[Non-inferiority trials]. / Gli studi di non-inferiorità.

Superiority trials are designed to test the hypothesis that a given diagnostic or therapeutic strategy is better than (i.e. "superior to") placebo or an active control. Conversely, non-inferiority trials test the hypothesis that a newer (i.e. alternative) strategy is not "unacceptably worse" than a control (i.e. "traditional", or "older") strategy. Non-inferiority trials are increasingly conducted in clinical medicine more often when a "newer" strategy is supposed to offer a relevant advantage in terms other than clinical efficacy (i.e. better tolerability, less cost, simpler regimen, etc.) versus a "gold standard" traditional strategy. The principle underlying non-inferiority trials is that the above advantage justifies the preferential use of the newer strategy in the clinical practice even if the clinical efficacy of the "new" appears to be a bit worse than that of the "old", albeit not unacceptably worse (i.e. not beyond a pre-specified value). The demonstration of non-inferiority requires that the confidence interval of the point estimate (e.g. the hazard ratio) does not cross a pre-specified limit. The definition of such pre-specified limit, the so called "non-inferiority margin", is a pivotal point when planning non-inferiority trials. It denotes the maximally tolerated worse effect of the alternative strategy, compared with the traditional one, required to conclude that an alternative strategy is non-inferior to the traditional "gold standard". The non-inferiority margin is derived from previous trials evaluating the efficacy of the traditional strategy vs placebo. We reviewed the principles and the practical aspects in the design and conduct of non-inferiority trials.

Catheter-based renal artery denervation: facts and expectations.

Catheter-based renal artery denervation (RAD) is entering a new era. After the disappointing results of SYMPLICITY-HTN 3 trial in year 2014, several technical and methodological advancements led to execution of important SHAM-controlled randomized trials with promising results. Now, the 2023 ESH Guidelines give RAD a class of recommendation II with a Level of Evidence B. Currently, catheter-based RAD has two main areas of application: (a) Hypertensive patients who are still untreated, in whom RAD is a sort of a first-line treatment; (b) Difficult-to-control or true resistant hypertensive patients. Notably, randomized SHAM-controlled trials met their primary end-point in both these conditions. So far, we do not dispose of established predictors of the antihypertensive response to RAD. Some data suggest that younger patients with systo-diastolic hypertension, absence of diffuse atherosclerosis and evidence of sympathetic nervous system overactivity experience a better BP response to the procedure. We reviewed the available data on catheter-based RAD and included an updated meta-analysis of the results of the available SHAM-controlled trials. Overall, the reduction in 24-h systolic blood pressure (BP) after RAD exceeded that after SHAM by 4.58 mmHg (95% CI 3.07-6.10) in untreated patients, and by 3.82 mmHg (95% CI 2.46-5.18) in treated patients, without significant heterogeneity across trials, patient phenotype (untreated versus treated patients) and technique (radiofrequency versus ultrasound). There were no important safety signals related to the procedure. Notably, some data suggest that RAD could be an effective additional approach in patients with atrial fibrillation and other conditions characterized by sympathetic nervous system overactivity.

Interpretation of Ambulatory Blood Pressure Monitoring for Risk Stratification in Hypertensive Patients: The 'Ambulatory Does Prediction Valid (ADPV)' Approach.

Several outcome-based prospective investigations have provided solid data which support the prognostic value of 24 h ambulatory blood pressure over and beyond cardiovascular traditional risk factors. Average 24 h, daytime, and nighttime blood pressures are the principal components of the ambulatory blood pressure profile that have improved cardiovascular risk stratification beyond traditional risk factors. Furthermore, several additional ambulatory blood pressure measures have been investigated. The correct interpretation in clinical practice of ambulatory blood pressure monitoring needs a standardization of methods. Several algorithms for its clinical use have been proposed. Implementation of the results of ambulatory blood pressure monitoring in the management of individual subjects with the aim of improving risk stratification is challenging. We suggest that clinicians should focus attention on ambulatory blood pressure components which have been proven to act as the main independent predictors of outcome (average 24 h, daytime, and nighttime blood pressure, pulse pressure, dipping status, BP variability).

