Validation of Becton Dickinson Barricor™ tubes for use with Abbott Alinity™ and Siemens Atellica® highly sensitive cardiac troponin I measuring systems.

BACKGROUND: BD Barricor™ tubes have been proposed to decrease laboratory turnaround time (TAT). We analytically validated and then clinically verified these tubes for use with Abbott Alinity™ and Siemens Atellica® highly sensitive cardiac troponin I (hs-cTnI) assays. METHODS: hs-cTnI measurements were undertaken in paired Barricor™ and in-use PSTII™ tubes on both systems. 359 matched samples with hs-cTnI levels between 3 and 15,000 ng/L (Atellica® values) were used to assess the hemolysis rate and make method comparisons. 599 paired patient samples were collected on emergency department (ED) admission to compare the performance of the rapid acute myocardial infarction (AMI) rule-out strategy based on hs-cTnI concentrations lower than recommended thresholds (<4 ng/L Alinity™; <5 ng/L Atellica®) when different tubes and systems were employed. RESULTS: No between-tube differences in hemolysis rate were seen when free hemoglobin concentrations in plasma samples were ≥0.25 g/L, even if PSTII™ showed a significant increase of hemolysis rate vs. Barricor™ (31% vs. 22%, p=0.007) when a lower cut-off for hemolysis (≥0.11 g/L) was employed on the Atellica® detection system. The alternate use of these tubes did not influence the hs-cTnI results obtained from either of the two assays, which remained markedly biased (~40%) irrespective of the tube used. The expected optimal ability of very low hs-cTnI values on ED admission for ruling out AMI was confirmed by using both systems regardless of the tube type. CONCLUSIONS: Barricor™ and PSTII™ tubes can provide analytically equivalent hs-cTnI results when used on either Alinity™ or Atellica® hs-cTnI assays.

Efficacy and Safety of P2Y12 monotherapy vs standard DAPT in patients undergoing percutaneous coronary intervention: meta-analysis of randomized trials.

BACKGROUND: Debates persist regarding the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in coronary artery disease (CAD). Recent trials have introduced a novel approach involving P2Y12 inhibitor monotherapy with ticagrelor or clopidogrel, after a short DAPT. However, the effectiveness and safety of this strategy remains to be established. We aimed to perform a meta-analysis comparing monotherapy with P2Y12 inhibitors versus standard DAPT in patients undergoing PCI at 12 months. METHODS: Multiple databases were searched. Six RCTs with a total of 24877 patients were included. The primary endpoint was all-cause mortality at 12 months of follow-up. The secondary endpoints were cardiovascular mortality, myocardial infarction, probable or definite stent thrombosis, stroke events, and major bleeding. The study is registered with PROSPERO (CRD42024499529). RESULTS: Monotherapy with P2Y12 inhibitor ticagrelor significantly reduced both allcause mortality (HR 0.71, 95 CI [0.55-0.91], P = 0.007) and cardiovascular mortality (HR 0.66, 95% CI [0.49-0.89], P = 0.006) compared to standard DAPT. In contrast, clopidogrel monotherapy did not demonstrate a similar reduction. The decrease in mortality associated with ticagrelor was primarily due to a lower risk of major bleeding (HR 0.56, 95% CI [0.43-0.72], P < 0.001), while the risk of myocardial infarction (MI) remained unchanged (HR 0.90, 95% CI [0.73-1.11], P = 0.32). The risk of stroke was found to be similar across treatments. CONCLUSIONS: In comparison to standard DAPT, P2Y12 inhibitor monotherapy with ticagrelor may lead to a reduced mortality. The clinical benefits are driven by a reduction of bleeding risk without ischemic risk trade-off.

Diagnostic and prognostic performance of the neutrophil-to-lymphocyte ratio in acute coronary syndromes: A meta-analysis of 90 studies including 45 990 patients.

