Vericiguat en insuficiencia cardíaca: de la evidencia científica a la práctica clínica / Vericiguat in heart failure: from scientific evidence to clinical practice

A pesar de los tratamientos actuales, el riesgo de muerte y hospitalizaciones en pacientes con insuficiencia cardíaca con fracción de eyección reducida (IC-FEr) sigue siendo elevado. La fisiopatología de la IC-FEr incluye activación neurohormonal caracterizada por la estimulación de las vías deletéreas (sistemas simpático y renina-angiotensina-aldosterona) y la supresión de las vías protectoras como las dependientes del óxido nítrico. La inhibición o estimulación de algunas de estas vías, pero no de todas, es insuficiente. En la IC-FEr existe una menor actividad de óxido nítrico, guanilato ciclasa soluble y GMPc que provoca efectos deletéreos a nivel miocárdico, vascular y renal. Vericiguat estimula la actividad de esta vía protectora. El estudio VICTORIA demostró, en pacientes con IC-FEr y descompensación reciente, que la adición de vericiguat al tratamiento médico óptimo reducía de forma significativa la incidencia del objetivo primario compuesto de muerte cardiovascular u hospitalización por IC, con un número de 24 pacientes que es necesario tratar, y una excelente tolerabilidad (AU)

Despite currently available treatments, risk of death and hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) remains high. The pathophysiology of HFrEF includes neurohormonal activation characterized by stimulation of deleterious pathways (i.e., sympathetic nervous and renin-angiotensin-aldosterone systems) and suppression of protective pathways such as nitric oxide-dependent pathways. Inhibition or stimulation of some, but not all, of these pathways is insufficient. In HFrEF, there is reduced nitric oxide, soluble guanylate cyclase, and cGMP activity, leading to deleterious effects in the myocardial, vascular, and renal systems. Vericiguat is able to stimulate the activity of this protective pathway. The VICTORIA study demonstrated that the addition of vericiguat to optimal medical treatment in patients with HFrEF and recent decompensation significantly reduced the incidence of the primary endpoint, a composite of cardiovascular death or HF hospitalization, with a number needed to treat of 24 patients and excellent tolerability (AU)

Vericiguat in heart failure: From scientific evidence to clinical practice.

Despite currently available treatments, risk of death and hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) remains high. The pathophysiology of HFrEF includes neurohormonal activation characterized by stimulation of deleterious pathways (i.e., sympathetic nervous and renin-angiotensin-aldosterone systems) and suppression of protective pathways such as nitric oxide-dependent pathways. Inhibition or stimulation of some, but not all, of these pathways is insufficient. In HFrEF, there is reduced nitric oxide, soluble guanylate cyclase, and cGMP activity, leading to deleterious effects in the myocardial, vascular, and renal systems. Vericiguat is able to stimulate the activity of this protective pathway. The VICTORIA study demonstrated that the addition of vericiguat to optimal medical treatment in patients with HFrEF and recent decompensation significantly reduced the incidence of the primary endpoint, a composite of cardiovascular death or HF hospitalization, with a number needed to treat of 24 patients and excellent tolerability.

La paradoja del tabaco en el síndrome coronario agudo. El abandono previo del hábito tabáquico como marcador de mejor pronóstico a corto plazo / The tobacco paradox in acute coronary syndrome. The prior cessation of smoking as a marker of a better short-term prognosis

