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1.
J Vasc Nurs ; 42(2): 138-140, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38823974

ABSTRACT

Medical decision-making surrounding high risk surgical procedures requires extensive consideration about the potential risks and benefits to the patient, including implications for concomitant medications and therapies. Managing cardiovascular risk in patients undergoing non-cardiac surgery is essential for safe and effective patient care. In instances where cardiac revascularization is needed prior to surgery, antiplatelet medication is also needed which can complicate future surgical procedures. This case report describes a patient who underwent percutaneous coronary intervention with drug eluting stent placement, who also needed urgent treatment for expanding thoracic abdominal aortic aneurysm (TAAA). Standard practice for endovascular repair of a TAAA includes placement of a lumbar drain to decrease the risk of spinal cord ischemia, however dual antiplatelet therapy is contraindicated. Cangrelor is the only intravenous platelet P2Y12 receptor inhibitor currently available. The use of Cangrelor, a short-acting P2Y12 inhibitor, was successfully utilized as a bridge in the setting of a patient requiring dual antiplatelet therapy (DAPT) and further surgical intervention. This medication may improve outcomes for this subset of patients.


Subject(s)
Adenosine Monophosphate , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Humans , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Male , Drug-Eluting Stents , Aged , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Abdominal/drug therapy , Purinergic P2Y Receptor Antagonists/therapeutic use
2.
J Am Heart Assoc ; 13(9): e034414, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38700032

ABSTRACT

BACKGROUND: Over the past decade, major society guidelines have recommended the use of newer P2Y12 inhibitors over clopidogrel for those undergoing percutaneous coronary intervention for acute coronary syndrome. It is unclear what impact these recommendations had on clinical practice. METHODS AND RESULTS: All percutaneous coronary intervention procedures (n=534 210) for acute coronary syndrome in England and Wales (April 1, 2010, to March 31, 2022) were retrospectively analyzed, stratified by choice of preprocedural P2Y12 inhibitor (clopidogrel, ticagrelor, and prasugrel). Multivariable logistic regression models were used to examine odds ratios of receipt of ticagrelor and prasugrel (versus clopidogrel) over time, and predictors of their receipt. Overall, there was a significant increase in receipt of newer P2Y12 inhibitors from 2010 to 2020 (2022 versus 2010: ticagrelor odds ratio, 8.12 [95% CI, 7.67-8.60]; prasugrel odds ratio, 6.14 [95% CI, 5.53-6.81]), more so in ST-segment-elevation myocardial infarction than non-ST-segment-elevation acute coronary syndrome indication. The most significant increase in odds of receipt of prasugrel was observed between 2020 and 2022 (P<0.001), following a decline/plateau in its use in earlier years (2011-2019). In contrast, the odds of receipt of ticagrelor significantly increased in earlier years (2012-2017, Ptrend<0.001), after which the trend was stable (Ptrend=0.093). CONCLUSIONS: Over a 13-year-period, there has been a significant increase in use of newer P2Y12 inhibitors, although uptake of prasugrel use remained significantly lower than ticagrelor. Earlier society guidelines (pre-2017) were associated with the highest rates of ticagrelor use for non-ST-segment-elevation acute coronary syndrome and ST-segment-elevation myocardial infarction cases while the ISAR-REACT 5 (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome) trial and later society guidelines were associated with higher prasugrel use, mainly for ST-segment-elevation myocardial infarction indication.


Subject(s)
Acute Coronary Syndrome , Clopidogrel , Percutaneous Coronary Intervention , Practice Guidelines as Topic , Prasugrel Hydrochloride , Purinergic P2Y Receptor Antagonists , Ticagrelor , Humans , Acute Coronary Syndrome/drug therapy , Acute Coronary Syndrome/surgery , Acute Coronary Syndrome/therapy , Percutaneous Coronary Intervention/trends , Purinergic P2Y Receptor Antagonists/therapeutic use , Male , Female , Ticagrelor/therapeutic use , Prasugrel Hydrochloride/therapeutic use , Aged , Middle Aged , Retrospective Studies , Wales , Clopidogrel/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Practice Patterns, Physicians'/trends , England , Guideline Adherence/trends , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/surgery , Non-ST Elevated Myocardial Infarction/drug therapy , Non-ST Elevated Myocardial Infarction/surgery , Non-ST Elevated Myocardial Infarction/therapy , Time Factors , Treatment Outcome
4.
Int J Mol Sci ; 25(10)2024 May 17.
Article in English | MEDLINE | ID: mdl-38791515