BACKGROUND: Cardiovascular disease is a leading cause of mortality worldwide and is likely to rise. Acute coronary syndrome (ACS) is consequent on inflammation. As a common and cost-effective inflammatory biomarker, the neutrophil-to-lymphocyte ratio (NLR) may be beneficial in cardiovascular medicine. AIMS: This meta-analysis examines the diagnostic and prognostic performance of the NLR in ACS. METHODS: We systematically searched PubMed Central, Medline, Scopus, EMBASE, Cochrane Central Register of Controlled Trials, and Clinicaltrial.gov databases. The search spanned from databases inception to January 10, 2024. The findings were aggregated into normalized mean differences with 95% confidence intervals. RESULTS: Ninety articles, with 45 990 participants, were included. Pooled analysis of the NLR varied and was higher in ST-segment elevation myocardial infarction (STEMI) vs. non-ST-segment elevation myocardial infarction patients (4.94 ± 3.24 vs. 3.24 ± 2.74), acute myocardial infarction vs. unstable angina (4.47 ± 3.43 vs. 2.97 ± 1.58), ACS vs. stable angina (SA) (5.45 ± 4.28 vs. 2.46 ± 2.15), and ACS vs. controls (5.31 ± 4.01 vs. 2.46 ± 2.45). The NLR also was associated with ACS mortality, with survivors having lower results (3.67 ± 2.72 vs. 5.56 ± 3.93). Subanalysis showed that differences in the NLR were observed in STEMI survivors (4.28 ± 3.24 vs. 6.79 ± 3.98). Of ACS patients with major cardiovascular events (MACE) vs. without MACE, the NLR was 6.29 ± 4.89 vs. 3.82 ± 4.12. In STEMI patients, the NLR differed between those with and without MACE (6.99 ± 5.27 vs. 4.99 ± 4.12). CONCLUSIONS: The NLR is an effective tool for differentiating between different types of ACS. A high NLR is associated with ACS and increased MACE at 30 days. The NLR also appears to be a good predictor of MACE risk, at least in STEMI patients.

Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels.

Lipoprotein(a) [Lp(a)] is made up of a low-density lipoprotein (LDL) particle and a specific apolipoprotein(a). The blood concentration of Lp(a) is approximately 90% genetically determined, and the main genetic factor determining Lp(a) levels is the size of the apo(a) isoform, which is determined by the number of KIV2 domain repeats. The size of the apo(a) isoform is inversely proportional to the blood concentration of Lp(a). Lp(a) is a strong and independent cardiovascular risk factor. Elevated Lp(a) levels ≥ 50 mg/dl (≥ 125 nmol/l) are estimated to occur in more than 1.5 billion people worldwide. However, determination of Lp(a) levels is performed far too rarely, including Poland, where, in fact, it is only since the 2021 guidelines of the Polish Lipid Association (PoLA) and five other scientific societies that Lp(a) measurements have begun to be performed. Determination of Lp(a) concentrations is not easy due to, among other things, the different sizes of the apo(a) isoforms; however, the currently available certified tests make it possible to distinguish between people with low and high cardiovascular risk with a high degree of precision. In 2022, the first guidelines for the management of patients with elevated lipoprotein(a) levels were published by the European Atherosclerosis Society (EAS) and the American Heart Association (AHA). The first Polish guidelines are the result of the work of experts from the two scientific societies and their aim is to provide clear, practical recommendations for the determination and management of elevated Lp(a) levels.

Gender-Related Effectiveness of Personalized Post-COVID-19 Rehabilitation.

