Dual Antiplatelet Therapy Strategy Research Articles

Dual antiplatelet management in the perioperative period: updated and expanded systematic review

BackgroundAntiplatelet agents are central in the management of vascular disease. The use of dual antiplatelet therapy (DAPT) for the management of thromboembolic complications must be weighed against bleeding risk in the perioperative setting. This balance is critical in patients undergoing cardiac or non-cardiac surgery. The management of patients on DAPT for any indication (including stents) is not clear and there is limited evidence to guide decision-making. This review summarizes current evidence since 2015 regarding the occurrence of major adverse events associated with continuing, suspending, or varying DAPT in the perioperative period.MethodsA research librarian searched PubMed and Cochrane from November 30, 2015 to May 17, 2022, for relevant terms regarding adult patients on DAPT for any reason undergoing surgery, with a perioperative variation in DAPT strategy. Outcomes of interest included the occurrence of major adverse cardiac events, major adverse limb events, all-cause death, major bleeding, and reoperation. We considered withdrawal or discontinuation of DAPT as stopping either aspirin or a P2Y12 inhibitor or both agents; continuation of DAPT indicates that both drugs were given in the specified timeframe.ResultsEighteen observational studies met the inclusion criteria. No RCTs were identified, and no studies were judged to be at low risk of bias. Twelve studies reported on CABG. Withholding DAPT therapy for more than 2 days was associated with less blood loss and a slight trend favoring less transfusion and surgical re-exploration. Among five observational CABG studies, there were no statistically significant differences in patient death across DAPT management strategies. Few studies reported cardiac outcomes. The remaining studies, which were about procedures other than exclusively CABG, demonstrated mixed findings with respect to DAPT strategy, bleeding, and ischemic outcomes.ConclusionThe evidence base on the benefits and risks of different perioperative DAPT strategies for patients with stents is extremely limited. The strongest signal, which was still judged as low certainty evidence, is that suspension of DAPT for greater than 2 days prior to CABG surgery is associated with less bleeding, transfusions, and re-explorations. Different DAPT strategies’ association with other outcomes of interest, such as MACE, remains uncertain. Systematic review registrationA preregistered protocol for this review can be found on the PROSPERO International Prospective Register of systematic reviews (http://www.crd.york.ac.uk/PROSPERO/; registration number: CRD42022371032).

An assessment of platelet response to ticagrelor in post-percutaneous coronary intervention patients using light transmission platelet aggregometry (LTA)

Background: Low on-treatment platelet reactivity (LTPR) or High on-treatment platelet reactivity (HTPR) with P2Y12 inhibitors is associated with bleeding (LTPR) or ischemic events (HTPR) in patients on dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). Objective: Mapping of Indonesian patients’ platelet response secondary to ticagrelor and thus identifying either LTPR or HTPR. Method: During May – June 2019, 20 post-PCI patients on aspirin–ticagrelor combination were included. Light transmission aggregometry (LTA) for monitoring platelet function was used. Ticagrelor’s LTA <40% is LTPR while >70% is HTPR. Result: Patients were mostly male (18 patients) and aged between 40-73 years old with a history of diabetes and/or hypertension and smoking. About eight patients (40%) were LTPR and one (5%) patient was HTPR. Conclusion: A personalised DAPT strategy for preventing bleeding events, a de-escalation, might be valuable for Indonesian patients.

One-Month Dual Antiplatelet Therapy in Patients With Chronic and Acute Coronary Syndromes Treated With Bioresorbable Polymer Everolimus-Eluting Stents

There is a paucity of data regarding the safety of a 1-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) presenting with acute coronary syndromes (ACS). We aimed to compare the clinical outcomes of patients at HBR with chronic coronary syndrome (CCS) or ACS treated with PCI using bioresorbable polymer everolimus-eluting stent (BP-EES) followed by 1-month DAPT. Patients at HBR who underwent PCI with BP-EES were prospectively enrolled in 10 Italian centers. All patients were treated with 1-month DAPT. In case of need for anticoagulation, patients received an oral anticoagulant in addition to a P2Y12 inhibitor for 1month, followed by oral anticoagulation only after that. The primary end point was a composite of cardiac death, myocardial infarction, or definite/probable stent thrombosis at 12months. Overall, 263 patients (59.4%) with CCS and 180 patients (40.6%) with ACS were enrolled. No significant difference was evident between patients with CCS and ACS for the primary end point (4.3% vs 5.6%, respectively, p=0.497) and for each isolated component. The risk for Bleeding Academic Research Consortium (BARC) type 1 to 5 or type 3 to 5 bleedings was also similar between patients with CCS and ACS (4.3% vs 5.2%, p=0.677, and 1.6% vs 2.9%, p=0.351, respectively). In conclusion, among HBR patients with ACS who underwent PCI with BP-EES, a 1-month DAPT strategy is associated with a similar risk of ischemic and bleeding events compared with those with CCS.