Therapy of Type 2 diabetes: more gliflozines and less metformin?

Metformin is a frequently used anti-diabetic drug. In addition to the well-known modulating properties on glyco-metabolic control, metformin reduces cardiovascular (CV) risk partly independently of its anti-hyperglycaemic effect. The use of 'new' anti-diabetic drugs, inhibitors of the renal Na-glucose co-transporter (SGLTs-I or 'gliflozines') and GLP-1 receptor agonists (GLP1-RAs), has further contributed to challenge the strictly 'gluco-centric' view of diabetic CV disease. Several controlled trials have demonstrated that the cardio-renal benefits of gliflozines and GLP1-RAs are present regardless of the presence of metformin as 'background' therapy. The impact on the 'cardio-renal continuum' exerted by SGLTs-I was also noted in non-diabetic patients with heart failure and reduced or preserved ventricular function and different levels of renal function. These drugs reduced re-hospitalization, CV mortality, and progression to end-stage renal disease. These clinical acquisitions, implemented by Scientific Societies, have led to a change in the therapeutic approach to diabetic cardio-renal disease. Although metformin still represents a valid therapeutic option to be offered particularly to 'naïve' diabetic patients without previous cardio-renal events, SGLTs-I and/or GLP1-RAs emerge as 'first-line' drugs in diabetic patients with previous CV events, or at high CV risk, without having to request 'on board' metformin therapy.

Cardiac complications of COVID-19 vaccination: now we know more.

The proliferation of good quality observational studies on the potential adverse effects of COVID-19 vaccination has greatly increased our knowledge on myocarditis and pericarditis, and also, more recently, on arterial hypertension. According to some recent studies, the incidence of a significant increase in blood pressure after COVID-19 vaccination is about 3.2% (95% CI: 1.62-6.21). The incidence of serious hypertensive emergencies or stage III hypertension has been reported as 0.6%. It is well known that the 'spike protein' of the Sars-CoV-2 virus, the synthesis of which is induced by vaccines, binds to ACE2 receptors, inducing their migration towards the inside of the cell. This would result in a lack of ACE2 activity on cell surfaces and therefore a relative deficiency of angiotensin1-7 with a relative excess of angiotensin II, which could explain, at least in part, the blood pressure increases. Regarding myo-pericarditis, there is evidence that the advantages of COVID-19 vaccination over non-vaccination remain preponderant in terms of prevented hospitalizations and serious complications of COVID-19, compared with the risk of developing myocarditis. In the age group most at risk of COVID-19 vaccine myocarditis (12-29 years), for every 100 000 vaccinated, compared to about four more cases of myocarditis we have 56 fewer hospitalizations, 13.8 admissions to intensive care and 0.6 fewer deaths. Several studies have shown that post vaccine myocarditis/pericarditis are generally short-lasting phenomena with favourable clinically course.

The myocardial bridge: incidence, diagnosis, and prognosis of a pathology of uncertain clinical significance.

The myocardial bridge (MB) is a common anomaly of the coronary tree, very often clinically silent. The artery typically involved is the left anterior descending in its proximal and/or middle portion. MB can cause ischaemia with various mechanisms, directly proportional to the degree of compression of the intra-myocardial tract, which impairs the coronary flow. It is a dynamic phenomenon that is affected by the adrenergic tone and is therefore often brought by physical exercise. MB, when symptomatic, often begins with angina from exertion; some patients have more severe conditions such as unstable angina or myocardial infarction. Coronary vasospasm related to MB-induced endothelial dysfunction can explain a number of cases that come to observation even with catastrophic pictures such as ventricular fibrillation caused by ischaemia. The diagnostic workup includes the non-invasive study using computed tomography angiography and the invasive study of the haemodynamic impact using pressure and Doppler guides. In symptomatic cases, drug therapy with a beta-blocker is enough to manage angina. When it fails, there is the option of coronary angioplasty or surgical treatment techniques.