Background: Post-COVID-19 syndrome (PCS) may affect a substantial proportion of patients who have had COVID-19. The rehabilitation program might improve the physical capacity, functioning of the cardiopulmonary system, and mental conditions of these patients. This study aimed to investigate the effectiveness of personalized rehabilitation in patients with PCS according to gender. Methods: Adults who underwent a 6-week personalized PCS rehabilitation program were enrolled in a prospective post-COVID-19 Rehabilitation (PCR-SIRIO 8) study. The initial visit and the final visit included the hand-grip strength test, the bioimpedance analysis of body composition, and the following scales: modified Borg's scale, Modified Fatigue Impact Scale (MFIS), Functioning in Chronic Illness Scale (FCIS), modified Medical Research Council (mMRC) dyspnea scale, and tests: 30 s chair stand test (30 CST), Six-Minute Walk Test (6MWT), Short Physical Performance Battery test (SPPB)e. Results: A total of 90 patients (54% female) underwent the rehabilitation program. Rehabilitation was associated with an increase in skeletal muscle mass (24.11 kg vs. 24.37 kg, p = 0.001) and phase angle (4.89° vs. 5.01°, p = 0.001) and with a reduction in abdominal fat tissue volume (3.03 L vs. 2.85 L, p = 0.01), waist circumference (0.96 m vs. 0.95 m, p = 0.001), and hydration level (83.54% vs. 82.72%, p = 0.001). A decrease in fat tissue volume and an increase in skeletal muscle mass were observed only in females, while an increase in grip strength was noticed selectively in males. Patients' fatigue (modified Borg's scale, MFIS), physical capacity (30 CST, 6MWT), balance (SPPB), dyspnea (mMRC), and functioning (FICS) were significantly improved after the rehabilitation regardless of gender. Conclusions: Personalized rehabilitation improved the body composition, muscle strength, and functioning of patients diagnosed with PCS. The beneficial effect of rehabilitation on body composition, hydration, and phase angle was observed regardless of gender.

Achieving Cardiovascular Risk Management Goals and Patient Quality of Life.

(1) Background: Eliminating or reducing the severity of modifiable risk factors of cardiovascular disease (CVD) and undertaking health-promoting behaviors is the basis for prevention. (2) Methods: This study included 200 subjects without a history of CVD, aged 18 to 80 years, who had been diagnosed with hypertension, hypercholesterolemia, or diabetes 6 to 24 months before study enrolment. (3) Results: The median 10-year CV risk assessed by the SCORE2 and SCORE2-OP algorithms was 3.0 (IQR 1.5-7.0). An increase in mean cardiovascular risk in the range from low and moderate to very high was associated with a decrease in quality of life both in individual subscales and the overall score. The median number of controlled risk factors was 4.0 (IQR 3.0-5.0). As the mean number of controlled risk factors increased, the quality of life improved in both of HeartQoL questionnaire subscales (emotional p = 0.0018; physical p = 0.0004) and the overall score (global p = 0.0001). The median number of reported health-promoting behaviors undertaken within 3 years before study enrolment was 3.0 (IQR 2.0-4.0). The highest quality of life in each of the studied dimensions was found in people who reported undertaking three health-promoting behaviors. (4) Conclusions: Controlling CVD risk factors and undertaking health-promoting behaviors has a positive impact on the quality of life of patients without a history of atherosclerotic CVD.

First-year follow-up costs of myocardial infarction management in Poland from the payer's perspective.

BACKGROUND: Myocardial infarction (MI) remains a major burden for healthcare systems. Therefore, we intended to analyze the determinants of cost management of patients hospitalized for MI in Poland. METHODS: Data on patients hospitalized and discharged with the diagnosis of acute MI were derived from the public payer claims database. Adult patients, reported between October 1, 2017 and December 31, 2019, were included. Costs of hospitalization for acute MI and cumulative one-year follow-up were analyzed. RESULTS: The median (IQR) of the total direct cost was €3804.7 (2674.1-5712.7) per patient and 29% (€1113.6 [380.5-2490.4]) of these were costs related to the use of post-hospitalization healthcare resources. The median cost of cardiovascular disease management was €3624.7 (2582.1-5258.5), and 26% of this sum were follow-up costs. The analysis of the total cost for individual years showed a slight increase in median costs in subsequent years: €3450.7 (2407.8-5205.2) in 2017, €3753.8 (2642.6-5681.9) in 2018, and €3944.9 (2794.8-5844.4) in 2019. Male sex, heart failure, atrial fibrillation, diabetes, kidney disease, chronic obstructive pulmonary disease, and history of stroke in addition to hospitalization in a department other than cardiology or internal disease were independently related to the cost of MI patient management. CONCLUSIONS: The high cost of management of MI patients was independently related to sex, heart failure, atrial fibrillation, diabetes, kidney disease, chronic obstructive pulmonary disease, and history of stroke as well as hospitalization in other than cardiology or internal disease department.