Net clinical benefit of dual antiplatelet therapy in elderly patients with acute coronary syndrome: A systematic review and meta-analysis.

Contemporary dual antiplatelet therapy (DAPT) strategies, such as short-term DAPT or de-escalation of DAPT, have emerged as attractive strategies to treat patients with acute coronary syndrome (ACS). However, it remains uncertain whether they are suitable for elderly patients. PubMed, Embase, and Cochrane CENTRAL databases were searched in September 2022. Randomized controlled trials (RCTs) investigating DAPT strategies, including standard (12 months), short-term, uniform de-escalation, and guided-selection strategies for elderly patients with ACS (age ≥ 65 years) were identified, and a network meta-analysis was conducted. The primary endpoint was the net clinical benefit outcome, a composite of major adverse cardiovascular events (MACEs: cardiovascular death, myocardial infarction, or stroke) and clinically relevant bleeding (equivalent to bleeding of at least type 2 according to the Bleeding Academic Research Consortium). The secondary outcomes were MACE and major bleeding. Sixteen RCTs with a combined total of 47,911 patients were included. The uniform de-escalation strategy was associated with an improved net clinical benefit compared with DAPT using potent P2Y12 inhibitors. The short-term DAPT strategy was associated with reduced risks of the primary outcome and major bleeding compared with DAPT using potent P2Y12 inhibitors, however, it was ranked as the least effective strategy for MACE compared with other DAPT strategies. Uniform de-escalation and short-term DAPT strategies may be advantageous for elderly patients, but need to be tailored based on individual bleeding and ischemic risks. Further RCTs of contemporary DAPT strategies specifically designed for elderly patients are warranted to confirm the findings of the present study.

Short Versus Long Duration of Dual Antiplatelet Therapy After Second-Generation Drug-Eluting Stents Implantation in Patients with Diabetes.

Duration of dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) remains uncertain, with increasing data suggestive of acceptable short-term duration. Metabolically accelerated atherosclerosis associated with diabetes makes it essential to study short-term DAPT in this subgroup. With limited studies determining optimal DAPT strategies after second-generation stents in this subset, we aimed to establish the optimal duration of DAPT in the diabetic population using second-generation stents. To determine optimal DAPT duration in diabetic population undergoing PCI in 2nd generation stents. We conducted an electronic database search of randomized controlled trials from PubMed/Medline, Embase, Cochrane, and Web of Science databases. A meta-analysis was conducted comparing outcomes of short-term (3-6 months) DAPT therapy versus long-term (12 months) DAPT therapy in the diabetic population undergoing PCI with second-generation stents. A total of 5 randomized controlled trials were included with a total of 3117 diabetic patients. Short-term DAPT did not show any statistical difference from long-term DAPT in achieving primary outcomes (relative ratio: 0.96, 95% confidence interval (CI) 0.68-1.35, P = 0.84). Overall mortality (OR 0.92; 95% CI, 0.52-1.63, P = 0.98), myocardial infarction [odds ratio (OR)OR 1.02; 95% CI, 0.53-1.94, P = 0.85], stent thrombosis (OR 1.20; 95% CI, 0.55-2.60, P = 0.55), target vessel revascularization (OR 1.10; 95% CI, 0.45-2.73, P = 0.74), and stroke (OR 0.50; 95% CI, 0.082-2.43, P = 0.81) did not show any statistical difference between the 2 groups. Similarly, a subgroup analysis of study population comparing 6 versus 12 months of DAPT in diabetic population did not show any difference in net primary outcomes (relative ratio: 0.86, 95% CI 0.45-1.45, P = 0.60). There was no significant heterogeneity noted between the 2 groups. This meta-analysis showed no statistically significant benefit of longer DAPT over shorter DAPT therapy in patients undergoing PCI with drug-eluting stent in patients with diabetes.