[Substance abuse and cardiovascular risk: cocaine]. / Sostanze d'abuso e rischio cardiovascolare: la cocaina.

Cocaine abuse is widely increasing, especially in younger individuals. Cocaine is a major cause of chest pain and acute coronary syndrome and is the leading cause for drug abuse-related visits to emergency departments, most of which are due to cardiovascular complaints. Cocaine use, especially long-term, is associated with an increased risk of all-cause mortality, and with several significant, life-threatening cardiovascular diseases although the multifactorial underlying cellular and molecular pathophysiological mechanisms of acute and chronic cocaine cardiotoxicity are not well established due to limited studies. Current findings have important public health implications, reinforcing recommendations for substance use screening among young adults with heart diseases, and highlighting the need for education on its deleterious effects. Cocaine should be considered a cardiovascular risk factor, requiring attention to early detection of vascular disease in cocaine users.

[Diagnostic, therapeutic and prognostic aspects of type 2 myocardial infarction]. / Infarto miocardico di tipo 2: aspetti diagnostici, terapeutici e prognostici.

Type 2 myocardial infarction is the ischemic necrosis of cardiomyocytes due to oxygen supply/demand imbalance. The most common causes are surgery, sepsis, arrhythmias, hypo/hypertension. Patients with type 2 myocardial infarction, a disease that accounts for about 25% of total myocardial infarctions, have more comorbidities and are older than patients with type 1 myocardial infarction. Coronary angiography is not mandatory, but it may be useful for the differential diagnosis with acute coronary syndrome. The prognosis in these patients is severe and burdened by high non-cardiovascular and cardiovascular mortality. Treatment is poorly codified and involves the management of trigger events and/or treatment of the underlying coronary artery disease, which is often present; revascularization has an uncertain benefit. Ongoing studies will provide insight on this complex disease.

[The OIBOH Registry (Optimal Intensification therapy in a Broad Observed High risk patient population with coronary disease): an Italian observational study of secondary prevention after a coronary event during the pandemic COVID-19 outbreak]. / Il registro OIBOH (Optimal Intensification therapy in a Broad Observed High risk patient population with coronary disease): studio italiano osservazionale di prevenzione secondaria dopo evento coronarico durante la pandemia COVID-19.

