Triple Antiplatelet Therapy Group Research Articles

Adjunctive cilostazol in patients with acute ST-elevation myocardial infarction: a multicenter, randomized, open-label, phase 4 trial

Abstract Background/Aims Previous studies showed that triple antiplatelet therapy (TAT), involving the addition of cilostazol to conventional dual antiplatelet therapy (DAT; aspirin + clopidogrel), has better clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) than that with DAT; however, the optimal duration of TAT has not yet been determined. Methods Altogether, 985 patients who underwent primary percutaneous coronary intervention (PCI) with drug-eluting stents (DES) were prospectively enrolled in 14 medical centers in Korea. We randomly assigned patients into three groups: DAT (aspirin and clopidogrel for 12 months), TAT 1M (aspirin, clopidogrel, and cilostazol for 1 month), and TAT 6M (aspirin, clopidogrel, and cilostazol for six months). The primary endpoint was 1-year major adverse cardiovascular events (MACEs), defined as the composite of all-cause death, recurrent myocardial infarction (MI), stroke, or repeat revascularization. Results The primary endpoint was not different among the three groups (8.8% in the DAT, 11.0% in the TAT 1M, and 11.6% in the TAT 6M; hazard ratio for TAT 1M vs. DAT, 1.302; 95% confidence interval [CI], 0.792–2.141; p=0.297; hazard ratio for TAT 6M vs. DAT, 1.358; 95% CI, 0.829–2.225; p=0.225). With in-hospital outcomes, more bleeding events occurred in the TAT group than in the DAT group (1.3% vs. 4.7% vs. 2.6%, p=0.029) without significant differences in major bleeding. Besides, the TAT groups had higher incidence of headache (0% vs. 1.6% vs. 2.6%, p=0.020). Conclusions The addition of cilostazol to the DAT did not reduce the incidence of 1-year MACE compared to that with DAT alone. Instead, it may be associated with an increased risk of cumbersome side effects such as in-hospital bleeding and headaches.

Efficacy and safety of cilostazol-based triple antiplatelet therapy compared with clopidogrel-based dual antiplatelet therapy in patients with acute ST-elevation myocardial infarction undergoing percutaneous coronary intervention: A multicenter, randomized, open-label, phase 4 trial

Previous studies reported that compared to conventional dual antiplatelet therapy (DAT; aspirin+clopidogrel), triple antiplatelet therapy (TAT), involving the addition of cilostazol to DAT, had better clinical outcomes in patients with ST-elevation myocardial infarction (STEMI). However, the optimal duration of TAT is yet to be determined. In total, 985 patients with STEMI who underwent primary percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) were prospectively enrolled in 15 PCI centers in South Korea and China. We randomly assigned patients into 3 groups: DAT (aspirin and clopidogrel for 12 months), TAT 1M (aspirin, clopidogrel, and cilostazol for 1 month), and TAT 6M (aspirin, clopidogrel, and cilostazol for 6 months). The primary endpoint was 1-year major adverse cardiovascular events (MACEs), defined as a composite of all-cause death, recurrent myocardial infarction, stroke, or repeat revascularization. The primary endpoint did not differ among the 3 groups (8.8% in DAT, 11.0% in TAT 1M, and 11.6% in TAT 6M; hazard ratio for TAT 1M vs DAT, 1.302; 95% confidence interval [CI], 0.792-2.141; P=.297; hazard ratio for TAT 6M vs DAT, 1.358; 95% CI, 0.829-2.225; P=.225). With respect to in-hospital outcomes, more bleeding events occurred in the TAT group than in the DAT group (1.3% vs 4.7% vs 2.6%, P=.029), with no significant differences in major bleeding events. Additionally, the TAT group had a higher incidence of headaches (0% vs 1.6% vs 2.6%, P=.020). The addition of cilostazol to DAT did not reduce the incidence of 1-year MACEs compared with DAT alone. Instead, it may be associated with an increased risk of drug intolerance and side effects, including in-hospital bleeding and headaches.

The Efficacy of P2Y12 Reactive Unit to Predict the Periprocedural Thromboembolic and Hemorrhagic Complications According to Clopidogrel Responsiveness and Safety of Modification of Dual Antiplatelet Therapy : A Meta-Analysis.

