THROMBOSIS

CARDIOLOGY

No Rebound Effect Post Clopidogrel Withdrawal

<p>Watch the video of subgroup analysis of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial showed no rebound increase in the risk of ischemic stroke, stroke, transient ischemic attack (TIA), and composite events during the 90 days after discontinuation of clopidogrel therapy in patients with TIA or minor stroke.</p>

Effectiveness and safety of Clopidogrel vs Aspirin

<p>Watch the video and get to know more on how Clopidogrel is a safe and effective alternative to Aspirin as an Antiplatelet agent for secondary prevention of stroke in patients aged over 80 years.</p>

DAPT in Elderly with CAD Meta Analysis

<p>Watch the video and get to know more on the crucial insights from this systematic review and meta-analysis of DAPT in elderly patients with acute coronary syndrome (ACS). Dual oral antiplatelet therapy (DAPT) with prasugrel or ticagrelor is associated with a higher risk of bleeding events in elderly patients with ACS compared to clopidogrel, with no difference in primary efficacy endpoint rates between the treatment groups.</p>

Understanding de-escalation in Antiplatelet therapy

<p>Watch the video of Prof. Thomas Cuisset M.D, Ph.D, Interventional Cardiology Unit and Head of the Cathlab in University Hospital, La Timone, Marseille, France where he explains The de-escalation strategy and which patients are good candidates for proactive de-escalation.</p>

Ticagrelor vs Clopidogrel in Older Patients With ACS PCI

<p>Watch the video and get to know more on older patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI); clopidogrel is an effective alternative to the more potent P2Y12 inhibitor ticagrelor.</p>

Single Antiplatelet therapy: Insights on earlier use

<p>Watch the video of Prof. Dominick Angiolillo, M.D., Ph.D., Professor &amp; Medical Director of the Cardiovascular Research Program, University of Florida College of Medicine, Jacksonville USA, sharing insights on recent studies that show an emphasis on the early use of single Antiplatelet therapy in PCI patients.</p>

Clopidogrel as the standard of care for elective PCI: Findings from the Alpheus

<p>Watch the video and get to know more on Alpheus trial. Since Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients, then stronger platelet inhibition could potentially lower these events and make the PCI procedure safer.</p>

<h2>Main Takeaway</h2>
<ul>
 <li><strong>Risk for net adverse clinical events (NACE) was not significantly different</strong>&nbsp;between ticagrelor at 12 months compared with clopidogrel 
  <ul>
   <li>Study population: 62,580 patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) in routine clinical practice</li>
  </ul></li>
 <li>Ticagrelor was associated with&nbsp;<strong>higher risks for haemorrhagic events and dyspnoea</strong>&nbsp;vs clopidogrel</li>
</ul>
<h2>Why This Matters</h2>
<ul>
 <li>Recent observational studies&nbsp;<strong>question whether ticagrelor vs clopidogrel is associated with better outcomes</strong>&nbsp;in routine clinical practice 
  <ul>
   <li>Current guidelines: recommend ticagrelor with aspirin in preference to clopidogrel in patients with ACS</li>
  </ul></li>
</ul>
<h2>Study Design</h2>
<p><strong>Retrospective cohort study:</strong>&nbsp;183,579 patients (age range, 30-89 years) with ACS who underwent PCI and received ticagrelor or clopidogrel</p>