Preferred monotherapy after short-term dual antiplatelet therapy: Systematic review and network meta-analysis of randomized trials

BackgroundRandomized controlled trials (RCTs) have demonstrated the efficacy and safety of P2Y12 inhibitor monotherapy following short-term dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI). However, no studies have compared P2Y12 inhibitor and aspirin monotherapy following short-term DAPT. We aimed to compare available strategies for DAPT duration and post-DAPT antiplatelet monotherapy following PCI. MethodsSeven DAPT strategies [ticagrelor or clopidogrel following 1-month DAPT, ticagrelor following 3-month DAPT, aspirin following 3–6 months of DAPT (reference strategy), aspirin or P2Y12 inhibitor following 6–18-months of DAPT, and DAPT for ≥18 months] were compared using a network meta-analysis. The primary efficacy outcome was defined as a composite of all-cause death, myocardial infarction, and stroke. The primary bleeding outcome was trial-defined major or minor bleeding. ResultsOur analysis identified 25 eligible RCTs, including 89,371 patients who underwent PCI. Overall, none of the strategies negatively affected the primary efficacy outcomes. For primary bleeding outcomes, ticagrelor following 3-month DAPT was associated with a reduced risk of primary bleeding outcomes (HR 0.73; 95 % CI 0.57–0.95). Clopidogrel following 1-month DAPT was also associated with a reduced risk of primary bleeding outcomes (HR 0.54; 95 % CI 0.34–0.85), however, the strategy was associated with an increased risk of myocardial infarction or stent thrombosis. Similar trends were observed among patients with acute coronary syndrome and high bleeding risk. ConclusionsCompared with aspirin monotherapy following short-term DAPT, ticagrelor following 3-month DAPT was associated with a reduced risk of primary bleeding outcomes without increasing any ischemic outcomes.

P2Y12 inhibitor monotherapy after complex percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials

It remains unknown whether the recent trend of short dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy can simply be applied to patients undergoing complex percutaneous coronary intervention (PCI). We performed a systematic review and meta-analysis to evaluate P2Y12 inhibitor monotherapy vs. conventional DAPT in patients undergoing complex PCI and non-complex PCI (PROSPERO: CRD42022335723). Primary endpoint was the 1-year Net Adverse Clinical Event (NACE). Among 5,323 screened studies, six randomized trials fulfilled the eligibility criteria. A total of 10,588 complex PCI patients (5,269 vs. 5,319 patients) and 25,618 non-complex PCI patients (12,820 vs 12,798 patients) were randomly assigned to P2Y12 inhibitor monotherapy vs. conventional DAPT. In complex PCI patients, P2Y12 inhibitor monotherapy was associated with a lower risk of NACE than conventional DAPT [Odds ratio (OR) 0.76, 95% confidence interval (CI) 0.63–0.91, P = 0.003], whereas in non-complex PCI patients, P2Y12 inhibitor monotherapy was associated with a trend toward lowering the risk of NACE (OR 0.86, 95% CI 0.72–1.02, P = 0.09). This meta-analysis across randomized trials demonstrated that a strategy of short DAPT followed by P2Y12 inhibitor monotherapy reduces the risk of 1-year NACE in patients undergoing complex PCI.

Efficacy and safety of different dual antiplatelet strategies in patients undergoing percutaneous coronary intervention: A systematic review and network meta-analysis.

Dual antiplatelet therapy (DAPT) is key for preventing ischaemic events post-percutaneous coronary intervention (PCI). Various DAPT modifications like the shortened duration or P2Y12 inhibitor (P2Y12i) de-escalation are implemented to reduce bleeding risk. However, these strategies lack direct comparative studies. This study aimed to assess the efficacy and safety of such DAPT strategies, including de-escalated and short DAPT, in patients undergoing PCI. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for relevant randomized controlled trials (RCTs). We performed a network meta-analysis (NMA) to estimate risk ratios (RRs) and 95% confidence intervals (CIs). The primary efficacy endpoint was major adverse cardiac events (MACEs), and the primary safety endpoint was major bleeding. Secondary endpoints included individual components of MACEs and net adverse clinical events (NACEs). A total of 17 RCTs comprising 53,156 patients (median age, 62.0 years, 24.8% female) were included. NMA suggested that de-escalation DAPT was associated with a significantly lower risk of MACEs (risk ratio [RR] = 0.79, 95% confidence interval [CI] = 0.64-0.98), bleeding (RR = 0.63, 95% CI = 0.49-0.82), and NACEs (RR = 0.69, 95% CI = 0.60-0.79) compared with standard DAPT. Short DAPT followed by P2Y12i monotherapy exhibited a significantly decreased risk of major bleeding (RR = 0.63, 95% CI = 0.46-0.86) compared with standard DAPT. De-escalation DAPT was the most effective strategy for preventing the risk of MACEs without increasing bleeding events, while short DAPT followed by P2Y12i monotherapy was the most effective strategy for reducing the risk of bleeding among patients undergoing PCI.