Razionale. In Italia la pandemia COVID-19 ha determinato importanti riorganizzazioni logistiche nell'erogazione delle cure ospedaliere e di specialistica ambulatoriale. Ciò ha spinto clinici e decisori pubblico-amministrativi della Sanità ad adottare nuovi modelli organizzativi in molteplici scenari clinici. Materiali e metodi. Il registro OIBOH (Optimal Intensification therapy in a Broad Observed High risk patient population with coronary disease) è uno studio osservazionale "cross-sectional" condotto in vari centri italiani di cardiologia ambulatoriale per valutare durante la pandemia COVID-19 la capacità di identificare in breve tempo i pazienti ad altissimo rischio cardiovascolare residuo dopo un evento coronarico recente (<12 mesi). Successivamente alla valutazione clinica iniziale, venivano arruolati i pazienti ritenuti ad altissimo rischio, registrando le caratteristiche cliniche e di trattamento in una scheda di raccolta dati elettronica.Risultati. Al registro hanno partecipato 134 centri di cardiologia ambulatoriale che hanno arruolato 1428 pazienti su 3227 esaminati fra quelli che avevano avuto accesso ad una visita cardiologica durante la pandemia nel periodo ottobre 2020-marzo 2021. Il criterio di arruolamento era costituito dall'aver avuto una diagnosi di coronaropatia confermata angiograficamente negli ultimi 12 mesi, per sindrome coronarica acuta (SCA) o cronica (SCC). La SCA come evento indice era presente nel 93% dei pazienti arruolati mentre la SCC nel 7%. L'età media era 67 ± 10 anni, il 25% era di sesso femminile. Il 96.1% dei pazienti con SCA e il 67.6% dei pazienti con SCC sono stati sottoposti a rivascolarizzazione coronarica. Il 46% e 47% dei pazienti con SCA e SCC, rispettivamente, era diabetico. Oltre il 65% dei pazienti presentava una malattia coronarica multivasale. È stata osservata una importante prevalenza di arteriopatia periferica (17.5% nei pazienti con SCA e 19.6% nei pazienti con SCC). I valori di pressione arteriosa e frequenza cardiaca risultavano ben controllati (128 ± 25.2 mmHg e 65 ± 12.3 b/min nei pazienti con SCA; 127 ± 23.4 mmHg e 67 ± 13.2 b/min nei pazienti con SCC). Viceversa, è stato riportato uno scarso controllo dei livelli di colesterolemia LDL, con un valore medio di 88.8 ± 38.6 mg/dl nei pazienti con SCA e 86 ± 36.6 mg/dl nei pazienti con SCC. Solo il 16.4% dei pazienti con SCA raggiungeva i livelli raccomandati dalle attuali linee guida europee. Nonostante l'estensivo uso di statine (>90%), si è rilevato un utilizzo limitato dell'associazione statina ad alta intensità + ezetimibe (solo il 22.4% dei pazienti). Estremamente basso è stato l'utilizzo di inibitori di PCSK9 (2.5%). La duplice terapia antiaggregante piastrinica (DAPT) è risultata complessivamente ben condotta fin dalla dimissione ospedaliera. Nei pazienti in DAPT, l'inibitore P2Y12 più utilizzato è risultato il ticagrelor alla dose di 90 mg, soprattutto dopo un evento coronarico acuto (in circa l'80% dei pazienti con SCA). Nella stragrande maggioranza dei casi (>90%) i cardiologi ambulatoriali hanno posto indicazione a prosecuzione della DAPT oltre i 12 mesi con aspirina e ticagrelor 60 mg bid. Conclusioni. La gestione del paziente con coronaropatia in fase cronica stabilizzata è molto complessa. Tale complessità logistico-gestionale si è accentuata durante la pandemia COVID-19. Il registro OIBOH ha evidenziato un'ottima capacità di identificare le problematiche clinico-prognostiche delle cardiologie ambulatoriali italiane, specie nei pazienti ad altissimo rischio residuo. Rimangono importanti aree di miglioramento come uno stretto controllo della colesterolemia LDL, mentre altre raccomandazioni delle linee guida, come la prosecuzione della DAPT con ticagrelor 60 mg oltre i 12 mesi, risultano ben applicate. L'implementazione dell'assistenza con la medicina digitale e l'intelligenza artificiale potrebbe migliorare di molto la performance dei clinici.

Soluble CD40 ligand and outcome in patients with coronary artery disease undergoing percutaneous coronary intervention.

OBJECTIVES: CD40 ligand (CD40L), a transmembrane glycoprotein belonging to the tumor necrosis factor family and expressed by a variety of cells, is involved in the basic mechanisms of inflammation, atherosclerosis and thrombosis. Some studies suggest that the soluble form of CD40L (sCD40L) is a predictor of major cardiovascular events and mortality in a variety of clinical settings, but data from literature are conflicting. METHODS: We studied consecutive patients with acute (ACS) or chronic (CCS) coronary syndrome who underwent percutaneous coronary artery intervention (PCI). Blood samples for sCD40L dosage were taken at baseline immediately before PCI. We tested the relation between sCD40L and pre-specified outcome measures consisting of new ACS, clinical restenosis and all-cause mortality. We recruited 3,841 patients (mean age 64 ± 11 years, 79% men) with ACS (n=2,383) or CCS (n=1,458). RESULTS: During a mean follow-up of two years (±0.6 years), 642 patients developed ACS, 409 developed restenosis (≥70% of at least one of the previously treated coronary segments) and 175 died. For each 1-standard deviation increase in sCD40L (0.80 ng/mL), the hazard ratios (HRs) for ACS, restenosis, and mortality were 1.11 (95% confidence interval [CI]: 1.05 to 1.18, p<0.0001), 1.10 (95% CI: 1.02 to 1.19, p=0.010), and 1.00 (95% CI: 0.86 to 1.16, p=0.983), respectively. In multivariable Cox regression models with adjustment for several potential confounders including age, acute or chronic coronary syndrome, multi-vessel disease, stent placement, diabetes, previous coronary events and dyslipidemia, sCD40L remained an independent predictor of ACS and coronary restenosis. There were no interactions between sCD40L and acute or chronic coronary syndrome or stent placement. CONCLUSIONS: Among patients with ACS or CCS who undergo PCI, higher levels of sCD40L predict an increased risk of acute coronary events and coronary restenosis, but not of mortality.

