[NNT and NNH: statistics and stochastics in the evaluation of added therapeutic value].

Any pharmacological, invasive, surgical health intervention should have an added therapeutic value as well as the requirements of quality, safety, efficacy, to be considered as a medical device based on scientific evidence and of clinical utility for the patient. The intervention should be shared between the doctor and the patient who should have rigorous but simple tools to decide on the best therapy to undertake. Assessment of relative risk reduction is commonly used in the scientific literature to quantify both statistical and clinical significance.

[Shared decision-making in metaclinical medicine: from informed consent to shared probability].

At the dawn of "metaclinical medicine" era, shared decision-making represents the overcoming of modern medicine guidelines and classical medicine experience. The patient's life plan, the doctor's health plan, the scientist's evidence-based plan, the administrator's plan and the beliefs of the society for healthcare options should be integrated into the shared decision-making process to avoid patient's unrealistic expectations, doctor's self-referential and defensive medicine, the science without compassion of the scientist, the administered medicine of the politician, the herd mentality of artificial intelligence. For a doctor who must evaluate according to science and conscience, it becomes difficult to make decisions about a patient who thinks that there can be "no decisions about me without me".

[The statistical literacy of "my" patient].

The fundamental questions asked by the patient to the doctor are: "What is the best cure for my disease?"; "How likely am I to benefit from the intervention you propose?". To answer on a scientific basis, the doctor can use seven parameters: 1) the relative reduction of the risk; 2) its absolute reduction; 3) the necessary number of patients to be treated to obtain a benefit; 4) the number of patients to be treated to avoid an adverse event; 5) average life time gained; 6) average life time gained in good health; 7) the residual risk.The doctor, not a statistician or scientist, must explain to the patient the reason for his proposals, to pass from consent to sharing; this requires strong commitment and cultural growth of both the patient and the doctor.

Spironolactone effect on circulating procollagen type I carboxy-terminal propeptide: Pooled analysis of three randomized trials.

Background: Spironolactone might improve the prognosis of patients with heart failure with preserved left ventricular ejection fraction (HFpEF), but the mechanisms by which it acts are uncertain. Serum concentrations of procollagen type I carboxy-terminal propeptide (PICP) reflect the synthesis of type I collagen and correlate well with histologically proven cardiac fibrosis.

Aims: To investigate the effect of spironolactone on serum PICP concentration in patients with stage B and C HFpEF across three trials (HOMAGE, ALDO-DHF, and TOPCAT) for which measurements of serum PICP were available.

Spironolactone effect on cardiac structure and function of patients with heart failure and preserved ejection fraction: a pooled analysis of three randomized trials.

Aims: Spironolactone is currently used in a large proportion of patients with heart failure and preserved ejection fraction (HFpEF), yet its effect on cardiac structure and function in a large population has not been well established. The aim of this study was to evaluate the impact of spironolactone on key echocardiographic parameters in HFpEF.

Methods And Results: An individual-patient-data meta-analysis of three randomized trials (HOMAGE, Aldo-DHF, and TOPCAT) was performed comparing spironolactone (9-12 month exposure) to placebo (or control) for the changes in left atrial volume index (LAVi), left ventricular mass index (LVMi), interventricular septum (IVS) thickness, E/e' ratio, and left ventricular ejection fraction (LVEF) among patients with stage B (HOMAGE) or C (Aldo-DHF and TOPCAT) HFpEF.

[Scientific communication to "my" patient].

In scientific communication, "my" patient should be differentiated from the "average" patient of randomized controlled clinical trials. Communication addressed to "my" patient takes place in the delicate and a certain sense intimate doctor-patient relationship in which various components are involved, such as the patient's expectations, needs and hopes, the professional, emotional and bureaucratic fatigue of the doctor, scientist's rigor and superficiality, the administrator's economic and organizational sustainability, social, media and judicial control. The simple trust required in the era of "paternalism" has undergone a transition first into "informed consent" and then into "shared decision-making".

Dyskalemia in people at increased risk for heart failure: findings from the heart 'OMics' in AGEing (HOMAGE) trial.

Aims: In people at risk of heart failure (HF) enrolled in the Heart 'OMics' in AGEing (HOMAGE) trial, spironolactone reduced circulating markers of collagen synthesis, natriuretic peptides, and blood pressure and improved cardiac structure and function. In the present report, we explored factors associated with dyskalaemia.

