Management of significant proximal left anterior descending coronary artery disease

INTRODUCTION — The prognosis of patients with coronary artery disease is related to the extent of myocardium at risk. Proximal left anterior descending coronary artery (LAD) lesions often supply a high percentage of the left ventricular myocardium, compared to proximal lesions in the circumflex or right coronary arteries. A study reported that the prevalence of significant proximal LAD disease in stable patients undergoing diagnostic coronary catheterization was 7.2 percent in New York State and 13.4 percent in Ontario, Canada [1].

This topic will discuss both the choice between medical therapy and revascularization for treatment of proximal LAD disease in stable patients as well as the choice between coronary artery bypass graft surgery and percutaneous coronary intervention in those patients in whom revascularization is chosen. This discussion will focus on the outcomes of survival, myocardial infarction, and revascularization rates. Revascularization to improve angina refractory to medical therapy in patients for whom survival will not be improved is discussed separately. (See "Chronic coronary syndrome: Indications for revascularization" and "Chronic coronary syndrome: Overview of care".)

The management of patients with stable, nonproximal LAD disease is similar to disease identified in the circumflex and right coronary arteries. (See "Chronic coronary syndrome: Indications for revascularization" and "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)

The discussion of coronary artery revascularization in the large subgroup of patients with diabetes is found elsewhere. (See "Coronary artery revascularization in stable patients with diabetes mellitus".)

DEFINITION OF SIGNIFICANT DISEASE — For the purposes of this topic, significant disease of the proximal (proximal to and including the first major septal branch) left anterior descending coronary artery is present when coronary angiography reveals one or more obstructive lesions and one of the following criteria:

●Angina pectoris that is reasonably attributed to the lesion(s). Usually, the visual estimate of the severity of the stenosis is 70 percent or greater luminal narrowing.

●A stress test, with or without imaging, showing evidence of moderate to severe myocardial ischemia consistent with a proximal left anterior descending coronary artery lesion.

●Physiologic evidence at the time of cardiac catheterization supporting the finding of a significant lesion, such as an abnormal (low) fractional flow reserve or abnormal instantaneous wave-free ratio. (See "Clinical use of coronary artery pressure flow measurements", section on 'Introduction'.)

GENERAL MANAGEMENT OF CORONARY ARTERY DISEASE — Most patients with coronary artery disease should have their risk of subsequent cardiovascular events assessed with stress testing and some should have evaluation of left ventricular systolic function. All patients require aggressive risk-factor reduction. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk" and "Prognostic features of stress testing in patients with known or suspected coronary disease" and "Chronic coronary syndrome: Overview of care", section on 'Measurement of left ventricular systolic function'.)

The management of angina is discussed separately. (See "Chronic coronary syndrome: Overview of care", section on 'Antianginal therapy'.)

INDICATIONS FOR REVASCULARIZATION — For patients with significant proximal left anterior descending (LAD) coronary artery disease, similar to all patients with coronary artery disease, the principal indications for revascularization are to improve the quality of life in patients who have angina refractory to medical therapy and to improve survival (see 'General management of coronary artery disease' above). However, a survival benefit from revascularization has not been demonstrated in stable patients with significant proximal LAD disease, as discussed below. Despite this, many of our contributors have unease about relying on medical therapy alone and recommend revascularization to their patients who have significant proximal LAD, documented ischemia, and stable and tolerable angina. This approach is based on clinical experience during which the following has been observed:

●Some patients' symptoms ultimately progress to unacceptable angina.

●Large myocardial infarctions may occur in these patients who are not revascularized.

Two randomized trials that enrolled patients with significant disease of the proximal left coronary artery did not demonstrate that survival is improved with revascularization.

●The 2020 ISCHEMIA trial randomly assigned 5179 patients with chronic coronary syndrome and moderate to severe ischemia on testing to an initial invasive strategy of cardiac catheterization and revascularization in addition to optimal medical therapy or an initial strategy of optimal medical therapy with revascularization reserved for failure of medical therapy [2]. In ISCHEMIA, 47 percent of patients had disease involving the proximal segment of the LAD. Revascularization did not reduce the primary endpoint of cardiovascular death, myocardial infarction, or cardiac arrest; hospitalization for unstable angina or heart failure; or the single endpoint of cardiac death at five years. ISCHEMIA is discussed in detail elsewhere. (See "Chronic coronary syndrome: Indications for revascularization", section on 'Patients with high-risk anatomy'.)

It is important to recognize that the findings of ISCHEMIA do not apply to patients who are symptomatic despite the use of medical therapy.

●The COURAGE trial, which also compared PCI with medical therapy, included a group of patients with isolated proximal LAD disease [3]. In COURAGE, which excluded patients with severe angina, a markedly positive treadmill test (eg, significant ST-segment depressions and/or a hypotensive blood pressure response during stage I of the Bruce protocol), and left ventricular ejection fraction of less than 30 percent, there was no significant difference between aggressive medical therapy or aggressive medical therapy plus PCI using bare metal stents with regard to survival. (See "Chronic coronary syndrome: Indications for revascularization", section on 'Patients with high-risk anatomy'.)