The ISCHEMIA trial: optimal medical therapy against PTCA in the stable patient: the endless story.

In patients with acute coronary syndrome, an aggressive approach with coronary angiography and revascularization leads to important benefits compared to medical therapy alone. On the contrary, the prognostic impact of coronary revascularization in patients suffering from stable coronary artery disease has long been the subject of debate. The pivotal study in this area is COURAGE, published in 2007, in which coronary revascularization showed no benefit about the combined endpoint of death from all causes and acute myocardial infarction (AMI), compared to medical therapy. The ISCHEMIA study, published in 2020, compared selective coronary angiography and revascularization vs. a non-invasive approach. By protocol, the patients were initially evaluated with coronary computed axial tomography angiography: in case of coronary stenosis >50%, they were then randomized to the two strategies. While in the invasive arm patients were revascularized, in the non-invasive arm revascularization was used only in case of patient destabilization. As in COURAGE, the results of ISCHEMIA did not demonstrate superiority of revascularization over medical therapy alone for a combined endpoint of cardiovascular death, AMI, or hospitalization for unstable angina, heart failure, or cardiac arrest. Based on recent evidence from ISCHEMIA, it is therefore confirmed that coronary revascularization in stable patients does not seem to improve the prognosis compared to medical therapy alone.

Acute kidney injury in patients with acute coronary syndrome undergoing invasive management treated with bivalirudin vs. unfractionated heparin: insights from the MATRIX trial.

AIMS: Acute kidney injury (AKI) is a critical complication among patients with acute coronary syndrome (ACS) undergoing invasive management. The value of adjunctive antithrombotic strategies, such as bivalirudin or unfractionated heparin (UFH) on the risk of AKI is unclear. METHODS AND RESULTS: Among 7213 patients enrolled in the MATRIX-Antithrombin and Treatment Duration study, 128 subjects were excluded due to incomplete information on serum creatinine (sCr) or end-stage renal disease on dialysis treatment. The primary endpoint was AKI defined as an absolute (>0.5 mg/dL) or a relative (>25%) increase in sCr. AKI occurred in 601 patients (16.9%) treated with bivalirudin and 616 patients (17.4%) treated with UFH [odds ratio (OR): 0.97; 95% confidence interval (CI): 0.85-1.09; P = 0.58]. A >25% sCr increase was observed in 597 patients (16.8%) with bivalirudin and 616 patients (17.4%) with UFH (OR: 0.96; 95% CI: 0.85-1.08; P = 0.50), whereas a >0.5 mg/dL absolute sCr increase occurred in 176 patients (5.0%) with bivalirudin vs. 189 patients (5.4%) with UFH (OR: 0.92; 95% CI: 0.75-1.14; P = 0.46). By implementing the Kidney Disease Improving Global Outcomes (KDIGO) criteria, the risk of AKI was not significantly different between bivalirudin and UFH groups (OR: 0.88; 95% CI: 0.72-1.07; P = 0.21). Subgroup analyses of the primary endpoint suggested a benefit with bivalirudin in patients randomized to femoral access. CONCLUSION: Among ACS patients undergoing invasive management, the risk of AKI was not significantly lower with bivalirudin compared with UFH. TRIAL REGISTRATION: clinicaltrials.gov NCT01433627.

