ABSTRACT
INTRODUCTION: Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, improves cardiovascular outcomes in heart failure patients, but data regarding the efficacy of empagliflozin in the setting of acute myocardial infarction (AMI) is still unclear. The current study aimed to evaluate whether treatment with empagliflozin before primary percutaneous coronary intervention (PCI) improves parameters associated with patients' outcomes. METHODS: We randomly assigned 101 non-diabetic and non-heart failure patients with ST-elevation myocardial infarction (STEMI) who underwent primary PCI to receive either empagliflozin (10 mg before PCI and once daily for 40 days) or placebo, in addition to the standard treatment. The primary outcomes were changes in left ventricular ejection fraction (LVEF) 40 days after PCI, changes in cardiac troponin I (cTnI) and estimates of its area under the curve (AUC) and the peak level, and resolution of ST-segment in > 50% of leads 90 min after PCI. RESULTS: No significant difference was observed in terms of the occurrence of ST-segment resolution > 50% (46.0% versus 45.0%; p = 0.92) and the mean level of cTnI at each time point between the two groups. The estimated mean [standard deviation (SD)] AUC of cTnI was 955.0 (595.7) ng h/ml in the intervention and 999.7 (474.7) ng h/ml in the control groups (p = 0.85) without any significant difference in peak cTnI level. The mean (SD) LVEF 40 days after primary PCI was significantly higher in empagliflozin-treated patients than the placebo group [43.2% (5.8%) versus 39.2% (6.7%); p = 0.002]. CONCLUSION: In this study, no significant differences were observed across the groups in terms of cTnI levels and ST-segment resolution in patients with STEMI undergoing primary PCI. However, it shed light on the potential benefits of empagliflozin in improving LVEF following STEMI. REGISTRATION: Iranian Registry of Clinical Trials Platform ( https://irct.behdasht.gov.ir/ ) identifier number IRCT20111206008307N42.
Subject(s)
Benzhydryl Compounds , Glucosides , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Sodium-Glucose Transporter 2 Inhibitors , Humans , Glucosides/therapeutic use , Glucosides/administration & dosage , Benzhydryl Compounds/therapeutic use , Benzhydryl Compounds/administration & dosage , Percutaneous Coronary Intervention/methods , Male , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/surgery , Female , Middle Aged , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/administration & dosage , Aged , Stroke Volume/drug effects , Ventricular Function, Left/drug effects , Double-Blind Method , Treatment Outcome , Troponin I/bloodABSTRACT
While the efficacy of GpIIb-IIIa-inhibitors during primary PCI (pPCI) for ST-elevated myocardial infarction (STEMI) has previously been demonstrated, its ongoing role and safety in combination with newer P2Y12-inhibitors is unclear. We therefore sought to compare outcomes between two centers with divergent approaches to the use of GpIIbIIIa antagonists in pPCI. We performed a retrospective chart review of all-comer STEMI patients treated with pPCI at two high-volume Montreal academic tertiary care centers. One center tended to use GpIIb-IIIa-inhibitors up-front in a large proportion of patients (liberal strategy) and the other preferring a bail-out approach (conservative strategy). Baseline patient characteristics and procedural data were compared between the two groups. The main efficacy outcome was rate of no-reflow/slow-reflow and the main safety outcome was BARC ≥ 2 bleeding events. A total of 459 patients were included, of whom 167 (36.5%) were exposed to a GpIIb-IIIa-antagonist. There was a significant overall difference in use of GpIIb-IIIa-antagonist between the two centers (60.5% vs. 16.1%, p < 0.01). Rate of no-reflow/slow-reflow was similar between groups (2.6% vs. 1.4%, p = 0.22). In-hospital rates of unplanned revascularization, stroke and death were also not different between groups. Use of a liberal GpIIb--IIIa-antagonist strategy was however associated with a higher risk of bleeding (OR 3.16, 95% CI 1.57-6.37, p < 0.01), which persisted after adjustment for covariables (adjusted OR 2.85, 95% CI 1.40-5.81, p < 0.01). In this contemporary retrospective cohort, a conservative, bail-out only GpIIb--IIIa-antagonist strategy was associated with a lower incidence of clinically relevant bleeding without any signal for an increase in no-reflow/slow-reflow or ischemic clinical events.