Proposal and practicality of an alternative blue-light hazard risk assessment method for high-intensity white-light sources at workplaces.

Objectives. It is prescribed to determine blue-light hazard (BLH) weighted radiances, LB, for an assessment of spotlights with an angular subtense α≥11mrad. The BLH weighted irradiance, EB, can be used alternatively for smaller sources. Appropriate instruments are not common among persons commissioned with risk assessment (RA), and especially LB measurements may be challenging. Therefore, a practical BLH RA approach is proposed that is based on illuminance, Ev, pre-calculated blackbody BLH efficacies of luminous radiation, KB,vPlanck, and solid angle considerations. Methods. The practicality of this method was examined and compared against other RA approaches. Results. To ensure comparability of the applied instruments, measurements were performed close to a radiance standard, showing deviations within the lamp's expanded uncertainties (<4%), whereas the deviations were ±15% for longer distances. Focusing on a complex light-emitting diode (LED) spotlight, all detected values could be converted to LB by means of the RA methods within ±20%. Two field tests with several spotlights yielded maximum permissible exposure durations (MPED) obtained from the different RA approaches that agreed among each other within uncertainties largely below ±30%. Conclusion. The general practicality of the proposed Ev method can be concluded for a workplace BLH RA of white-light sources.

The use of andexanet alpha in the Polish setting: An interdisciplinary protocol. Expert consensus statement of the Polish Cardiac Society.

Andexanet alfa (AA) is a recombinant inactive analog of human activated factor X (FXa), effectively reversing the effects of its inhibitors - rivaroxaban and apixaban, which are available in Poland. The drug was approved for clinical use registration after the publication of the results of the ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors 4), in which its efficacy in restoring hemostasis in life-threatening hemorrhages in patients receiving using the aforementioned anticoagulants was demonstrated. Hence, AA is now recommended for patients on apixaban or rivaroxaban therapy with massive and uncontrollable hemorrhages, including hemorrhagic strokes (HS) and gastrointestinal bleeding. Drug-specific chromogenic anti-Xa assays are generally best suited for estimating rivaroxaban and apixaban plasma levels, aside from direct assessment of their concentrations. The absence of anti-Xa activity, determined using these assays, allows us to rule out the presence of clinically relevant plasma concentrations of any FXa inhibitor. On the other hand, the dose of AA should not be modified based on the results of coagulation tests, as it depends solely on the time that elapsed since the last dose of FXa inhibitor and oon the dose and type of FXa inhibitor. AA is administered as an intravenous (i.v.) bolus, followed by an i.v. infusion of the drug. The maximum reversal of anti-Xa activity occurs within two minutes of the end of the bolus treatment, with the continuation of the continuous i.v. infusion allowing the effect to be maintained for up to two hours afterwards. Because anticoagulant activity can reappear after the infusion is completed, it is currently unclear at what point after AA administration FXa inhibitors or heparin should be re-administered. In Poland AA is starting to become available and its urgent need to administer it to patients with severe bleeding on apixaban or rivaroxaban.

Cangrelor - Expanding therapeutic options in patients with acute coronary syndrome.