The efficacy of P2Y12 reaction unit (PRU) of VerifyNow still remains as a controversial issue in neurointervention. So we investigated the usefulness of PRU of VerifyNow to predict the peri-procedural thromboembolic events (TE) and hemorrhagic events (HE). And we evaluated the safety of modified dual antiplatelet therapy (DAPT) or triple antiplatelet therapy (TAPT) for clopidogrel hyporesponders. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science and Scopus on August 19 2018. Data was collected the 1) incidence of TE between clopidogrel responder and clopidogrel hypo-responder, 2) incidence of HE between clopidogrel hyper-responder and clopidogrel responder and hypo-responder, and 3) incidence of TE and HE between modified DAPT or TAPT and standard DAPT in clopidogrel hypo-responder. High cut-off value of PRU was defined as PRU >40% or <220. Fifteen studies were enrolled. Clopidogrel responder showed lower incidence of TE than hypo-responder (risk ratio [RR], 0.32; 95% confidence interval [CI], 0.17–0.61; p<0.001). With the high cut-off value of PRU, clopidogrel responder showed more lower incidence of TE than hypo-responder (RR, 0.11; 95% CI, 0.02–0.45; p=0.002). The incidence of periprocedural HE have higher on clopidogrel hyper-responder than clopidogrel responder and hypo-responder (RR, 4.26; 95% CI, 1.10–16.44; p=0.04; I2=66%). The incidence of periprocedural TE after changing regimen of DAPT for clopidogrel hypo-responder have a tendency to reduce, but there was no significant difference between modified DAPT or TAPT group and standard DAPT group (p>0.05). The incidence of periprocedural HE after changing regimen of DAPT for clopidogrel hypo-responder was no significant difference between modified DAPT or TAPT group and standard DAPT group (p>0.05). PRU is a useful tool as a predictor of peri-procedural TE or HE on neurointervention. PRU has a threshold effect of cut-off value to predict the peri-procedural TE. Modified DAPT or TAPT to prevent TE in clopidogrel hypo-responders could not reduce the incidence of TE. We should investigate the further research about modification of regiment on neurointervention.

The safety of triple antiplatelet therapy under thromboelastography guidance in patients undergoing stenting for ischemic cerebrovascular disease

ObjectiveTo investigate the safety of triple antiplatelet therapy (TAT) with cilostazol in patients undergoing stenting for extracranial and/or intracranial artery stenosis.MethodsA prospectively collected database was reviewed to identify patients who...

Comparison of 1-Year Outcomes of Triple (Aspirin + Clopidogrel + Cilostazol) Versus Dual Antiplatelet Therapy (Aspirin + Clopidogrel + Placebo) After Implantation of Second-Generation Drug-Eluting Stents into One or More Coronary Arteries: from the DECREASE-PCI Trial

This study sought to evaluate the impact of triple antiplatelet therapy on clinical outcomes in patients treated with second-generation drug-eluting stents (DES) for coronary artery disease. There are limited data regarding the impact of triple antiplatelet therapy in patients who underwent implantation of second-generation DES. We planned to randomly assign 2,110 patients treated with second-generation DES to triple (aspirin, clopidogrel, and cilostazol) and dual (aspirin, clopidogrel, and placebo) antiplatelet therapy groups. The primary end point was a composite of death, myocardial infarction, ischemic stroke, or target vessel revascularization (TVR) at 1 year since randomization. The study was stopped early owing to slow enrollment. In total, 404 patients (202 patients each in the triple and dual antiplatelet therapy groups) were finally enrolled. At 1 year, the primary end point had occurred in 3.6% and 9.4% of patients in the triple and dual antiplatelet therapy groups, respectively (hazard ratio [HR] of the triple group 0.396; 95% confidence interval [CI] 0.166 to 0.949; p = 0.038). There was no significant difference between the 2 groups regarding the occurrence of a composite of all-cause death, myocardial infarction, or ischemic stroke (HR 0.583; 95% CI 0.229 to 1.481; p = 0.256). However, the rates of TVR were significantly lower in the triple antiplatelet therapy group than in the dual antiplatelet therapy group (HR 0.118; 95% CI 0.015 to 0.930; p = 0.043). In conclusion, triple antiplatelet therapy with cilostazol after implantation of second-generation DES improved clinical outcomes, mainly by reducing TVR.

Sarpogrelate Based Triple Antiplatelet Therapy Improved Left Ventricular Systolic Function in Acute Myocardial Infarction: Retrospective Study.