Strategy of dual antiplatelet therapy for patients with ST-elevation myocardial infarction and non-ST-elevation acute coronary syndromes: A systematic review and network meta-analysis

BackgroundVarious durations and de-escalation strategies of dual antiplatelet therapy (DAPT) after ST-elevation myocardial infarction (STEMI) or non-ST-elevation acute coronary syndromes (NSTE-ACS) have been tested in randomized controlled trials (RCT)s. However, evidence by specific ACS subtype is unknown. MethodsPubMed, EMBASE, and Cochrane CENTRAL were searched in February 2023. RCTs on DAPT strategies included STEMI or NSTE-ACS patients with standard DAPT (12 months) with clopidogrel or potent P2Y12 inhibitors, short-term DAPT (≤6 months) followed by potent P2Y12 inhibitors or aspirin, unguided de-escalation from potent P2Y12 inhibitors to low-dose potent P2Y12 inhibitors or clopidogrel at one month, and guided selection with genotype or platelet function tests were identified. The primary outcome was the net adverse clinical events (NACE) defined as a composite of major adverse cardiovascular events (MACE) and clinically relevant bleeding events. ResultsTwenty RCTs with a combined total population of 24,745 STEMI and 37,891 NSTE-ACS patients were included. In STEMI patients, unguided de-escalation strategy was associated with a lower rate of NACE compared with standard DAPT using potent P2Y12 inhibitors (HR:0.57; 95% CI:0.34–0.96) without increased risk of MACE. In NSTE-ACS patients, unguided de-escalation strategy was associated with a lower rate of NACE compared with the guided selection strategy (HR:0.65; 95% CI:0.47–0.90), standard DAPT using potent P2Y12 inhibitors (HR:0.62; 95% CI:0.50–0.78) and standard DAPT using clopidogrel (HR:0.73; 95% CI:0.55–0.98) without increased risk of MACE. ConclusionUnguided de-escalation strategy was associated with a reduced risk of NACE and may be the most effective DAPT strategy for STEMI and NSTE-ACS.

Short Versus Long-Term Dual Antiplatelet Therapy in Patients at High Bleeding Risk Undergoing PCI in Contemporary Practice: A Systemic Review and Meta-analysis.

Patients at high bleeding risk (HBR patients) represent an important subset of patients undergoing percutaneous coronary intervention (PCI). It remains unclear whether a shortened duration of dual antiplatelet therapy (DAPT) confers benefits compared with prolonged duration of DAPT in this patient population. The aim of this study was to investigate and compare bleeding and ischemic outcomes among HBR patients receiving short- versus long-term DAPT after PCI. A meta-analysis of studies comparing short-term (1-3months) and long-term (6-12months) DAPT after PCI with second-generation drug-eluting stents in HBR patients was performed. Six studies [1 randomized controlled trial (RCT), 2 RCT subanalyses, and 3 prospective propensity-matched studies] involving 15,908 patients were included in the meta-analysis. During a follow-up of 12months, short-term DAPT was associated with a reduction in major bleeding events [odds ratio (OR) 0.63, 95% confidence interval (CI) 0.42-0.95; p = 0.03, I2 = 71] and comparable definite/probable stent thrombosis, all-cause mortality, cardiovascular mortality, myocardial infarction (MI), and ischemic stroke, compared with long-DAPT. Single antiplatelet therapy (SAPT) with aspirin was comparable to SAPT with P2Y12 inhibitor, with no treatment-by-subgroup interaction for major bleeding events (p-interaction = 0.27). In studies including patients presenting with MI, a trend of more frequent MI was noted in the short-DAPT arm (OR 1.25, 95% CI 0.98-1.59; p = 0.07; I2 = 0). In a sensitivity analysis comparing 3- and 12-month DAPT, the 3-month DAPT strategy was associated with a higher risk of ischemic stroke (OR 2.37, 95% CI 1.15-4.87; p = 0.02, I2 = 0%). Short-term DAPT after PCI in HBR patients was associated a reduction in major bleeding events and similar ischemic outcomes. However, a higher risk of ischemic stroke and MI at 1 year of follow-up was seen in some subsets.