ABSTRACT

Myocardial necrosis following the successful reperfusion of a coronary artery occluded by thrombus in a patient presenting with ST-elevation myocardial infarction (STEMI) continues to be a serious problem, despite the multiple attempts to attenuate the necrosis with agents that have shown promise in pre-clinical investigations. Possible reasons include confounding clinical risk factors, the delayed application of protective agents, poorly designed pre-clinical investigations, the possible effects of routinely administered agents that might unknowingly already have protected the myocardium or that might have blocked protection, and the biological differences of the myocardium in humans and experimental animals. A better understanding of the pathobiology of myocardial infarction is needed to stem this reperfusion injury. P2Y12 receptor antagonists minimize platelet aggregation and are currently part of the standard treatment to prevent thrombus formation and propagation in STEMI protocols. Serendipitously, these P2Y12 antagonists also dramatically attenuate reperfusion injury in experimental animals and are presumed to provide a similar protection in STEMI patients. However, additional protective agents are needed to further diminish reperfusion injury. It is possible to achieve additive protection if the added intervention protects by a mechanism different from that of P2Y12 antagonists. Inflammation is now recognized to be a critical factor in the complex intracellular response to ischemia and reperfusion that leads to tissue necrosis. Interference with cardiomyocyte inflammasome assembly and activation has shown great promise in attenuating reperfusion injury in pre-clinical animal models. And the blockade of the executioner protease caspase-1, indeed, supplements the protection already seen after the administration of P2Y12 antagonists. Importantly, protective interventions must be applied in the first minutes of reperfusion, if protection is to be achieved. The promise of such a combination of protective strategies provides hope that the successful attenuation of reperfusion injury is attainable.


Subject(s)
Inflammation , Myocardial Reperfusion Injury , NLR Family, Pyrin Domain-Containing 3 Protein , Purinergic P2Y Receptor Antagonists , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Humans , Purinergic P2Y Receptor Antagonists/pharmacology , Purinergic P2Y Receptor Antagonists/therapeutic use , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , Inflammation/drug therapy , Inflammation/pathology , Inflammation/metabolism , Receptors, Purinergic P2Y12/metabolism
5.
J Am Heart Assoc ; 13(11): e031606, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38804216

ABSTRACT

Ticagrelor is a platelet P2Y12 receptor inhibitor approved for use in patients with acute coronary syndromes, coronary artery disease, and low-moderate risk acute ischemic stroke or high-risk transient ischemic attack. Clinical trials have evaluated the efficacy and safety of ticagrelor on ischemic and bleeding outcomes for different indications and with varying treatment approaches. As a result, there is a large body of clinical evidence demonstrating different degrees of net clinical benefit compared with other platelet inhibitor drugs based on indication, patient characteristics, clinical presentation, treatment duration, and other factors. We provide a review of the major trials of ticagrelor in the context of other randomized trials of clopidogrel and prasugrel to organize the volume of available information, elevate corroborating and conflicting data, and identify potential gaps as areas for further exploration of optimal antiplatelet treatment.


Subject(s)
Platelet Aggregation Inhibitors , Purinergic P2Y Receptor Antagonists , Ticagrelor , Humans , Ticagrelor/therapeutic use , Ticagrelor/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Purinergic P2Y Receptor Antagonists/therapeutic use , Purinergic P2Y Receptor Antagonists/adverse effects , Acute Coronary Syndrome/drug therapy , Randomized Controlled Trials as Topic , Treatment Outcome , Coronary Artery Disease/drug therapy , Hemorrhage/chemically induced
8.
Lancet ; 403(10439): 1866-1878, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38599220

