Evaluation of Drug Interactions in Patients Treated with DAAs for Hepatitis C Therapy with Comorbidities and Cardiovascular Issues—A Delphi Consensus Project

Orally administered direct-acting antivirals (DAAs) have dramatically changed the possibility of curing HCV (hepatitis C virus) infection, with the two principal HCV regimens based on the combination of glecaprevir + pibrentasvir (GLE-PIB) and sofosbuvir + velpatasvir (SOF-VEL). A combination of drugs containing NS3/4A protease inhibitors, as well as the fact that almost all HCV patients can be treated at present, may expose patients to a higher rate of drug–drug interactions (DDIs). The hepatitis C treatment recommendations from the EASL (European Association for the Study of the Liver) state that, prior to starting treatment with a DAA, a detailed drug history should be taken; yet, the decision on managing the potential DDIs is not always clear. For this reason, a group of Italian cardiologists and hepatologists promoted a survey among colleagues to assess the controversial issues when treating patients with chronic hepatitis C taking concomitant cardiovascular drugs, aiming to reach a consensus on the best practice to apply when treating a patient with chronic hepatitis C who is taking concomitant drugs for cardiovascular diseases. Two consecutive questionnaires were proposed between June and July 2022 to a qualitative Expert Panel (EP) of 14 gastroenterologists, infectologists, hepatologists, and internists, with statistical analyses performed on 100% of the responses for both questionnaires. Agreement among experts was assessed following the Delphi method as developed by the RAND Corporation. The interviewed experts consider DDIs a critical clinical problem to be evaluated in HCV patients. Therefore, dose changes, drug substitution, and discontinuation of concomitant cardiovascular drugs should be discouraged, even if planned for a relatively short period. Since oral DAAs have different DDIs profiles, hepatologists should prefer the antiviral DAA combination presenting the lowest instance of potential interactions

A META-ANALYSIS REPORTING EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS IN PATIENTSWITHOUT HEART FAILURE

Translation articles: G. Savarese, P. Costanzo, J.G.F. Cleland, E. Vassallo, D. Ruggiero, G. Rosano, P. Perrone-Filardi «A Meta-Analysis Reporting Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Patients Without Heart Failure» J Am Coll Cardiol 2013;61(2):131-42; http://dx.doi.org/10.1016/j.jacc.2012.10.01

Do rebreathing manoeuvres for non-invasive measurement of cardiac output during maximum exercise test alter the main cardiopulmonary parameters?

Background: Inert gas rebreathing has been recently described as an emergent reliable non-invasive method for cardiac output determination during exercise, allowing a relevant improvement of cardiopulmonary exercise test clinical relevance. For cardiac output measurements by inert gas rebreathing, specific respiratory manoeuvres are needed which might affect pivotal cardiopulmonary exercise test parameters, such as exercise tolerance, oxygen uptake and ventilation vs carbon dioxide output (VE/VCO2) relationship slope. Method: We retrospectively analysed cardiopulmonary exercise testing of 181 heart failure patients who underwent both cardiopulmonary exercise testing and cardiopulmonary exercise test+cardiac output within two months (average 16 \ub1 15 days). All patients were in stable clinical conditions (New York Heart Association I\u2013III) and on optimal medical therapy. Results: The majority of patients were in New York Heart Association Class I and II (78.8%), with a mean left ventricular ejection fraction of 31 \ub1 10%. No difference was found between the two tests in oxygen uptake at peak exercise (1101 (interquartile range 870\u20131418) ml/min at cardiopulmonary exercise test vs 1103 (844\u20131389) at cardiopulmonary exercise test-cardiac output) and at anaerobic threshold. However, anaerobic threshold and peak heart rate, peak workload (75 (58\u2013101) watts and 64 (42\u201390), p < 0.01) and carbon dioxide output were significantly higher at cardiopulmonary exercise testing than at cardiopulmonary exercise test+cardiac output, whereas VE/VCO2 slope was higher at cardiopulmonary exercise test+cardiac output (30 (27\u201335) vs 33 (28\u201337), p < 0.01). Conclusion: The similar anaerobic threshold and peak oxygen uptake in the two tests with a lower peak workload and higher VE/VCO2 slope at cardiopulmonary exercise test+cardiac output suggest a higher respiratory work and consequent demand for respiratory muscle blood flow secondary to the ventilatory manoeuvres. Accordingly, VE/VCO2 slope and peak workload must be evaluated with caution during cardiopulmonary exercise test+cardiac output