Cangrelor is the only intravenous P2Y12 receptor antagonist. It is an adenosine triphosphate analog that selectively, directly, and reversibly binds to the platelet P2Y12 receptors exerting its antiaggregatory effect. Cangrelor is characterized by linear, dose-dependent pharmacokinetics and rapid onset of action providing potent platelet inhibition exceeding 90%. Cangrelor is rapidly metabolized by endothelial endonucleotidase; thus, its half-life is 2.9 to 5.5 min, and its antiplatelet effect subsides within 60 to 90 min. Data originating from three pivotal cangrelor trials (CHAMPION PLATFORM, CHAMPION PCI, and CHAMPION PHOENIX) indicate that cangrelor reduces the risk of periprocedural thrombotic complications during percutaneous coronary intervention at the expense of mild bleedings. Its unique pharmacological properties allow it to overcome the limitations of oral P2Y12 receptor inhibitors, mainly related to the delayed and decreased bioavailability and antiplatelet effect of these agents, which are often observed in the setting of acute coronary syndrome. Subgroups of patients who could theoretically benefit the most from cangrelor include those in whom pharmacokinetics and pharmacodynamics of oral P2Y12 receptor antagonists are most disturbed, namely patients with ST-segment elevation myocardial infarction, those treated with opioids, with mild therapeutic hypothermia, or in cardiogenic shock. Cangrelor could also be useful if bridging is required in patients undergoing surgery. According to the current guidelines cangrelor may be considered in P2Y12 receptor inhibitor-naïve patients undergoing percutaneous coronary intervention in both acute and stable settings.

Independent Causal Effect of Remnant Cholesterol on Atherosclerotic Cardiovascular Outcomes: A Mendelian Randomization Study.

BACKGROUND: Observational studies suggested that residual risk of cardiovascular events after LDL (low-density lipoprotein) cholesterol lowering may be linked to remnant cholesterol (RC). We conducted a large-scale Mendelian randomization study to investigate the causal role of RC to predict coronary artery disease (CAD), myocardial infarction (MI), and stroke risk. METHODS: We extracted single-nucleotide polymorphisms for RC and LDL from large-scale genome-wide association databases. We estimated the genetic association with outcomes from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Plus the Coronary Artery Disease Genetics), the Metastroke consortium, as well as the GLGC (Global Lipids Genetics Consortium). Genetic variants were used as instruments, thereby minimizing residual confounding and reverse causation biases of observational studies. RESULTS: By leveraging data from a combined sample of 958 434 participants, we found evidence for a significant causal effect of RC on the risk of CAD (odds ratio [OR], 1.51 per SD unit increase in RC [95% CI, 1.42-1.60]; P=5.3×10-5), MI (OR, 1.57 [95% CI, 1.21-2.05]; P=9.5×10-4), and stroke (OR, 1.23 [95% CI, 1.12-1.35]; P=3.72×10-6). There was no evidence of pleiotropy. The effect of RC on CAD and MI remained consistent after accounting for the effects of RC-associated genetic variants on LDL cholesterol: OR, 1.49 (95% CI, 1.37-1.61) for CAD and OR, 1.80 (95% CI, 1.70-19.1) for MI without a meaningful indirect effect exerted on these outcomes via the LDL cholesterol mediator. CONCLUSIONS: This large-scale Mendelian randomization study showed a robust genetic causal association between RC and cardiovascular outcomes. The effect on CAD and MI is independent of LDL cholesterol. Early screening for RC along with long-term inhibition of RC should be the focus of future therapeutic interventions.

Conley-Morse-Forman theory for generalized combinatorial multivector fields on finite topological spaces.

We generalize and extend the Conley-Morse-Forman theory for combinatorial multivector fields introduced in Mrozek (Found Comput Math 17(6):1585-1633, 2017). The generalization is threefold. First, we drop the restraining assumption in Mrozek (Found Comput Math 17(6):1585-1633, 2017) that every multivector must have a unique maximal element. Second, we define the dynamical system induced by the multivector field in a less restrictive way. Finally, we also change the setting from Lefschetz complexes to finite topological spaces. Formally, the new setting is more general, because every Lefschetz complex is a finite topological space, but the main reason for switching to finite topologcial spaces is because the latter better explain some peculiarities of combinatorial topological dynamics. We define isolated invariant sets, isolating neighborhoods, Conley index and Morse decompositions. We also establish the additivity property of the Conley index and the Morse inequalities.