ABSTRACT

BACKGROUND: Following percutaneous coronary intervention with stent placement to treat acute coronary syndromes, international clinical guidelines generally recommend dual antiplatelet therapy with aspirin plus a P2Y12 receptor inhibitor for 12 months to prevent myocardial infarction and stent thrombosis. However, data on single antiplatelet therapy with a potent P2Y12 inhibitor earlier than 12 months after percutaneous coronary intervention for patients with an acute coronary syndrome are scarce. The aim of this trial was to assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin, could reduce the incidence of clinically relevant bleeding events without an accompanying increase in major adverse cardiovascular or cerebrovascular events (MACCE). METHODS: In this randomised, placebo-controlled, double-blind clinical trial, patients aged 18 years or older with an acute coronary syndrome who completed the IVUS-ACS study and who had no major ischaemic or bleeding events after 1-month treatment with dual antiplatelet therapy were randomly assigned to receive oral ticagrelor (90 mg twice daily) plus oral aspirin (100 mg once daily) or oral ticagrelor (90 mg twice daily) plus a matching oral placebo, beginning 1 month and ending at 12 months after percutaneous coronary intervention (11 months in total). Recruitment took place at 58 centres in China, Italy, Pakistan, and the UK. Patients were required to remain event-free for 1 month on dual antiplatelet therapy following percutaneous coronary intervention with contemporary drug-eluting stents. Randomisation was done using a web-based system, stratified by acute coronary syndrome type, diabetes, IVUS-ACS randomisation, and site, using dynamic minimisation. The primary superiority endpoint was clinically relevant bleeding (Bleeding Academic Research Consortium [known as BARC] types 2, 3, or 5). The primary non-inferiority endpoint was MACCE (defined as the composite of cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, or clinically driven target vessel revascularisation), with an expected event rate of 6·2% in the ticagrelor plus aspirin group and an absolute non-inferiority margin of 2·5 percentage points between 1 month and 12 months after percutaneous coronary intervention. The two co-primary endpoints were tested sequentially; the primary superiority endpoint had to be met for hypothesis testing of the MACCE outcome to proceed. All principal analyses were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Sept 21, 2019, and Oct 27, 2022, 3400 (97·0%) of the 3505 participants in the IVUS-ACS study were randomly assigned (1700 patients to ticagrelor plus aspirin and 1700 patients to ticagrelor plus placebo). 12-month follow-up was completed by 3399 (>99·9%) patients. Between month 1 and month 12 after percutaneous coronary intervention, clinically relevant bleeding occurred in 35 patients (2·1%) in the ticagrelor plus placebo group and in 78 patients (4·6%) in the ticagrelor plus aspirin group (hazard ratio [HR] 0·45 [95% CI 0·30 to 0·66]; p<0·0001). MACCE occurred in 61 patients (3·6%) in the ticagrelor plus placebo group and in 63 patients (3·7%) in the ticagrelor plus aspirin group (absolute difference -0·1% [95% CI -1·4% to 1·2%]; HR 0·98 [95% CI 0·69 to 1·39]; pnon-inferiority<0·0001, psuperiority=0·89). INTERPRETATION: In patients with an acute coronary syndrome who had percutaneous coronary intervention with contemporary drug-eluting stents and remained event-free for 1 month on dual antiplatelet therapy, treatment with ticagrelor alone between month 1 and month 12 after the intervention resulted in a lower rate of clinically relevant bleeding and a similar rate of MACCE compared with ticagrelor plus aspirin. Along with the results from previous studies, these findings show that most patients in this population can benefit from superior clinical outcomes with aspirin discontinuation and maintenance on ticagrelor monotherapy after 1 month of dual antiplatelet therapy. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and the Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.


Subject(s)
Acute Coronary Syndrome , Aspirin , Drug Therapy, Combination , Hemorrhage , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Ticagrelor , Humans , Ticagrelor/therapeutic use , Aspirin/therapeutic use , Aspirin/administration & dosage , Percutaneous Coronary Intervention/methods , Acute Coronary Syndrome/therapy , Double-Blind Method , Male , Female , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Aged , Hemorrhage/chemically induced , Purinergic P2Y Receptor Antagonists/therapeutic use , Purinergic P2Y Receptor Antagonists/administration & dosage , Dual Anti-Platelet Therapy/methods , Treatment Outcome
9.
Int J Cardiol ; 406: 132073, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38643804

ABSTRACT

BACKGROUND: Platelet P2Y12 antagonist ticagrelor reduces cardiovascular mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release proatherogenic and proinflammatory microRNAs, including miR-125a, miR-125b and miR-223, we hypothesized that the expression of these miRNAs is lower on ticagrelor, compared to clopidogrel. OBJECTIVES: We compared miR-125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel. METHODS: After percutaneous coronary intervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel. Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 months of treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determine platelet reactivity in response to P2Y12 inhibitors. RESULTS: Expression of miR-125b was higher in patients with AMI 72 h and 6 months, compared to healthy volunteers (p = 0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor. CONCLUSIONS: Ticagrelor treatment leads to lower plasma expression of miR-125b after AMI, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.


