Outcomes of outflow graft stenting in HeartMate 3 left ventricular assist devices: A systematic review and individual patient data meta-analysis.

PURPOSE: LVAD outflow graft stenosis continues to remain prevalent with a high complication rate. We sought to pool the existing evidence on indications, utilization patterns, and outcomes of transcatheter interventions for outflow graft stenosis in the HeartMate 3 LVAD. METHODS: An electronic search was performed to identify all studies in the English literature reporting on HeartMate 3 LVAD outflow graft stenting. Patient-level data were extracted for analysis. RESULTS: Thirteen published reports and one unpublished case comprising a total of 28 patients were included. Median patient age was 68.5 years [Interquartile range: 58, 71] and 25.9% (7/27) were female. Dyspnea [60.7% (17/28)] was the most common presenting symptom. Low flow alarms were present in 60% (15/25) of patients. Findings included external compression [35.7% (10/28)], graft twist [21.4% (6/28)], graft twist and external compression [14.3% (4.28)], intraluminal thrombus [10.7% (3/28)], graft twist and intraluminal thrombus [3.6% (1/28)], and pseudoaneurysm of outflow graft [3.6% (1/28)]. Median time from LVAD implantation to stenting was 2.1 years [1.4, 3]. Immediate flow normalization after stenting was observed in 85.7% (24/28). The 30-day mortality was 12% (3/25). Overall mortality was 12% (3/25) at a median follow-up of 3.9 months [1, 17]. CONCLUSION: Outflow graft stenting in the HeartMate 3 LVAD appears to be a reasonable treatment option for outflow graft stenosis, with low overall rates of complications and mortality. Further refinement of indications and approaches may improve outcomes.

Clinical Outcomes in Adult Patients With an Anomalous Right Coronary Artery from the Left Sinus of Valsalva.

An anomalous origin of the right coronary artery from the opposite sinus of Valsalva with an intramural course (R-ACAOS-IM) may cause sudden cardiac death in children and adolescents. However, the natural history and management of patients in whom this anomaly is detected later during adulthood remains uncertain. The goals of this study were to assess the impact of an R-ACAOS-IM on the clinical outcomes in an adult population and to determine if adult patients with this anomaly who do not have significant coronary artery disease (CAD) can be managed safely without surgical intervention. A database review identified patients aged >35 years with anomalous coronary arteries diagnosed by cardiac catheterization or coronary computed tomography angiography. The outcomes of patients with R-ACAOS-IM were compared with patients with anomalous left circumflex coronary arteries with retroaortic course (LCx-RA) (an anomaly not associated with ischemic events). The primary outcome was all-cause mortality. The study population consisted of 185 patients aged 59 ± 12 years. Clinical characteristics were similar in the R-ACAOS-IM (n = 88) and LCx-RA (n = 97) groups. At a follow-up of 6.6 ± 4.5 years, there was no difference in mortality (hazard ratio 0.64, 95% confidence interval 0.32 to 1.28, p = 0.20) when adjusted for gender, age, and CAD. A subgroup analysis of 88 patients with no obstructive CAD managed nonoperatively found no difference between the LCx and R-ACAOS-IM groups in mortality (hazard ratio 2.45, 95% confidence interval 0.45 to 13.40, p = 0.30). There was no significant difference between the 2 groups in the composite outcome of death, nonfatal myocardial infarction, or survived cardiac arrest. The outcome of adult patients who have anomalous R-ACAOS-IM are similar to patients who have anomalous LCx-RA with a known benign course. In conclusion, these results suggest that most patients who survive this anomaly into adulthood may be managed conservatively without intervention.

Transcatheter Aortic Valve Implantation in Cardiac Amyloidosis and Aortic Stenosis.

Aortic stenosis (AS) and cardiac amyloidosis (CA) occur concomitantly in a significant number of patients and portend a higher risk of all-cause mortality. Previous studies have investigated outcomes in patients with concomitant CA/AS who underwent transcatheter aortic valve implantation (TAVI) versus medical therapy alone, but no evidence-based consensus regarding the ideal management of these patients has been established. Medline, Scopus, and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. Methodologic bias was assessed using the modified Newcastle-Ottawa scale for observational studies. A total of 4 observational studies comprising 83 patients were included. Of these, 45 patients (54%) underwent TAVI, whereas 38 (46%) were managed conservatively. Of the 3 studies that included baseline characteristics by treatment group, 30% were women. The risk of all-cause mortality was found to be significantly lower in patients who underwent TAVI than those treated with conservative medical therapy alone (odds ratio 0.24, 95% confidence interval 0.08 to 0.73). In conclusion, this meta-analysis suggests a lower risk of all-cause mortality in patients with CA with AS who underwent TAVI than those managed with medical therapy alone.