<p>Patients were matched using propensity score:</p>
<ul>
 <li>Ticagrelor (n=31,290)</li>
 <li>Clopidogrel (n=31,290)</li>
</ul>
<p><strong>Primary endpoint:</strong>&nbsp;NACE at 12 months</p>
<ul>
 <li><strong>Ischaemic events</strong><br>
   [recurrent acute myocardial infarction, revascularisation or ischaemic stroke]</li>
 <li><strong>Haemorrhagic events</strong><br>
   [haemorrhagic stroke or gastrointestinal bleeding]</li>
</ul>
<p><strong>Secondary outcomes:</strong>&nbsp;NACE or mortality, all-cause mortality, composite ischaemic events, composite haemorrhagic events, individual components of the primary outcome, dyspnoea at 12 months</p>
<h2>Key Results</h2>
<p><strong>95.5% of matched patients used aspirin</strong>&nbsp;with ticagrelor or clopidogrel among the 31,290 propensity-matched pairs</p>
<p>The risk for NACE was not significantly different between ticagrelor and clopidogrel groups (HR, 1.05; 95% CI, 1.00-1.10; P=0.06)</p>
<ul>
 <li>No significant difference was found between the 2 groups for: 
  <ul>
   <li>NACE or mortality (HR, 1.03; 95% CI, 0.98-1.08; P=0.21)</li>
   <li>Ischaemic events (HR, 1.03; 95% CI, 0.98-1.08; P=0.32)</li>
   <li>All-cause mortality (HR, 0.97; 95% CI, 0.81-1.16; P=0.74)</li>
  </ul></li>
 <li>Ticagrelor vs clopidogrel group showed a significantly higher risk for: 
  <ul>
   <li>Haemorrhagic events (HR, 1.35; 95% CI, 1.13-1.61; P=0.001)</li>
   <li>Dyspnoea (HR, 1.21; 95% CI, 1.17-1.26; P&lt;0.001)</li>
  </ul></li>
</ul>
<h2>Limitations</h2>
<ul>
 <li>The study did not include information on aspirin dosage, angiographic findings, or PCI procedure</li>
 <li>The burden of overall bleeding events could have been underestimated or overestimated</li>
 <li>Neither the proportion of patients who switched antiplatelet drugs nor its effects were quantified</li>
 <li>The effect of pre-treatment with an antiplatelet agent was not assessed</li>
 <li>The mortality rate might have been underestimated</li>
 <li>Patients who used prasugrel for dual antiplatelet therapy were not included</li>
</ul>

Reference

Ticagrelor vs Clopidogrel in ACS patients undergoing PCI in routine clinical practice

<h2>Main Takeaway</h2>
<ul>
 <li>Clopidogrel-based DAPT (CDAPT) was associated with a&nbsp;<strong>lower risk of bleeding events, major adverse cardiac and cerebral events</strong>&nbsp;(MACCE), and net adverse clinical events (NACE) than ticagrelor-based DAPT (TDAPT) 
  <ul>
   <li>Risks were similar between CDAPT and prasugrel-based DAPT (PDAPT)</li>
  </ul></li>
</ul>
<h2>Why This Matters</h2>
<ul>
 <li>The findings from this study support&nbsp;<strong>clopidogrel as a viable first-choice P2Y12 inhibitor for DAPT after PCI</strong>&nbsp;in an East-Asian patient population 
  <ul>
   <li>Recent European guidelines recommended potent P2Y12 inhibitors (ticagrelor and prasugrel) over clopidogrel in acute coronary syndromes, due to their rapid onset of action and strong antiplatelet activity 
    <ul>
     <li>Their safety and effectiveness in the East-Asian patients has often been questioned</li>
    </ul></li>
  </ul></li>
</ul>
<h2>Study Design</h2>
<p><strong>Retrospective study</strong>:&nbsp;57,197 patients in the South Korean HIRA database underwent PCI (from January 1 2014 to December 31 2016) and were treated with DAPT including aspirin and one of three P2Y12 inhibitors</p>
<ul>
 <li>Clopidogrel + aspirin (CDAPT) (n=37,500)</li>
 <li>Ticagrelor + aspirin (TDAPT) (n=15,723)</li>
 <li>Prasugrel + aspirin (PDAPT) (n=3,974)</li>
</ul>
<h3><strong>Key exclusion criteria:</strong></h3>
<ul>
 <li>Age &lt;18 years as of the index date (n=6)</li>
 <li>History of PCI or CABG during the baseline period (n=3,434)</li>
 <li>Severe liver or chronic kidney disease (stage 4-5, n=1,315))</li>
 <li>Use of P2Y12 inhibitors during the baseline period (n=39,134)</li>
 <li>Use of oral antithrombotic agents (except low-dose aspirin) during the study period (n=19,849)</li>
</ul>
<p><strong>Key outcomes</strong>:&nbsp;the risk of bleeding events, risk of MACCE (a composite of all-cause death, myocardial infarction, stroke and revascularisation), risk of NACE, persistence and adherence rates</p>
<h2>Key Results</h2>
<p><strong>The risk of bleeding events, MACCE, and NACE was significantly higher in the TDAPT group versus the CDAPT group</strong>, both at 1-year and in the prolonged periods</p>
<ul>
 <li>Risk of bleeding event: 1-year hazard ratio (HR) = 1.37; 95% confidence interval (CI), 1.28–1.46; prolonged HR = 1.39; 95% CI, 1.31–1.47</li>
 <li>Risk of MACCE: 1-year HR = 1.10; 95% CI, 1.03–1.18; prolonged HR = 1.24; 95% CI, 1.16–1.31</li>
 <li>Risk of NACE: 1-year HR = 1.23; 95% CI, 1.18–1.29; prolonged HR = 1.31; 95% CI, 1.25–1.36</li>
 <li>No significant differences were reported for the risk of bleeding events, MACCE, and NACE between the PDAPT and CDAPT groups (1-year and prolonged periods)</li>
</ul>
<p>The&nbsp;use of clopidogrel correlated with better adherence to DAPT&nbsp;than potent P2Y12 inhibitors</p>
<ul>
 <li><strong>34.9% of patients remained on CDAPT until the end of the prolonged period</strong>,&nbsp;whereas only 7.8% and 9.2% remained on TDAPT and PDAPT, respectively</li>
</ul>
<h2>Limitations</h2>
<ul>
 <li>Any association between P2Y12 inhibitors and clinical outcomes should be interpreted cautiously, owing to the observational nature of the study</li>
 <li>There was a lack of information regarding lesion complexity and location at index PCI, baseline laboratory findings, and cardiac function</li>
 <li>The information bias from voluntary/involuntary miscoding may lead to underestimation or overestimation of the outcomes</li>
 <li>The reporting of death was limited to in-hospital death</li>
 <li>It is difficult to generalise study findings in ethnic groups other than the East-Asian populations</li>
 <li>Reasons for P2Y12 inhibitor discontinuation were not identified</li>
</ul>