Subject(s)
Clopidogrel , Down-Regulation , MicroRNAs , Ticagrelor , Humans , Clopidogrel/pharmacology , Clopidogrel/therapeutic use , Ticagrelor/pharmacology , Ticagrelor/therapeutic use , MicroRNAs/blood , MicroRNAs/biosynthesis , MicroRNAs/genetics , Male , Female , Middle Aged , Aged , Down-Regulation/drug effects , Purinergic P2Y Receptor Antagonists/pharmacology , Purinergic P2Y Receptor Antagonists/therapeutic use , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Myocardial Infarction/drug therapy , Myocardial Infarction/blood , Myocardial Infarction/genetics , Percutaneous Coronary Intervention , Adenosine/analogs & derivatives , Adenosine/therapeutic use , Ticlopidine/analogs & derivatives , Ticlopidine/pharmacology , Ticlopidine/therapeutic use
10.
Circ J ; 88(6): 876-884, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38569870

ABSTRACT

BACKGROUND: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain.Methods and Results: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. CONCLUSIONS: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.


Subject(s)
Absorbable Implants , Clopidogrel , Drug-Eluting Stents , Dual Anti-Platelet Therapy , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Purinergic P2Y Receptor Antagonists , Registries , Humans , Male , Aged , Female , Percutaneous Coronary Intervention/adverse effects , Middle Aged , Purinergic P2Y Receptor Antagonists/administration & dosage , Purinergic P2Y Receptor Antagonists/adverse effects , Purinergic P2Y Receptor Antagonists/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Clopidogrel/therapeutic use , Clopidogrel/adverse effects , Clopidogrel/administration & dosage , Prospective Studies , Japan , Dual Anti-Platelet Therapy/methods , Hemorrhage/chemically induced , Prasugrel Hydrochloride/administration & dosage , Prasugrel Hydrochloride/therapeutic use , Prasugrel Hydrochloride/adverse effects , Polymers , Treatment Outcome
11.
Turk Kardiyol Dern Ars ; 52(2): 116-124, 2024 03.
Article in English | MEDLINE | ID: mdl-38465531

ABSTRACT

OBJECTIVE: Deciding on the optimal duration of dual antiplatelet treatment (DAPT) remains a complex decision. This survey aims to explore the preferences for antiplatelet therapy and the daily routine regarding DAPT duration in coronary artery disease among a group of cardiologists in Türkiye. METHOD: Using an online questionnaire with 38 questions, the preferences of 314 cardiologists were collected. Qualitative descriptive characteristics of the answers received from the participants were examined. RESULTS: Participating cardiologists mostly worked in training and research hospitals (51.59%) and university hospitals (21.66%). Participants primarily favored ticagrelor in patients undergoing PCI with a diagnosis of STEMI and NSTE-ACS (69.75% and 55.73% respectively). Clopidogrel was the most preferred P2Y12 treatment in patients with chronic coronary syndrome (CCS) after PCI (94.90%). Pre-treatment with a loading dose of a P2Y12 receptor inhibitor was administered to 57.01% of patients with NSTE-ACS, irrespective of the planned treatment strategy. In NSTE-ACS patients with low bleeding risk treated with PCI, 83.12% of participants recommended DAPT for 12 months and 14.65% for >12 months. In high-bleeding-risk NSTE-ACS patients treated with PCI, DAPT durations of six months (74.52%), three months (19.75%), and one month (5.73%) were chosen. Among CCS patients treated with PCI without an increased risk of bleeding, 12 months of DAPT was preferred by 68.15% of participants. Most participants (70.70%) were switching to a more potent P2Y12 receptor inhibitor therapy in emergency department clopidogrel-loaded patients with ACS. CONCLUSION: The aim of this survey to capture a snapshot of the preferences of a group of cardiologists in Türkiye regarding DAPT treatment and duration. The responses were both in accordance and in conflict with the current guidelines.