PurposeThe purpose of this study was to assess the potential benefit of a 5-hydroxytryptamine receptor antagonist, sarpogrelate-based triple antiplatelet therapy (TAPT) in comparison with dual antiplatelet therapy (DAPT) in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).Materials and Methods119 patients of STEMI were retrospectively assessed. All patients received aspirin and clopidogrel per standard of care. Among them, 53 patients received an additional loading dose of sarpogrelate and a maintenance dose for 6 months post-PCI (TAPT group), while others did not (DAPT group).ResultsThe rates of complete ST-segment resolution at 30 minutes post-PCI and post-procedural thrombolysis in myocardial infarction flow were not significantly different between the two groups (52.8% vs. 48.5%, p=0.200; 92.5% vs. 89.4%, p=0.080). In addition, no significant differences were observed between the two groups with regard to 30-day and 12-month clinical outcomes (cardiac death, myocardial infarction, stent thrombosis, target vessel revascularization, and severe bleeding). Meanwhile, improvement in left ventricular (LV) systolic function was observed in the TAPT group [ΔLV ejection fraction (LVEF)=17.1±9.4%, p<0.001; Δglobal longitudinal strain (GLS)=−9.4±4.2% , p<0.001] at 6 months, whereas it was not in the DAPT group (ΔLVEF= 8.8±6.5%, p=0.090; ΔGLS=−4.6±3.4%, p=0.106). In multivariate analyses, TAPT was an independent predictor for LV functional recovery (odds ratio, 2.61; 95% confidence interval, 1.16–5.87; p=0.003).ConclusionSarpogrelate-based TAPT improved LV systolic function at 6 months in STEMI patients undergoing primary PCI.

Cilostazol Added to Dual Antiplatelet Therapy for Patients with High Risk of Restenosis after Drug-Eluting Stent Implantation: A Systematic Review and Meta-Analysis of RCTs

Background: Cilostazol added to Dual Antiplatelet Therapy (DAT: aspirin, clopidogrel) reduces revascularization without increased bleeding in patients after Drug-Eluting Stent (DES) implantation. However, doubts remain about which patients benefit most from cilostazol-based Triple Antiplatelet Therapy (TAT) after DES. Materials and Results: PubMed, EMBASE, CENTRAL databases were systematically searched. Randomized Controlled Trials (RCTs) comparing TAT and DAT for patients with high risk of restenosis (defined as obesity, diabetes, and long and/or multivessel coronary lesions) were included. Five RCTs were included, involving 2442 patients. The TAT group showed a significant reduction in MACEs (4.16% vs. 8.86%, RR: 0.47, 95% CI: 0.32 to 0.68, p<0.001), in-stent late loss (0.34 vs. 0.46, SMD: -0.22, 95% CI: -0.32 to -0.11, p<0.001), TVR (3.36% vs. 6.80%, RR: 0.49, 95% CI: 0.34 to 0.71, p<0.001), and in-stent restenosis (6.86% vs. 11.45%, RR: 0.60, 95% CI: 0.43 to 0.84, p=0.003) compared with the DAT group. There was no difference in all-cause mortality (1.56% vs. 0.82%, RR: 1.82, 95% CI: 0.87 to 3.77, p=0.110), bleeding (3.52% vs. 3.28%, RR: 1.07, 95% CI: 0.71 to 1.63, p=0.745) and stent thrombosis (0.82% vs. 0.66%, RR: 1.4, 95% CI: 0.50 to 3.06, p=0.641) between the two groups, whereas the incidence of other adverse reactions (11.38% vs. 6.39%, RR: 1.78, 95% CI: 1.37 to 2.33, p<0.001) and drug discontinuation (16.29% vs. 5.15%, RR: 4.60, 95% CI: 1.24 to 17.08, p=0.023) was greater in the TAT group than in the DAT group. Conclusions: Compared with DAT, patients with a high risk of restenosis benefited from TAT in reduced stent restenosis and revascularization after DES implantation, without increases in all-cause mortality and bleeding, but accompanied by a higher incidence of other adverse reactions and drug discontinuation.

Long-term effectiveness and safety of triple versus dual antiplatelet therapy after percutaneous coronary intervention for unprotected left main coronary artery disease

