Stent thrombosis treatment

Stents are usually placed in the proximal segments of major epicardial vessels, hence in-stent thrombotic occlusion clinically present as severe ischemia or infarction^[1].Stent thrombosis is a medical emergency and is managed as an acute coronary syndrome, with emergent revascularization to restore vessel patency. Because the underlying abnormality is usually a mechanical or biological problem of the previously implanted stent rather than de novo atherothrombosis, restoring flow alone is not sufficient treatment. Intracoronary imaging is used at the time of the procedure to establish which mechanism is responsible; stent underexpansion, strut malapposition, uncovered struts, neoatherosclerosis, in-stent restenosis or edge-related disease; and the intervention is then directed at that mechanism. Balloon dilatation is the preferred treatment where underexpansion or malapposition is found, and a further stent is reserved for significant residual or edge dissection. The antiplatelet regimen is reviewed in every case, and a potent P2Y12 inhibitor is preferred to clopidogrel afterwards, chosen according to its own contraindications. Despite successful revascularization, mortality and recurrent thrombosis after a first stent thrombosis remain high.

The probable cause for stent thrombosis should be evaluated as the treatment varies with etiology.

While the patient is undergoing cardiac catheterization, a careful evaluation should be undertaken to exclude procedure related variables that could be amenable to further treatment such as:

• Suboptimal stent expansion and poor apposition,
• Procedure-related variables of persistent dissection, total stent length, and final lumen diameter were significantly associated with the probability of stent thrombosis^[1].
• Angiography alone cannot reliably demonstrate these abnormalities, so the search for a procedure-related cause should be made with intracoronary imaging rather than by angiographic appearance.^[2]

Likewise, the patient should be questioned thoroughly for the following clinical risk factors for stent thrombosis:

• Noncompliance with dual antiplatelet therapy,
• Premature discontinuation of dual antiplatelet therapy
• Cessation of dual antiplatelet therapy within the first month after implantation is among the strongest predictors of the event and should be asked about directly; many events nevertheless occur on uninterrupted therapy, so continued treatment does not exclude a mechanical cause.^[2]

If neither angiographic, procedural nor clinical variables appear to play a role, then clopidogrel resistance should be considered. This diagnosis can of course be confirmed through platelet function testing and genetic testing. If this is the case consideration should be made to switching the patient to prasugrel.^[3] The TIMI 38 or TRITON trial demonstrated that newer antiplatelet agents such as prasugrel^[4] may be used after weighing the risks of bleeding against benefits of decreased recurrence of stent thrombosis/coronary events. Patients who present with stent thrombosis after completing the recommended duration of treatment with clopidogrel restarting clopidogrel 75 mg daily along with aspirin and continuing for a minimum of one year should be considered.

• A potent P2Y12 inhibitor — prasugrel or ticagrelor — should be preferred to clopidogrel as the second antiplatelet agent after stent thrombosis, since these patients are by definition at heightened risk of a further ischemic event; agent selection should account for each drug’s own contraindications, below.^[5]
• Treatment with a new-generation P2Y12 inhibitor rather than clopidogrel after the event is associated with fewer subsequent myocardial infarctions, but this is supported only by observational data and should not be regarded as established.^[6]
• Platelet function testing or genetic testing should be considered in a patient with a history of recurrent ischemic events — a category that explicitly includes previous stent thrombosis — particularly where clinical or procedural ischemic risk is high, and should be performed early after the index procedure, since the first weeks to months carry the greatest combined bleeding and ischemic risk.^[7]
• High on-treatment platelet reactivity by the VerifyNow P2Y12 assay is defined as a reaction unit value above 208 (above 252 in Asian patients); where high on-treatment platelet reactivity or a CYP2C19 loss-of-function allele is identified, treatment should be escalated to prasugrel or ticagrelor rather than to a higher dose of clopidogrel.^[7]
• Where residual thrombus is seen after intervention, prolonged anticoagulation and antiplatelet therapy may be of benefit, and adherence and drug resistance should be evaluated in detail.^[8]
• Long-term oral anticoagulation is rarely necessary but may be considered in selected patients with recurrent stent thrombosis.^[8]