Coronary Obstruction From TAVR in Native Aortic Stenosis: Development and Validation of Multivariate Prediction Model.

BACKGROUND: Transcatheter aortic valve replacement (TAVR)-related coronary artery obstruction prediction remains unsatisfactory despite high mortality and novel preventive therapies. OBJECTIVES: This study sought to develop a predictive model for TAVR-related coronary obstruction in native aortic stenosis. METHODS: Preprocedure computed tomography and fluoroscopy images of patients in whom TAVR caused coronary artery obstruction were collected. Central laboratories made measurements, which were compared with unobstructed patients from a single-center database. A multivariate model was developed and validated against a 1:1 propensity-matched subselection of the unobstructed cohort. RESULTS: Sixty patients with angiographically confirmed coronary obstruction and 1,381 without obstruction were included. In-hospital death was higher in the obstruction cohort (26.7% vs 0.7%; P < 0.001). Annular area and perimeter, coronary height, sinus width, and sinotubular junction height and width were all significantly smaller in the obstructed cohort. Obstruction was most common on the left side (78.3%) and at the level of the coronary artery ostium (92.1%). Coronary artery height and sinus width, but not annulus area, were significant risk factors for obstruction by logistic regression but performed poorly in predicting obstruction. The new multivariate model (coronary obstruction IF cusp height > coronary height, AND virtual valve-to-coronary distance ≤4 mm OR culprit leaflet calcium volume >600 mm3) performed well, with an area under the curve of 0.93 (sensitivity = 0.93, specificity = 0.84) for the left coronary artery and 0.94 (sensitivity = 0.92, specificity = 0.96) for the right. CONCLUSIONS: A novel computed tomography-based multivariate prediction model that can be implemented routinely in real-world practice predicted coronary artery obstruction from TAVR in native aortic stenosis.

Microaxial circulatory support for percutaneous coronary intervention: A systematic review and meta-analysis.

BACKGROUND: Microaxial circulatory support devices have been used to support patients treated with percutaneous coronary intervention (PCI) for acute myocardial infarction complicated by cardiogenic shock (AMICS). The purpose of this systematic review and meta-analysis was to pool and analyze the existing evidence on the baseline characteristics, periprocedural data, and outcomes of microaxial support before and after PCI in AMICS. METHODS: An electronic database search was performed to identify all cohort studies on Impella and PCI for cardiogenic shock in the English language. A total of five articles comprising 543 patients were included. These patients received microaxial support either before (pre-PCI) or after (post-PCI) undergoing PCI. Comparative analyses were done between both groups. RESULTS: The mean patient age was 66 years [95% Confidence Interval (58-74)], and 22% (89/396) of patients were female. ST-elevation myocardial infarctions (MI) comprised 64% (44-80) of MIs and 50% (44-56) of MIs involved the left anterior descending artery. The mean number of diseased vessels was 2.21 (1.62-2.80). The mean left ventricular ejection fraction was 31% (23.4-38.6). The mean arterial pressure was 66.3 mm Hg (54.1-78.5). Mean serum lactate [6.1 mmol/L (3.3-8.9)] and serum creatinine [1.4 mg/dl (1.0-1.7)] were similar between groups. 30-day mortality was lower in the pre-PCI group [41% (34%-49%)] compared to the post-PCI group [61% (42%-77%), p < 0.01]. Pooled Kaplan-Meier analysis showed better early survival in the pre-PCI group (p < 0.001). CONCLUSION: Patients presenting with AMICS were similar at baseline in both pre-PCI and post-PCI groups. Nevertheless, pre-PCI group showed better early survival compared to post-PCI group.

Trends and Outcomes of TAVI and SAVR in Cancer and Noncancer Patients: A Nationwide Analysis.