Cardiovascular and Bleeding Events of Ticagrelor Monotherapy after Short-term Dual Antiplatelet Therapy (DAPT) in Diabetics and Non-Diabetics Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.

Ticagrelor monotherapy after short-term (1-3 months) dual antiplatelet therapy (DAPT) with aspirin and ticagrelor can reduce bleeding without increasing ischemic events after percutaneous coronary intervention (PCI). However, its effect in diabetic and non-diabetic individuals has not been evaluated as a meta-analysis so far. This systematic review and meta-analysis were conducted covering PubMed, ISI Web of Science, and Scopus without date restrictions for English published clinical trials. The authors searched the mentioned databases, wherein the screening led to 151 studies, of which 40 were assessed for eligibility, and finally, three studies were included. These trials compared ticagrelor monotherapy after a short duration of aspirin plus ticagrelor with conventional 12 months DAPT. The results showed that the risk of major bleeding (based on Bleeding Academic Research Consortium (BARC) type 3 or 5) for ticagrelor monotherapy subjects was lower in both diabetics and non-diabetics. It was especially significant in non-diabetic patients (HR 95%CI: 0.79(0.64, 0.98); p=0.029). In cardiovascular events assessment, the pooled estimate on cardiac deaths was significantly lower in diabetic subjects treated by ticagrelor monotherapy (HR 95%CI: 0.71(0.51, 1); p=0.05), while this reduction was not significant for non-diabetics (p=0.843) in comparison to patients treated by 12 months DAPT. However, there was no significant decrease or rise in myocardial infarction (MI) and ischemic stroke in patients treated by short-term DAPT strategy. In conclusion, discontinuing aspirin after short-duration DAPT could minimize the incidence of cardiac death and BARC type 3 or 5 bleeding in diabetic and non-diabetic patients who underwent PCI, with no increase in MI and ischemic stroke.

Antiplatelet Strategies Following PCI: A Review of Trials Informing Current and Future Therapies.

Dual antiplatelet therapy (DAPT) has been paramount in preventing thrombosis following percutaneous coronary intervention for nearly 3 decades. However, over the years, DAPT has seen significant changes in the agents utilized and duration of therapy as trials have raced to keep up with advancements made in stent technology and our understanding of bleeding and ischemic risk. Recently, there have been a number of trials demonstrating significant reductions in bleeding events with shorter DAPT durations, which are not yet reflected in practice guidelines. Further, there has been a shift toward more individualized antiplatelet regimens to meet patient-specific risk profiles. This review provides a comprehensive summary of the major trials that have informed current DAPT strategies, puts into context recent trials driving a shift toward more tailored antiplatelet regimens, and highlights gaps in knowledge that remain and the ongoing trials designed to address them.

Sex Differences in Outcomes of Ticagrelor Therapy With or Without Aspirin After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome: A Post Hoc Secondary Analysis of the TICO Randomized Clinical Trial.

We sought to explore the sex differences in clinical outcomes among patients with acute coronary syndrome treated with ticagrelor monotherapy after ticagrelor-based 3-month versus 12-month dual-antiplatelet therapy. This was a post hoc analysis of the TICO trial (Ticagrelor Monotherapy After 3 Months in the Patients Treated With New Generation Sirolimus-Eluting Stent for Acute Coronary Syndrome; n=3056)-a randomized controlled trial for patients with acute coronary syndrome treated with drug-eluting stent. The primary outcome was a net adverse clinical event (composite of major bleeding, death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization) 1 year after drug-eluting stent implantation. Secondary outcomes included major bleeding and major adverse cardiac and cerebrovascular events. There were 27.3% (n=628) women in the TICO trial; they were older with lower body mass index and higher prevalence of hypertension, diabetes, or chronic kidney disease than men. Compared with men, women had higher risk of net adverse clinical events (hazard ratio [HR], 1.89 [95% CI, 1.34-2.67]), major adverse cardiac and cerebrovascular events (HR, 1.69 [95% CI, 1.07-2.68]), and major bleeding (HR, 2.04 [95% CI, 1.25-3.35]). Among the groups stratified by sex and dual-antiplatelet therapy strategy, the incidences of primary and secondary outcomes were significantly different and the highest in women with ticagrelor-based 12-month dual-antiplatelet therapy (P<0.001). There was no significant heterogeneity in the impact of treatment strategy on the risks of primary and secondary outcomes between both sexes. Ticagrelor monotherapy was associated with a lower risk of the primary outcome in women (HR, 0.47 [95% CI, 0.26-0.85]; P=0.02) and comparable in men (HR, 0.77 [95% CI, 0.52-1.14]; P=0.19) without significant interaction (P for interaction, 0.18). After percutaneous coronary intervention for acute coronary syndrome, women demonstrated worse clinical outcomes than men. Ticagrelor monotherapy after 3-month dual-antiplatelet therapy was associated with significantly lower risk of net adverse clinical events in women without sex interaction.