• Intracoronary imaging by intravascular ultrasound or optical coherence tomography should be performed when stent thrombosis is treated, because angiography alone cannot assess stent-related pathology.^[2][11]
• Imaging is prioritized once the patient is stabilized and where dual antiplatelet therapy has not been interrupted, to assess stent apposition, expansion, and the presence of edge dissection or intramural hematoma.^[8]
• Optical coherence tomography may be preferred to intravascular ultrasound for determining the mechanism of stent thrombosis, particularly for late and very late presentations, given its higher resolution for strut-level findings such as uncovered struts, malapposition and neoatherosclerosis.^[8]
• An abnormality is demonstrable in almost every stent treated for thrombosis; strut malapposition, neoatherosclerosis and major stent underexpansion account for most events, with uncovered struts, coronary evagination, edge-related disease progression and neointimal hyperplasia making up the remainder.^[12]
• Malapposition and underexpansion predominate in acute and subacute events, whereas malapposition and neoatherosclerosis predominate in late and very late events, so the timing of presentation should shape what the operator looks for.^[12]
• Ruptured neoatherosclerotic lesions are the more frequent finding after bare metal stent implantation, and coronary evagination after drug-eluting stent implantation.^[12]
• Malapposition is regarded as significant at a strut-to-intima distance greater than 350 µm, or greater than 200 µm over a length exceeding 600 µm, and underexpansion at a stent cross-sectional area below 75% of the reference lumen area.^[5]
• Imaging-guided management of stent thrombosis is associated with better two-year survival free of cardiac death and target lesion revascularization than angiographic guidance alone, but is supported only by observational, propensity-matched data and should not be regarded as established.^[13]
• Where a new stent is implanted, imaging guidance should be used, since imaging-guided drug-eluting stent implantation reduces definite or probable stent thrombosis, target lesion failure, cardiac death and target vessel myocardial infarction compared with angiography alone.^[14]
• Imaging should be repeated after treatment and the result optimised before the procedure is concluded, targeting a minimal stent area above 5.5 mm² by intravascular ultrasound outside the left main coronary artery, above 4.5 mm² by optical coherence tomography, and stent expansion of at least 80% of the reference lumen.^[15]
• Acute malapposition of less than 0.4 mm in axial distance and less than 1 mm in longitudinal extent may be accepted without further intervention.^[15]

• Emergent target lesion or target vessel revascularization is the treatment of choice in stent thrombosis to restore vessel patency.
• Revascularization may be carried out by PCI or in some instances, thrombolytics if PCI is not available ^[16].
• If revascularization is not successful, urgent CABG should be considered.
• Most stent thrombosis occlusions can be treated initially with balloon angioplasty alone; adjunctive manual thrombus aspiration should be reserved for a large clot burden.^[8]
• After flow is re-established, the angiographic and clinical picture should be checked for evidence of distal embolization, which should be treated before the procedure is considered complete.^[8]
• Reopening the vessel is only the first half of the procedure; the mechanism responsible for the event must be identified and corrected at the same sitting, because recurrence is common when it is not.^[2]
• Most patients treated for stent thrombosis receive dual antiplatelet therapy afterwards, and additional stent implantation, mechanical thrombus removal and glycoprotein IIbIIIa inhibition are each used in roughly half of cases in contemporary practice.^[6]

• Balloon angioplasty alone is the preferred treatment where stent underexpansion or malapposition is the mechanism, and is effective in that setting.^[2][13]
• A further stent should be implanted where the mechanism is significant residual or edge dissection, particularly where dual antiplatelet therapy has recently been discontinued, and may be required for neoatherosclerosis.^[8][13][2]
• Underexpansion must be corrected at the index procedure, since a stent cross-sectional area below 75% of the reference lumen area is among the imaging findings most strongly associated with a further event.^[5]
• Where late stent thrombosis has occurred on a background of in-stent restenosis, a drug-coated balloon is a reasonable alternative to a further drug-eluting stent once lesion preparation has left less than 30% residual stenosis; drug-eluting stent implantation has nevertheless yielded lower target lesion failure than drug-coated balloon treatment for restenosis of a previous drug-eluting stent.^[5]