Background: Patients with severe aortic stenosis and cancer are often denied surgical aortic valve replacement (SAVR) due to a prohibitive risk of perioperative mortality. Objectives: The purpose of this study was to determine the safety of transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis and cancer. Methods: The Nationwide Inpatient Sample database (2002-2018) was used to study the outcomes of TAVI vs SAVR in patients with active or prior history of prostate, lung, colorectal, breast, and renal cancer. A propensity score-matched analysis to calculate adjusted odds ratios (aORs) for major adverse cardiovascular events (MACEs) and its components. Results: A total of 1,505,995 crude population and a subset of 345,413 noncancer and 33,565 cancer patients were selected on propensity score-matched analysis. The yearly trend showed a steep increase in the utilization of TAVI. Compared with SAVR, TAVI had a lower risk of in-hospital mortality in prostate cancer, while there was no difference among other cancer types. Patients with lung (aOR: 0.65; 95% CI: 0.43-0.97) and prostate cancer (aOR: 0.79; 95% CI: 0.66-0.96) had lower, while colorectal cancer (aOR: 1.43; 95% CI: 1.08-1.90) had higher odds of MACE with TAVI. The incidence of major bleeding was lower with TAVI (except for lung cancer), while the risk of stroke was similar (except for colorectal cancer) between TAVI and SAVR. Conclusions: TAVI in patients with prostate, breast, lung, and renal cancer appears to be a reasonable alternative to SAVR with lower or similar risks of mortality and MACE.

Percutaneous Decommissioning 11 Years After Initial CF-LVAD Placement.

An 80-year-old man with severe nonischemic cardiomyopathy status post left ventricular assist device (LVAD) placement 11 years prior presented for recurrent LVAD alarms from internal driveline fracture. Given his partial myocardial recovery and his preference to avoid surgical procedures, percutaneous LVAD decommissioning was performed by occlusion of the outflow graft and subsequently driveline removal. (Level of Difficulty: Advanced.).

Innovative use of biotrace tempo pacemaker lead following cardiac surgery.

The Tempo® Temporary Pacing Lead is a temporary, transvenous, active fixation pacemaker lead used exclusively in structural heart and electrophysiology procedures since regulatory approval in 2016. We utilized the Tempo lead for four patients undergoing redo-robotic cardiac surgery in which surgical epicardial leads could not be placed. No failure-to-pace events were encountered and patients were able to participate in various levels of physical activity without limitation.

Percutaneous coronary intervention of totally occluded coronary venous bypass grafts: An exercise in futility?

BACKGROUND: Percutaneous coronary intervention (PCI) of diseased saphenous vein grafts (SVG) continues to pose a clinical challenge. Current PCI guidelines give a class III recommendation against performing PCI on chronically occluded SVG. However, contemporary outcomes after SVG intervention have incrementally improved with distal protection devices, intracoronary vasodilators, drug-eluting stents, and prolonged dual antiplatelet therapy. AIM: To reassess the procedural and long-term outcomes of PCI for totally occluded SVG with contemporary techniques. METHODS: This was a retrospective observational study conducted at a single university hospital. The study population consisted of 35 consecutive patients undergoing PCI of totally occluded SVG. Post-procedure dual antiplatelet therapy was continued for a minimum of one year and aspirin was continued indefinitely. Clinical outcomes were assessed at a mean follow-up of 1221 ± 1038 d. The primary outcome was freedom from a major adverse cardiac event (MACE) defined as the occurrence of any of the following: death, myocardial infarction, stroke, repeat bypass surgery, repeat PCI, or graft reocclusion. RESULTS: The study group included 29 men and 6 women with a mean age of 69 ± 12 years. Diabetes was present in 14 (40%) patients. All patients had Canadian Heart Classification class III or IV angina. Clinical presentation was an acute coronary syndrome in 34 (97%) patients. Mean SVG age was 12 ± 5 years. Estimated duration of occlusion was acute (< 24 h) in 34% of patients, subacute (> 24 h to 30 d) in 26%, and late (> 30 d) in 40%. PCI was initially successful in 29/35 SVG occlusions (83%). Total stent length was 52 ± 35 mm. Intraprocedural complications of distal embolization or no-reflow occurred in 6 (17%) patients. During longer term follow-up, MACE-free survival was only 30% at 3 years and 17% at 5 years. CONCLUSION: PCI of totally occluded SVG can be performed with a high procedural success rate. However, its clinical utility remains limited by poor follow-up outcomes.

Non-Invasive Intra-cardiac Pressure Measurements Using Subharmonic-Aided Pressure Estimation: Proof of Concept in Humans.