Is Clopidogrel a viable first choice P2Y12 inhibitor for DAPT after PCI?

<h2>Main Takeaway</h2>
<p>A real-word study of Taiwanese patients with AMI undergoing PC</p>
<ul>
 <li><strong>Showed a comparable 1-year cardiovascular outcome</strong>&nbsp;with standard ticagrelor treatment 3 months after the event of AMI</li>
 <li><strong>Didn’t report statistically significant differences in:</strong>
  <ul>
   <li>Hazard risk of death</li>
   <li>AMI admission</li>
   <li>Major adverse</li>
   <li>Cardiovascular events (MACE)<br>
     &nbsp;</li>
  </ul></li>
 <li><strong>Didn’t show a difference in the risk of bleeding,</strong>&nbsp;including major or clinically relevant non-major bleeding</li>
</ul>

<h2>Why This Matters</h2>
<ul>
 <li><strong>Bleeding risks could be reduced</strong>&nbsp;P2Y12 inhibitor de-escalation approach is considered by physicians to reduce additional bleeding risks</li>
 <li><strong>Current studies are not enough</strong>&nbsp;Despite recent clinical studies, there’s limited and conflicting evidence on de-escalation strategies. This study aimed to assess the effect of de-escalated P2Y12 inhibitor switching in DAPT on MACE in patients with AMI undergoing PCI;</li>
</ul>

<h2>Study Design</h2>
<p>This retrospective and population-based cohort study utilized data from the Taiwan’s National Health Insurance Research Database (NHIRD).</p>
<p><strong>Key Inclusion Criteria:</strong></p>
<ul>
 <li>Patients who were hospitalized with a primary diagnosis of AMI</li>
</ul>
<p><strong>Key Exclusion Criteria:</strong></p>
<ul>
 <li>Patients aged &lt;18 years, without identification of sex, or Taiwanese citizenship</li>
 <li>Patients not on heparin or antiplatelet therapy, or were only on aspirin therapy, or</li>
 <li>received antiplatelet agents other than ticagrelor at index of AMI</li>
 <li>Patients who had a coronary artery bypass graft</li>
 <li>Death of the patient within 3 months after the index date of AMI</li>
</ul>
<p><strong>Key Outcomes:</strong></p>
<ul>
 <li>Death, AMI readmission, and MACE within one year during the follow-up period</li>
</ul>

