Prognostic Implications of the Timing of ST-Elevation Myocardial Infarction Development in Relation to COVID-19 Infection.

Background: Patients with ST-segment elevation myocardial infarction (STEMI) and COVID-19 infection have a worse clinical course and prognosis. The prognostic significance of the timing of STEMI in relation to COVID-19 infection was not investigated. Objectives: To assess whether the time of STEMI development in relation to COVID-19 infection (concurrent or following the infection) influenced the short-term prognosis. Methods: This was an observational study of consecutive COVID-19 patients with STEMI admitted to the COVID-hospital Batajnica (February 2021-March 2022). The patients were divided into the "STEMI first" group: patients with STEMI and a positive polymerase chain reaction test for COVID-19, and the "COVID-19 first" group: patients who developed STEMI during COVID-19 treatment. All patients underwent coronary angiography. The primary endpoint was in-hospital all-cause mortality. Results: The study included 87 patients with STEMI and COVID-19 (Mage, 66.7 years, 66% male). The "STEMI first" group comprised 54 (62.1%) patients, and the "COVID-19 first" group included 33 (37.9%) patients. Both groups shared a comparatively high burden of comorbidities, similar angiographic and procedural characteristics, and high percentages of performed percutaneous coronary interventions with stent implantation (90.7% vs. 87.9%). In-hospital mortality was significantly higher in the "COVID-19 first" group compared to the "STEMI first" group (51.5% vs. 27.8%). Following adjustment, the "COVID-19 first" group had a hazard ratio of 3.22 (95% confidence interval, 1.18-8.75, p = .022) for in-hospital all-cause death, compared with the "STEMI first" group (reference). Conclusion: Clinical presentation with COVID-19 infection, followed by STEMI ("COVID-19 first"), was associated with greater short-term mortality compared to patients presenting with STEMI and testing positive for COVID-19 ("STEMI first").

Impact on long-term mortality of access and non-access site bleeding after primary percutaneous coronary intervention.

OBJECTIVES: The influence of the bleeding site on long-term survival after the primary percutaneous coronary intervention (PCI) is poorly understood. This study sought to investigate the relationship between in-hospital access site versus non-access site bleeding and very late mortality in unselected patients treated with primary PCI. METHODS: Data of the 2715 consecutive patients with ST-segment elevation myocardial infarction treated with primary PCI, enrolled in a prospective registry of a high volume tertiary centre, were analysed. Bleeding events were assessed according to the Bleeding Academic Research Consortium (BARC) criteria. The primary outcome was 4-year mortality. RESULTS: The BARC type ≥2 bleeding occurred in 171 patients (6.3%). Access site bleeding occurred in 3.8%, and non-access site bleeding in 2.5% of patients. Four-year mortality was significantly higher for patients with bleeding (BARC type ≥2) than in patients without bleeding (BARC type 0+1), (36.3% vs 16.2%, p<0.001). Patients with non-access site bleeding had higher 4 year mortality (50.7% vs 26.5%, p=0.001). After multivariable adjustment, BARC type ≥2 bleeding was the independent predictor of 4 year mortality (HR 2.01; 95% CI 1.49 to 2.71, p<0.001). Patients with a non-access site bleeding were at 2-fold higher risk of very late mortality than patients with an access site bleeding (HR 2.62; 1.78 to 3.86, p<0.001 vs HR 1.57; 1.03 to 2.38, p=0.034). CONCLUSIONS: Both access and non-access site BARC type ≥2 bleeding is independently associated with a high risk of 4-year mortality after primary PCI. Patients with non-access site bleeding were at higher risk of late mortality than patients with access site bleeding.

Dabigatran - Metabolism, Pharmacologic Properties and Drug Interactions.