This study evaluated the feasibility of employing non-invasive intra-cardiac pressure estimation using subharmonic signals from ultrasound contrast agents in humans. This institutional review board-approved proof-of-concept study included 15 consenting patients scheduled for left and right heart catheterization. During the catheterization procedure, Definity was infused intra-venously at 4-10 mL/min. Ultrasound scanning was performed with a Sonix RP using pulse inversion, three incident acoustic output levels and 2.5-MHz transmit frequency. Radiofrequency data were processed and subharmonic amplitudes were compared with the pressure catheter data. The correlation coefficient between subharmonic signals and pressure catheter data ranged from -0.3 to -0.9. For acquisitions with optimum acoustic output, pressure errors between the subharmonic technique and catheter were as low as 2.6 mmHg. However, automatically determining optimum acoustic output during scanning for each patient remains to be addressed before clinical applicability can be decided.

Ventricular Perforation During Open Surgical Balloon Expandable Mitral Valve Replacement: A Case Report.

A 79-year-old woman with severe mitral annular calcification was scheduled for mitral valve replacement. A SAPIEN 3 valve was implanted in mitral position using an open surgical approach. Immediately after cardiopulmonary bypass, bleeding from an unidentified source was encountered. Cardiopulmonary bypass was emergently resumed and a laceration of the left ventricular apex due to the valve delivery system was detected. Risk factors specific to the open surgical approach include a decompressed ventricle, decreased annulus to apical distance, and the absence of continuous fluoroscopic and echocardiographic imaging. These create a clinical scenario where risk of ventricular perforation is increased compared with traditional intravascular transcatheter valve delivery.

Unrecognized coronary vasospasm in patients referred for percutaneous coronary intervention: Intracoronary nitroglycerin, the forgotten stepchild of cardiovascular guidelines.

OBJECTIVE: The goal of this study was to demonstrate the importance of intracoronary nitroglycerin (IC NTG) administration during diagnostic coronary angiography and prior to percutaneous coronary intervention (PCI). BACKGROUND: PCI has been a mainstay treatment for patients with symptomatic coronary artery disease. While current guidelines emphasize the importance of periprocedural antithrombotic medications, they fail to mention the use of nitroglycerin prior to PCI. METHODS: Retrospective chart and angiographic review was performed to identify patients referred for PCI who had significant angiographic stenoses that resolved after administration of IC NTG. RESULTS: The study group consisted of 6 patients (3 men, 3 women) with mean age 52 ± 4years (range 46-57 years). All had anginal symptoms and significant (>70%) stenosis on diagnostic coronary angiography. None had documented ST segment elevation. The median interval between diagnostic and staged PCI procedures was 3 days. IC NTG was not administered to any of the patients at the time of diagnostic coronary angiography. In each case, repeat coronary angiography following administration of IC NTG (155 ± 46 mcg) before planned PCI demonstrated resolution of the target stenosis. PCI was deferred and all patients were successfully managed medically. CONCLUSION: Coronary artery spasm is an under-recognized cause of chest pain in patients with significant angiographic lesions. Coronary spasm should be suspected especially in younger patients (less than 60 years old) with apparent single vessel disease. IC NTG should be routinely administered during diagnostic angiography and before PCI to avert unnecessary coronary interventions. © 2017 Wiley Periodicals, Inc.

Automated and Manual Measurements of the Aortic Annulus with ECG-Gated Cardiac CT Angiography Prior to Transcatheter Aortic Valve Replacement: Comparison with 3D-Transesophageal Echocardiography.