Objetivo. La paradoja del tabaco es un fenómeno insuficientemente explicado en estudios previos. Este estudio analiza el papel pronóstico del tabaquismo previo o activo en pacientes con síndrome coronario agudo. Métodos. Obtuvimos los datos del registro ARIAM, entre 2001 y 2012. Se incluyó a 42.827 pacientes con síndrome coronario agudo (edad media 65±13 años, 26,4% mujeres). Se analizó la influencia del hábito tabáquico o de la condición de exfumador en la mortalidad mediante análisis multivariados. Resultados. Los fumadores eran más jóvenes, más frecuentemente hombres, tenían menos diabetes, hipertensión e historia previa de insuficiencia cardiaca, ictus, arritmia e insuficiencia renal, así como más frecuentemente elevación del ST e historia familiar. Los exfumadores presentaban más dislipidemia e historia de angina, infarto de miocardio, cardiopatía isquémica, vasculopatía periférica y broncopatía crónica. Fumadores y exfumadores desarrollaron menos frecuentemente shock cardiogénico (fumadores 4,2%, exfumadores 4,7% y no fumadores 6,9%, p<0,001). La mortalidad hospitalaria fue del 7,8% en los no fumadores, un 4,9% en los exfumadores y un 3,1% en los fumadores (p<0,001). En el análisis multivariado, el carácter fumador perdió su influencia en el pronóstico (-0,26%, p = 0,52 mediante cálculo de probabilidad inversa; y +0,26%, p=0,691 mediante análisis de propensión). Sin embargo, el carácter exfumador mostró una reducción significativa de la mortalidad en ambos test (-2,4% en el análisis de probabilidad inversa, p < 0,001, y -1,5% en el análisis de propensión, p = 0,005). Conclusiones. La paradoja del tabaco es un hallazgo que puede explicarse por otros factores pronósticos. El abandono del hábito tabáquico previo a un ingreso por síndrome coronario agudo se asocia a un mejor pronóstico (AU)

Objective. The tobacco paradox is a phenomenon insufficiently explained by previous studies. This study analyses the prognostic role of prior or active smoking in patients with acute coronary syndrome. Methods. We obtained data from the ARIAM registry, between 2001 and 2012. The study included 42,827 patients with acute coronary syndrome (mean age, 65±13 years; 26.4% women). The influence of smoking and that of being an ex-smoker on mortality was analysed using a multivariate analysis. Results. The smokers were younger, were more often men, had less diabetes, hypertension and prior history of heart failure, stroke, arrhythmia and renal failure and more frequently had ST-elevation and a family history of smoking. The ex-smokers had more dyslipidaemia and history of angina, myocardial infarction, ischemic heart disease, peripheral vasculopathy and chronic bronchial disease. Smokers and ex-smokers less frequently developed cardiogenic shock (smokers 4.2%, ex-smokers 4.7% and nonsmokers 6.9%, P<.001). Hospital mortality was 7.8% for the nonsmokers, 4.9% for the ex-smokers and 3.1% for the smokers (P<.001). In the multivariate analysis, the smoker factor lost its influence in the prognosis (-0.26%, p=.52 using an inverse probability calculation; and+0.26%, P=.691 using a propensity analysis). However, the exsmoker factor showed a significant reduction in mortality in both tests (-2.4% in the inverse probability analysis, P<.001; and -1.5% in the propensity analysis, P=.005). Conclusions. The tobacco paradox is a finding that could be explained by other prognostic factors. Smoking cessation prior to hospitalization for acute coronary syndrome is associated with a better prognosis (AU)

The tobacco paradox in acute coronary syndrome. The prior cessation of smoking as a marker of a better short-term prognosis. / La paradoja del tabaco en el síndrome coronario agudo. El abandono previo del hábito tabáquico como marcador de mejor pronóstico a corto plazo.

OBJECTIVE: The tobacco paradox is a phenomenon insufficiently explained by previous studies. This study analyses the prognostic role of prior or active smoking in patients with acute coronary syndrome. METHODS: We obtained data from the ARIAM registry, between 2001 and 2012. The study included 42,827 patients with acute coronary syndrome (mean age, 65±13 years; 26.4% women). The influence of smoking and that of being an ex-smoker on mortality was analysed using a multivariate analysis. RESULTS: The smokers were younger, were more often men, had less diabetes, hypertension and prior history of heart failure, stroke, arrhythmia and renal failure and more frequently had ST-elevation and a family history of smoking. The ex-smokers had more dyslipidaemia and history of angina, myocardial infarction, ischemic heart disease, peripheral vasculopathy and chronic bronchial disease. Smokers and ex-smokers less frequently developed cardiogenic shock (smokers 4.2%, ex-smokers 4.7% and nonsmokers 6.9%, P<.001). Hospital mortality was 7.8% for the nonsmokers, 4.9% for the ex-smokers and 3.1% for the smokers (P<.001). In the multivariate analysis, the smoker factor lost its influence in the prognosis (-0.26%, p=.52 using an inverse probability calculation; and+0.26%, P=.691 using a propensity analysis). However, the exsmoker factor showed a significant reduction in mortality in both tests (-2.4% in the inverse probability analysis, P<.001; and -1.5% in the propensity analysis, P=.005). CONCLUSIONS: The tobacco paradox is a finding that could be explained by other prognostic factors. Smoking cessation prior to hospitalization for acute coronary syndrome is associated with a better prognosis.