<h2>Key Results</h2>
<p>Number Of Participants</p>
<ul>
 <li>10,100 patients were included (de-escalated DAPT group: n = 1,901; unchanged DAPT: n = 8,199)</li>
</ul>
<p>Incidence Rates And Adjusted Hazard Ratio</p>
<ul>
 <li><strong>All-cause death</strong>&nbsp;(unchanged vs de-escalated DAPT group):&nbsp;<strong>Incidence</strong>&nbsp;= 2.42&nbsp;(95% confidence interval [CI]: 2.02–2.90) vs 2.89 (95% CI: 2.05–3.91);&nbsp;<strong>adjusted HR&nbsp;</strong>= 1.20&nbsp;(95% CI: 0.83–1.73; P = 0.336)</li>
 <li><strong>AMI hospitalization</strong>&nbsp;(unchanged vs de-escalated DAPT group):&nbsp;<strong>Incidence&nbsp;</strong>= 3.28&nbsp;(95% CI: 2.81–3.83) vs 3.68 (95% CI: 2.75–4.88);&nbsp;<strong>adjusted HR</strong>&nbsp;= 1.12&nbsp;(95% CI: 0.80–1.56; P = 0.509)</li>
 <li><strong>MACE&nbsp;</strong>(unchanged vs de-escalated DAPT group):&nbsp;<strong>Incidence&nbsp;</strong>= 4.72&nbsp;(95% CI: 4.13–5.36) vs 4.91 (95% CI: 3.80–6.26);&nbsp;<strong>adjusted HR&nbsp;</strong>= 1.04&nbsp;(95% CI: 0.78–1.39; P = 0.766)</li>
 <li><strong>Major bleeding</strong>&nbsp;(unchanged vs de-escalated DAPT group):&nbsp;<strong>Incidence&nbsp;</strong>= 2.36&nbsp;(95% CI: 1.95–2.82) vs 2.12 (95% CI: 1.41–3.01);&nbsp;<strong>adjusted HR</strong>&nbsp;= 0.92&nbsp;(95% CI: 0.61–1.37; P = 0.669)</li>
</ul>

<h2>Limitations</h2>
<ul>
 <li>Patient information such as risk behaviors, diet, and physical activities are not available in the NHIRD.</li>
 <li>Hidden bias of medication selection was introduced as the study data was sourced from an administrative database.</li>
 <li>Missing clinical information, such as the severity of AMI at admission, might have induced non-differential misclassification bias.</li>
 <li>Study results might not be generalizable to other populations, as only Taiwanese patients were included in the analysis.</li>
</ul>

Effect of de-escalated P2Y12 inhibitor switching in dual antiplatelet therapy (DAPT)

<p>Real-world adherence and persistence of dual antiplatelet therapy over two years in patients with coronary artery diseases</p>
<p>Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA)/clopidogrel showed a statistically significant better persistence vs ASA/ticagrelor and ASA/prasugrel. However, no statistically significant differences were seen in adherence to ASA/clopidogrel fixed dose combination (FDC) vs the use of two different pills.</p>

<h2>Main Takeaway</h2>
<ul>
 <li>In this first study evaluating the difference in adherence between FDC vs each component taken as a separate pill, in patients with coronary artery disease treated with DAPT (at two years): 
  <ul>
   <li>No statistically significant difference was found between FDC of ASA/clopidogrel and the combination of the two ASA and clopidogrel pills taken separately (P = 0.0752).</li>
   <li>Adherence data were optimal for all types of DAPT analyzed (absolute value of adherence = 0.96).</li>
  </ul></li>
 <li>In this real-life analysis, persistence to therapy was observed to be better in the ASA/clopidogrel group vs the ASA/prasugrel and the ASA/ticagrelor groups (at two years). 
  <ul>
   <li>ASA/clopidogrel and ASA/clopidogrel (FDC) curves showed a statistically significant better persistence than ASA/prasugrel and ASA/ticagrelor curves (P &lt;0.001).</li>
   <li>However, the persistence data showed low adherence to the guidelines.</li>
  </ul></li>
</ul>