Impact of SARS-CoV-2 positivity on clinical outcome among STEMI patients undergoing mechanical reperfusion: Insights from the ISACS STEMI COVID 19 registry.

BACKGROUND AND AIMS: SARS-Cov-2 predisposes patients to thrombotic complications, due to excessive inflammation, endothelial dysfunction, platelet activation, and coagulation/fibrinolysis disturbances. The aim of the present study was to evaluate clinical characteristics and prognostic impact of SARS-CoV-2 positivity among STEMI patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: We selected SARS-CoV-2 positive patients included in the ISACS-STEMI COVID-19, a retrospective multicenter European registry including 6609 STEMI patients treated with PPCI from March 1st until April 30th, in 2019 and 2020. As a reference group, we randomly sampled 5 SARS-Cov-2 negative patients per each SARS-CoV-2 positive patient, individually matched for age, sex, and hospital/geographic area. Study endpoints were in-hospital mortality, definite stent thrombosis, heart failure. RESULTS: Our population is represented by 62 positive SARS-CoV-2 positive patients who were compared with a matched population of 310 STEMI patients. No significant difference was observed in baseline characteristics or the modality of access to the PCI center. In the SARS-CoV-2 positive patients, the culprit lesion was more often located in the RCA (p < 0.001). Despite similar pre and postprocedural TIMI flow, we observed a trend in higher use of GP IIb-IIIa inhibitors and a significantly higher use of thrombectomy in the SARS-CoV-2 positive patients. SARS-CoV-2 positivity was associated with a remarkably higher in hospital mortality (29% vs 5.5%, p < 0.001), definite in-stent thrombosis (8.1% vs 1.6%, p = 0.004) and heart failure (22.6% vs 10.6%, p = 0.001) that was confirmed after adjustment for confounding factors. CONCLUSIONS: Our study showed that among STEMI patients, SARS-CoV-2 positivity is associated with larger thrombus burden, a remarkably higher mortality but also higher rates of in-stent thrombosis and heart failure.

Impact of renin-angiotensin system inhibitors on mortality during the COVID Pandemic among STEMI patients undergoing mechanical reperfusion: Insight from an international STEMI registry.

BACKGROUND: Concerns have been raised on a potential interaction between renin-angiotensin system inhibitors (RASI) and the susceptibility to coronavirus disease 2019 (COVID-19). No data have been so far reported on the prognostic impact of RASI in patients suffering from ST-elevation myocardial infarction (STEMI) during COVID-19 pandemic, which was the aim of the present study. METHODS: STEMI patients treated with primary percutaneous coronary intervention (PPCI) and enrolled in the ISACS-STEMI COVID-19 registry were included in the present sub-analysis and divided according to RASI therapy at admission. RESULTS: Our population is represented by 6095 patients, of whom 3654 admitted in 2019 and 2441 in 2020. No difference in the prevalence of SARSCoV2 infection was observed according to RASI therapy at admission (2.5% vs 2.1%, p = 0.5), which was associated with a significantly lower mortality (adjusted OR [95% CI]=0.68 [0.51-0.90], P = 0.006), confirmed in the analysis restricted to 2020 (adjusted OR [95% CI]=0.5[0.33-0.74], P = 0.001). Among the 5388 patients in whom data on in-hospital medication were available, in-hospital RASI therapy was associated with a significantly lower mortality (2.1% vs 16.7%, OR [95% CI]=0.11 [0.084-0.14], p < 0.0001), confirmed after adjustment in both periods. Among the 62 SARSCoV-2 positive patients, RASI therapy, both at admission or in-hospital, showed no prognostic effect. CONCLUSIONS: This is the first study to investigate the impact of RASI therapy on the prognosis and SARSCoV2 infection of STEMI patients undergoing PPCI during the COVID-19 pandemic. Both pre-admission and in-hospital RASI were associated with lower mortality. Among SARSCoV2-positive patients, both chronic and in-hospital RASI therapy showed no impact on survival.

Impact of COVID-19 Pandemic on Mechanical Reperfusion for Patients With STEMI.