RATIONALE AND OBJECTIVES: Multimodality evaluation of the aortic annulus is generally advocated to plan for transcatheter aortic valve replacement (TAVR). We compared aortic annular measurements by cardiac computed tomography angiography (cCTA) to three-dimensional transesophageal echocardiography (3D-TEE), and also evaluated the use of semi-automated software for cCTA annular measurements. MATERIALS AND METHODS: A retrospective cohort of 74 patients underwent 3D-TEE and electrocardiogram-gated cCTA of the heart within 30 days for TAVR planning. 3D-TEE measurements were obtained during mid-systole; cCTA measurements were obtained during late-systole (40% of R-R interval) and mid-diastole (80% of R-R interval). Annular area was measured independently by manual planimetry and with semi-automated software. RESULTS: cCTA measurements in systole and diastole were highly correlated for short-axis diameter (r = 0.91), long-axis diameter (r = 0.92), and annular area (r = 0.96), although systolic measurements were significantly larger (P < 0.001), most notably for the short-axis diameter. Good correlation was observed between 3D-TEE and cCTA for short-axis diameter (r = 0.84-0.90), long-axis diameter (r = 0.77-0.79), and annular area (r = 0.89-0.90). As compared to 3D-TEE, annular area is overmeasured by 28 mm2 on systolic phase cCTA (P < 0.008), but nearly identical with 3D-TEE on diastolic phase cCTA. Semi-automated and manual cCTA annulus measurements were highly correlated in systole (r = 0.94) and diastole (r = 0.93), although the semi-automated annular area measured 11-30 mm2 greater than manual planimetry. Of note, the 95% limits of agreement in our Bland-Altman analysis suggest that the variability in annular area estimates for individual patients between cCTA and 3D-TEE (-100.9 to 99.6 mm2), as well as the variability between manual and automated measurements with cCTA (-105.9 to 45.2 mm2), may be sufficient to alter size selection for an aortic prosthesis. CONCLUSIONS: Although all cCTA measurements are highly correlated with measurements by 3D-TEE, diastolic phase cCTA measurements tend to be closer to standard mid-systolic 3D-TEE measurements. Semi-automated measurement of the aortic annulus with cCTA is highly correlated with manual planimetry. Nonetheless, annular contours derived by semi-automated software should be visually inspected, as the variability in area estimates for individual cases between manual and automated measurements may alter the sizing of an aortic prosthesis.

"Very" very late stent thrombosis: acute myocardial infarction from drug-eluting stent thrombosis more than 5 years after implantation.

A serious long-term complication of drug-eluting stent (DES) implantation is the occurrence of very late stent thrombosis (VLST) beyond 1 year after implantation. While VLST has been observed as late as 3 to 5 years following the initial procedure, it remains unknown whether DES thrombosis is a finite phenomenon that abates over time or is a risk that persists indefinitely. We identified a series of patients who presented with acute myocardial infarction (MI) due to "very" very late stent thrombosis (VVLST), defined as occurring more than 5 years after DES implantation. The study group consisted of 7 patients (6 men and 1 woman), ages 32 to 70 years, who had angiographically confirmed definite VVLST. Six patients were active smokers and 4 were diabetic. The interval between stent implantation and VVLST ranged from 5.6 to 7.1 years. The DES was sirolimus-eluting in 4 patients and paclitaxel-eluting in 3 patients. None of the patients were taking clopidogrel and only 2 patients were taking aspirin at the time of VVLST. Therefore, 5 of the 7 patients were not on any antiplatelet therapy prior to VVLST. The clinical presentation of VVLST was an acute MI in all patients, with ST-segment elevation in 6 of the 7 patients. Six patients were treated successfully by emergent repeat percutaneous coronary intervention and 1 patient who was postoperative from neurosurgery was managed medically. In conclusion, the risk of stent thrombosis persists even beyond 5 years after first-generation DES implantation. These sobering findings underscore the importance of long-term clinical vigilance in these patients and reinforce current PCI guidelines, which recommend continuing at least aspirin indefinitely after DES.

Carotid artery stenting for recurrent carotid artery restenosis after previous ipsilateral carotid artery endarterectomy or stenting: a report from the National Cardiovascular Data Registry.

OBJECTIVES: The purpose of this study was to evaluate and compare outcomes of patients undergoing carotid artery stenting (CAS) for ipsilateral restenosis, after either previous CAS or carotid artery endarterectomy (CEA) (CAS-R group), with those of patients who had CAS performed for de novo carotid atherosclerotic stenosis (CAS-DN group). BACKGROUND: Therapeutic revascularization strategies to reduce stroke include CAS and CEA. Limited data exist concerning the outcomes of CAS in the setting of previous ipsilateral carotid revascularization. METHODS: Patients enrolled in the CARE (Carotid Artery Revascularization and Endarterectomy) registry who underwent CAS were identified and separated into 2 groups: those undergoing CAS after previous ipsilateral CEA or CAS (CAS-R group, n = 1,996) and those who had CAS performed for de novo atherosclerotic carotid stenosis (CAS-DN group, n = 10,122). We analyzed the clinical and procedural factors associated with CAS-R and CAS-DN between January 1, 2005, and October 8, 2012. Propensity score matching using 19 clinical and 9 procedural characteristics was used, yielding 1,756 patients in each CAS cohort. RESULTS: The primary endpoint composite of in-hospital death or stroke or myocardial infarction (MI) occurred less often in the CAS-R compared with CAS-DN patients (1.9% vs. 3.2%; p = 0.019). In-hospital adverse cerebrovascular events (stroke or transient ischemic attack) occurred less frequently in the CAS-R cohort (2.2% vs. 3.6%; p < 0.001). However, there was no significant difference in the composite of death, stroke, or MI at 30 days between both groups. CONCLUSIONS: Patients who underwent CAS for restenosis after previous ipsilateral revascularization had lower periprocedural adverse event rates and comparable 30-day adverse event rates compared with CAS for de novo carotid artery stenosis.