BACKGROUND: The superiority of dabigatran has been well proven in the standard dosing regimen in prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and extended venous thromboembolism (VTE) treatment. Dabigatran, an anticoagulant with a good safety profile, reduces intracranial bleeding in patients with atrial fibrillation and decreases major and clinically relevant non-major bleeding in acute VTE treatment. However, several important clinical issues are not fully covered by currently available directions with regard to dabigatran administration. The prominent one is reflected in the fact that dynamic impairment in renal function due to dehydratation may lead to haemorragic complications on the one hand, while on the other hand glomerular hyperfiltration may be a possible cause of dabigatran subdosing, hence reducing the drug's efficacy. Furthermore, limitations of the Cockcroft-Gault formula, considered a standard equation for assessing the renal function, may imply that other calculations are likely to obtain more accurate estimates of the kidney function in specific patient populations. Method and Conclusions: Although not routinely recommended, a possibility of monitoring dabigatran in special clinical settings adds to optimization of its dosage regimens, timely perioperative care and administration of urgently demanded thrombolytic therapy, therefore significantly improving this drug's safety profile. Despite the fact that dabigatran has fewer reported interactions with drugs, food constituents, and dietary supplements, certain interactions still remain, requiring considerable caution, notably in elderly, high bleeding risk patients, patients with decreased renal function and those on complex drug regimens. Additionally, upon approval of idarucizumab, an antidote to dabigatran solution, hitherto being a major safety concern, has been finally reached, which plays a vital role in life-threatening bleeding and emergency interventions and surgery.

Economic analysis of pharmacogenomic-guided clopidogrel treatment in Serbian patients with myocardial infarction undergoing primary percutaneous coronary intervention.

INTRODUCTION: Clopidogrel, which is activated by the CYP2C19 enzyme, is among the drugs for which all major regulatory agencies recommend genetic testing to be performed to identify a patient's CYP2C19 genotype in order to determine the optimal antiplatelet therapeutic scheme. The CYP2C19*2 and CYP2C19*3 variants are loss-of-function alleles, leading to abolished CYP2C19 function and thus have the risk of thrombotic events for carriers of these alleles on standard dosages, while the CYP2C19*17 allele results in CYP2C19 hyperactivity. AIMS: Here, we report our findings from a retrospective study to assess whether genotyping for the CYP2C19*2 allele was cost effective for myocardial infarction patients receiving clopidogrel treatment in the Serbian population compared with the nongenotype-guided treatment. RESULTS: We found that 59.3% of the CYP2C19*1/*1 patients had a minor or major bleeding event versus 42.85% of the CYP2C19*1/*2 and *2/*2, while a reinfarction event occurred only in 2.3% of the CYP21C9*1/*1 patients, compared with 11.2% of the CYP2C19*1/*2 and CYP2C19*2/*2 patients. There were subtle differences between the two patient groups, as far as the duration of hospitalization and rehabilitation is concerned, in favor of the CYP2C19*1/*1 group. The mean cost for the CYP2C19*1/*1 patients was estimated at €2547 versus €2799 in the CYP2C19*1/*2 and CYP2C19*2/*2 patients. Furthermore, based on the overall CYP2C19*1/*2 genotype frequencies in the Serbian population, a break-even point analysis indicated that performing the genetic test prior to drug prescription represents a cost-saving option, saving €13 per person on average. CONCLUSION: Overall, our data demonstrate that pharmacogenomics-guided clopidogrel treatment may represent a cost-saving approach for the management of myocardial infarction patients undergoing primary percutaneous coronary intervention in Serbia.

Incidence, predictors and prognostic implications of bleeding complicating primary percutaneous coronary intervention.

BACKGROUND/AIM: Data about bleeding complicating primary percutaneous coronary intervention (PCI) are more frequently obtained from randomized clinical trials on patients with acute coronary syndromes (ACS), but less frequently from surveys or registries on patients with ST-elevation myocardial infarction (STEMI). The aim of this study was to investigate the incidence, predictors and prognostic impact of in-hospital major bleeding in the population of unselected real-world patients with acute STEMI undergoing primary PCI. METHODS: All consecutive patients presenting with STEMI who underwent primary PCI at a single large tertiary healthcare center between January 2005 and July 2009, were studied. Major bleeding was defined according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) study criteria. We examined the association between in-hospital major bleeding and death or major adverse cardiac events (MACE) in patients treated with PCI. The primary outcomes were in-hospital and 6-month mortality and MACE. RESULTS: Of the 770 STEMI patients treated with primary PCI, in-hospital major bleeding occurred in 32 (4.2%) patients. Independent pre-dictors of major bleeding were advanced age (≥ 65 years), female gender, baseline anemia and elevated white blood cell (WBC) count and signs of congestive heart failure at admission (Killip class II-IV). In-hospital and 6 month mortality and MACE, rates were more than 2.5-fold-higher in patients who developed major bleeding compared with those who did not. Major bleeding was predictor of 6-month MACE, independent of a few risk factors (previous MI, previous PCI, diabetes mellitus and hypertension); (OR = 3.02; 95% CI for OR 1.20-7.61; p = 0.019) but was not a true independent predictor of MACE and mortality in the fully adjusted models. CONCLUSION: Patients of advanced age, female gender, with baseline anemia and elevated WBC count and those with Killip class II-IV at presentation are at particularly high risk of bleeding after primary PCI. Bleeding is associated with adverse outcome and may be an important marker of patient frailty, but it is not a true independent predictor of mortality/MACE.