We sought to compare the long-term effectiveness and safety of triple antiplatelet therapy (TAPT) versus dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for unprotected left main coronary artery disease (uLMCAD). An additional strategy to reduce recurrent ischemia after PCI for uLMCAD is needed to improve the long-term clinical outcomes and match the efficacy of bypass surgery. We evaluated 245 patients who underwent PCI with drug-eluting stents for uLMCA stenosis of at least 50% from the Sejong General Institute PCI database between April 2003 and December 2010. TAPT was defined as the addition of cilostazol for at least 3 months to conventional DAPT after PCI. A total of 124 patients received TAPT and 121 patients received DAPT. The TAPT group had a higher number of male patients, need for the two-stent technique, and Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) scores and longer stent length compared with the DAPT group. During a median 30.6 months, major adverse cardiac and cerebrovascular events (MACCE) occurred in 43 patients (17.6%): 23 (18.5%) in the TAPT group and 20 (16.5%) in the DAPT group (P=0.68). In the multivariate analysis, TAPT was not associated with a lower incidence of MACCE (hazard ratio: 0.69, 95% confidence interval: 0.34-1.43). Thrombolysis in myocardial infarction (TIMI) major and minor bleeding occurred at similar rates (5.6 vs. 3.3%, P=0.565, for TIMI major bleeding; and 14.5 vs. 14.9%, P=0.718, for TIMI minor bleeding). TAPT after drug-eluting stent implantation in patients with uLMCAD did not improve the long-term clinical outcome when compared with conventional DAPT, although it was a safe strategy.

Prognosis and antithrombotic therapy of patients with atrial fibrillation after undergoing percutaneous coronary intervention)

Objective: To elucidate the clinical status of the patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). Method: PCI was performed on 660 consecutive patients in our institution from January 2010 to August 2012, of which 18 patients with cardiopulmonary arrest on arrival were excluded and 642 patients were investigated retrospectively. Results: The 642 patients consisted of 493 male and 149 female patients, the average age 69.9±11.4 years and follow up period 441.6±315.9 days. Coexisting AF was seen in 77 (12.0%) patients, of which 49 were paroxysmal AF and 28 were persistent/ chronic AF.The rate of AF group was significantly higher than that of non-AF group in mortality (14.3% vs. 6.9%, P=0.038) and hemorrhagic events (19.5% vs. 6.9%,P=0.001). Multivariate analysis showed the AF was an independent prognostic marker on mortality (OR2.3, 95% CI1.1-4.8,P=0.032) and hemorrhage (OR2.1, 95% CI1.1-4.3,P=0.035), events from age, diabetes, chronic kidney disease and hyperlipidemia. The incidence of thromboembolic events were similar in the both groups (3.1% vs 3.1%,P=1.00).Comparing paroxysmal AF and persistent/chronic AF, mortality and rate of hemorrhage events was more common in paroxysmal AF group than persistent/chronic AF (mortality 16.3% vs. 10.7%, hemorrhage events 22.4% vs 14.2%). On the other hand, triple therapy (oral anticoagulant with aspirin and clopidogrel or ticropidine) were performed in 63 (81.8%) patients with AF, and dual antiplatelet therapy (DAPT: aspirin and clopidogrel or ticropidine) were performed in 14 (18.2%). Mortality rate of the triple antiplatelet therapy group was higher than that of the DAPT group (15.9%vs 7.1%) and hemorrhage events (20.6% vs 14.3%). Conclusion: Hemorrhage events and mortality were more common in patients with AF after PCI. Triple therapy was found to reduce thromboembolic events; however, its usage may have more harmful influences than the severity of AF regarding mortality and the hemorrhage events.

GW24-e1373 Effect and security with triple antiplatelet therapy in patients undergoing drug-eluting stents for the treatment of complex coronary lesions

ObjectivesTo evaluate the efficacy and safety of triple antiplatelet therapy (cilostazol combined with clopidogrel and aspirin) in patients undergoing multiple drug-eluting stents (DES) implantation of complex coronary lesions.MethodsTotally 128 senile...

Triple versus dual antiplatelet therapy for coronary heart disease patients undergoing percutaneous coronary intervention: A meta-analysis

Coronary heart disease (CHD) is the leading cause of mortality worldwide. Previous studies have suggested that cilostazol-based triple antiplatelet therapy (TAT) may be more effective than conventional dual antiplatelet therapy (DAT) at improving the clinical outcomes of patients with CHD undergoing percutaneous coronary intervention (PCI). However, individually published results are inconclusive. The present meta-analysis evaluated controlled clinical studies to compare the clinical outcomes between TAT and DAT in patients with CHD undergoing PCI. Ten controlled clinical studies were included, with a total of 7,670 patients with CHD undergoing PCI. The total number included 3,925 patients treated with DAT (aspirin and clopidogrel) and 3745 patients treated with TAT (addition of cilostazol to DAT). The crude odds ratio (OR) with a 95% confidence interval (CI) was calculated with either the fixed or random effects model. The meta-analysis results indicated that patients in the TAT group had a significantly lower rate of restenosis compared with that of the DAT group (OR=0.59, 95% CI: 0.45–0.77; P<0.001). The rate of major adverse cardiac events (MACE) and target lesion revascularization (TLR) in the TAT group were significantly lower compared with those in the DAT group (MACE: OR=0.69, 95% CI: 0.56–0.85, P<0.001; TLR: OR=0.61, 95% CI: 0.43–0.88, P=0.008). However, no significant differences between the TAT and DAT groups in terms of mortality rate, myocardial infarction, target vessel revascularization and stent thrombosis were observed. In conclusion, the results of the present meta-analysis indicated that the efficacy and safety of cilostazol-based TAT therapy is greater than that of conventional DAT therapy for patients with CHD undergoing PCI.

