What are the potential side effects of the Synergy Megatron (drug-eluting) stent?

Side Effects of the Synergy Megatron Drug-Eluting Stent

The Synergy stent, like all drug-eluting stents, carries a risk of stent thrombosis (particularly if dual antiplatelet therapy is discontinued prematurely), delayed endothelialization, hypersensitivity reactions to the polymer or drug, bleeding complications from required antiplatelet therapy, and restenosis, though its bioabsorbable polymer design may reduce some long-term inflammatory complications compared to permanent polymer stents. 1, 2

Stent Thrombosis Risk

The most catastrophic complication of drug-eluting stents is stent thrombosis, which results in death or myocardial infarction in 64.4% of cases, with mortality rates ranging from 20-45%. 3

• In the current era of dual antiplatelet therapy, subacute stent thrombosis occurs in approximately 1% of patients 3
• Late stent thrombosis (1-12 months post-implantation) occurs in 0.19% of patients with drug-eluting stents, which was not readily apparent with bare-metal stents 3
• Very late stent thrombosis can occur up to 1.5 years after implantation, particularly when antiplatelet agents are discontinued 3

Risk Factors for Stent Thrombosis

The following factors significantly increase thrombosis risk 3:

• Premature discontinuation of antiplatelet therapy (the single most important predictor)
• Stenting of small vessels
• Multiple or long stents
• Overlapping stents
• Ostial or bifurcation lesions
• Prior brachytherapy
• Suboptimal stent result (underexpansion, malapposition, or residual dissection)
• Low ejection fraction
• Advanced age
• Diabetes mellitus
• Renal failure
• Acute coronary syndrome presentation

Premature Antiplatelet Discontinuation: The Critical Risk

Stopping dual antiplatelet therapy prematurely is associated with catastrophic outcomes and is the leading independent predictor of stent thrombosis. 3

• Stent thrombosis occurred in 29% of patients who discontinued antiplatelet therapy prematurely 3
• Premature discontinuation carries a hazard ratio of 161 (95% CI: 26-998) for subacute stent thrombosis and 57 (95% CI: 15-220) for late stent thrombosis 3
• In patients who stopped clopidogrel within the first month, 25% suffered stent thrombosis—a 30-fold increased risk 3
• Mortality at 11 months was 7.5% in those who stopped thienopyridine therapy versus 0.7% in those who continued (hazard ratio 9.0) 3

Perioperative Risk

For patients requiring noncardiac surgery within the first 6 weeks to 12 months after stent placement, the risk of major adverse cardiac events is substantially elevated. 3

• Early surgery (within required DAPT timeframe) resulted in 13.3% major adverse cardiac events versus 0.6% in late surgery 3
• When antiplatelet therapy was discontinued in the early-surgery group, the incidence of major adverse cardiac events was 30.7% (all fatal) versus 0% in those who continued therapy 3
• The risk appears highest in the initial 6 weeks after stent placement (8-10%) but plateaus at 6 months (1-2%) 3

Delayed Healing and Hypersensitivity Reactions

Drug-eluting stents delay endothelialization and healing, which increases the risk of late thrombosis. 3

• The antiproliferative drugs (everolimus in the Synergy stent) inhibit neointimal formation but also delay endothelialization 3, 1
• Very late stent thrombosis results from delayed hypersensitivity to components of the drug-polymer-device combination, causing necrotizing vasculitis and late malapposition 3
• The Synergy stent's bioabsorbable poly-DL-lactide-co-glycolide polymer is designed to reduce long-term inflammatory complications by completely resorbing within 3-4 months 1, 2

Bleeding Complications from Required Antiplatelet Therapy

Dual antiplatelet therapy required after drug-eluting stent placement carries significant bleeding risk. 3

• Patients at increased bleeding risk represent a relative contraindication to drug-eluting stent use 3
• In perioperative studies, major bleeding occurred in approximately 4-5% of patients continuing antiplatelet therapy 3
• The bleeding risk must be balanced against the substantially higher thrombotic risk when antiplatelet therapy is interrupted 3

Contraindications Related to Bleeding Risk

The following situations represent relative clinical contraindications to drug-eluting stent use 3:

• Expected poor compliance with dual antiplatelet therapy
• Patients with multiple comorbidities and polypharmacy
• Non-elective surgery required in the short term that would require interruption of DAPT
• Increased baseline risk of bleeding
• Known allergy to aspirin or clopidogrel/prasugrel/ticagrelor
• Absolute indication for long-term anticoagulation

Allergic Reactions to Clopidogrel

Adverse reactions to clopidogrel occur in a subset of patients, requiring either desensitization or switch to alternative antiplatelet agents. 4

• Mucocutaneous, bronchial, or anaphylactic responses can occur 4
• Clopidogrel desensitization protocols have shown success in 24 consecutive patients, with acute success in all cases and sustained remission in 23 of 24 patients at 6 months 4
• Only 2 patients required repeat desensitization, and 1 had persistent but improved pruritus controlled with antihistamines 4

Restenosis Risk

While drug-eluting stents significantly reduce restenosis compared to bare-metal stents, restenosis remains a potential complication. 5, 2

• In-stent restenosis historically occurred in 10-40% of patients with bare-metal stents 5
• Drug-eluting stents with strong antiproliferative properties (late lumen loss ≤0.2 mm) show the best angiographic outcomes 3
• The Synergy stent's everolimus-eluting design aims to minimize restenosis while promoting healing 1, 2

Neoatherosclerosis

First-generation drug-eluting stents demonstrated neoatherosclerosis as a long-term complication, though newer-generation stents like Synergy may have reduced this risk. 2

• Neoatherosclerosis contributed to a steady increase in major adverse cardiovascular events over time with first-generation stents 2
• Newer-generation stents with bioabsorbable polymers and improved designs aim to reduce this complication 2

Required Dual Antiplatelet Therapy Duration

The Synergy stent requires dual antiplatelet therapy for a minimum of 6-12 months to minimize thrombotic complications. 3, 6

• Convincing data exist for continuation up to 6 months, with possibly 3 months sufficient under some circumstances, though evidence is not robust 3
• The American College of Cardiology/American Heart Association recommends ideally up to 12 months if patients are not at high risk for bleeding 3
• Diabetic patients may require longer duration of dual antiplatelet therapy 3

Perioperative Management Algorithm

For patients requiring surgery after Synergy stent placement 3, 6:

• Within 6-12 weeks of stent placement: Either continue both antiplatelet agents or stop one agent 7-10 days before surgery, depending on bleeding risk versus thrombotic risk 3
• Beyond 12 weeks but within 12 months: Stop P2Y12 inhibitor (clopidogrel) 7-10 days before surgery while continuing aspirin 3, 6
• Elective surgery: Postpone until completion of recommended DAPT duration (6-12 months) whenever possible 6
• If surgery cannot be postponed: Maintain aspirin throughout the perioperative period 6
• Resume clopidogrel: As soon as possible after surgery, preferably within 5 days 6