Subject(s)
Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , Platelet Glycoprotein GPIIb-IIIa Complex , ST Elevation Myocardial Infarction , Humans , Male , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Female , Middle Aged , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/therapy , Aged , Retrospective Studies , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Treatment Outcome , HemorrhageABSTRACT
Studies assessing the treatment of refractory no-reflow in patients with ST-elevation myocardial infarction (STEMI) are limited to clinical cases and pilot studies. This study aimed to evaluate the efficacy and safety of intracoronary adrenaline administration in such patients. Ninety consecutive patients with refractory coronary no-reflow during percutaneous coronary intervention (PCI) were prospectively included after the initial failure of conventional treatment. They were randomized into 2 groups: 45 patients in Group 1 received adrenaline, and 45 patients in Group 2 (control) received conventional treatments alone. After intracoronary drug administration, the adrenaline group demonstrated significantly higher rates of coronary flow restoration in the infarct-related artery to the level of thrombolysis in myocardial infarction grade 3 (56% vs 29% [p = 0.01]) and resolution of STEMI >50% after PCI (78% vs 36% [p <0.001]). Additionally, the adrenaline group showed a lower indexed microvascular obstruction (MVO) volume compared with the control group (0.9 [0.3; 3.1] % vs 1.9 [0.6; 7.9] % [p = 0.048]). A significant improvement in ejection fraction (EF) was observed in the adrenaline group (p = 0.025). Intracoronary adrenaline administration during PCI in patients with STEMI with refractory no-reflow is more effective compared with conventional treatments. This approach improves coronary flow in the infarct-related artery, facilitates a faster resolution of STEMI, enhances EF, and reduces MVO volume. Intracoronary adrenaline administration demonstrates a comparable safety profile to conventional treatment strategies in terms of life-threatening arrhythmias occurrence. The study suggests that intracoronary adrenaline administration during PCI could be an effective treatment strategy for patients with STEMI with refractory no-reflow.
Subject(s)
Coronary Angiography , Coronary Circulation , Epinephrine , No-Reflow Phenomenon , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Male , Female , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/physiopathology , Epinephrine/administration & dosage , Middle Aged , No-Reflow Phenomenon/etiology , Treatment Outcome , Prospective Studies , Coronary Circulation/drug effects , Coronary Circulation/physiology , Coronary Vessels , Aged , Injections, Intra-ArterialABSTRACT
Tongxinluo, a traditional Chinese medicine compound, has shown promise in improving outcomes for patients with ST-segment elevation myocardial infarction (STEMI). This randomized, double-blind, placebo-controlled trial investigated the efficacy of Tongxinluo in reducing major adverse cardiac and cerebrovascular events (MACCEs) in STEMI patients. The study enrolled 3777 patients from 124 hospitals in China, all of whom received standard STEMI treatments in addition to either Tongxinluo or placebo for 12 months. The primary endpoint was the occurrence of MACCEs at 30 days, with secondary endpoints including individual components of MACCEs, severe STEMI complications, major bleeding, and all-cause mortality at 1 yr. Results showed that Tongxinluo significantly reduced the 30-day MACCE rate compared to placebo (3.4 % vs 5.2 %), and this benefit persisted at 1 year (5.3 % vs 8.3 %). Cardiac death and myocardial reinfarction rates were also significantly lower in the Tongxinluo group. These findings underscore the importance of integrating traditional Chinese medicine with conventional Western medical treatments, providing significant evidence to support the development of evidence-based practices in traditional Chinese medicine. This study represents a pivotal advancement in the field of TCM, demonstrating its potential to contribute meaningfully to modern clinical practice and highlighting the necessity for further high-quality research in this area.