Patients with prior CABG — For symptomatic patients who previously underwent coronary artery bypass surgery (CABG) without prior placement of a left internal thoracic artery and have ischemia in multiple territories, CABG is preferred to PCI.

Patients with ischemia in other locations and those with a patent left internal mammary artery to the LAD artery are unlikely to experience a survival benefit from repeat revascularization, and the decision to revascularize should be made primarily for the goal of reducing anginal symptoms [4,5]. (See "Chronic coronary syndrome: Indications for revascularization", section on 'Relief of angina'.)

For patients with a diseased saphenous vein graft to the LAD who undergo PCI, intervention of the native vessel is generally preferred over treatment of the diseased saphenous vein graft [6].

PCI VERSUS CABG — During the past 30 years, several trials and meta-analyses comparing the efficacy of percutaneous coronary intervention (PCI) with CABG for patients with proximal LAD disease have been conducted, and none has shown a survival advantage for either form of revascularization [7-14].

Accordingly, the 2021 ACC/AHA/SCAI coronary revascularization guideline does not mention a general preference for one form of revascularization over the other [6].

For those patients in whom revascularization is chosen, however, the choice between PCI and CABG depends on clinical parameters as well as the patient's preference for the potential burdens associated with each form of revascularization. Specifically scenarios are described as follows:

●We prefer PCI with stenting in many patients with less complex coronary artery disease and relatively well preserved left ventricular systolic function.

●CABG might be preferred to PCI in patients with complex, proximal left anterior descending coronary artery (LAD) disease with other unfavorable lesions (eg, chronic total occlusion in another vessel).

●Other patient and angiographic characteristics also may affect the decision such as age, left ventricular dysfunction, the inability to take or tolerate dual antiplatelet therapy for an appropriate duration, and diabetes mellitus (in which the outcome may be better with CABG) [15].

Whenever PCI is performed, drug-eluting stents should be used for their superior safety and efficacy compared with bare metal stents, which are now rarely used; similarly, surgical revascularization of the LAD should be performed using the internal thoracic artery as the conduit of choice. (See "Long-term antiplatelet therapy after coronary artery stenting in stable patients", section on 'Summary and recommendations' and "Coronary artery revascularization in stable patients with diabetes mellitus", section on 'PCI versus CABG'.)

In suitable candidates with proximal LAD disease, PCI can usually be performed with a high chance of success and low risk of complications. When faced with more complex lesions such as true ostial location, particularly with involvement of the distal left main coronary artery, adjacent circumflex ostial disease, or complex bifurcation lesions involving a large first diagonal branch, consideration of CABG should be made. Complex LAD-diagonal bifurcation lesions and ostial LAD lesions that are flush with the distal left main should only be attempted by highly experienced operators in institutions with cardiac surgical facilities.

Patients with multivessel disease — Patients with less diffuse coronary artery disease (eg, lower SYNTAX scores) have lower event rates than those with moderate or severely diffuse coronary artery disease (eg, intermediate or high scores) [15]. (See "Percutaneous coronary intervention of specific coronary lesions", section on 'Left main and left anterior descending disease' and "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)

In the SYNTAX trial, 1800 patients with three-vessel or left main coronary artery disease were randomly assigned to either CABG or PCI with paclitaxel-eluting stents [16]. After 12 months of follow-up, the composite primary end point (death from any cause, stroke, MI, or repeat revascularization) was significantly higher in the PCI group (17.8 versus 12.4 percent), with the result driven primarily by more frequent revascularization with PCI (13.5 versus 5.9 percent). After five years, however, CABG was also associated with fewer myocardial infarctions (MIs) and the lower rate of the composite outcome of death, stroke, or MI. This trial is discussed in detail elsewhere. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)

In a patient-level meta-analysis, which included the SYNTAX trial, patients with low SYNTAX scores had comparable outcomes after either PCI or CABG, whereas patients with higher SYNTAX score had better outcomes after CABG [15] (see "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention", section on 'Outcomes based on lesion severity'). Accordingly, for patients with a significant narrowing of the proximal LAD associated with multivessel disease, we prefer CABG over PCI. (See "Percutaneous coronary intervention of specific coronary lesions", section on 'Left main and left anterior descending disease' and "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)

Patients with single-vessel disease — For most patients with significant single vessel, proximal LAD disease in whom revascularization has been recommended, we suggest PCI rather than CABG. This preference is based on the desire to avoid the potential complications of CABG (such as stroke) despite a higher rate of repeat revascularization with PCI [10,17,18]. The prevalence of significant proximal LAD disease in stable patients undergoing diagnostic coronary catheterization was found to be 7.2 percent in New York State and 13.4 percent in Ontario, Canada in a 2013 study [1].