Impact of the Antiplatelet Strategy Following Patent Foramen Ovale Percutaneous Closure.

Temporary dual antiplatelet therapy (DAPT) is recommended following patent foramen ovale (PFO) percutaneous closure although its benefit, compared to single antiplatelet therapy (SAPT), has not been demonstrated in this setting. We aimed at assessing outcomes following PFO closure according to the antiplatelet strategy at discharge. The ambispective AIR-FORCE cohort included consecutive patients from 7 centers in France and Canada undergoing PFO closure and discharged without anticoagulation. Patients treated in French and Canadian centers were mostly discharged with DAPT and SAPT, respectively. The primary endpoint was the composite of death, stroke, transient ischemic attack, peripheral embolism, myocardial infarction, or BARC type ≥2 bleeding with up to 5 years of follow-up. The impact of the antiplatelet strategy on outcomes was evaluated with a marginal Cox model (cluster analyses per country) with inverse probability weighting according to propensity score. A total of 1,532 patients (42.2% female, median age: 49 [40-57] years) were included from 2001 to 2022, of whom 599 (39.1%) were discharged with SAPT and 933 (60.9%) with DAPT, for ≤3 months in 894/923 (96.9%) cases. After a median follow-up of 2.4[1.1-4.4] years, a total of 58 events were observed. In the weighted analysis the rate of the primary endpoint up to 5 years was 7.8% in the SAPT strategy and 7.3% in the DAPT strategy (weighted hazard ratio 1.04, 95% confidence interval 0.59-1.83). The antiplatelet strategy following PFO closure did not seem to impact clinical outcomes, thus challenging the current recommendations of temporary DAPT.

Antiplatelet therapy de-escalation in a patient after percutaneous coronary intervention with a high risk of bleeding

According to recommendations of ESC 2020-year, de-escalation of therapy with a P2Y12 receptor inhibitor (transition from prasugrel or ticagrelor to clopidogrel) It can be considered as an alternative strategy of dual antiplatelet therapy (DAPT) for patients with acute coronary syndrome (ACS) who are unsuitable for the use of a strong platelet inhibitor.De-escalation can be performed based on an individual clinical evaluation under the supervision of platelet function testing or CYP2C19 genotyping, depending on the patient’s risk profile and the availability of appropriate diagnostic methods. The optimal dosage of strong P2Y12 receptor inhibitors, such as ticagrelor or prasugrel is not entirely clear and is especially difficult to define for patients of Asian nationality.The article describes a clinical case of antiplatelet therapy de-escalation, particularly a dose reduction of the potent P2Y12 receptor inhibitor ticagrelor in a patient after percutaneous coronary intervention (PCI) with a high risk of bleeding based on platelet function determination and genetic testing. A 47-year-old patient of Kazakh nationality was hospitalized with gastrointestinal bleeding.Given bleeding type 3 by BARC (Bleeding Academic Research Consortium) associated with DAPT, it was decided to apply a strategy to de-escalate antiplatelet therapy under the control of platelet function testing (PFT) and genetic testing.In this case, replacement of ticagrelor with the weak P2Y12 receptor inhibitor clopidogrel was not possible as the patient appeared to be a carrier of the CYP2C19*2 polymorphism contributing to loss of function of the cytochrome P-450(CYP) enzyme.

Tailoring oral antiplatelet therapy in acute coronary syndromes: from guidelines to clinical practice.

The assessment of bleeding and ischemic risk is a crucial step in establishing appropriate composition and duration of dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) treated with percutaneous coronary angioplasty. Evidence from recent randomized clinical trials led to some paradigm shifts in current guidelines recommendations. Options alternative to the standard 12-month DAPT duration include shorter periods of DAPT followed by single antiplatelet treatment with either aspirin or P2Y12 monotherapy, guided or unguided de-escalation DAPT, prolonged DAPT beyond the 12-month treatment period. Although DAPT composition and duration should be selected for each ACS patient on an individual basis weighing clinical and procedural variables, data from latest trials and meta-analyses may permit suggesting the most appropriate DAPT strategy according to the ischemic and bleeding risk assessed using validated tools and scores.