Methods And Results: The HOMAGE trial was an open-label study comparing spironolactone (up to 50 mg/day) versus standard care in people at risk for HF.

The association between markers of type I collagen synthesis and echocardiographic response to spironolactone in patients at risk of heart failure: findings from the HOMAGE trial.

Aims: Procollagen type I C-terminal propeptide (PICP) and procollagen type III N-terminal propeptide (PIIINP) are markers reflecting collagen synthesis in cardiac fibrosis. However, they may be influenced by the presence of non-cardiac comorbidities (e.g.

Influence of ejection fraction on biomarker expression and response to spironolactone in people at risk of heart failure: findings from the HOMAGE trial.

Aims: Left ventricular ejection fraction (LVEF) can provide haemodynamic information and may influence the response to spironolactone and other heart failure (HF) therapies. We aimed to study patient characteristics and circulating protein associations with LVEF, and whether LVEF influenced the response to spironolactone.

Methods And Results: HOMAGE enrolled patients aged >60 years at high risk of developing HF with a LVEF ≥45%.

[Process to insulin for type 2 diabetes mellitus therapy].

In type 1 diabetes mellitus and in symptomatic and critical hyperglycemic states, insulin is a lifesaving drug; however, its value in long-term type 2 diabetes therapy, which represents more than 90% of diabetes, has not been assessed. This happens despite the fact that, in randomized studies on type 2 diabetes, insulin is used in two-thirds of cases when intensive hypoglycemic treatment is needed and in half of the patients when treatment is the standard one. This is a major issue from a clinical, economic and social-health organization point of view as insulin therapy is expensive and needs a complex organization.

The Effect of Spironolactone in Patients With Obesity at Risk for Heart Failure: Proteomic Insights from the HOMAGE Trial.

Background: Adipose tissue influences the expression and degradation of circulating biomarkers. We aimed to identify the biomarker profile and biological meaning of biomarkers associated with obesity to assess the effect of spironolactone on the circulating biomarkers and to explore whether obesity might modify the effect of spironolactone.

Methods And Results: Protein biomarkers (n = 276) from the Olink Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline, 1 month and 9 months from the HOMAGE randomized controlled trial participants.

Biomarker-based assessment of collagen cross-linking identifies patients at risk of heart failure more likely to benefit from spironolactone effects on left atrial remodelling. Insights from the HOMAGE clinical trial.

Aims: The HOMAGE randomized trial found that spironolactone reduced left atrial volume index (LAVI), E:A ratio, and a marker of collagen type I synthesis (procollagen type I C-terminal propeptide) in patients at risk of heart failure (HF). Previous trials showed that patients with HF, preserved ejection fraction and low serum collagen type I C-terminal telopeptide to matrix metalloproteinase-1 ratio (CITP:MMP-1), associated with high collagen cross-linking, had less improvement in diastolic function with spironolactone. We evaluated the interaction between serum CITP:MMP-1 and spironolactone on cardiac function in the HOMAGE trial.

Proteomic mechanistic profile of patients with diabetes at risk of developing heart failure: insights from the HOMAGE trial.

Background: Patients with diabetes mellitus (DM) are at increased risk of developing heart failure (HF). The "Heart OMics in AGEing" (HOMAGE) trial suggested that spironolactone had beneficial effect on fibrosis and cardiac remodelling in an at risk population, potentially slowing the progression towards HF. We compared the proteomic profile of patients with and without diabetes among patients at risk for HF in the HOMAGE trial.

Spironolactone effect on the blood pressure of patients at risk of developing heart failure: an analysis from the HOMAGE trial.

Aims: Uncontrolled blood pressure (BP) increases the risk of developing heart failure (HF). The effect of spironolactone on BP of patients at risk of developing HF is yet to be determined. To evaluate the effect of spironolactone on the BP of patients at risk for HF and whether renin can predict spironolactone's effect.

Proteomic and Mechanistic Analysis of Spironolactone in Patients at Risk for HF.

Objectives: This study sought to further understand the mechanisms underlying effect of spironolactone and assessed its impact on multiple plasma protein biomarkers and their respective underlying biologic pathways.