Subject(s)
Acute Coronary Syndrome , Cardiologists , Percutaneous Coronary Intervention , Humans , Platelet Aggregation Inhibitors , Clopidogrel/therapeutic use , Purinergic P2Y Receptor Antagonists/therapeutic use , Purinergic P2Y Receptor Antagonists/adverse effects , Percutaneous Coronary Intervention/adverse effects , Turkey , Drug Therapy, Combination , Acute Coronary Syndrome/drug therapy , Hemorrhage/chemically induced , Treatment Outcome
12.
J Thromb Thrombolysis ; 57(4): 537-546, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38555552

ABSTRACT

Low-dose prasugrel demonstrated a similar effectiveness profile to clopidogrel in East Asian ACS patients, but its comparison with another new-generation potent P2Y12 inhibitor, ticagrelor, remains unclear. To compare the effectiveness and safety of low-dose prasugrel against those of standard-dose ticagrelor in East Asian patients with ACS. This retrospective cohort study used Taiwan's National Health and Welfare Database. This study included ACS patients who underwent percutaneous coronary intervention and, at discharge between January 1, 2018 and December 31, 2020, were prescribed with low-dose prasugrel plus aspirin or standard-dose ticagrelor plus aspirin. Stabilized inverse probability of treatment weighting was used to balance the covariates across these two groups. The primary effectiveness outcome was a composite of acute myocardial infarction, ischemic stroke, and cardiovascular death; the secondary effectiveness outcome was each of the individual components of the primary outcome, transient ischemic attack, and repeat revascularization. The primary safety outcome was a composite of intracranial hemorrhage and gastrointestinal bleeding, and the two secondary safety outcomes were intracranial hemorrhage and gastrointestinal bleeding. A total of 24,807 patients were included in this study. Among them, 1,493 were low-dose prasugrel users and 23,314 were standard-dose ticagrelor users. No significant differences were found in primary effectiveness [HR: 0.97 (0.74-1.28)] or primary safety outcomes [HR: 1.22 (0.73-2.01)] between the two study groups. For East Asian patients with ACS, low-dose prasugrel provides comparable effectiveness without increasing bleeding risk compared to standard-dose ticagrelor. Low-dose prasugrel may be an appropriate alternative for East Asian populations.


Subject(s)
Acute Coronary Syndrome , Prasugrel Hydrochloride , Ticagrelor , Humans , Acute Coronary Syndrome/drug therapy , Aspirin/therapeutic use , East Asian People , Gastrointestinal Hemorrhage/etiology , Intracranial Hemorrhages/etiology , Platelet Aggregation Inhibitors/therapeutic use , Prasugrel Hydrochloride/therapeutic use , Purinergic P2Y Receptor Antagonists/therapeutic use , Retrospective Studies , Ticagrelor/therapeutic use , Treatment Outcome
14.
JAMA Cardiol ; 9(5): 437-448, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38506796

ABSTRACT

Importance: Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor. Objective: To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI. Data Sources: MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction. Study Selection: Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI. Data Extraction and Synthesis: Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data. Main Outcomes and Measures: The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding. Results: Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04). Conclusions and Relevance: This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.


Subject(s)
Clopidogrel , Dual Anti-Platelet Therapy , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Ticagrelor , Ticagrelor/therapeutic use , Percutaneous Coronary Intervention/methods , Humans , Clopidogrel/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , Dual Anti-Platelet Therapy/methods , Purinergic P2Y Receptor Antagonists/therapeutic use , Hemorrhage/chemically induced
15.
Eur Heart J Cardiovasc Pharmacother ; 10(3): 201-209, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38453426