BACKGROUND: The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality. OBJECTIVES: The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of "at-risk" patient cohorts for failure to present or delays to treatment. METHODS: This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality. RESULTS: A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p < 0.0001). The heterogeneity among centers was not related to the incidence of death due to COVID-19. A significant interaction was observed for patients with arterial hypertension, who were less frequently admitted in 2020 than in 2019. Furthermore, the pandemic was associated with a significant increase in door-to-balloon and total ischemia times, which may have contributed to the higher mortality during the pandemic. CONCLUSIONS: The COVID-19 pandemic had significant impact on the treatment of patients with STEMI, with a 19% reduction in PPCI procedures, especially among patients suffering from hypertension, and a longer delay to treatment, which may have contributed to the increased mortality during the pandemic. (Primary Angioplasty for STEMI During COVID-19 Pandemic [ISACS-STEMI COVID-19] Registry; NCT04412655).

Treatment of stable ischaemic heart disease: the old and the new.

Stable ischaemic heart disease is a frequent and very heterogeneous condition. Drug therapy is important, in these patients, for improving their prognosis and controlling their symptoms. The typical clinical manifestation of obstructive coronary disease is angina pectoris. This symptom can be improved by various classes of compounds, namely beta-blockers (BBs), calcium antagonist, and nitrates. More recently, ranolazine and ivabradine have been introduced. All these drugs have been proven to reduce significantly angina. On the other hand, there are no evidences supporting improvement in prognosis, besides for the use of BBs, in patients with previous myocardial infarction (MI) or systolic dysfunction. Besides drugs for symptoms control, these patients also receive antiplatelet drugs, specifically aspirin, and lipid lowering compounds such as statins. Furthermore, recent evidences supported the use of low doses direct anticoagulant, or a second antiplatelet agent in patients with previous MI. Similarly, a very low LDL cholesterol level, such as obtained with PCKS9 inhibitors, seems very beneficial in these patients. It is possible that in the near future a specific role for neo-angiogenesis factors and cellular therapies, could be proven, albeit, presently these treatments are not supported by solid evidences.

Predictors of in-hospital and long-term mortality in unselected patients admitted to a modern coronary care unit.

AIMS: Objective data on epidemiology, management and outcome of patients with acute cardiac illness are still scarce, and producing evidence-based guidelines remains an issue. In order to define the clinical characteristics and the potential predictors of in-hospital and long-term mortality, we performed a retrospective, observational study, in a tertiary cardiac centre in Italy. METHODS: One thousand one hundred and sixty-five consecutive patients, admitted to our intensive cardiac care unit (ICCU) during the year 2016, were included in the study. The data were collected from the hospital discharge summary and the electronic chart records. RESULTS: Global in-hospital mortality was 7.2%. Predictors of in-hospital mortality were age [odds ratio (OR): 2.0; P = 0.011], female sex (OR: 2.18; P = 0.003), cardiac arrest (OR: 12.21; P = 0.000), heart failure/cardiogenic shock (OR: 9.99; P = 0.000), sepsis/septic shock (OR: 5.54; P = 0.000), acute kidney injury (OR: 3.25; P = 0.021) and a primary diagnosis of acute heart failure or a condition other than acute heart failure and acute coronary syndrome. During a mean follow-up period of 17.4 ± 4.8 months, 96 all-cause deaths occurred in patients who were still alive at discharge. One-year mortality rate was 8.2%. Predictors of long-term mortality were age (hazard ratio: 1.08; P = 0.000), female sex (hazard ratio: 0.59; P = 0.022), comorbidity at least 3 (hazard ratio: 1,60; P = 0.047), acute kidney injury (hazard ratio: 3.15; P = 0.001), inotropic treatment (hazard ratio: 2.54; P = 0.002) and a primary diagnosis of acute heart failure. CONCLUSION: In our Level-2 ICCU, predictors of in-hospital and long-term mortality are similar to those commonly found in a Level-3 ICU. These data strongly suggest that ICUs dealing with acute cardiovascular patients should be reorganized with a necessary upgrading of competences and resources for medical and nursing staff.