Background: In addition to their beneficial effects in established heart failure (HF), mineralocorticoid receptor antagonists may act upstream on mechanisms, preventing incident HF. In people at risk for developing HF, the HOMAGE (Heart OMics in AGEing) trial showed that spironolactone treatment could provide antifibrotic and antiremodeling effects, potentially slowing the progression to HF.

The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart 'OMics' in AGEing (HOMAGE) randomized clinical trial.

Aims: To investigate the effects of spironolactone on fibrosis and cardiac function in people at increased risk of developing heart failure.

Methods And Results: Randomized, open-label, blinded-endpoint trial comparing spironolactone (50 mg/day) or control for up to 9 months in people with, or at high risk of, coronary disease and raised plasma B-type natriuretic peptides. The primary endpoint was the interaction between baseline serum galectin-3 and changes in serum procollagen type-III N-terminal pro-peptide (PIIINP) in participants assigned to spironolactone or control.

[The patient in clinical research: disposable guinea pig or involved actor?].

Background: The request for informed consent to join a clinical trial often creates mistrust and hesitation in the patient who should be enrolled. In our study, we evaluated the reasons for refusing to participate in a clinical trial.

Methods: In the last 10 years of cardiovascular clinical research, we asked an informed consent to 2586 patients for intervention studies.

Effects of spironolactone on serum markers of fibrosis in people at high risk of developing heart failure: rationale, design and baseline characteristics of a proof-of-concept, randomised, precision-medicine, prevention trial. The Heart OMics in AGing (HOMAGE) trial.

Aims: Asymptomatic patients with coronary artery disease (CAD), hypertension and/or type 2 diabetes mellitus (T2DM) are at greater risk of developing heart failure (HF). Fibrosis, leading to myocardial and vascular dysfunction, might be an important pathway of progression. The Heart OMics in AGing (HOMAGE) trial aims to investigate the effects of spironolactone on serum markers of collagen metabolism and on cardiovascular structure and function in people at risk of developing HF and potential interactions with a marker of fibrogenic activity, galectin-3.

Stable atypical chest pain with negative anatomical or functional diagnostic test: Diagnosis no matter what or prevention at any cost?

Background: Approximately 1% to 2% of patients with stable atypical chest pain (SACP) experienced a major coronary event, even after a negative functional or anatomical test.

Methods: Over the past 15 years, 1706 patients with SACP evaluated in our clinics underwent functional stress testing or coronary computed tomographic angiography (CTA). In these patients, we also assessed the presence of three major modifiable lifestyle-related risk factors (cigarette smoking, low intake of fruit and vegetables, and physical inactivity).

Insulin treatment and clinical outcomes in patients with diabetes and heart failure with preserved ejection fraction.

Aims: Insulin causes sodium retention and hypoglycaemia and its use is associated with worse outcomes in heart failure (HF) with reduced ejection fraction. We have investigated whether this is also the case in HF with preserved ejection fraction (HFpEF).

Methods And Results: We examined the association between diabetes/diabetes treatments and the risk of the primary composite of cardiovascular death or HF hospitalization, as well as other outcomes in adjusted analyses in CHARM-Preserved (left ventricular ejection fraction ≥ 45%), I-Preserve and TOPCAT (Americas) pooled.

[Medical intensive care unit patients with hyperglycemia: is it possible a hypoglycemic risk close to zero?].

Background: In patients with diabetic or stress hyperglycemia hospitalized for acute cardiovascular disease, the occurrence of hypoglycemia increases the risk of mortality and morbidity without this being counterbalanced by a reduction in events related to a tighter glycemic control. The guidelines on this topic agree in excluding intensive treatment, but are very discordant in recommending a conventional (<180 mg/dl) or milder (<200 mg/dl) blood glucose control.

Methods: In 1256 hyperglycemic patients (mean age 74 ± 12 years) admitted to the medical intensive care unit (MICU) for acute coronary syndrome or acute heart failure, we adopted a nurse-led protocol of mild blood glucose control with subcutaneous administration of insulin, called "BBC200" (basal-bolus correction insulin regimen with glycemic target <200 mg/dl), with the aim at maintaining average blood glucose <200 mg/dl and an indication for intravenous insulin only for blood glucose >350 mg/dl.