Introduction
CABG is the most commonly performed cardiac surgical procedure worldwide and is preferred over percutaneous coronary intervention in patients with diabetes, reduced left ventricular ejection fraction, and three vessel and complex coronary artery disease.¹ Both arterial and saphenous vein grafts (SVG) can be used as conduits. Grafting the left anterior descending artery with the left internal thoracic artery is the gold standard in CABG because patency rates of this construction surpass SVG,² decrease the incidence of coronary reoperation, and improve survival.^3,4 Use of multiple arterial grafts, compared to only a single arterial graft, potentially provides long-term survival benefit in selected patients, but this remains a topic for discussion. As such, SVG remains the most used second conduit. An important and recalcitrant issue with the use of SVG remains vein graft failure. SVG failure rates range from 6% to 26% in the first year and are estimated to be 40-50% at 10 years after CABG.^5,6 Although SVG failure is not one-on-one related with adverse events, it is associated with anginal complaints, myocardial infarction, and long-term mortality after CABG.^7-9 This article discusses therapies to improve vein graft patency after CABG.

Pathophysiology
SVG failure is a complex, multifactorial process. In the first month after CABG, mechanical factors and endothelial damage after surgery cause thrombotic occlusion.¹⁰ Thereafter, until 1 year after CABG, the predominant process causing failure is intimal hyperplasia. Activated platelets trigger inflammation, causing smooth muscle cell migration from the media to the intima.¹¹ Both thrombosis and intimal hyperplasia provide the foundation for accelerated atherosclerosis, which is the principal cause of failure beyond the first year after CABG.¹²

Technical Improvements
Technical improvements in SVG construction during CABG should be taken into account to improve vein graft patency. Regarding SVG harvest and preservation, early studies showed reduced patency rates for endoscopic vein harvesting compared with the conventional open harvest technique,¹³ although a recent clinical trial that included 1,150 patients demonstrated no difference in major adverse cardiac events between the endoscopic-harvest group and the open-harvest group at a median follow-up of 2.8 years.¹⁴ A small randomized controlled trial that included 54 patients demonstrated that the "no-touch technique" for SVG harvesting is superior to conventional harvesting and provides long-term patency rates that are comparable with the left internal thoracic artery.¹⁵ SVG preservation in buffered solutions preserves intimal integrity and can improve patency over grafts preserved in normal saline or blood-based solutions.¹⁶ The appropriate length of the SVG is of importance to avoid both overstretching and kinking¹⁷ and to preserve good target runoff.¹⁸ Measuring intraoperative graft flow potentially identifies technical problems with the anastomoses and outflow targets, thus identifying the need for revision to improve early graft patency.¹⁹ Some studies report sequential grafting providing inferior patency rates compared with single grafts,²⁰ although as many studies report no difference between both strategies.²¹ Additionally, the risk for competitive (native coronary) flow causing reduction or even reversal of graft flow when grafting less then high-grade stenotic coronary arteries is less important in SVG than in arterial grafts and has to be taken in consideration when planning the revascularization.²² Furthermore, competitive flow presumably has more impact in sequential grafts including Y- or T-constructions. Last, off-pump CABG has been reported to be associated with inferior patency rates,²³ although the current consensus is that in experienced hands, both off-pump and on-pump CABG attain excellent clinical outcomes in most patients.

Postoperative Therapies

Lifestyle
Lifestyle and behavioral factors are associated with risk for SVG failure. It is established that smoking¹⁸ and hyperlipidaemia²⁴ are associated with SVG failure. Diabetes and probably hypertension influence graft occlusion after CABG,^25,26 and management of both decreases adverse clinical events.^27,28 Therefore, addressing risk factors by adequate secondary prevention remains the cornerstone of strategies to improve graft patency.

