Multivessel coronary artery disease
See also the chapter on Chronic stable angina revascularization

# Overview
Multi-vessel coronary artery disease (CAD) is a disease stage in which at least two or three of the epicardial coronary arteries is involved with atherosclerosis of significant severity. Multivessel disease is often associated with a higher burden of comorbidities, left ventricular dysfunction, and cardiovascular risk. In general, PCI is preferred in patients with single or low risk two vessel disease. In contrast, coronary artery bypass graft surgery is recommended in patients with complex two vessel disease, three vessel disease and in some cases of isolated left main disease. Diabetics with left anterior descending coronary artery disease may benefit more from coronary artery bypass surgery. The goal in the treatment of multivessel disease is to reduce angina and heart failure symptoms and to reduce a patient's subsequent risk of adverse cardiovascular events.

# Medical Therapy
Medical therapy consists of antianginal and antiplatelet medications as well as high dose statins. All patients, whether they undergo PCI, CABG or not, should receive optimal medical therapies to reduce cardiovascular event-risk and angina. Patients with lower-risk, stable CAD may be effectively treated by medical therapy. Medical therapy has no procedural risk or prolonged convalescence, but the COURAGE Trial showed an increased risk of angina and a decreased quality of life in patients treated with medical therapy. Moreover, 30% of the patients treated with medical therapy eventually needed revascularization. Approximately 2/3 of the study population in COURAGE had multi-vessel CAD, and randomization to an initial strategy of medical therapy resulted in similar rates of death and myocardial infarction (MI) to an initial strategy of PCI.

# Revascularization Utilizing Coronary Artery Bypass Grafting (CABG)
When compared to medical therapy and percutaneous coronary intervention, CABG is associated with a lower incidence of recurrent angina and a lower need for repeat revascularization. It reduces late cardiac mortality in diabetic patients who received at least 1 internal mammary (IMA) graft. The rate of revascularization may be comparable in the era of drug eluting stents, but the definitive results of ongoing trials are pending.

## CABG Versus Medical Therapy
Recommendations are limited by the quality of data. For instance, older trials of CABG vs. medical therapy had little use of an IMA conduit (which has greater durability) and limited use of ASA, ACE inhibitors, and statins. Several randomized trials of CABG versus medical therapy support the concept of greater absolute benefit associated with CABG with respect to long-term survival in patients with more extensive or proximal CAD, or in patients with impaired left ventricular function. These older data are limited by low usage of internal mammary artery (IMA) grafting, antiplatelet agents, and a high cross-over of the medical treatment arm to CABG. CABG offers survival benefit in patients with left main stenosis, multivessel disease and LV systolic dysfunction, 3-vessel disease with proximal LAD stenosis regardless of left ventricular function, and 2-vessel disease and LV systolic dysfunction, especially with proximal disease and severe angina.

## CABG Versus PCI
Many PCI vs. CABG trials did not have widespread use of stents (either bare metal or drug-eluting) or GP IIb/IIIa inhibitors, and <10% of patients who were screened for trials of PTCA vs. CABG were actually randomized, and therefore represent a highly select population. With multivessel stenting, the target lesion revascularization (TLR) rates become cumulative. Diabetics with both retinopathy and nephropathy appear to have very high major adverse cardiac events (MACE) rates with PCI (up to 50%).

# Revascularization by Percutaneous Coronary Intervention (PCI)

## PCI Versus Medical Therapy
The subgroup analysis of patients with stable, multi-vessel CAD in the COURAGE trial suggested no difference in death and MI rates between PCI- and medically-treated groups.

## PCI Versus CABG
One must be confident in their ability to achieve complete revascularization with PCI when offering it as an alternative to CABG.

### Mortality and MI
Mortality and nonfatal MI rates are not significantly different between the two strategies. The BARI trial showed similar 5-year survival among over 1800 patients randomized to an initial strategy of PTCA or CABG for multi-vessel CAD, despite the higher rates of complete revascularization in the CABG arm. This trial preceded the use of drug eluting stents.

### Recurrent Revascularization
There are higher rate of recurrent angina and repeat revascularization after PCI (most trials in low-risk patients with 2-vessel disease and normal left ventricular function); this may change in future with the evolution of drug eluting stents. In BARI, CABG was associated with a lower rate of repeat revascularizations.

### Symptom Relief
CABG has been associated with a greater relief of anginal symptoms.

### Costs
- In comparison to CABG, PCI is less invasive, has a shorter hospital stay and convalescence, and has a less expensive initial hospital stay. However, the cost advantage may be lost over the long-term due to the potential need for repeat revascularization.

### Trial Results
The ARTS and SYNTAX trials showed higher primary event rates in patients randomized to PCI versus CABG, driven by a higher need for revascularization. Rates of hard events, such as death and MI, were similar between the treatment groups.
Several trials (ARTS I, MASS II, ERACI-II, AWESOME) involving bare metal stents compared to CABG have shown similar survival rates but higher revascularization rates among patients with bare metal stents at 5 years. The SYNTAX trial, a randomized trial of multi-vessel or left main CAD to CABG or paclitaxel-eluting stents, showed higher primary adverse event rates in the PCI group (17.8% vs. 12.4% for CABG; p=0.002), largely due to an increased rate of repeat revascularization (13.5% vs. 5.9%, p<0.001).