Triple anti-platelet therapy protecting acute coronary syndrome patients from complication within 30 days after PCI

Objective To investigate the efficacy and safety of triple anti-platelet therapy (low-dose tirofiban plus aspirin and clopidogrel) comparing to dual anti-platelet therapy (aspirin and clopidogrel) in preventing stent thrombosis (ST) and major adverse cardiac events (MACE) within 30 days after implantation of drug-eluting stent (DES) in ACS patients.Methods A total of 2904 ACS patients treated with DES from March 2004 to November 2010 were enrolled for retrospective study.Of them,1145 patients were treated with dual anti-platelet therapy (DAT) and 1759 patients with triple anti-platelet therapy (TAT).The incidences of ST,MACE (cardiac death,urgent target vessel revasculanization and myocardial infarction) and side effects occurred within 30 days after PCI were compared between two groups by Fisher' s exact test.Results (1)Although there were significant differences in age,the degree of coronary stenosis,the number of smokers,diabetes,hyperlipidemia and coronary diffuse lesion between two groups,but these differences did not impact on the end point events showed by Cox analysis.The rest of the general condition of patients between two groups was no difference.(2) The incidence of ST as primary end point was lower in TAT group than that in DAT group (0.11％ vs.1.05％,P =0.0036),reducing the relative risk by 89.52％.In addition,the incidence of MACT as secondary end point was also lower in TAT group than that in DAT group (0.17％ vs.1.48％,P =0.0005),reducing the relative risk by 88.51％.Among the total,the incidences of cardiac death and urgent target vessel re-vascularization in TAT group were lower than those in DAT group with significant differences.However,there was no difference in the incidence of myocardial infarction between two groups.(3) Both two groups had no severe hemorrhage complication,the incidence of mild hemorrhage was similar in two groups (0.45％ vs.0.35％,P =0.6720).Nesides,the incidence of acute thrombocytopenia between two groups was also similar (0.45％ vs.0.09％,P =0.083).Conclusions The patients with ACS in the TAT group have significant lower incidence of ST and MACE than those in the DAT group within 30 days after PCI.While the risk of bleeding and the incidence of acute thrombocytopenia do not increase. Key words: Stent thrombosis; Major adverse cardiac events; Triple anti-platelet therapy; Dual anti-platelet therapy

Cilostazol-Based Triple Antiplatelet Therapy Compared to Dual Antiplatelet Therapy in Patients with Coronary Stent Implantation: A Meta-Analysis of 5,821 Patients

Background: Uncertainties still remain in terms of what kinds of patients benefit most from cilostazol-based triple antiplatelet therapy (TAT) after coronary stenting. Methods: We performed a meta-analysis of all relevant randomized controlled trials (RCTs) to investigate the effect of TAT versus dual antiplatelet therapy (DAT) in terms of major adverse cardiovascular events (MACEs) in patients undergoing coronary stenting. Results: Fourteen RCTs with 5,821 patients were included in this study. TAT was associated with a significant reduction in the risk of MACEs compared to DAT [9.2 vs. 13.4%; odds ratio 0.59 (0.46, 0.76)] with consistent benefits among patients with diabetes, long lesions and small vessels. There were no significant between-group differences in the risk of cardiac death, myocardial infarction, stent thrombosis and bleeding events; however, the risk of target lesion revascularization was significantly lower in the TAT group. TAT resulted in borderline significant reduction in the risk of cardiovascular thrombotic events in unselected patients and significant decrease in patients with acute coronary syndrome [odds ratio 0.51 (0.27, 0.94)]. Conclusion: Under the treatment of standard DAT, the addition of cilostazol is an effective and relatively safe strategy in preventing MACEs after coronary stenting, especially for patients at high risk of restenosis or clinical events.