Effects of Elective Coronary Revascularization vs Medical Therapy Alone on Noncardiac Mortality: A Meta-Analysis.

BACKGROUND: Uncertainty exists whether coronary revascularization plus medical therapy (MT) is associated with an increase in noncardiac mortality in chronic coronary syndrome (CCS) when compared with MT alone, particularly following recent data from the ISCHEMIA-EXTEND (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. OBJECTIVES: This study conducted a large-scale meta-analysis of trials comparing elective coronary revascularization plus MT vs MT alone in patients with CCS to determine whether revascularization has a differential impact on noncardiac mortality at the longest follow-up. METHODS: We searched for randomized trials comparing revascularization plus MT vs MT alone in patients with CCS. Treatment effects were measured by rate ratios (RRs) with 95% CIs, using random-effects models. Noncardiac mortality was the prespecified endpoint. The study is registered with PROSPERO (CRD42022380664). RESULTS: Eighteen trials were included involving 16,908 patients randomized to either revascularization plus MT (n = 8,665) or to MT alone (n = 8,243). No significant differences were detected in noncardiac mortality between the assigned treatment groups (RR: 1.09; 95% CI: 0.94-1.26; P = 0.26), with absent heterogeneity (I2 = 0%). Results were consistent without the ISCHEMIA trial (RR: 1.00; 95% CI: 0.84-1.18; P = 0.97). By meta-regression, follow-up duration did not affect noncardiac death rates with revascularization plus MT vs MT alone (P = 0.52). Trial sequential analysis confirmed the reliability of meta-analysis, with the cumulative Z-curve of trial evidence within the nonsignificance area and reaching futility boundaries. Bayesian meta-analysis findings were consistent with the standard approach (RR: 1.08; 95% credible interval: 0.90-1.31). CONCLUSIONS: In patients with CCS, noncardiac mortality in late follow-up was similar for revascularization plus MT compared with MT alone.

Determinants of Lipid Parameters in Patients without Diagnosed Cardiovascular Disease-Results of the Polish Arm of the EUROASPIRE V Survey.

To assess the determinants of lipid parameters in primary care patients without diagnosed cardiovascular disease (CVD), a cross-sectional study was conducted during 2018-2019 with a total of 200 patients. The following lipid parameters were measured: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), small, dense LDL (sdLDL-C), and lipoprotein (a) (Lp(a)). Predictors of elevated and adequately controlled lipid parameters were assessed with logistic regression analysis. Older age was related to higher risk of TC ≥ 6.2 mmol/L [OR 1.03 (95% CI 1.0-1.05)], sdLDL-C ≥ 1.0 mmol/L [OR 1.05 (95% CI 1.0-1.1)], and decreased risk of Lp(a) ≥ 50 mg/dL [OR 0.97 (95% CI 0.94-0.99)]. Patients with diabetes mellitus (DM) had increased probability of TG ≥ 2.25 mmol/L [OR 3.77 (95% CI 1.34-10.6)] and Lp(a) ≥ 50 mg/dL [OR 2.97 (1.34-6.10)] as well as adequate control of TG and Lp(a). Higher material status was related to lower risk of TC ≥ 6.2 mmol/L [OR 0.19 (95% CI 0.04-0.82)] and LDL-C ≥ 3.6 mmol/L [OR 0.33 (95% CI 0.12-0.92)]. High BMI was related to increased [OR 1.14 (95% CI 1.02-1.29)], and female gender [OR 0.33 (95% CI 0.12-0.96)] and hypertension [OR 0.29 (95% CI 0.1-0.87)] to decreased risk of TG ≥ 2.25 mmol/L [OR 1.14 (95% CI 1.02-1.29)]. Taking lipid-lowering drugs (LLD) was associated with LDL-C < 2.6 mmol/L [OR 2.1 (95% CI 1.05-4.19)] and Lp(a) < 30 mg/dL [OR 0.48 (95% CI 0.25-0.93)]. Physical activity was related to LDL-C < 2.6 mmol/L [OR 2.02 (95% CI 1.02-3.98)]. Higher abdominal circumference was associated with decreased risk of TG < 1.7 mmol/L [OR 0.96 (95% CI 0.93-0.99)]. Elevated lipid parameters were related to age, gender, material status, BMI, history of DM, and hypertension. Adequate control was associated with age, education, physical activity, LLD, history of DM, and abdominal circumference.