# Selecting a Therapeutic Strategy or Strategies

## Optimal Medical Therapy
- Risk factor modification should be undertaken in all patients (smoking cessation, treatment of hypertension, correction of dyslipidemia).
- Optimal medical therapy should be advised for all patients. Medical therapy may be an acceptable choice as the sole treatment when LV systolic function is normal or mildly depressed, and when the lifestyle is acceptable with medical therapy.
- Revascularization is chosen when unacceptable symptoms persist despite optimal medical therapy and when lesions and risk factors are present for which revascularization improves morbidity and mortality compared with medical therapy (e.g. a left main lesion). Specifically, revasulcarization is appropriate for patients with:
Refractory symptoms
More extensive or proximal disease
Left ventricular dysfunction
- Refractory symptoms
- More extensive or proximal disease
- Left ventricular dysfunction

## Scenarios Favoring CABG Over Medical Therapy to Prolong Survival
- Left main stenosis >50%,
- Multivessel disease and LV systolic dysfunction,
- 3-vessel disease with proximal LAD stenosis regardless of LV function,
- 2-vessel disease and LV systolic dysfunction (especially with proximal disease and severe angina)

## Scenarios Favoring PCI over CABG
- CAD anatomy and complexity is suitable for PCI (single or two vessel disease for instance)
- Younger patients who will likely require CABG in future in order to delay the inevitable surgery
- Limited life-expectancy
- High operative risk (including: cerebrovascular disease and severe chronic obstructive pulmonary disease), or other illnesses limiting survival
- Poor graft conduits (no IMA available or poor vein quality)
- Patient prefers to avoid surgery
- In non diabetic patients with 3-vessel disease and poor LV systolic function, consider PCI in select patients with low-risk lesions if complete revascularization can be achieved. The risks and benefits of lifelong plavix and risks of stent thrombosis must be discussed extensively with the patient. Stenting is not an ideal choice for the patient who is not compliant with medication such as thienopyridines.

## Scenarios Favoring CABG over PCI
- In the presence of concurrent valvular disease requiring surgical repair,
- Complete functional revascularization unlikely to be achieved with PCI,
- Lesions not suitable for stenting (low likelihood of success, high risk of complications, high risk of restenosis),
- Patient prefers to limit number of revascularization procedures
- Patients with diabetes mellitus and multi-vessel disease may benefit more from CABG than PTCA. In general, CABG is recommended because the BARI trial showed improved survival after CABG compared with multivessel PCI if at least one IMA conduit was used, and if there were 4 or more lesions, especially in patients with LV systolic dysfunction. However, the BARI trial was done in the pre- stent era and before the widespread use of GP IIb/IIIa inhibitors. It should be noted that there was no difference in survival among diabetic patients treated with CABG vs. PCI in 2 nonrandomized trials, including 5-year survival in BARI registry. Randomized data of diabetic patients using contemporary stents and CABG techniques are lacking. The NHLBI sponsored FREEDOM trial is currently enrolling patients with diabetes and multi-vessel CAD for a comparison of PCI and CABG outcomes.
A collaborative analysis of data from 10 randomized controlled trials (N= 7812) was pooled to compare effectiveness of CABG with PCI in view of long term effects on mortality in various clinical subgroups. PCI was done with balloon angioplasty in six trials and with bare metal stents in four trials. The results showed that the long term mortality is similar with PCI and CABG in most patient subgroups who had multivessel disease. Based on this, the choice of the procedure should be made depending on patient's preference for other outcomes. CABG proved a better option in diabetics and elderly over 65 years.

## Scenarios Favoring a Hybrid of CABG and PCI
- Adjunctive PCI may be performed before after CABG in lesions that are not amenable to coronary artery bypass grafting. This may include lesions in very distal arteries, or lesions in very small vessels
- Due to higher CABG mortality in patients with UA/NSTEMI, a strategy of PCI to the culprit artery followed by elective revascularization (as needed) of the residual disease may be employed. Identification of the culprit artery requires localizing ECG, echocardiographic, or angiographic features (coronary thrombus, ulcerative plaque, slow flow, a high grade stenosis, or pressure wire technique).

# Technical Considerations in the Performance of Multivessel PCI
- One may need to stage the procedure because of contrast load and radiation dose, as well as procedure time.
- Starting with the most challenging lesion in patients for whom CABG is an option, may be advisable to evaluate feasibility of complete revascularization.
- Assessment of patients ability to comply with lifetime dual antiplatelet therapy is also crucial especially with bifurcation stenting, long lesions and small vessels, which are common in patients with multivessel disease where risk of stent thrombosis is highest.