As discussed above, the finding of isolated disease in the proximal LAD is sometimes, but not always, an indication for revascularization, but clinical trials have not shown a survival benefit compared with medical therapy [2]. (See 'Indications for revascularization' above.) The main indication for intervention in this setting is for symptoms due to failure of medical therapy. However, given the safety and low procedural morbidity associated with PCI and stenting, most cardiologists favor revascularization of the proximal LAD given the large area at risk. It is not uncommon to find that patients may also have arrived at this decision themselves based on what they have been told by other physicians or from their own research

A 2008 meta-analysis of nine randomized trials, including 1210 patients, found no 5- or 10-year survival difference between CABG and PCI for management of single vessel LAD disease, although rates of repeat revascularization were higher at five years with PCI (33.5 versus 7.3 percent) [10].

Randomized trials using a lateral or anterolateral thoracotomy (MID CABG) in patients with isolated LAD stenosis have suggested that this surgical approach is associated with equivalent mortality but better symptom control and a lower rate of target vessel revascularization than PCI with bare metal stents [13,14,19].

Two studies have compared PCI with drug-eluting stents (DES) to CABG:

●A randomized trial comparing first generation DES to minimally invasive direct coronary artery bypass surgery (MIDCAB) evaluated outcomes in 130 patients with isolated proximal LAD disease [8]. The primary clinical end point was freedom from death, MI, or the need for target vessel revascularization. At one year, PCI with DES was noninferior to MIDCAB, with an event rate of 7.7 percent in both groups. Patients who received PCI had a higher rate of revascularization (6.2 versus 0 percent), while those who received MIDCAB had a higher rate of MI (7.7 versus 1.5 percent), most of which was periprocedural. (See "Early cardiac complications of coronary artery bypass graft surgery", section on 'Perioperative MI'.)

●Using New York (United States) state clinical registries, CABG was compared to DES in 715 matched pairs of patients with isolated proximal LAD disease [20]. There was no significant difference in the rates of three-year mortality (adjusted hazard rate [AHR] 1.14, 95% CI 0.70-1.85) or mortality, MI, and/or stroke (AHR 1.15, 95% CI 0.76-1.73). The rate of repeat revascularization was significantly lower for CABG (AHR 0.54, 95% CI 0.36-0.81). The stents used in these patients, although not reported in the publication, were likely represented by a majority of second generation DES, which have improved results compared with first generation DES and represent the standard of care at present.

In the patient with severe single vessel disease involving only the proximal LAD, it is important for the patient to be made aware of the strengths and weakness of either approach. For patients with more complex lesions, such as ostial location, diffuse disease, or bifurcation lesions, the risks with PCI increase. Shared decision-making with the patient and a heart team approach should be strongly considered. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention", section on 'Outcomes based on lesion severity'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Percutaneous coronary intervention".)

SUMMARY AND RECOMMENDATIONS

●Background – The general approach to patients with proximal left anterior descending coronary artery (LAD) disease is similar to that of all patients with coronary heart disease. This should include appropriate secondary prevention strategies and risk stratification, as well as the use of revascularization in patients with angina refractory to medical therapy.

●Indications for revascularization

•For patients with a significant narrowing of the proximal LAD who have high-risk criteria (left ventricular ejection fraction [LVEF] <30 percent or evidence of a large area of potentially ischemic myocardium), regardless of anginal severity, we recommend revascularization rather than medical therapy (Grade 1B). (See 'Indications for revascularization' above.)

•For most patients, we suggest revascularization rather than medical therapy (Grade 2C). It is important to discuss this with the patient using a shared decision-making approach. Our preference for revascularization increases as the severity of underlying risk factors increases (eg, LVEF falls or the extent of myocardium at risk increases) or if angina is refractory to medical therapy.

●Indications for coronary artery bypass graft surgery

•For patients with a significant narrowing of the proximal LAD with multivessel coronary artery disease who have a moderately reduced LVEF of 30 to 50 percent, diabetes mellitus, or a large area of myocardium at risk, we suggest coronary artery bypass graft surgery (CABG) rather than percutaneous coronary intervention (PCI) (Grade 2B). For these patients with multivessel disease who have a LVEF <30 percent, we suggest CABG rather than PCI (Grade 2C). For patients without these high-risk predictors, PCI is a reasonable option. (See 'Patients with multivessel disease' above.)

•For patients with significant single vessel, proximal LAD disease in whom revascularization has been recommended, we suggest PCI rather than CABG (Grade 2B). However, for those patients who prefer to accept the higher early morbidity (including an increased risk of stroke) with CABG in exchange for a lower rate of subsequent revascularization, CABG is an appropriate strategy. (See 'Patients with single-vessel disease' above.)

●Decision-making for type of revascularization – For patients in whom a decision has been made to perform revascularization, it should be kept in mind that not all proximal lesions carry the same prognosis or success rate with PCI. This information may influence decision-making between PCI and CABG, and a heart team approach may be recommended. (See 'PCI versus CABG' above.)