Antithrombotic Therapies
SVG failure is up to five times more frequent in patients who are not treated with aspirin postoperatively,²⁹ and early postoperative use is associated with a reduced risk of death and ischemic complications, albeit with a slight increase in perioperative bleeding.^30,31 Therefore, guidelines recommend the preoperative or early postoperative use of aspirin.^1,32,33 More potent platelet inhibition could potentially provide better patency after CABG. However, studies investigating additional antithrombotic therapies after CABG have not provided definite conclusions. Addition of dipyridamole does not appear to improve SVG patency³⁴ and might lead to worse clinical outcomes after CABG³⁵; therefore, it is not recommended.^32,33

The addition of the P2Y12 inhibitor clopidogrel to aspirin did not improve SVG patency in certain studies,⁵ whereas in others it showed better SVG patency.³⁶ This may be due to 30% of patients having an inadequate inhibitory response to clopidogrel. Nonetheless, addition of the stronger P2Y12 inhibitor ticagrelor to aspirin does not conclusively render better SVG patency,^37,38 although ticagrelor has hardly any variability in response.

Oral anticoagulation provides no improvement in SVG patency rates compared with aspirin,^39,40 but it causes more bleeding complications.⁴⁰ Guidelines therefore advise against routinely administering vitamin K antagonists in patients undergoing CABG without other indications for vitamin K antagonists.³³ There is currently only limited evidence concerning the effect of novel oral anticoagulants after CABG. The recent COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) CABG substudy (n = 1,448 patients) did not show an effect on graft patency of rivaroxaban plus aspirin compared with rivaroxaban monotherapy or aspirin monotherapy.⁴¹

Lipid-Lowering Therapies
Statin therapy reduces SVG occlusion rates as well as adverse events after CABG.^42,43 Guidelines recommend statin therapy in all patients with diagnosed coronary artery disease,¹ and in patients undergoing CABG, statin therapy is to be initiated preoperatively and continued for life.¹ Addition of ezetimibe in patients with prior CABG might amplify the clinical benefits of statin therapy,⁴⁴ as might treatment with PCSK9 inhibitors,⁴⁵ although more definite conclusions regarding the effect on SVG patency are awaited (NCT03900026, NCT03542110).

Other Therapies
Applying external support on the outer surface of the SVG by using an external stent targets factors such as high wall tension and disturbed flow patterns, which could lead to deterioration of the graft. This technique of external stenting is promising for preventing intimal hyperplasia and improving SVG patency.⁴⁶ New techniques like immunomodulation⁴⁷ and gene therapy⁶ are currently being investigated.

Conclusion
SVG failure is a complex, multifactorial process and is related to adverse outcomes after CABG. SVG occlusion rates are around 11% at 1 year after CABG. Technical factors during surgery and SVG construction are important in optimizing SVG patency. Secondary prevention aimed at preserving SVG patency should address risk factors for SVG failure and include antithrombotic therapy with aspirin and lipid-lowering therapies. Attempts to further improve SVG patency have resulted in the development of promising new targets, such as external stenting of the SVG.

References

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Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Pericardial Disease, Prevention, Stable Ischemic Heart Disease, Aortic Surgery, Cardiac Surgery and SIHD, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and ACS, Interventions and Imaging, Angiography, Echocardiography/Ultrasound, Nuclear Imaging, Hypertension, Chronic Angina

Keywords: Platelet Aggregation Inhibitors, Blood Pressure, Timolol, Cholesterol, LDL, Patient Discharge, PCSK9 protein, human, Cholesterol, HDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Proprotein Convertase 9, Proprotein Convertase 9, Coronary Vessels, Aspirin, Hydrochlorothiazide, Mammary Arteries, Cardiac Rehabilitation, Exercise Test, Exercise Test, Heart Rate, Angina, Stable, Acute Coronary Syndrome, Triglycerides, Hyperlipidemias, Constriction, Pathologic, Pericardial Effusion, Ophthalmic Solutions, Follow-Up Studies, Coronary Artery Bypass, Electrocardiography, Percutaneous Coronary Intervention, Hypotension, Hypertension, Echocardiography, Stents, Ischemia, Diuresis, Hospitals, Angiography

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