Advances in Pharmacoepidemiology and Drug Safety

Minimizing Stent Thrombosis with Drug-eluting Stent and Dual-Antiplatelet Therapy

Mehvish Sohail^1* and Muhammad Waqas Farooqi^{2 1}Department of Internal Medicine, Bahria University Medical and Dental College, Karachi, Pakistan
²NYC Health Hospitals/Metropolitan, New York, USA
^*Correspondence: Mehvish Sohail, Department of Internal Medicine, Bahria University Medical and Dental College, Karachi, Pakistan, Email:

Received: 02-Oct-2023, Manuscript No. PDS-23-23450; Editor assigned: 04-Oct-2023, Pre QC No. PDS-23-23450 (PQ); Reviewed: 18-Oct-2023, QC No. PDS-23-23450; Revised: 25-Oct-2023, Manuscript No. PDS-23-23450 (R); Published: 01-Nov-2023, DOI: 10.35248/2167-1052.23.12.333

Description

Stent Thrombosis (ST) refers to the formation of blood clot that block a coronary stent, occurring because the stent doesn’t have adequate endothelial coverage within the treated vessel following Percutaneous Coronary Intervention (PCI). This complication is concerning but relatively infrequent, especially with the development of Drug-Eluting Stent (DES) and Dual Anti-Platelet Therapy (DAPT) [1]. ST affects only around 0.5% to 1% of patients within a year, and there is 10% to 25% mortality rate within 30 days [2].

ST is a multifactorial process involving many pathophysiological factors ranging patient associated, lesion related, intra procedural or post procedural. Diabetes and kidney failure are considered strong independent predictors of the most prevalent type of ST with reference to time i.e. sub-acute ST (within 24 hours to 30 days) and Late ST-LST (up to a year). Furthermore ST is also classified on the basis of certainty. Definite ST is when angiographic or pathological confirmation of partial or total thrombotic occlusion within the persistent region is observed. Any unexplained death<30 days of stent implantation is called probable ST; whereas possible ST is defined with any unexplained death beyond 30 days [1].

DES are vascular prostheses with anti-proliferative drug-loaded polymeric matrix coating a metal platform stent Cobalt–Chromium (CoCr) or Platinum–Chromium (PtCr). These alloys provide good radial strength, reduces platelet and inflammatory cell adhesion being advantageous in minimizing in stent restenosis and ST [3].

Polymers used, carry drugs either in biodegradable or in durable form. Biodegradable polymers abolish the long-term implications of inflammation and hypersensitivity of permanent polymer. The anti-proliferative agents used in DES slows reendothelization which predisposes to the development of ST [1].

Second generation DES are preferred over first generation DES due to their superior mechanical performance. They are favored for their reduced risk of LST and VLST especially in high risk patients. They offer thinner, more biocompatible polymer with sustained anti-proliferative drug release which reduces inflammation allowing adequate neointimal growth and endothelization over stent sruts preventing development of ST. Among this class are Zotarolimus- Eluting Stent (ZES) and Everolimus-Eluting Stents (EESs). EES significantly reduce the incidence of MI and ST, making them the safest type of DES [1].

Type of DES used and the complexity of the lesion (unprotected left main disease, more than two lesions per vessel, lesion length ≥ 30 mm, bifurcation lesion with side branch ≥ 2.5 mm, vein bypass graft or thrombus-containing lesion) can influence the risk of events during or after DAPT. With the use of modern DES, early discontinuation of DAPT can be implemented, which provides the added benefit by reducing bleeding events in patients at high hemorrhagic risk. A shorter duration of DAPT or a switch from high-potency P2Y12 inhibitors to clopidogrel might be associated with reduced bleeding without compromising the anti-ischemic protection [1,3]. Intracoronary imaging modalities e.g., via Intra Vascular Ultra Sound (IVUS) and Optical Coherence Tomography (OCT), minimize and thus prevent the ST occurrence by allowing early evaluation of risk factors contributing to future ST. Increased strut thickness influence the risk of early ST with definite certainty risk in small vessels and calcified lesions, malposition and evaginations determine the increased risk of late ST [1,3].

DAPT, which includes aspirin plus P2Y12 inhibitors, is the most effective approach to reduce the risk of ST in the post procedural stage after PCI. Complexity of the lesion can influence the risk of adverse events but it can be modified by use of DAPT. The most important consideration to be done in selecting DAPT drug and duration is the particular patient risk of ischemia or bleeding. Furthermore, managing DAPT duration requires careful evaluation of risk factors involved in mechanism of ST. PRECISE- DAPT score has been formulated to identify DAPT duration considering bleeding risk. Similarly DAPT score helps to identify DAPT Continuation beyond 12 months (Table 1) [1].

