Clinical and economic aspects of the use of nebivolol in the treatment of elderly patients with heart failure

Heart failure is a common and disabling condition with morbidity and mortality that increase dramatically with advancing age. Large observational studies, retrospective subgroup analyses and meta-analyses of clinical trials in systolic heart failure, and recently published randomized studies have provided data supporting the use of beta-blockers as a baseline therapy in heart failure in the elderly. Despite the available evidence about beta-blockers, this therapy is still less frequently used in elderly compared to younger patients. Nebivolol is a third-generation cardioselective beta-blocker with L-arginine/nitric oxide-induced vasodilatory properties, approved in Europe and several other countries for the treatment of essential hypertension, and in Europe for the treatment of stable, mild, or moderate chronic heart failure, in addition to standard therapies in elderly patients aged 70 years old or older. The effects of nebivolol on left ventricular function in elderly patients with chronic heart failure (ENECA) and the study of effects of nebivolol intervention on outcomes and rehospitalization in seniors with heart failure (SENIORS) have been specifically aimed to assess the efficacy of beta-blockade in elderly heart failure patients. The results of these two trials demonstrate that nebivolol is well tolerated and effective in reducing mortality and morbidity in older patients, and that the beneficial clinical effect is present also in patients with mildly reduced ejection fraction. Moreover, nebivolol appears to be significantly cost-effective when prescribed in these patients. However, further targeted studies are needed to better define the efficacy as well as safety profile in frail and older patients with comorbid diseases

Local delivery of thrombolytics before thrombectomy in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention — The DISSOLUTION randomized trial

Background: Ranolazine decreases the frequency of arrhythmias during the acute phases of ischemic heart disease (IHD), but it remains unknown if it has similar effects in the chronic phase of the disease. We performed a prospective, randomized, cross-over pilot trial to test the hypothesis that chronic treatment with ranolazine can reduce the incidence of documented arrhythmias and the related symptoms of palpitation in stable patients with IHD. Methods: We randomized 105 patients with stable IHD and symptoms of angina and palpitations already on therapy with betablockers and/or calcium antagonists to ranolazine (750 mg bid, N = 53) or placebo (N = 52) for 30 days (until T-1). After a washout period to avoid any carryover effect, cross-over was performed,and patients were switched to the other drug which was continued for 30 days (until T-2). All patients underwent symptomlimited exercise stress testing and 48-hour ECG Holter monitoring at T1 and T2. During the study period, patients were told to use a OmronN® portable ECG monitor HCG-801 device in case of symptoms of palpitations. Results: Ranolazine reduced the number of anginal episodes more commonly than placebo (5 ± 8 episodes/30 days vs. 21 ± 24 episodes/30 day, p = 0.001) and increased exercise durations at 1 mm ST-segment depression (514 ± 211 s vs. 402 ± 287 s, p = 0.025) and at onset of angina (614 ± 199 s vs. 519 ± 151 s, p = 0.007) at stress testing. These effects were coupled by significant decreases with ranolazine as compared with placebo treatment periods in the occurrence of frequent (N1000 beats) supraventricular arrhythmias (33% vs 52%, p = 0.01) and complex ventricular arrhythmias (17% vs 30%, p = 0.045). Complete resolution of symptoms of palpitations was significantly more common with ranolazine than placebo (31/53 vs 16/52 patients, p = 0.008). Also, portable ECG recordings showed that arrhythmias were less common during ranolazine vs. placebo, with significant decreases in number (7 ± 10 episodes/30 days vs. 23 ± 29 episodes/30 day, p = 0.001) and duration (10 ± 18 min/ 30 days vs. 19 ± 21 min/30 day, p = 0.021) of symptomatic arrhythmic episodes. No severe side effects were recorded during the trial period. Conclusion: The antianginal and antiischemic properties of ranolazine are paralleled by significant decreases in the occurrence of both arrhythmias and the related symptoms of palpitations in stable patients with IHD. (ClinicalTrials.gov identifier: NCT01495520)

Cardiac rehabilitation is safe and effective also in the elderly, but don't forget about drugs!