Long-term outcome in heart transplant patients with pretransplant malignancies.

INTRODUCTION: Neoplasms have classically been considered a contraindication for heart transplantation (HT) because of the possibility of recurrence during immunosuppressive therapy. There are few cases of patients who suffered a pretransplant malignancy (PTM); however the appropriate interval free of a malignancy (IFoM) before heart transplantation is unclear. Our study sought to determine the long-term outcomes after transplantation among patients who had suffered a prior neoplasm compared with our overall cohort. METHODS: This retrospective, single-center study included 595 heart transplant recipients ungrafted between 1991 and 2009. We determined PTM location, histology, and IFoM. We examined donor and recipient factors and post-HT data of rejections, infections, neoplasms, and survival associated with a poor prognosis. RESULTS: Twelve patients with different types, locations, and histological grades of PTM represented 66.7% women versus 16.1% women in the overall series (P<.01). There were no differences in recipient age or clinical characteristics (diabetes mellitus, arterial hypertension, previous renal failure, or New York Heart Association class), number of emergency cases, or graft ischemia time. Mean IFoM was 114.3 months (range=5.3-350.4). After heart transplantation, there were no significant differences between the number of infections (47.9%; n=[279] vs 33.3% n=4; P=.39), rejection episodes (44.4% [259] vs 50% [6], P=0.77) or post-HT malignancies (12.2% [70] vs 0%, P=0.37) between the overall series and the patients with PTM. None of the patients with PTM suffered a recurrence of the neoplasm. Actuarial survivals at 1, 3, and 5 years were 82%, 76%, and 70% among patients without PTM and 75%, 75%, and 56% among those with PTM (P=.70). CONCLUSION: Patients with PTM and an appropriate IFoM with regard to tumor lineage showed similar rates of survival and complications as those of the overall series. This series suggested that appropriately selected patients with a cured PTM can be candidates for HT.

Clinical trials update from the European Society of Cardiology Congress in Vienna, 2007: PROSPECT, EVEREST, ARISE, ALOFT, FINESSE, Prague-8, CARESS in MI and ACUITY.

The Clinical Trials described in this article were presented at the Hotline and Clinical Trial Update Sessions of the European Society of Cardiology Congress held in September 2007 in Vienna, Austria. The sessions chosen for this article represent the scope of interest of Cardiovascular Drugs and Therapy. The presentations should be considered preliminary, as further analyses could alter the final publication of the results of these studies. PROSPECT evaluated echocardiographic criteria for optimal selection of patients with moderate to severe heart failure who may benefit from cardiac resynchronisation therapy, however concluded that no single echocardiographic measure can be recommended. EVEREST found that tolvaptan, a vasopressin V(2) antagonist, resulted in early weight reduction and improvement of dyspnoea in patients with acute heart failure, but lacked long term improvement. In ARISE, the anti-oxidant succinobucal did not affect the primary outcome in high risk cardiovascular patients, but improved the combination of cardiovascular death, myocardial infarction and stroke, and diabetic control in diabetics. ALOFT showed that the addition of the renin inhibitor aliskiren to an ACE inhibitor or ARB and a beta-blocker leads to favourable effects on neurohormonal actions in heart failure. FINESSE markedly improved coronary patency before PCI with half-dose reteplase/abciximab in STEMI patients, however without significantly improving short-term outcome. The Prague-8 Study evaluated whether routine clopidogrel administered >6 h pre-angiography would be a safe way to achieve therapeutic drug levels in case a follow-up intervention would be considered immediately, but appeared not justified because of bleeding complications. CARESS in MI showed that high risk patients with evolving STEMI who undergo thrombolytic therapy should undergo PCI early after the thrombolysis. Finally, the ACUITY trial found that in moderate or high risk Non ST elevation ACS patients triaged to PCI, coronary artery bypass graft (CABG) surgery, or medical management, bivalirudin, with or without associated GPIIb/IIIa inhibitor therapy, resulted in a marked reduction of bleeding at 30 days whilst preserving the ischemic and mortality benefit at 1 year follow up.

Prolongación del intervalo QT en un paciente con enfermedad coronaria tratado con mianserina / Enlargement of QT-interval in a patient with coronary disease treated with mianserin

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