Abstract 12107: Short-Term and De-Escalation Dual Antiplatelet Therapy for Patients With Acute Coronary Syndrome: A Systematic Review and Network Meta-Analysis

Background: Short-term (&lt;6 month) or de-escalation (e.g. switching potent P2Y 12 inhibitors to less potent/lower-dose agents a month after the event) dual antiplatelet therapy (DAPT) have become an attractive therapeutic strategy for patients with acute coronary syndrome (ACS). However, these strategies have never been randomly compared. Methods: PubMed, EMBASE, and Cochrane Central were searched in April 2022. Randomized controlled trials (RCTs) or their subgroup analyses that included ACS patients, with standard (12 months), extended (≥18 months), short-term and unguided de-escalation DAPT strategy, along with the guided DAPT strategy with genotype or platelet function tests were identified. The efficacy outcome (major adverse cardiovascular events: MACE) was defined as a composite of cardiovascular death, myocardial infarction, or stroke. The safety outcomes were mainly defined as major or minor bleeding, and major bleeding. Results: This network meta-analysis included 32 RCTs with 103,497 patients. While there was no significant difference in efficacy among the short DAPT, unguided de-escalation and guided-selection strategy, the unguided de-escalation strategy alone was associated with reduced risks of MACE compared with standard DAPT (e.g. versus DAPT with clopidogrel; HR [95% CI]: 0.66 [0.48-0.91]). Both the short DAPT and de-escalation strategies were associated with reduced risks of major or minor bleeding compared with other strategies including the guided-selection (HR [95% CI]: 0.66 [0.47-0.93], 0.48 [0.33-0.71], respectively); the short DAPT strategy alone was associated with a reduced risk of major bleeding compared with standard, extended and guided-selection DAPT (HR [95%CI]: 0.55 [0.33-0.92]). Conclusions: In ACS patients, the unguided de-escalation strategy was associated with reduced risks of MACE, while the short DAPT strategy was associated with decreased rates of major bleeding compared with standard DAPT, suggesting both strategies can be used in select patients by balancing patients’ ischemic and bleeding risks.

Abstract 11472: De-Escalation of Dual Antiplatelet Therapy in Elderly Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis

Background: Recent randomized controlled trials (RCTs) have demonstrated the superiority of treating patients with acute coronary syndrome (ACS) with dual antiplatelet therapy (DAPT) uniform de-escalation strategy (i.e., switching from potent P2Y 12 inhibitors to clopidogrel one month after the event). However, it remains unclear if this strategy would be effective in elderly patients. We aimed to assess the efficacy of the available DAPT strategies, including the uniform de-escalation strategy, in ACS patients older than 65. Methods: We searched the PubMed, EMBASE, and Cochrane CENTRAL databases up to December 2021 for RCTs or subgroup analyses investigating DAPT strategies for elderly ACS patients (age ≥65 years) and conducted a network meta-analysis. The endpoint was net clinical benefit outcome, defined as a composite of major adverse cardiovascular events and bleeding. The P-score was used to rank the treatments. Results: Seven RCTs with 5,079 patients were included. The uniform de-escalation strategy was associated with a better net clinical benefit outcome (hazard ratio: 0.62; 95% confidence interval [0.41-0.92]) compared with DAPT using potent P2Y 12 inhibitors, and it was similarly effective compared with other DAPT strategies. There was no significant heterogeneity ( I 2 =0%; p =0.82) or inconsistency ( p =0.40). The uniform de-escalation strategy was ranked as the most effective strategy (by P score) superior to DAPT using clopidogrel or low-dose prasugrel. Conclusions: The uniform de-escalation strategy was an effective strategy for older ACS patients. Compared with conventional DAPT using potent P2Y 12 inhibitors, this strategy decreased the composite of major adverse cardiovascular events and bleeding events.

De-Escalation Dual Antiplatelet Therapy Prevail over Potent P2Y12 Inhibitor Monotherapy in Patients with Acute Coronary Syndrome Undergone Percutaneous Coronary Intervention: A Network Meta-Analysis.