In the setting of heart failure (HF) pharmacotherapy demonstrates a quantifiable improvement in exercise tolerance also in HF with preserved ejection fraction (HFpEF). For patients with HFpEF, often older, with higher prevalence of hypertension, diabetes mellitus, atrial fibrillation and other comorbidities, endpoints such as quality of life and functional capacity may be more clinically relevant. However several study show as the use of ACE-I and B-blocker were lesser than expected. Beta-blocker therapy is the keystone of pharmacotherapy of HF patients and exercise training is the essential core of rehabilitation programs, it is important to elucidate the relationship between these therapies. Exercise training improves the clinical status of HF, improving left ventricular ejection fraction and improving quality of life, but it is possible that b-blocker may attenuate exercise training adaptations. Despite this, possible adverse b-blocker effects are just presumed and not confirmed by published randomized clinical trials. Metanalysis suggests that b-blocker compared with placebo enhances improvements in cardiorespiratory performance in exercise training intervention. Despite these evidences, prescription of gold standard therapy and adherence are still suboptimal and should be a priority goal for all CR program.  Riassunto Nell’ambito dei pazienti con scompenso cardiaco (SC) la terapia farmacologica permette di ottenere un miglioramento della tolleranza all’esercizio fisico anche nei pazienti con frazione di eiezione conservata. Questi pazienti spesso più anziani, con una più elevata incidenza di ipertensione, diabete mellito, fibrillazione atriale e comorbidità, endpoints quali qualità della vita e capacità funzionale dovrebbero risultare più clinicamente rilevanti. Tuttavia molti studi mostrano come l’utilizzo di ACE-I e Beta-bloccanti sia minore di quanto ci si aspetterebbe. Va evidenziato comunque come la terapia beta-bloccante costituisca il cardine della terapia farmacologica dello SC e come l’esercizio fisico sia il cuore dei programmi di riabilitazione, pertanto è importante valutarne le possibili interazioni. L’esercizio fisico migliora lo stato clinico dei pazienti con SC, ma è possibile che la terapia con Beta-bloccanti possa attenuare questi vantaggi. Tale assunto tuttavia rimane solo presunto e non confermato dai risultati dei trial pubblicati. Infatti una metanalisi suggerisce che la terapia Beta-bloccante, confrontata con il placebo, migliori la performance cardiorespiratoria nel gruppo sottoposto ad esercizio fisico. Malgrado tali evidenze, la prescrizione di una terapia medica ottimale e l’aderenza alla stessa rimangono ancora non ottimali e dovrebbe rappresentare un obiettivo primario per tutti i programmi di riabilitazione.

Barriers to cardiac rehabilitation access of older heart failure patients and strategies for better implementation

In heart failure (HF), cardiac rehabilitation (CR) may reduce decompensations, hospitalization, and ultimately mortality in long term. Many studies over the past decade have demonstrated that aerobic exercise training is effective and safe in stable patients with HF. Exercise CR resulted in a clinically important improvement in the QOL. Several clinical and psychosocial factors are associated with decreased participation in CR programs of elderly HF patients, such as perception of exercise as tiring or painful, comorbidities, lack of physician encouragement, and opinion that CR will not improve their health status. Besides low functional capacity, and chronic deconditioning may also deter patients from participating in CR programs.  Recent data suggest that current smoking, a BMI ≥30 kg/m2, diabetes mellitus, and cognitive dysfunction are associated with failure to enroll in outpatient CR in older age group. Moreover the lack of availability of CR facilities or the absence of financial refunds for enrolment of CHF patients in cardiac rehabilitation programs can play a crucial role. Many of this factors are modifiable through patient education and self care strategy instruction, health providers sensibilization, and implementing economic measures in order to make CR affordable.  Riassunto Numerosi studi hanno dimostrato come la riabilitazione cardiovascolare (RC) con esercizio aerobico sia risultato efficace e sicuro nei pazienti con scompenso cardiaco (SC), nel ridurre ospedalizzazioni, mortalità ed indurre un miglioramento della qualità di vita. Tuttavia numerosi fattori clinici e psicosociali, come la bassa capacità funzionale, le comorbidità, la percezione dell’esercizio fisico come noioso o doloroso, sono associati a ridotta partecipazione a RC da parte di pazienti anziani con SC.  Inoltre dati recenti mostrano come l’abitudine tabagica, un BMI ≥30 kg/m2, il diabete mellito ed il deterioramento cognitivo siano associati con il mancato arruolamento di pazienti anziani in programmi di RC.  In aggiunta la mancanza di disponibilità di strutture per la RC o l'assenza di rimborsi finanziari per l'iscrizione dei pazienti con SC in programmi di riabilitazione cardiaca possono svolgere un ruolo cruciale. Molti di questi fattori risultano modificabili attraverso programmi di educazione sanitaria del paziente, sensibilizzazione del personale sanitario ed attraverso un’implementazione delle misure economiche al fine di rendere accessibile la RC

Exercise-induced ST-segment elevation

Exercise-induced ST-segment elevation in patients without previous myocardial infarction is a relatively uncommon finding. When it does occur, it may be associated with significant coronary artery disease or coronary vasospasm. Here we describe a case of exercise-induced ST-segment elevation in both anterior and inferior leads in a patient with a critical stenosis on a wrapped left anterior descending artery, successfully treated with transluminal coronary artery angioplasty. © 2009 Italian Federation of Cardiology