ABSTRACT

AIMS: Guidelines recommend extended dual pathway inhibition (DPI) with aspirin and rivaroxaban in patients with chronic coronary syndrome (CCS) at high ischaemic risk. The CHADS-P2A2RC score improves risk prediction and enables antithrombotic treatment allocation in these patients. This study evaluated the net clinical benefit of DPI treatment according to baseline risk as classified by the CHADS-P2A2RC score in patients with CCS included in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial. METHODS AND RESULTS: COMPASS patients with CCS (n = 14 670), randomized to aspirin alone or DPI, were stratified according to cardiovascular risk using the CHADS-P2A2RC score. Endpoints were major adverse cardiovascular events (MACE), all-cause death, fatal/critical organ bleeding, and composite adverse events (MACE and bleeding). Net clinical benefit was the 30-month risk difference of MACE and bleeding. Thirty-month incidences of MACE [7.9% vs. 3.9%, hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.83-2.18] and fatal/critical organ bleeding (1.2% vs. 0.8%, HR 1.49, 95% CI 1.06-1.92) were higher in high-risk (CHADS-P2A2RC ≥ 4) than in low/moderate-risk (CHADS-P2A2RC < 4) patients. DPI reduced MACE (low/moderate risk: HR 0.62, 95% CI 0.47-0.82; high risk: HR 0.82, 95% CI 0.68-0.99, P for interaction 0.09) and all-cause death (low/moderate risk: HR 0.65, 95% CI 0.46-0.91; high risk: HR 0.81, 95% CI 0.65-1.00, P for interaction 0.29), without substantially increasing fatal/critical organ bleeding (low/moderate risk: HR 1.35, 95% CI 0.72-2.53; high risk: HR 1.18, 95% CI 0.73-1.90, P for interaction 0.73). DPI provided net clinical benefit of similar magnitude in low/moderate-risk (-1.81%, 95% CI -3.00 to -0.62) and high-risk (-1.96%, 95% CI -3.60 to -0.33) CCS patients. CONCLUSION: As classified by the CHADS-P2A2RC score, low/moderate- and high-risk patients with CCS derived similar net clinical benefit and reduction in all-cause death from DPI treatment.


Subject(s)
Aspirin , Factor Xa Inhibitors , Hemorrhage , Platelet Aggregation Inhibitors , Rivaroxaban , Humans , Male , Female , Aged , Risk Assessment , Hemorrhage/chemically induced , Treatment Outcome , Middle Aged , Time Factors , Aspirin/adverse effects , Aspirin/administration & dosage , Aspirin/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/therapeutic use , Rivaroxaban/adverse effects , Rivaroxaban/administration & dosage , Chronic Disease , Purinergic P2Y Receptor Antagonists/adverse effects , Purinergic P2Y Receptor Antagonists/administration & dosage , Purinergic P2Y Receptor Antagonists/therapeutic use , Dual Anti-Platelet Therapy/adverse effects , Heart Disease Risk Factors
16.
Eur J Clin Invest ; 54(6): e14193, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38481088

ABSTRACT

BACKGROUND: Limited data are available on patients with chronic lung disease (CLD) presenting with acute myocardial infarction (AMI). We aimed to analyse baseline characteristics, treatment and outcome of those patients enrolled in the Swiss nationwide prospective AMIS Plus registry. METHODS: All AMI patients enrolled between January 2002 and December 2021 with data on CLD, as defined in the Charlson Comorbidity Index, were included. The primary endpoints were in-hospital mortality and major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, reinfarction and cerebrovascular events. Baseline characteristics, in-hospital treatments and outcomes were analysed using descriptive statistics and logistic regression. RESULTS: Among 53,680 AMI patients enrolled during this time, 5.8% had CLD. Compared with patients without CLD, CLD patients presented more frequently with non-ST-elevation myocardial infarction (MI) and type 2 MI (12.8% vs. 6.5%, p < 0.001). With respect to treatment, CLD patients were less likely to receive P2Y12 inhibitors (p < 0.001) and less likely to undergo percutaneous coronary interventions (68.7% vs. 82.5%; p < 0.001). In-hospital mortality declined in AMI patients with CLD over time (from 12% in 2002 to 7.3% in 2021). Multivariable regression analysis showed that CLD was an independent predictor for MACCE (adjusted OR was 1.28 [95% CI 1.07-1.52], p = 0.006). CONCLUSION: Patients with CLD and AMI were less likely to receive evidence-based pharmacologic treatments, coronary revascularization and had a higher incidence of MACCE during their hospital stay compared to those without CLD. Over 20 years, in-hospital mortality was significantly reduced in AMI patients, especially in those with CLD.


