI (or thrombolytic therapy) and, more rarely, CABG to restore an interrupted or inadequate blood supply at rest to an area of myocardium. This is the main mechanism of action in the treatment of acute myocardial infarction and acute ischemia. Reperfusion is the decisive mechanism to preserve vital myocardial tissue in addition to its symptom-relieving effects. Whether this principle also applies to the treatment of chronic CAD – or whether chronic ischemia even exists at all – is as conceivable on the one hand as it is controversial on the other (39, 40).

Improvement of coronary flow capacity

When it comes to improving coronary flow capacity, PCI or CABG increase the maximum possible blood flow, which in chronic CAD is sufficient at rest but often not during exercise. This mechanism of action applies to exercised-induced ischemia which is detected by most ischemia diagnostic procedures, including stress MRI, stress echo, or classic myocardial scintigraphy. According to randomized trials, treatment of exercise-induced ischemia with PCI relieves symptoms but does not improve survival (9, 19).

Infarction prevention

CABG and, to some extent, PCI can prevent infarctions by either performing surgical collateralization to bridge the infarct-causing lesions with a bypass (34) or by direct stenting. Because up to 90% of all myocardial infarctions result from coronary lesions that are non-flow limiting and are therefore not stented (34) (figure 3), such a preventive effect of PCI cannot be that large. A bypass graft therefore has the greatest infarction-preventive effect because of its collateralizing function. The prognostic potential is particularly high when the presenting CAD is complex with a subsequent high risk of infarction. This also explains the good complementary effect of bypass surgery and medical therapy (12, 13). This, in turn, emphasizes once again the need for intersectoral collaboration between invasive physicians and those in private practice.

Summarizing this mechanistic approach to the treatment of CAD, increasing coronary flow capacity and preventing infarction are the primary mechanisms of action for chronic CAD, while reperfusion is utilized in acute coronary syndrome.

Outlook

Current treatment options for CAD require a mechanistic approach, individualized treatment recommendation, and close collaboration between disciplines and sectors. Whereas a patient with acute ischemia must undergo immediate invasive therapy with the aim of immediately providing reperfusion, the focus of interest with chronic CAD, apart from treating symptoms, is to determine the risk of infarction from a prognostic point of view. Invasive treatment of exercise-induced ischemia primarily reduces symptoms and, from this perspective, is less critical in terms of time. The updated chapter “Revascularization Therapy” of the German National Health Care Guideline “Chronic CAD” provides physicians and patients with evidence-based decision guidance (11).

Conclusion

Treatment of CAD is always based on medication, which may also be supplemented by invasive procedures. The effect of PCI and bypass surgery basically comprises three components which are utilized to different degrees by the two procedures: improvement of coronary flow capacity in exercise-induced ischemia, reperfusion in acute ischemia, and prevention of myocardial infarction by surgical collateralization or PCI of lesions that cause infarction.

In acute ischemia, immediate reperfusion is decisive for prognostic benefit. This is best achieved by PCI.

In the presence of chronic CAD, invasive procedures can supplement optimal conservative therapy: When symptoms are persistent or pronounced, improving coronary flow capacity can help alleviate symptoms and increase quality of life. With anatomically complex CAD, especially in the presence of diabetes mellitus and/or heart failure, bypass surgery provides additional prognostic benefit, presumably by means of infarction prevention through surgical collateralization.

Figure 1a.

Figure 1a

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Forest plots for mortality from a meta-analysis comparing PCI with medical therapy for the treatment of chronic coronary syndrome.

D+L, DeSimonian and Laird; I-V, inverse variance; CI, confidence interval; N, sample size; PCI, percutaneous coronary intervention

From (16), reprinted with the kind permission of Wolters Kluwer GmbH

Figure 1b.

Figure 1b

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Forest plots for mortality from a meta-analysis comparing PCI with medical therapy for the treatment of chronic coronary syndrome.

D+L, DeSimonian and Laird; I-V, inverse variance; CI, confidence interval; N, sample size; PCI, percutaneous coronary intervention

From (16), reprinted with the kind permission of Wolters Kluwer GmbH

Acknowledgments

Translated from the original German by Dr. Grahame Larkin

Footnotes

Conflict of interest statement

Prof. Thiele is the incoming president of the German Society of Cardiology.

Dr. Haasenritter is a member of the German Society of General Practice and Family Medicine (DEGAM), the German Network for Evidence-based Medicine, and the Association of Cardiovascular Nursing & Allied Professions in the European Society of Cardiology. He receives travel support as part of his voluntary work in the DEGAM Standing Guideline Commission.

The other authors declare that no conflict of interest exists.

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