Subject(s)
Drugs, Chinese Herbal , ST Elevation Myocardial Infarction , Humans , Drugs, Chinese Herbal/therapeutic use , ST Elevation Myocardial Infarction/drug therapy , Treatment Outcome , Randomized Controlled Trials as Topic , Medicine, Chinese Traditional/methods , Double-Blind Method , Myocardial Infarction/drug therapy , China/epidemiologyABSTRACT
BACKGROUND: no-reflow can complicate up to 25% of pPCI and is associated with significant morbidity and mortality. We aimed to compare the outcomes of intracoronary epinephrine and verapamil with intracoronary adenosine in the treatment of no-reflow after primary percutaneous coronary intervention (pPCI). METHODS: 108 STEMI patients had no-reflow during pPCI were assigned into four groups. Group 1, in which epinephrine and verapamil were injected through a well-cannulated guiding catheter. Group 2, in which same drugs were injected in the distal coronary bed through a microcatheter or perfusion catheter. Group 3, in which adenosine was injected through a guiding catheter. Group 4, in which adenosine was injected in distal coronary bed. Primary end point was the achievement of TIMI III flow and MBG II or III. Secondary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during hospital stay. RESULTS: The study groups did not differ in their baseline characteristics. Primary end point was achieved in 15 (27.8%) patients in the guide-delivery arm compared with 34 (63%) patients in the local-delivery arm, p < 0.01. However, the primary end point did not differ between the epinephrine/verapamil group and the adenosine group (27 (50%) vs 22 (40.7%), p = 0.334). The secondary end points were similar between the study groups. CONCLUSION: Local delivery of epinephrine, verapamil and adenosine in the distal coronary bed is more effective in achieving TIMI III flow with MBG II or III compared with their guide-delivery in patients who suffered no-reflow during pPCI. There was no difference between epinephrine/verapamil Vs. adenosine.
Subject(s)
Adenosine , Epinephrine , No-Reflow Phenomenon , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Verapamil , Humans , Verapamil/administration & dosage , Male , Female , Adenosine/administration & dosage , Epinephrine/administration & dosage , Middle Aged , Percutaneous Coronary Intervention/methods , No-Reflow Phenomenon/etiology , No-Reflow Phenomenon/drug therapy , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/surgery , Aged , Vasodilator Agents/administration & dosage , Treatment Outcome , Prospective StudiesSubject(s)
Interleukin 1 Receptor Antagonist Protein , ST Elevation Myocardial Infarction , Humans , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Interleukin 1 Receptor Antagonist Protein/administration & dosage , ST Elevation Myocardial Infarction/drug therapy , Male , Female , Middle Aged , Aged , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/administration & dosageABSTRACT
BACKGROUND: The purpose of this study was to investigate a therapeutic approach targeting the inflammatory response and consequent remodeling from ischemic myocardial injury. METHODS AND RESULTS: Coronary thrombus aspirates were collected from patients at the time of ST-segment-elevation myocardial infarction and subjected to array-based proteome analysis. Clinically indistinguishable at myocardial infarction (MI), patients were stratified into vulnerable and resilient on the basis of 1-year left ventricular ejection fraction and death. Network analysis from coronary aspirates revealed prioritization of tumor necrosis factor-α signaling in patients with worse clinical outcomes. Infliximab, a tumor necrosis factor-α inhibitor, was infused intravenously at reperfusion in a porcine MI model to assess whether infliximab-mediated immune modulation impacts post-MI injury. At 3 days after MI (n=7), infliximab infusion increased proregenerative M2 macrophages in the myocardial border zone as quantified by immunofluorescence (24.1%±23.3% in infliximab versus 9.29%±8.7% in sham; P<0.01). Concomitantly, immunoassays of coronary sinus samples quantified lower troponin I levels (41.72±7.34 pg/mL versus 58.11±10.75 pg/mL; P<0.05) and secreted protein analysis revealed upregulation of injury-modifying interleukin-2, -4, -10, -12, and -18 cytokines in the infliximab-treated cohort. At 4 weeks (n=12), infliximab treatment resulted in significant protective influence, improving left ventricular ejection fraction (53.9%±5.4% versus 36.2%±5.3%; P<0.001) and reducing scar size (8.31%±10.9% versus 17.41%±12.5%; P<0.05). CONCLUSIONS: Profiling of coronary thrombus aspirates in patients with ST-segment-elevation MI revealed highest association for tumor necrosis factor-α in injury risk. Infliximab-mediated immune modulation offers an actionable pathway to alter MI-induced inflammatory response, preserving contractility and limiting adverse structural remodeling.
