Did Prasugrel and Ticagrelor Offer the Same Benefit in Patients with Acute Coronary Syndromes after Percutaneous Coronary Interventions Compared to Clopidogrel? Insights from Randomized Clinical Trials, Registries and Meta-analysis

2018 ◽  
Vol 24 (4) ◽  
pp. 465-477 ◽  
Author(s):  
Alfredo E. Rodriguez ◽  
Alfredo M. Rodriguez-Granillo ◽  
Sergio D. Ascarrunz ◽  
Francisco Peralta-Bazan ◽  
Mi Y. Cho
Keyword(s):  
Clinical Trials ◽  
Acute Coronary Syndromes ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Indirect Comparison ◽  
Bleeding Risk ◽  
Cardiac Events ◽  
P2y12 Inhibitor ◽  
P2y12 Inhibitors ◽  
Coronary Syndromes

Background: According to ACC/ AHA guidelines, a minimum of 1 year of dual anti- platelet therapy (DAPT) consisting of aspirin and a platelet ADP-receptor antagonist (P2Y12 inhibitor) is recommended for patients presenting acute coronary syndromes (ACS), regardless of which type of revascularization is performed during the acute event. Methods: The purpose of this presentation was to review the present data either from a direct randomized comparison among the three compounds and also large prospective observational registries and meta-analysis were analyzed in detail. With this aim, we performed an extensive large search from PubMed/Medline Journals identifying studies comparing fashion the new P2Y12 inhibitors in patients with ACS including ST elevation myocardial infarction (STEMI) in direct and indirect manner. Results: Pivotal large randomized clinical trials (RCT) in patients with ACS including STEMI, comparing clopidogrel, a first generation P2Y12 inhibitor against the newer prasugrel and ticagrelor showed major efficacy advantages of the latters although both drugs had more bleeding risk than clopidogrel. Direct comparisons of prasugrel and ticagrelor from large RCT are not yet available, however, several observational registries and metaanalysis reported results from an indirect comparison between both compounds. Major findings and limitations of each of these studies were identified, highlighted and discussed. Conclusion: Prasugrel and ticagrelor are both more effective than clopidogrel to prevent adverse cardiac events in patients with ACS. Compared to ticagrelor, prasugrel appears to be more effective in patients with STEMI, although lack of randomized data didn’t allow to draw definitive conclusions.

Is there Sex-related Outcome Difference According to oral P2Y12 Inhibitors in Patients with Acute Coronary Syndromes? A Systematic Review and Meta-Analysis of 107,126 Patients

2019 ◽  
Vol 17 (2) ◽  
pp. 191-203
Author(s):  
Oliver Brown ◽  
Jennifer Rossington ◽  
Gill Louise Buchanan ◽  
Giuseppe Patti ◽  
Angela Hoye
Keyword(s):  
Systematic Review ◽  
Acute Coronary Syndromes ◽  
Meta Analysis ◽  
Indirect Comparison ◽  
Bleeding Risk ◽  
Cardiovascular Death ◽  
P2y12 Inhibitors ◽  
Significant Difference ◽  
Coronary Syndromes ◽  
Randomised Controlled