• Peri-stent calcium underlying an underexpanded segment may itself require modification before the stent can be re-expanded; an arc of calcium greater than 270°, or a thickness greater than 0.67 mm, favours calcium-modification before high-pressure balloon re-expansion, and if expansion remains inadequate, coronary artery bypass grafting may become necessary.^[8]
• A stepwise, imaging-guided escalation is preferred: a conventional non-compliant balloon at high pressure is used first; a cutting or scoring balloon, or a super-high-pressure non-compliant balloon, is used next, particularly where intimal hyperplasia or calcific underexpansion resists a standard balloon.^[17][18]
• Intravascular lithotripsy is preferred where underexpansion is calcium-dominant; excimer laser coronary atherectomy, preferably with concurrent contrast injection to potentiate the photomechanical effect, is an alternative for extensive peristent calcium, though contrast injection increases the risk of no reflow, dissection and perforation.^[17][18]
• Rotational atherectomy or orbital atherectomy should be reserved for bailout, given the risk of burr entrapment and disruption of stent struts — particularly within the first three to six months after implantation — and repeat stenting or a drug-coated balloon should be anticipated afterward because stent integrity has been compromised.^[17][18]
• Intravascular lithotripsy has reduced efficacy when delivered through multiple stent layers, and a super-high-pressure balloon inflated above 30 atmospheres may fuse to a hydrophilic-coated guidewire.^[17]
• Where adequate expansion cannot be achieved despite these measures — especially with multiple stent layers or severe circumferential calcium — escalation to further high-risk mechanical maneuvers should be avoided and surgical revascularization considered instead.^[17][18]

• Manual thrombus aspiration may be considered where thrombus burden is large, to limit distal embolization and improve myocardial perfusion, but it has produced favourable angiographic rather than clear clinical benefit and is supported only by observational data.^[5]
• Mechanical or extraction thrombectomy has been used anecdotally in stent thrombosis, but no large-scale study has evaluated its benefit or identified which patients are most likely to gain from it.^[8]
• Glycoprotein IIbIIIa inhibition should be reserved for bailout use where there is no reflow or a thrombotic complication during the procedure.^[5][11]
• Cangrelor may be considered on a case-by-case basis in a patient who is P2Y12 inhibitor-naive at the time of the procedure.^[11]
• Intracoronary abciximab, with or without preceding manual aspiration, improves angiographic measures of myocardial perfusion and infarct size relative to standard PCI; benefit on clinical endpoints has not been established.^[5]
• Intracoronary fibrinolysis may be considered as an adjunct where thrombus burden is large, but is supported only by angiographic results and should not be regarded as established treatment.^[5]

• Routine aspiration thrombectomy is not recommended, and should not be used in place of establishing and correcting the underlying stent abnormality.^[11][5]
• Pretreatment with glycoprotein IIbIIIa inhibition before angiography is not recommended, and routine systemic use should be limited to the bailout indications above.^[11][5]
• Additional stent implantation should be avoided unless significant residual dissection or neoatherosclerosis requires it, because it adds metal without addressing underexpansion or malapposition.^[8][2]
• The procedure should not be concluded while stent underexpansion or significant malapposition remains uncorrected.^[5][15]
• Prasugrel is contraindicated in a patient with a prior transient ischemic attack or stroke; ticagrelor is the potent P2Y12 inhibitor of choice in this setting instead.^[19]
• Prasugrel is contraindicated in active pathological bleeding, including intracranial hemorrhage.^[19]
• Prasugrel should generally be avoided at 75 years of age or older because of increased fatal and intracranial bleeding risk and uncertain benefit, except in high-risk patients with diabetes mellitus or a prior myocardial infarction, where it may still be considered; the maintenance dose should be reduced to 5 mg daily in patients weighing less than 60 kg.^[19]
• Prasugrel should not be started in a patient likely to need urgent CABG, and should be stopped at least 7 days before any surgery.^[19]
• Ticagrelor is contraindicated in a prior intracranial hemorrhage and in active pathological bleeding.^[20]
• Ticagrelor should be avoided in severe hepatic impairment and with concomitant strong CYP3A4 inhibitors, and should not be started in a patient likely to need urgent CABG; it should be stopped at least 5 days before major bleeding-risk surgery.^[20]