Intellectual disability, sensation and thinking through affect

Acute coronary syndromes (ACSs) represent a high-risk condition, as enhanced platelet reactivity importantly influences myocardial perfusion and procedural results after percutaneous coronary intervention (PCI). In fact, higher rate of periprocedural myocardial infarction (PMI) and reduced event-free survival have been reported in these patients. The single nucleotide polymorphism Leu33Pro of platelet glycoprotein IIIa has been related to an increased platelet reactivity, a lower response to antiplatelet agents and higher risk of stent restenosis. Therefore, our aim was to evaluate the impact of this polymorphism on PMI in patients undergoing PCI for non-ST-segment elevation MI (NSTEMI). Our population is represented by 478 consecutive patients undergoing coronary angioplasty for NSTEMI. Cardiac biomarkers were monitored at intervals from 8 to 48 h after the procedure. Genetic analysis was performed to assess the presence of Leu33Pro polymorphism. A total of 156 patients (32.6%) were polymorphic. Clinical features did not differ according to genetic status, neither pharmacological treatment pre and during angioplasty. PlA carriers had lower rate of calcifications (P = 0.01) and higher coronary tortuosity (P = 0.03) at angiography and underwent more frequently to thrombectomy (P = 0.05). PCI-related complications did not differ according to genotype. Leu33Pro polymorphism was not associated with increased risk of periprocedural myonecrosis and PMI even after correction for baseline differences, [odds ratio (OR) (95% confidence interval (CI) = 0.70 (0.44-1.13), P = 0.15 for PMI and OR (95% CI) = 0.77 (0.53-1.11), P = 0.17 for myonecrosis, respectively]. Results were confirmed in high-risk subgroups of patients. In conclusion, among patients undergoing PCI for ACS, the polymorphism Leu33Pro of platelet glycoprotein IIIa is not associated with increased risk of PMI

Long-term persistence with evolocumab treatment and sustained reductions in LDL-cholesterol levels over 30 months: final results from the European observational HEYMANS study

BACKGROUND AND AIMS: Variability in low-density lipoprotein-cholesterol (LDL-C) level control at a population level is associated with poor cardiovascular outcomes. Limited data exist on LDL-C level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. Using data from the HEYMANS registry, this analysis aimed to assess evolocumab persistence and discontinuation over 30 months of evolocumab treatment and to evaluate at a population level the variability in LDL-C level reductions during the study period. METHODS: HEYMANS was a prospective registry of adults initiating evolocumab in routine clinical practice in 12 European countries. Data were collected for up to and including 6 months before evolocumab initiation and up to 30 months after. Evolocumab discontinuation was analysed for two time periods: 0-12 months and 12-30 months. RESULTS: In total, 1951 patients were included in the study. The median reduction in LDL-C levels was 58% within 3 months after evolocumab initiation; this reduction was maintained over 30 months. More than 90% of patients continued receiving evolocumab at 12 months and 30 months of follow-up. Of patients with an LDL-C level measurement during follow-up, approximately 85% achieved a ≥30% reduction from baseline at each follow-up visit and approximately 60% achieved a ≥50% reduction. CONCLUSIONS: Evolocumab therapy was associated with sustained LDL-C level reductions up to 30 months, and persistence with evolocumab remained high, both at 12 and 30 months. Expanding the use of monoclonal antibodies such as evolocumab could provide improvements in LDL-C level control at a population level in European clinical practice

Antimicrobial activity of resveratrol-derived monomers and dimers against foodborne pathogens