<h2>Why This Matters</h2>
<ul>
 <li>There is a lack of consensus regarding the optimal duration of DAPT for patients with coronary artery disease.</li>
 <li>Additionally, long-term adherence to DAPT remains a challenge in the management of patients with cardiovascular diseases in real-life, due to various factors like need for prolonged therapy, lack of proper prescription in the context of primary care, and the instructions provided at hospital discharge.</li>
 <li>This real-world study therefore, evaluated adherence and persistence over two years in patients receiving DAPT.</li>
</ul>

<h2>Study Design</h2>
<ul>
 <li>This non-interventional, retrospective study included all patients treated with DAPT in the Hospital of Pescara (Italy) utilizing data from the Hospital reimbursement database.</li>
 <li>The study population consisted of prevalent users of clopidogrel, ASA, prasugrel, and ticagrelor (administered as first-line therapy).</li>
</ul>

<h2>Key Results</h2>
<ul>
 <li>Overall, 519 patients treated with DAPT were included in the analysis (male = 83%; median age = 63; ASA/clopidogrel, n = 277; ASA/prasugrel, n = 77; ASA/ticagrelor, n = 57, and ASA/clopidogrel FDC, n = 108).</li>
 <li>Persistence (at two years): Persistence to therapy was observed to be better in the ASA/clopidogrel group vs the ASA/prasugrel and the ASA/ticagrelor groups 
  <ul>
   <li>ASA/clopidogrel and ASA/clopidogrel (FDC) curves showed a statistically significant better persistence than ASA/prasugrel and ASA/ticagrelor curves (P &lt;0.001).</li>
   <li>In total, 34 patients remained on ASA/clopidogrel and 18 patients remained on ASA/clopidogrel (FDC); while 1 patient each remained on ASA/prasugrel and ASA/ticagrelor therapies.</li>
   <li>Overall persistence data showed low adherence to the guidelines.</li>
  </ul></li>
 <li>Adherence (at two years): Adherence to therapy was optimal for all types of DAPT analyzed and remained stable over the study period 
  <ul>
   <li>Absolute value of adherence at two years was 0.96 and adherence ≥ 0.8 was observed in 94% of the patients</li>
   <li>ASA/prasugrel group had better adherence vs the other groups: Absolute value of adherence was 0.98; and adherence value ≥ 0.8 was seen in 97% of the patients</li>
   <li>FDC ASA/clopidogrel group had poor adherence vs the other groups: Absolute value of adherence was 0.94; and adherence value ≥ 0.8 was seen in 88% of the patients</li>
   <li>No statistically significant difference was found between FDC of ASA/clopidogrel and the combination of the two ASA and clopidogrel pills taken separately (P = 0.0752).</li>
  </ul></li>
</ul>

<h2>Limitations</h2>
<ul>
 <li>The reasons for non-persistence of therapy were not evaluated as the analysis was based on data from an administrative database.</li>
</ul>

Adherence and persistence analysis in patients treated with DAPT

Management of antithrombotic therapy in patients with AF undergoing PCI

<p>Watch the video and discover more on the need for antithrombotic strategies which associated with a lower risk of bleeding while maintaining efficacy of treatment options.</p>