Dual antiplatelet therapy (DAPT) with potent P2Y12 inhibitor is the cornerstone of acute coronary syndrome (ACS) management. Balancing the effects of different strategies of antiplatelet therapy including DAPT de-escalation, potent P2Y12 inhibitor monotherapy, and conventional DAPT is a hot topic. A systematic search was conducted from the MEDLINE, PubMed, and Embase through October 2021 to identify various DAPT strategies in randomized controlled trials (RCTs) for treatment of ACS patients after undergoing PCI with drug-eluting stent (DES). The network meta-analysis was performed to investigate the net clinic benefit of the DAPT de-escalation, potent P2Y12 inhibitor monotherapy, as well as conventional DAPT. The primary outcome was net adverse clinical events, defined as a composite of major bleeding and cardiac death, myocardial infarction, stroke, stent thrombosis, or target-vessel revascularization. The secondary outcomes include major adverse cardiac events and trial-defined major or minor bleeding. A total of 14 RCTs with 63,982 patients were included. The DAPT de-escalation was associated with a lower risk of the primary outcome compared with potent P2Y12 inhibitor monotherapy (De-escalation vs monotherapy odds ratio (OR): 0.72 95% confidence interval (CI): 0.55-0.96), and other antiplatelet strategies (De-escalation vs clopidogrel + aspirin OR: 0.49 95% CI: 0.39-0.63; De-escalation vs prasugrel + aspirin OR: 0.76 95% CI: 0.59-0.98; De-escalation vs ticagrelor + aspirin OR: 0.76 95% CI: 0.55-0.90). There were no statistical differences in the incidence of bleeding (DAPT de-escalation vs P2Y12 inhibitor monotherapy OR: 0.73 95% CI: 0.47-1.12) and major adverse cardiac events (DAPT de-escalation vs P2Y12 inhibitor monotherapy OR: 0.79 95% CI: 0.59-1.08) between DAPT de-escalation and potent P2Y12 inhibitor monotherapy. This network meta-analysis showed that DAPT de-escalation would reduce the net adverse clinical events, compared with potent P2Y12 inhibitor monotherapy, for ACS patients undergone PCI treatment.

Comparing dual antiplatelet therapy strategies post-acute coronary syndrome: network meta-analysis

Abstract Background Various approaches to dual antiplatelet therapy (DAPT) management exist to balance thrombotic and bleeding risks following acute coronary syndrome (ACS). Purpose The aim of this study was to compare and rank different DAPT management strategies in patients with ACS with or without percutaneous coronary interventions. Methods We conducted a systematic review with network meta-analysis of randomized controlled trials comparing DAPT strategies in patients with ACS using MEDLINE, Embase, and CENTRAL (2007-July 2021). The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included all-cause death and major bleeding. We performed Bayesian network meta-analyses to compare all interventions simultaneously using the Markov-chain Monte Carlo method, conducted under the assumption of transitivity. We generated odds ratios (ORs) with 95% credible intervals (CrI) from the medians and 2.5th and 97.5th percentiles of the posterior distributions using a hierarchical Bayesian framework, using a random-effects model with informative priors for between-study heterogeneity based on pharmacological interventions with semi-objective outcomes (MACE or bleeding) or death. To rank interventions for each outcome, we calculated the mean surface under the cumulative ranking (SUCRA) curve. Results From 5941 articles, we included 24 trials (89,620 patients). Both clopidogrel- and ticagrelor-based DAPT increased MACE compared with pharmacogenomics-guided P2Y12 inhibitor selection (odds ratio [OR] 1.37, 95% credible interval [CrI] 1.08–1.74 and 1.35, 1.05–1.79, respectively) and empiric P2Y12 inhibitor de-escalation (OR 1.53, 95%CrI 1.00–2.30 and 1.51, 1.00–2.27, respectively). Compared with short-duration DAPT, standard DAPT duration with all P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) and pharmacogenomics-guided P2Y12 inhibitor selection increased major bleeding. Ticagrelor-based DAPT increased major bleeding compared with platelet function testing-guided DAPT (OR 1.60, 95%CrI 1.00–2.55). Empiric P2Y12 inhibitor de-escalation ranked best for MACE (SUCRA 0.89), whereas short-duration DAPT ranked best for death (SUCRA 0.89) and major bleeding (SUCRA 0.93). Conclusions In patients with ACS, empiric P2Y12 inhibitor de-escalation was most efficacious whereas short-duration DAPT was the safest compared to other DAPT strategies. Funding Acknowledgement Type of funding sources: None.