Subject(s)
Disease Models, Animal , Infliximab , Ventricular Remodeling , Infliximab/therapeutic use , Infliximab/pharmacology , Animals , Humans , Male , Middle Aged , Ventricular Remodeling/drug effects , Female , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/immunology , Ventricular Function, Left/drug effects , Swine , Aged , Tumor Necrosis Factor-alpha/metabolism , Stroke Volume/drug effects , Coronary Thrombosis/prevention & control , Coronary Thrombosis/drug therapy , Myocardium/pathology , Myocardium/metabolism , Myocardium/immunology , Troponin I/blood , Troponin I/metabolism , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolismSubject(s)
Platelet Aggregation Inhibitors , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/therapy , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Administration, IntravenousABSTRACT
BACKGROUND: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. METHODS: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. RESULTS: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. CONCLUSIONS: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.
Subject(s)
Adenosine Monophosphate , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Male , Female , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/diagnostic imaging , Middle Aged , Double-Blind Method , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adenosine Monophosphate/administration & dosage , Aged , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Treatment Outcome , Singapore , Ticagrelor/therapeutic use , Ticagrelor/administration & dosageABSTRACT
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 OutcomeABSTRACT
The early unfractionated heparin (UFH) treatment in patients with ST-elevation myocardial infarction (STEMI) is a single-center, open-label, randomized controlled trial. The study population are patients with STEMI that undergo primary percutaneous coronary intervention (PPCI). The trial was designed to investigate whether early administration of unfractionated heparin immediately after diagnosis of STEMI is beneficial in terms of patency of infarct-related coronary artery (IRA) when compared to established UFH administration at the time of coronary intervention. The patients will be randomized in 1:1 fashion in one of the two groups. The primary efficacy endpoint of the study is Thrombolysis in myocardial infarction (TIMI) flow grades 2 and 3 on diagnostic coronary angiography. Secondary outcome measures are: TIMI flow after PPCI, progression to cardiogenic shock, 30-day mortality, ST-segment resolution, highest Troponin I and Troponin I values at 24 hours. The safety outcome is bleeding complications. The study of early heparin administration in patients with STEMI will address whether pretreatment with UFH can increase the rate of spontaneous reperfusion of infarct-related coronary artery.
Subject(s)
Heparin , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Heparin/administration & dosage , Heparin/therapeutic use , Humans , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/diagnostic imaging , Male , Treatment Outcome , Female , Anticoagulants/therapeutic use , Anticoagulants/administration & dosage , Coronary Angiography , Middle Aged , Adult , AgedABSTRACT
The use of intravenous antiplatelet therapy during primary percutaneous coronary intervention (PPCI) is not fully standardized. The aim is to evaluate the effectiveness and safety of periprocedural intravenous administration of cangrelor or tirofiban in a contemporary ST-segment elevation myocardial infarction (STEMI) population undergoing PPCI. This was a multicenter prospective cohort study including consecutive STEMI patients who received cangrelor or tirofiban during PPCI at seven Italian centers. The primary effectiveness measure was the angiographic evidence of thrombolysis in myocardial infarction (TIMI) flow < 3 after PPCI. The primary safety outcome was the in-hospital occurrence of BARC (Bleeding Academic Research Consortium) 2-5 bleedings. The study included 627 patients (median age 63 years, 79% males): 312 received cangrelor, 315 tirofiban. The percentage of history of bleeding, pulmonary edema and cardiogenic shock at admission was comparable between groups. Patients receiving cangrelor had lower ischemia time compared to tirofiban. TIMI flow before PPCI and TIMI thrombus grade were comparable between groups. At propensity score-weighted regression analysis, the risk of TIMI flow < 3 was significantly lower in patients treated with cangrelor compared to tirofiban (adjusted OR: 0.40; 95% CI: 0.30-0.53). The risk of BARC 2-5 bleeding was comparable between groups (adjusted OR:1.35; 95% CI: 0.92-1.98). These results were consistent across multiple prespecified subgroups, including subjects stratified for different total ischemia time, with no statistical interaction. In this real-world multicenter STEMI population, the use of cangrelor was associated with improved myocardial perfusion assessed by coronary angiography after PPCI without increasing clinically-relevant bleedings compared to tirofiban.