[Which role today for intra-aortic balloon counterpulsation?] / Quale ruolo oggi per la contropulsazione aortica?

Intra-aortic balloon pump (IABP) is a percutaneous assist device that is easy to implant, is associated with low complication rates and, therefore, is widely used. It is commonly applied by femoral access, although it can be used with axillary access. It reduces afterload and preload, with a slight increase in mean arterial pressure and coronary perfusion. For these characteristics, it has been extensively used in cardiogenic shock, even without a clear demonstration of efficacy from randomized clinical trials; the IABP-SHOCK II study, the largest trial carried out so far, failed to demonstrate the usefulness of IABP in this setting. Furthermore, the routine use of IABP in patients with acute anterior myocardial infarction was not associated with any benefit in reducing ischemic area at cardiac magnetic resonance, as shown by the CRISP-AMI trial. For these reasons, the international guidelines do not support the routine use of IABP in acute myocardial infarction complicated by cardiogenic shock, suggesting instead its use in different scenarios such as heart failure associated with acute mechanical complications or acute myocarditis. IABP is currently used in patients undergoing percutaneous coronary interventions or surgical coronary revascularization judged at high risk of complications. In the former scenario, the evidence from the literature is very scarce; in the latter one, small trials and meta-analytical studies suggest a treatment benefit with IABP in the preoperative period.Despite limited evidence of efficacy, IABP will continue to play an important role in today's cardiology and is going to remain the most widely used mechanical circulatory support device.

Use of the Dual-Antiplatelet Therapy Score to Guide Treatment Duration After Percutaneous Coronary Intervention.

BACKGROUND: The dual-antiplatelet therapy (DAPT) score was developed to identify patients more likely to derive harm (score <2) or benefit (score ≥2) from prolonged DAPT after percutaneous coronary intervention (PCI). OBJECTIVE: To evaluate the safety and efficacy of DAPT duration according to DAPT score. DESIGN: Retrospective assessment of DAPT score-guided treatment duration in a randomized clinical trial. (ClinicalTrials.gov: NCT00611286). SETTING: PCI patients. PATIENTS: 1970 patients undergoing PCI. INTERVENTION: DAPT (aspirin and clopidogrel) for 24 versus 6 months. MEASUREMENTS: Primary efficacy outcomes were death, myocardial infarction, or cerebrovascular accident. The primary safety outcome was type 3 or 5 bleeding according to the Bleeding Academic Research Consortium definition. Outcomes were assessed between 6 and 24 months. RESULTS: 884 patients (44.9%) had a DAPT score of at least 2, and 1086 (55.1%) had a score less than 2. The reduction in the primary efficacy outcome with 24- versus 6-month DAPT was greater in patients with high scores (risk difference [RD] for score ≥2, -2.05 percentage points [95% CI, -5.04 to 0.95 percentage points]; RD for score <2, 2.91 percentage points [CI, -0.43 to 6.25 percentage points]; P = 0.030). However, the difference by score for the primary efficacy outcome varied by stent type; prolonged DAPT with high scores was effective only in patients receiving paclitaxel-eluting stents (RD, -7.55 percentage points [CI, -12.85 to -2.25 percentage points]). The increase in the primary safety outcome with 24- versus 6-month DAPT was greater in patients with low scores (RD for score ≥2, 0.20 percentage point [CI, -1.20 to 1.60 percentage points]; RD for score <2, 2.58 percentage points [CI, 0.71 to 4.46 percentage points]; P = 0.046). LIMITATION: Retrospective calculation of the DAPT score. CONCLUSION: Prolonged DAPT resulted in harm in patients with low DAPT scores undergoing PCI but reduced risk for ischemic events in patients with high scores receiving paclitaxel-eluting stents. Whether prolonged DAPT benefits patients with high scores treated with contemporary drug-eluting stents requires further study. PRIMARY FUNDING SOURCE: None.