Pretreatment with P2Y12 Receptor Inhibitors in Acute Coronary Syndromes-Is the Current Standpoint of ESC Experts Sufficiently Supported?

Excessive platelet reactivity plays a pivotal role in the pathogenesis of acute myocardial infarction. Today, the vast majority of patients presenting with acute coronary syndromes qualify for invasive treatment strategy and thus require fast and efficient platelet inhibition. Since 2008, in cases of ST-elevation myocardial infarction, the European Society of Cardiology guidelines have recommended pretreatment with a P2Y12 inhibitor. This approach has become the standard of care in the majority of centers worldwide. Nevertheless, the latest guidelines for the management of patients presenting with acute coronary syndrome without persisting ST-elevation preclude routine pretreatment with the P2Y12 receptor inhibitor. Those who oppose pretreatment support their stance with trials failing to prove the benefits of this strategy at the cost of an increased risk of major bleeding, especially in individuals inappropriately diagnosed with an acute coronary syndrome, thus having no indication for platelet inhibition. However, adequate platelet inhibition requires even up to several hours after application of a loading dose of P2Y12 receptor inhibitors. Omission of data from pharmacokinetic and pharmacodynamic studies in the absence of data from clinical studies makes generalization of the pretreatment recommendations difficult to accept. We aimed to review the scientific evidence supporting the current recommendations regarding pretreatment with P2Y12 inhibitors.

Comparison of reorganized versus unaltered cardiology departments during the COVID-19 era: A subanalysis of the COV-HF-SIRIO 6 study.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, numerous cardiology departments were reorganized to provide care for COVID-19 patients. We aimed to compare the impact of the COVID-19 pandemic on hospital admissions and in-hospital mortality in reorganized vs. unaltered cardiology departments. METHODS: The present research is a subanalysis of a multicenter retrospective COV-HF-SIRIO 6 study that includes all patients (n = 101,433) hospitalized in 24 cardiology departments in Poland between January 1, 2019 and December 31, 2020, with a focus on patients with acute heart failure (AHF). RESULTS: Reduction of all-cause hospitalizations was 50.6% vs. 21.3% for reorganized vs. unaltered cardiology departments in 2020 vs. 2019, respectively (p < 0.0001). Considering AHF alone respective reductions by 46.5% and 15.2% were registered (p < 0.0001). A higher percentage of patients was brought in by ambulance to reorganized vs. unaltered cardiology departments (51.7% vs. 34.6%; p < 0.0001) alongside with a lower rate of self-referrals (45.7% vs. 58.4%; p < 0.0001). The rate of all-cause in-hospital mortality in AHF patients was higher in reorganized than unaltered cardiology departments (10.9% vs. 6.4%; p < 0.0001). After the exclusion of patients with concomitant COVID-19, the mortality rates did not differ significantly (6.9% vs. 6.4%; p = 0.55). CONCLUSIONS: A greater reduction in hospital admissions in 2020 vs. 2019, higher rates of patients brought by ambulance together with lower rates of self-referrals and higher all-cause in-hospital mortality for AHF due to COVID-19 related deaths were observed in cardiology departments reorganized to provide care for COVID-19 patients vs. unaltered ones.

PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.

BACKGROUND: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. OBJECTIVES: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. METHODS: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. RESULTS: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: -56% vs -21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: -37.50%; 95% CI: -68.20% to -6.70%). CONCLUSIONS: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).