Table 1: PRECISE-DAPT score to determine DAPT duration w.r.t bleeding risk.

American guidelines for DAPT after PCI, especially considering newer generation DES, recommends continued reduced six months DAPT in the non-ACS group and three months DAPT in patients at risk for bleeding or in low-risk patients with stable angina. High risk patients for ischemia should be kept on 12 months of DAPT. In a study absolute risk reduction of 0.25% in major bleeding with the short DAPT group was observed in comparison to standard term DAPT (0.32% versus 0.57%) [1].

Drug-drug interactions impact the effect of anti-platelet agents. Proton-pump inhibitors (especially omeprazole), lipophilic statins (especially atorvastatin), Ca²⁺-channel blockers (especially amlodipine), morphine have all been associated with interaction with P2Y12 inhibitors, which mostly inhibits their antiplatelet activity. Interactions between clopidogrel and parathyroid hormone levels, serum uric acid levels, mean platelet volume and chronic obstructive pulmonary disease, among other factors, have also been reported, leading to high on therapy platelet reactivity, which can potentially lead to increased risk of thrombotic events, including ST [3]. Patients with CYP2C19 Loss-Of Function (LOF) alleles cannot metabolize clopidogrel. This requires optimization with alternative P2Y12 inhibitor antiplatelet therapy, such as prasugrel and ticagrelor. Although this is not done as routine testing and is limited to patients with high-risk anatomy, high-risk heart failure Killip class IIb patients or in patients with diabetic complications [1].

TAILOR-PCI trial conducted over 12 months follow-up period, focused on genotype-guided selection of P2Y12 inhibitors in patients carrying CYP2C19 LOF gene. These patients presented with Acute Coronary Syndrome (ACS) or stable Coronary Artery Disease (CAD) and underwent PCI. The study compared conventional clopidogrel therapy in patients who did not have point-of-care genotyping and found that there was no statistically significant difference in the outcome of ST prevention in comparison to the group undergoing genotype testing [4].

A post-hoc analysis of the TAILOR-PCI trial extracted (ABCD- gene) score which ranges from 0 to 38 and includes factors such as Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping, to identify patients who are at increased risk of High Platelet Reactivity (HPR) when taking clopidogrel (a score of 10 points or more is considered high risk for ischemia identification). After 12 months the study found that patients with high ABCD- gene score had significantly higher rates of primary and secondary adverse ischemic events in comparison to low scorers. This suggests that ABCD-gene score helps in identifying individuals who are more likely to experience adverse outcomes e.g., ST, when taking clopidogrel after PCI. This suggests the potential benefits of genotype guided therapy at 3 months in consideration with individual patient factors aiding to select most desired anti-platelet to be continued after PCI (Table 2) [5].

Table 2: ABCD-GENE score to determine clopidogrel use.

DAPT use to reduce the risk of ST, requires optimal duration of DAPT to be continued related to individual risk factors. Numerous randomized, controlled trials and meta-analyses have compared different durations and intensities of DAPT while studying the effects of DAPT discontinuation over time, as a predictor of ST [1] Following are some trials discussing different DAPT durations (Table 3) [1,6-8].

Table 3: Illustrates trials discussing different DAPT durations.

Newer P2Y12 inhibitors prasugrel was studied in TL-PAS trial. The results showed reduced MI/ ST ischemic events but severe bleeding was documented. Older age (≥75 years), body weight<60 kg, and previous stroke or Transient Ischemic Attack (TIA) were most susceptible population. This paradoxical bleeding risk with use of antithrombotic is called trade-off between bleeding and thrombosis. PLATO trial, a cohort, studied ticagrelor with clear superiority over clopidogrel, with lower incidence of ST. No significant difference in bleeding risk was observed between the two groups [1].

To combat the bleeding risk associated with aspirin, SMART-CHOICE trial, the STOPDAPT-2 trial, and the TWILIGHT study supported the idea of P2Y12 antagonist monotherapy following a short duration of three months of DAPT with aspirin [1].

Conclusion

Intracoronary imaging offers valuable insight in predicting ST development risk. This complication can further be reduced by personalizing DAPT specific to patient ischemia and bleeding risk according to recommended guidelines, along with selection of efficient DES favoring patient outcomes.

References

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