Outcomes of carotid endarterectomy in the elderly: report from the National Cardiovascular Data Registry.

BACKGROUND AND PURPOSE: Benchmark trials of carotid endarterectomy often did not include elderly patients, and the results may not be easily extrapolated to the general population. Using the Carotid Artery Revascularization and Endarterectomy registry, we sought to determine real-world outcomes of carotid endarterectomy in the elderly. METHODS: This was a retrospective cohort study of patients aged >70 years. We compared outcomes stratified by age among symptomatic and asymptomatic patients. RESULTS: There were 4149 patients who underwent carotid endarterectomy; 1376 (33.1%) were symptomatic. Overall mortality rate was 0.5%. The primary outcome of in-hospital death, stroke, and myocardial infarction showed a significant trend and was highest in the age >85 years group (5.6%). Among symptomatic patients, mortality and the primary outcome were not statistically different between those aged >75 years and those aged 70 to 74 years. Among asymptomatic elderly patients, mortality rate was significantly higher in age group >75 years compared with <75 years (0.7% vs 0.0%); however, the combined outcome of stroke, death, and myocardial infarction was not statistically different. CONCLUSIONS: Elderly patients >85 years of age were at increased risk for death or perioperative complications of stroke, death, and myocardial infarction compared with those who were relatively younger. More elderly patients underwent carotid endarterectomy for asymptomatic carotid stenosis and had higher mortality than the younger counterparts, underlining need for caution in subjecting them to the procedure.

Saphenous vein graft disease: review of pathophysiology, prevention, and treatment.

Saphenous vein graft (SVG) disease after coronary artery bypass grafting (CABG) occurs in three phases: thrombosis, intimal hyperplasia, and atherosclerosis. Within the first month, thrombosis plays a major role. From month 1 to month 12, intimal hyperplasia occurs. Beyond 12 months, atherosclerosis becomes the primary cause for late graft failure. Endothelial damage has been shown to be the major underlying pathophysiology of SVG disease. Many factors contribute to endothelial damage from the moment the vein is harvested to when the vein is grafted into an arterial environment. To address this disease process, various therapeutic modalities, from surgical methods to medical treatment, have been evaluated. Surgically, the technical method of harvesting the vein has been shown to affect SVG patency. From a pharmacologic perspective, only two guideline class I recommended medications, aspirin and statins, have been shown to improve short- and long-term SVG patency after CABG. Despite these surgical and medical advances, SVG disease remains a significant problem with 1-year patency rates of 89% dropping to 61% after 10 years. This review discusses the pathogenesis of SVG disease, predictors of SVG failure, and current surgical and pharmacologic therapies to address SVG disease, including possible future treatment.

Modern antiplatelet agents in coronary artery disease.

Dual antiplatelet therapy is well recognized in the prevention of thrombotic complications of acute coronary syndrome and percutaneous coronary interventions. Despite clinical benefits of aspirin and clopidogrel therapy, a number of limitations curtail their efficacy: slow onset of action, variability in platelet inhibitory response and potential drug-drug interactions. Furthermore, the single platelet-activation pathway targeted by these agents allows continued platelet activation via other pathways, ensuring incomplete protection against ischemic events, thus, underscoring the need for alternate antiplatelet treatment strategies. A number of novel antiplatelet agents are currently in advance development and many have established superior effects on platelet inhibition, clinical outcomes and safety profile than clopidogrel in high-risk patients. The aim of this review is to provide an overview of the current status of P2Y12 receptor inhibition and PAR-1 antagonists in determining a future strategy for individualized antiplatelet therapy.