Step 1: Restore vessel patency

• Emergent target lesion or target vessel revascularization by PCI.^[16]
• Treat most occlusions with balloon angioplasty alone; add manual thrombus aspiration only where thrombus burden is large.^[8]
• Use glycoprotein IIbIIIa inhibition as bailout for no reflow or a thrombotic complication.^[5]

Step 2: Address distal embolization and stabilize

• Once flow is restored, look for and treat angiographic or clinical evidence of distal embolization before proceeding further.^[8]

Step 3: Establish the mechanism

• Image the stented segment with intravascular ultrasound or optical coherence tomography in every case where dual antiplatelet therapy has not been interrupted.^[8][11]
• Acute or subacute presentation → look first for malapposition and underexpansion.^[12]
• Late or very late presentation → look first for malapposition and neoatherosclerosis.^[12]

Step 4: Treat according to the mechanism found

• Underexpansion or malapposition → high-pressure balloon angioplasty alone.^[2][13]
• Underexpansion refractory to balloon dilatation → calcium-modification (cutting/scoring balloon, intravascular lithotripsy or excimer laser) before re-attempting high-pressure balloon expansion, escalating to atherectomy only as bailout.^[17][18]
• Significant residual or edge dissection → implant a new stent.^[8][13]
• Neoatherosclerosis → implant a new stent where balloon treatment is inadequate.^[2]
• In-stent restenosis as the substrate → drug-coated balloon once residual stenosis is below 30%, or a drug-eluting stent.^[5]
• No modality achieves adequate expansion (multilayer stent, severe circumferential calcium) → consider surgical revascularization rather than further high-risk mechanical maneuvers.^[17]

Step 5: Confirm optimisation before finishing

• Repeat imaging and post-dilate until minimal stent area and expansion targets are met.^[15]
• Use imaging guidance for any new stent implanted.^[14]

Step 6: Secure long-term antiplatelet therapy

• Prescribe a potent P2Y12 inhibitor in preference to clopidogrel, selecting between prasugrel and ticagrelor according to each drug’s contraindications.^[5][19][20]
• Address adherence and any interruption of dual antiplatelet therapy; consider platelet function or genetic testing where risk is high or the event recurs.^[2][7]

• No reflow and distal embolization are the principal immediate complications; angiography-derived measures of coronary microvascular obstruction are present in about 40% of patients treated for stent thrombosis.^[5]
• Mortality remains high despite successful revascularization, at roughly 5% in hospital, 13% at one year and 24% at five years, and cardiac death occurs in about one in five patients by five years.^[21][6]
• Recurrent stent thrombosis is common after treatment, affecting roughly 10% to 25% of patients within five years depending on the definition applied, so a further event should be anticipated rather than regarded as unexpected.^[21][6]
• Cardiogenic shock at presentation, a left anterior descending artery culprit and a history of stroke or transient ischemic attack identify the patients at highest risk of further events after treatment.^[6]
• Increasing age, diabetes mellitus, current smoking and a bifurcation location of the thrombosed stent are independently associated with major adverse cardiac and cerebrovascular events to five years.^[21]
• Atherectomy performed within a previously implanted stent for refractory underexpansion carries a specific risk of burr or crown entrapment and physical disruption of the stent struts, and repeat stenting should be anticipated after such a procedure because stent integrity has been compromised.^[17]

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