<p>Risk factor profile and outcomes of young patients suffering their first acute myocardial infarction: Results from Gulf Coast</p>
<p>Findings from this first prospective cohort study evaluating Gulf-Arabs without prior cardiovascular disease presenting with first acute myocardial infarction (AMI) highlight important age-related care gaps in this patient population.</p>
<h2>Main Takeaway</h2>
<ul>
 <li>This&nbsp;<strong>Gulf-Coast study in adults without established atherosclerotic cardiovascular disease (ASCVD)</strong>&nbsp;presenting with first AMI highlights significant differences in the clinical presentation, treatment patterns, and age-related care gaps between young ( 50 years of age) and older (&gt;50 years of age) patients with first AMI. 
  <ul>
   <li>Young patients with first AMI had a high burden of modifiable ASCVD risk factors, and were more prone to be obese, smokers, and have a family history of premature coronary artery disease (CAD).</li>
   <li>This study noted a crucial treatment paradox: Older patients with AMI were less likely to receive potentially lifesaving interventions vs younger patients.</li>
   <li>Young patients had significantly lower odds of any major adverse cardiovascular events (MACE: adjusted odds ratio [aOR] = 0.53; P = 0.006) and had significantly lower odds of cumulative death up to 12-months post-discharge (aOR = 0.34; P &lt;0.001).</li>
  </ul></li>
</ul>

<h2>Why This Matters</h2>
<ul>
 <li>The incidence of AMI in young adults is on the rise, yet the modifiable ASCVD risk factors accounting for the majority of AMI risk&nbsp;may remain undiagnosed or undertreated until the time of first AMI.</li>
 <li>Alarmingly high rates of&nbsp;cardiovascular risk factors were seen in the younger population in the Middle Eastern Gulf region;&nbsp;however, limited information is available regarding the risk profile of young patients with AMI in this region.</li>
</ul>
<h2>Study Design</h2>
<ul>
 <li>This study analyzed a subset of patients enrolled in the&nbsp;Gulf COAST registry&nbsp;(from January 2012 to January 2013): 
  <ul>
   <li>Key inclusion criteria: Individuals with no prior history of clinical ASCVD who presented with acute coronary syndrome and carried the diagnosis of AMI as their admission event</li>
   <li>Key exclusion criteria: Prior percutaneous coronary interventions, coronary artery bypass surgery, prior history of transient ischemic attack or stroke, renal dysfunction requiring dialysis, or patients presenting with concomitant stroke or severe bleeding, chronic obstructive pulmonary disease exacerbation, or pneumonia</li>
   <li>ASCVD risk factors: Modifiable (hypertension, dyslipidemia, diabetes, smoking, obesity and central adiposity) and non-modifiable risk factors (sex or family history of premature CAD) were obtained</li>
   <li>Study outcomes: Associations between age group and in-hospital MACE (re-infarction, heart failure, cardiogenic shock, cardiac arrest, stroke, and in-hospital death) and post-discharge mortality</li>
  </ul></li>
</ul>
<h2>Key Results</h2>
<ul>
 <li>95.5% of matched patients used aspirin with ticagrelor or clopidogrel among the 31,290 propensity-matched pairs 
  <ul>
   <li>Of note, 59% of the young patients had 2 modifiable ASCVD risk factors.</li>
   <li>At the time of AMI, young patients were more likely to present with typical ischemic symptoms, and less signs of heart failure on presentation.</li>
   <li>Treatment patterns (guideline-proven therapies in young vs older patients): -blockers = 83.0% vs 74.4% (P &lt;0.001); clopidogrel = 82.3% vs 76.0% (P = 0.009); and primary reperfusion therapy = 85.6% vs 75.6% (P = 0.003)</li>
   <li>Young patients had significantly lower odds of any MACE (aOR = 0.53 [95% CI: 0.34–0.83]; P = 0.006) vs older patients.</li>
   <li>Young patients had lower likelihood of cumulative death (including in-hospital death) at 12-month post-discharge. 
    <ul>
     <li>In-hospital death: aOR = 0.37 (95% CI: 0.16–0.86; P = 0.021)</li>
     <li>Cumulative death at 12 months: aOR = 0.34 (95% CI: 0.19-0.59; P &lt;0.001)</li>
    </ul></li>
  </ul></li>
</ul>
<h2>Limitations</h2>
<ul>
 <li>This study only included patients presenting to the hospital with suspected acute coronary syndrome.</li>
 <li>The sensitivities in detecting elevated troponin levels may have varied across the different centers (data for the type of troponin assay used in each enrolling center was not collected).</li>
 <li>The success rate of primary reperfusion therapy was not documented.</li>
</ul>

In hospital outcomes in young patients with AMI: Results from Gulf Coast

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