Multicenter Randomized Trial Evaluating the Efficacy of Cilostazol on Ischemic Vascular Complications After Drug-Eluting Stent Implantation for Coronary Heart Disease: Results of the CILON-T (Influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation) Trial

We aimed to test whether cilostazol has beneficial effects in the real-world patients treated with intracoronary drug-eluting stents (DES). The addition of cilostazol on the conventional dual antiplatelet therapy has been reported to reduce platelet reactivity and to improve clinical outcomes after percutaneous coronary intervention in previous studies. In a randomized multicenter trial, we enrolled 960 patients who received DES. They were randomized to receive either dual antiplatelet therapy (DAT) (aspirin and clopidogrel) or triple antiplatelet therapy (TAT) (aspirin, clopidogrel, and cilostazol) for 6 months. Primary end point was the composite of cardiac death, nonfatal myocardial infarction, ischemic stroke, or target lesion revascularization (TLR). Secondary end points were P2Y₁₂ reaction unit (PRU) measured with the VerifyNow P2Y12 assay (Accumetrics, San Diego, California) at discharge and at 6 months after the index procedure. All-cause death, stent thrombosis, and each component of the primary end point at 6 months were other secondary end points. Analysis was done on an intention-to-treat basis. At 6 months' follow-up, there was no difference in the primary end point between the 2 groups (8.5% in TAT vs. 9.2% in DAT, p = 0.74). In secondary end point analysis, the TAT group achieved lower PRU levels than the DAT group both at discharge (206.6 ± 90.3 PRU vs. 232.2 ± 80.3 PRU, p < 0.001) and at 6 months (210.7 ± 87.9 PRU vs. 255.7 ± 73.7 PRU, p < 0.001). In the Cox proportional hazards analysis, lesion length (≥28 mm, hazard ratio [HR]: 2.10, 95% confidence interval [CI]: 1.25 to 3.52), and PRU level at discharge (every increase in tertile, HR: 1.61, 95% CI: 1.16 to 2.25) were predictors of the primary end point, but not the use of cilostazol (HR: 0.90, 95% CI: 0.54 to 1.52). Despite the greater reduction of platelet reactivity by addition of cilostazol to conventional DAT, TAT did not show superiority in reducing the composite of adverse cardiovascular outcomes after DES implantation. (The Efficacy of CILostazol ON Ischemic Complications After DES Implantation [CILON-T]; NCT00776828).

Antiplatelet Therapy After Percutaneous Coronary Intervention

Current guidelines recommend dual antiplatelet therapy (DAPT) that includes aspirin and the platelet P2Y12 ADP receptor antagonist clopidogrel after percutaneous coronary intervention (PCI). These recommendations are based on data that DAPT with the P2Y12 inhibitors clopidogrel reduces major adverse cardiac events after PCI in stable angina and acute coronary syndrome (ACS) patients when compared with aspirin, or aspirin in combination with warfarin.1 Despite treatment with DAPT, patients with ACS undergoing PCI are at elevated risk for recurrent ischemic events compared with stable angina patients in part because of increased platelet thrombotic activity in ACS. In addition, there is considerable interindividual variability in the degree of platelet inhibition achieved by clopidogrel, and high residual platelet activity in the setting of clopidogrel therapy (hyporesponsiveness) is associated with adverse cardiovascular (CV) events after PCI. Clopidogrel hyporesponsiveness is related to a variety of clinical and genetic factors that alter pharmacokinetics, and diabetes, congestive heart failure (CHF), and obesity are associated with reduced efficacy. Clopidogrel is a prodrug that requires conversion by the hepatic cytochrome P450 system (CYP) to an active metabolite, and it can take up to 6 hours for clopidogrel to have maximal effect after the loading dose. Genetic polymorphisms that reduce CYP activity result in decreased hepatic metabolism of clopidogrel. Among persons treated with clopidogrel, carriers of specific reduced function CYP2C19 alleles have impaired clopidogrel conversion, significantly lower levels of active metabolite, diminished platelet inhibition, and higher rates of adverse CV events and stent thrombosis after PCI.2 The prevalence of CYP2C19 polymorphisms ranges from 30% to 60% depending on ethnicity.2,3 Medications that inhibit CYP activity also reduce clopidogrel conversion, and some proton pump inhibitors (PPI) that reduce CYP function (eg, omeprazole) diminish clopidogrel metabolite levels and efficacy measured by platelet function testing. The interaction between clopidogrel and …