Background and Objectives: The majority of patients included in trials of anti-platelet therapy are male. This systematic review and meta-analysis aimed to determine whether, in addition to aspirin, P2Y12 blockade is beneficial in both women and men with acute coronary syndromes. </P><P> Methods: Electronic databases were searched and nine eligible randomised controlled studies were identified that had sex-specific clinical outcomes (n=107,126 patients). Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated for a composite of cardiovascular death, myocardial infarction or stroke (MACE), and a safety endpoint of major bleeding for each sex. Indirect comparison analysis was performed to statistically compare ticagrelor against prasugrel. </P><P> Results: Compared to aspirin alone, clopidogrel reduced MACE in men (RR, 0.79; 95% CI, 0.68 to 0.92; p=0.003), but was not statistically significant in women (RR, 0.88; 95% CI, 0.75 to 1.02, p=0.08). Clopidogrel therapy significantly increased bleeding in women but not men. Compared to clopidogrel, prasugrel was beneficial in men (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02) but not statistically significant in women (RR, 0.94; 95% CI, 0.83 to 1.06; p=0.30); ticagrelor reduced MACE in both men (RR, 0.85; 95% CI, 0.77 to 0.94; p=0.001) and women (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02). Indirect comparison demonstrated no significant difference between ticagrelor and prasugrel in either sex. Compared to clopidogrel, ticagrelor and prasugrel increased bleeding risk in both women and men. </P><P> Conclusion: In summary, in comparison to monotherapy with aspirin, P2Y12 inhibitors reduce MACE in women and men. Ticagrelor was shown to be superior to clopidogrel in both sexes. Prasugrel showed a statistically significant benefit only in men; however indirect comparison did not demonstrate superiority of ticagrelor over prasugrel in women.

Optimal P2Y12 inhibition in older adults with acute coronary syndromes: a network meta-analysis of randomized controlled trials

2020 ◽  
Author(s):  
Claudio Montalto ◽  
Nuccia Morici ◽  
Andrea Raffaele Munafò ◽  
Antonio Mangieri ◽  
Alessandro Mandurino-Mirizzi ◽  
...  
Keyword(s):  
Older Adults ◽  
Stent Thrombosis ◽  
Primary Endpoint ◽  
Acute Coronary Syndromes ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Bleeding Risk ◽  
P2y12 Inhibitors ◽  
Fixed Proportion ◽  
Coronary Syndromes

Abstract Aims Dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor on top of aspirin is the cornerstone of therapy after acute coronary syndromes (ACS). Nonetheless, the safest and most efficacious P2Y12 for older patients who are both at high ischaemic and bleeding risk remains uncertain. We aimed to examine the effect of available P2Y12 inhibitors on ischaemic and bleeding endpoints in older adults with ACS. Methods and results Randomized clinical trials that reported separately the results of adults older &gt;70 years for at least the primary endpoint [composite of death, myocardial infarction (MI), and stroke]. Seven studies (14 485 patients-years) were included. Network meta-analysis showed that prasugrel was associated with similar occurrence of the primary endpoint and of a secondary ischaemic endpoint (composite of MI and stroke) and was most likely the best treatment [Surface Under the Cumulative Ranking curve Analysis (SUCRA) 54.5 and 59.8, respectively]. With regards to major bleedings, clopidogrel showed the highest likelihood of event reduction (SUCRA 70.1%), while ticagrelor of stent thrombosis (SUCRA 55.6%). Our meta-regression with a fixed proportion of patients managed invasively of 100% confirmed these trends with increasing SUCRA. Conclusion Among older subjects with ACS, DAPT should be balanced upon ischaemic and bleeding risks as prasugrel is associated with the highest probability of reduction of ischaemic events and clopidogrel of bleedings. Ticagrelor had highest SUCRA for stent thrombosis reduction but seems suboptimal in older adults.

scholarly journals Prasugrel versus ticagrelor in acute coronary syndromes

2021 ◽  
pp. 1-7
Author(s):  
Luiz Tanajura ◽  
José Costa Júnior ◽  
Áurea Chaves ◽  
Marinella Centemero ◽  
Fausto Feres
Keyword(s):  
Clinical Trials ◽  
Acute Coronary Syndromes ◽  
Therapeutic Option ◽  
High Morbidity ◽  
Cardiac Events ◽  
Invasive Treatment ◽  
New Agents ◽  
Advantages And Disadvantages ◽  
Coronary Syndromes ◽  
New Generation