Prognostic implications of bleeding measured by Bleeding Academic Research Consortium (BARC) categorisation in patients undergoing primary percutaneous coronary intervention.

OBJECTIVE: To investigate the relationship between inhospital bleeding as defined by Bleeding Academic Research Consortium (BARC) consensus classification and short-term and long-term mortality in unselected patients admitted for primary percutaneous coronary intervention (PCI). METHODS: We analysed data of all consecutive patients with ST segment elevation myocardial infarction (STEMI) admitted for primary PCI, enrolled in a prospective registry of a high volume centre. The BARC-defined bleeding events were reconstructed from the detailed, prospectively collected clinical data. The primary outcome was mortality at 1 year. RESULTS: Of the 1808 patients with STEMI admitted for primary PCI, 115 (6.4%) experienced a BARC type ≥2 bleeding. As the BARC bleeding severity worsened, there was a gradient of increasing rates of 1-year death. The 1-year mortality rate increased from 11.5% with BARC 0+1 type to 43.5% with BARC type 3b bleeding. After multivariable adjustment for demographic and clinical characteristics of patients, the independent predictors of 1-year death were BARC type 3a (HR 1.99; 95% CI 1.16 to 3.40, p=0.012) and BARC type 3b bleeding (HR 3.22; 95% CI 1.67 to 6.20, p<0.0001). CONCLUSIONS: The present study demonstrated that bleeding events defined according to the BARC classification hierarchically correlate with 1-year mortality after admission for primary PCI. The strongest predictor of 1-year mortality is the BARC type 3b bleeding.

The long-term risk of stroke in patients with acute myocardial infarction complicated with new-onset atrial fibrillation.

BACKGROUND: The long-term risk of stroke after acute myocardial infarction (AMI) complicated with new-onset atrial fibrillation (AF) remains unclear. The aim of this study was to determine the long-term risk of AF and stroke in patients with AMI complicated with new-onset AF. METHODS: Patients with AMI complicated with new-onset AF (n = 260) and those without new-onset AF (n = 292) were followed for a mean of 7 years. All patients had sinus rhythm at hospital discharge. RESULTS: During the follow-up, AMI patients with new-onset AF had more frequent AF than those without new-onset AF (10.4% vs 2.7%, respectively; P < 0.0001). New-onset AF during AMI was a significant predictor of subsequent AF occurrence (the time elapsing between 2 consecutive R waves [RR] = 3.15, P = 0.004); but AF recurrence in follow-up (RR = 5.08, P = 0.001) and non-anticoagulation at discharge (RR = 0.29, P = 0.008) were independent predictors of stroke (Cox regression analysis). A period of 3.5 hours of AF within the first 48 hours of AMI was the high sensitivity cut-off level for the prediction of low long-term risk of stroke obtained by receiver operating characteristic analysis. Among patients who did not receive anticoagulants at discharge, the patients with short AF did not experience stroke and AF recurrence during follow-up, while those in the other group developed it (10.8%, P = 0.038 and 13.5%, P = 0.019, respectively). CONCLUSION: New-onset AF during AMI identifies the patients at long-term risk for stroke who may potentially benefit from anticoagulant therapy. Atrial fibrillation recurrence in follow-up was independently related to the development of stroke. However, for low-risk patients with AF (those with short AF occurring early in AMI) long-term anticoagulants might not be required.