Subject(s)
Adenosine Monophosphate , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors , ST Elevation Myocardial Infarction , Tirofiban , Aged , Female , Humans , Male , Middle Aged , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/therapeutic use , Adenosine Monophosphate/adverse effects , Administration, Intravenous , Hemorrhage/chemically induced , Italy , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Prospective Studies , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/drug therapy , Tirofiban/administration & dosage , Tirofiban/therapeutic use , Treatment OutcomeABSTRACT
AIM: The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI. METHODS: Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72-0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57-0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66-0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72-0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13-2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24-0.65; P = 0.0003). CONCLUSION: Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI.
Subject(s)
Antithrombins , Heparin , Hirudins , Peptide Fragments , Percutaneous Coronary Intervention , Platelet Glycoprotein GPIIb-IIIa Complex , Recombinant Proteins , ST Elevation Myocardial Infarction , Humans , Hirudins/adverse effects , Hirudins/administration & dosage , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/therapy , Peptide Fragments/therapeutic use , Peptide Fragments/adverse effects , Percutaneous Coronary Intervention/methods , Percutaneous Coronary Intervention/adverse effects , Recombinant Proteins/therapeutic use , Recombinant Proteins/adverse effects , Recombinant Proteins/administration & dosage , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Heparin/adverse effects , Heparin/therapeutic use , Heparin/administration & dosage , Antithrombins/therapeutic use , Antithrombins/adverse effects , Hemorrhage/chemically induced , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Secreted glycoproteins of the Dickkopf (DKK) family modify Wnt signaling and may influence plaque destabilization but their modulation by statins in MI patients is not known. METHODS: We measured plasma DKK-1 and DKK-3 in patients with acute ST-segment elevation MI (STEMI) before percutaneous coronary intervention (PCI) and after 2 and 7 days and 2 months in patients receiving short-term high-dose (40 mg rosuvastatin, given before PCI; n = 25) and moderate dose (20 mg simvastatin, given the day after PCI; n = 34). In vitro modulation of DKK-1 in human umbilical vein endothelial cells (HUVECs) by statins were assessed. RESULTS: (i) Patients receiving high dose rosuvastatin had a marked decline in DKK-1 at day 2 which was maintained throughout the study period. However, a more prevalent use of ß-blockers in the simvastatin group, that could have contributed to higher DKK-1 levels in these patients. (ii) There was a strong correlation between baseline DKK-1 levels and change in DKK-1 from baseline to day 2 in patients receiving high dose rosuvastatin treatment. (iii) DKK-3 increased at day 2 but returned to baseline levels at 2 months in both treatment groups. (iv) Statin treatment dose-dependently decreased DKK-1 mRNA and protein levels in HUVEC. CONCLUSIONS: Our findings suggest that high dose statin treatment with 40 mg rosuvastatin could persistently down-regulate DKK-1 levels, even at 2 months after the initial event in STEMI patients.