Acute coronary syndromes are common situations in medical practice, with high morbidity and mortality. Consequent to its relevance, its clinical management has always been subject of discussion and controversy. Since the past decade, the dual antiplatelet regimen has been the main therapeutic option used in its passivation, whereas percutaneous interventions have become the most common therapeutic option. Clopidogrel, the drug initially used in combination with aspirin, is effective and safe; however, it has disadvantages that led to the development of a new generation of more efficient antiplatelet drugs, such as prasugrel and ticagrelor. In large comparative clinical trials, these two drugs proved superior to clopidogrel in reducing major combined cardiac events. Hence the main guidelines currently support the two new agents, which are considered first-line drugs. Due to the clear differences between the protocols of clinical trials corroborating their inclusion in clinical practice, it is not possible to make direct comparison without the risk of generating hasty impressions. More recently, a large prospective, randomized clinical trial provided an appropriate head-to-head comparison between prasugrel and ticagrelor in cases of acute coronary disease, in a population submitted to invasive treatment. The study demonstrated a significant advantage of prasugrel. In this review, we discuss the primary details of these more contemporary drugs and the most relevant clinical trials related to them, identifying the advantages and disadvantages of each agent. At the end, we state our view on their current prescription.

Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials

The Lancet ◽  
2002 ◽  
Vol 359 (9302) ◽  
pp. 189-198 ◽  
Author(s):  
Eric Boersma ◽  
Robert A Harrington ◽  
David J Moliterno ◽  
Harvey White ◽  
Pierre Théroux ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Coronary Syndromes ◽  
Meta Analysis ◽  
Randomised Clinical Trials ◽  
Platelet Glycoprotein ◽  
Coronary Syndromes

scholarly journals Factor V Leiden and the Risk of Bleeding in Patients With Acute Coronary Syndromes Treated With Antiplatelet Therapy: Pooled Analysis of 3 Randomized Clinical Trials

2021 ◽  
Author(s):  
Bakhtawar K. Mahmoodi ◽  
Niclas Eriksson ◽  
Stephanie Ross ◽  
Daniel M. F. Claassens ◽  
Folkert W. Asselbergs ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Antiplatelet Therapy ◽  
Lower Risk ◽  
Acute Coronary Syndromes ◽  
Randomized Clinical Trials ◽  
Factor V Leiden ◽  
Minor Bleeding ◽  
Factor V ◽  
Risk Of Bleeding ◽  
Coronary Syndromes

Background Whether factor V Leiden is associated with lower bleeding risk in patients with acute coronary syndromes using (dual) antiplatelet therapy has yet to be investigated. Methods and Results We pooled data from 3 randomized clinical trials, conducted in patients with acute coronary syndromes, with adjudicated bleeding outcomes. Cox regression models were used to obtain overall and cause‐specific hazard ratios (HRs) to account for competing risk of atherothrombotic outcomes (ie, composite of ischemic stroke, myocardial infarction, and cardiovascular death) in each study. Estimates from the individual studies were pooled using fixed effect meta‐analysis. The 3 studies combined included 17 623 patients of whom 969 (5.5%) were either heterozygous or homozygous (n=23) carriers of factor V Leiden. During 1 year of follow‐up, a total of 1289 (7.3%) patients developed major (n=559) or minor bleeding. Factor V Leiden was associated with a lower risk of combined major and minor bleeding (adjusted cause‐specific HR, 0.75; 95% CI, 0.56–1.00; P =0.046; I 2 =0%) but a comparable risk of major bleeding (adjusted cause‐specific HR, 0.93; 95% CI, 0.62–1.39; P =0.73; I 2 =0%). Adjusted pooled cause‐specific HRs for the association of factor V Leiden with atherothrombotic events alone and in combination with bleeding events were 0.75 (95% CI, 0.55–1.02; P =0.06; I 2 =0%) and 0.75 (95% CI, 0.61–0.92; P =0.007; I 2 =0%), respectively. Conclusions Given that the lower risk of bleeding conferred by factor V Leiden was not counterbalanced by a higher risk of atherothrombotic events, these findings warrant future assessment for personalized medicine such as selecting patients for extended or intensive antiplatelet therapy.

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