Subject(s)
Hospital Mortality , Myocardial Infarction , Percutaneous Coronary Intervention , Registries , Humans , Female , Male , Aged , Myocardial Infarction/epidemiology , Myocardial Infarction/therapy , Middle Aged , Percutaneous Coronary Intervention/statistics & numerical data , Chronic Disease , Switzerland/epidemiology , Non-ST Elevated Myocardial Infarction/therapy , Non-ST Elevated Myocardial Infarction/epidemiology , Non-ST Elevated Myocardial Infarction/mortality , Purinergic P2Y Receptor Antagonists/therapeutic use , Aged, 80 and over , Lung Diseases/epidemiology , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/therapy , Recurrence , Treatment Outcome , Cause of Death
17.
Indian Heart J ; 76(2): 133-135, 2024.
Article in English | MEDLINE | ID: mdl-38485052

ABSTRACT

Evidence on comparative effectiveness and safety of prasugrel and ticagrelor post-percutaneous transluminal coronary angioplasty is scarce in Indian population. In a 1:1 propensity score-matched cohort with 71 individuals in each group, the incidence of a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization was not significantly different in prasugrel and ticagrelor group (7.04% vs 9.86%; absolute difference, 2.8%; HR, 0.65; 95% CI, 0.21-2.1; p = 0.49). There was no significant difference in bleeding (5.63% vs 9.86%; absolute difference, -4.20%; 95% CI, -13.0%-4.5%) and dyspnea (7.04% vs 12.7%; absolute difference, -5.60%; 95% CI, -15.4%-4.1%).


Subject(s)
Acute Coronary Syndrome , Prasugrel Hydrochloride , Propensity Score , Ticagrelor , Humans , Prasugrel Hydrochloride/therapeutic use , Ticagrelor/therapeutic use , Acute Coronary Syndrome/therapy , Male , Female , Middle Aged , Treatment Outcome , Retrospective Studies , Platelet Aggregation Inhibitors/therapeutic use , Follow-Up Studies , Percutaneous Coronary Intervention/methods , India/epidemiology , Purinergic P2Y Receptor Antagonists/therapeutic use , Purinergic P2Y Receptor Antagonists/adverse effects , Purinergic P2Y Receptor Antagonists/administration & dosage , Incidence , Angioplasty, Balloon, Coronary/methods
19.
Arch Gerontol Geriatr ; 122: 105370, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38367524

ABSTRACT

AIM: To evaluate the association between frailty and initiating, continuing, or discontinuing secondary prevention medications following myocardial infarction (MI). METHODS: We conducted a cohort study using linked health data, including all adults aged ≥65 years who discharged from hospital following MI from January 2013 to April 2018 in Victoria, Australia (N = 29,771). The Hospital Frailty Risk Score (HFRS) was used to assess frailty. Logistic regression was used to investigate associations of frailty with initiation, continuation, and discontinuation of secondary prevention medications (P2Y12 inhibitor antiplatelets, beta-blockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and lipid-lowering therapies) in the 90 days from discharge post-MI, by HFRS, adjusted for age, sex, and Charlson Comorbidity Index. RESULTS: Increasing frailty was associated with lower probability of initiating and continuing P2Y12 inhibitors, RAAS inhibitors, and lipid-lowering therapies, but not beta-blockers. At at an HFRS of 0, the predicted probabiliy of having all four medications initiated or continued was 0.59 (95 %CI 0.57-0.62) for STEMI and 0.35 (0.34-0.36) for non-STEMI, compared to 0.38 (0.33-0.42) and 0.16 (0.14-0.18) at an HFRS of 15. Increasing frailty was associated with higher probability of discontinuing these medications post-MI. The predicted probability of discontinuing at least one secondary prevention medication post-MI at an HFRS of 0 was 0.10 (0.08-0.11) for STEMI and 0.14 (0.13-0.15) for non-STEMI, compared to 0.27 (0.22-0.32) and 0.34 (0.32-0.36) at an HFRS of 15. CONCLUSION: People with higher levels of frailty were managed more conservatively following MI than people with lower levels of frailty. Whether this conservative treatment is justified warrants further study.


Subject(s)
Frailty , Myocardial Infarction , Secondary Prevention , Humans , Aged , Male , Female , Secondary Prevention/methods , Myocardial Infarction/prevention & control , Myocardial Infarction/epidemiology , Aged, 80 and over , Frailty/complications , Cohort Studies , Adrenergic beta-Antagonists/therapeutic use , Victoria/epidemiology , Platelet Aggregation Inhibitors/therapeutic use , Hypolipidemic Agents/therapeutic use , Frail Elderly/statistics & numerical data , Purinergic P2Y Receptor Antagonists/therapeutic use
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