Subject(s)
Adaptor Proteins, Signal Transducing , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Intercellular Signaling Peptides and Proteins , Rosuvastatin Calcium , Humans , Male , Female , Rosuvastatin Calcium/administration & dosage , Rosuvastatin Calcium/therapeutic use , Middle Aged , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Aged , Intercellular Signaling Peptides and Proteins/blood , Dose-Response Relationship, Drug , Simvastatin/administration & dosage , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Myocardial Infarction/drug therapy , Myocardial Infarction/blood , Biomarkers/blood , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/drug therapy , Cells, CulturedABSTRACT
BACKGROUND: The effect of administering a crushed prasugrel loading dose is uncertain in patients presenting with a large myocardial infarction and ST-segment elevation myocardial infarction (STEMI). AIMS: The aim of this study was to investigate if patients with a large myocardial infarction may benefit from prehospital administration of a crushed prasugrel loading dose. METHODS: Patients from the CompareCrush trial with an available ambulance electrocardiography (ECG) were included in the study. An independent core laboratory confirmed a prehospital large myocardial area. We compared pre- and postprocedural angiographic markers, including Thrombolysis in Myocardial Infarction (TIMI) 3 flow in the infarct-related artery, high thrombus burden, and myocardial blush grade 3, in STEMI patients with and without a prehospital large myocardial area. RESULTS: Ambulance ECG was available for 532 patients, of whom 331 patients were identified with a prehospital large myocardial area at risk. Crushed prasugrel significantly improved postprocedural TIMI 3 flow rates in STEMI patients with a prehospital large myocardial area at risk (92% vs 79%, odds ratio [OR] 3.00, 95% confidence interval [CI]: 1.50-6.00) but not in STEMI patients without a prehospital large myocardial area at risk (91% vs 95%, OR 0.47, 95% CI: 0.14-1.57; pinteraction=0.009). CONCLUSIONS: Administration of crushed prasugrel may improve postprocedural TIMI 3 flow in STEMI patients with signs of a large myocardial area at risk on the ambulance ECG. The practice of crushing tablets of prasugrel loading dose might, therefore, represent a safe, fast and cost-effective strategy to improve myocardial reperfusion in this high-risk STEMI subgroup undergoing primary percutaneous coronary intervention.
Subject(s)
Emergency Medical Services , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Myocardial Infarction/drug therapy , Percutaneous Coronary Intervention/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Prasugrel Hydrochloride/therapeutic use , ST Elevation Myocardial Infarction/drug therapy , Treatment OutcomeABSTRACT
BACKGROUND: The impact of statin therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real- world patients is understudied. AIMS: To identify predictors of low adherence and discontinuation to statin therapy within 6 months after STEMI and to estimate their impact on cardiovascular outcomes at one year follow-up. METHODS: We evaluated real-world adherence to statin therapy by comparing the number of bought tablets to the expected ones at 1 year follow-up through pharmacy registries. A total of 6043 STEMI patients admitted from 2012 to 2017 were enrolled in the FAST STEMI registry and followed up for 4,7 ± 1,6 years; 304 patients with intraprocedural and intrahospital deaths were excluded. The main outcomes evaluated were all-cause death, cardiovascular death, myocardial infarction, major and minor bleeding events, and ischemic stroke. The compliance cut-off chosen was 80% as mainly reported in literature. RESULTS: From a total of 5744 patients, 418 (7,2%) patients interrupted statin therapy within 6 months after STEMI, whereas 3337 (58,1%) presented >80% adherence to statin therapy. Statin optimal adherence (>80%) resulted as protective factor towards both cardiovascular (0.1% vs 4.6%; AdjHR 0.025, 95%CI 0.008-0.079, p < 0.001) and all-cause mortality (0.3% vs 13.4%; Adj HR 0.032, 95%CI 0.018-0.059, p < 0.001) at 1 year follow-up. Further, a significant reduction of ischemic stroke incidence (1% vs 2.5%, p = 0.001) was seen in the optimal adherent group. Statin discontinuation within 6 months after STEMI showed an increase of both cardiovascular (5% vs 1.7%; AdjHR 2.23; 95%CI 1.37-3.65; p = 0,001) and all-cause mortality (14.8% vs 5.1%, AdjHR 2.32; 95%CI 1.73-3.11; p ã0,001) at 1 year follow-up. After multivariate analysis age over 75 years old, known ischemic cardiopathy and female gender resulted as predictors of therapy discontinuation. Age over 75 years old, chronic kidney disease, previous atrial fibrillation, vasculopathy, known ischemic cardiopathy were found to be predictors of low statin adherence. CONCLUSIONS: n our real-world registry low statin adherence and discontinuation therapy within 6 months after STEMI were independently associated to an increase of cardiovascular and all-cause mortality at 1 year follow-up. Low statin adherence led to higher rates of ischemic stroke.