Plant polyphenolic compounds are considered a promising source for new antibacterial agents. In this study, we evaluated the antimicrobial activity of a collection of resveratrol-derived monomers and dimers screened as single molecules against a panel of nine foodborne pathogens. The results demonstrated that two monomers (i.e., pterostilbene 2 and (E)-3-hydroxy-4\u2032,5-dimethoxystilbene 9) and three dimers (i.e., \u3b4-viniferin 10, viniferifuran 14 and dehydro-\u3b4-viniferin 15) were endowed with significant antibacterial activity against gram-positive bacteria. The exposure of gram-positive foodborne pathogens to 100 \ub5g/mL of 2, 9 and 15 induced severe cell membrane damage, resulting in the disruption of the phospholipid bilayer. The most promising dimeric compound, dehydro-\u3b4-viniferin 15, was tested against Listeria monocytogenes, resulting in a loss of cultivability, viability and cell membrane potential. TEM analysis revealed grave morphological modifications on the cell membrane and leakage of intracellular content, confirming that the cell membrane was the principal biological target of the tested derivative

SGLT-2 inhibitors for treatment of heart failure in patients with and without type 2 diabetes: A practical approach for routine clinical practice

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i), initially studied and approved for the treatment of diabetes, are now becoming a promising class of agents to treat heart failure (HF) and chronic kidney disease (CKD), even in patients without diabetes. While the potential benefits in several diseases (usually treated by different medical specialties) is amplifying the interest in these drugs, their use in frail patients with multiple pathologies and on polypharmacy can be complex, requiring a composite multidisciplinary approach. Following a brief overview of the evidence supporting the benefits of SGLT-2i in patients with HF or CKD, we herein provide guidance for prescribing SGLT-2i in daily practice using a multidisciplinary approach. A shared treatment algorithm is presented for initiating an SGLT-2i in patients already being treated for diabetes and HF. Tools to prevent hypoglycemia, blood pressure drop, genital infections, euglycemic diabetic ketoacidosis and eGFR dip are also provided. It is hoped that this practical, multidisciplinary guidance for initiating SGLT-2i in patients with HF and/or CKD, whatever therapy they are currently on, can help to offer SGLT-2i to the largest population of patients possible to provide the most therapeutic benefit

Efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation and heart failure: A meta-analysis

Objectives This study investigated the efficacy and safety of novel oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and heart failure (HF) by a meta-analysis. Background AF is quite prevalent in patients with HF. Methods Four phase III clinical trials comparing NOACs to warfarin in patients with AF were included. Each patient was defined as affected by HF according to the criteria of the trial in which the patient was enrolled. Pre-specified outcomes were the composite of stroke/systemic embolism (SSE); major, intracranial, and any bleeding; and cardiovascular (CV) and all-cause death. Results A total of 55,011 patients were enrolled, 26,384 (48%) with HF, and 28,627 (52%) without HF; 27,518 receiving NOACs and 27,493 receiving warfarin (median, 70 years of age; 36% females; follow-up: 1.5 to 2.8 years). Rates of SSE (relative risk [RR]: 0.98; 95% confidence interval [CI]: 0.90 to 1.07]; p = 0.68) and major bleeding (RR: 0.95; 95% CI: 0.88 to 1.03; p = 0.21) were comparable in patients with and without HF. HF patients had reduced rates of any (RR: 0.86; 95% CI: 0.81 to 0.91; p 0.05 for each). Conclusions Patients with AF and HF had increased mortality but reduced rates of intracranial and any bleeding compared with the no-HF patients, with no differences in rates of SSE and major bleeding. NOACs significantly reduced SSE, major bleeding, and intracranial hemorrhage in HF patients. No interactions in efficacy and safety of NOACs were observed between AF patients with and without HF

An expert opinion paper on statin adherence and implementation of new lipid-lowering medications by the ESC Working Group on Cardiovascular Pharmacotherapy: Barriers to be overcome.

Benefits and safety on statins have been well-established over 20 years of research. Despite this, the vast majority of patients are not adequately treated and do not achieve the low-density lipoprotein cholesterol target levels. This is mainly due to poor adherence, which is associated with dangerous and sometimes fatal outcomes. To increase adherence and prevent worse outcomes, a combination therapy with lower dosage of statins and new lipid-lowering drugs may be used. However, the implementation of new lipid-lowering drugs in European countries is still at the beginning. For these reasons, the aim of this position paper is to give an up-to-date indication from the ESC Working Group on Cardiovascular Pharmacotherapy in order to discuss the barriers towards statins adherence and new lipid-lowering drugs implementation in Europe