Small interfering RNA (siRNA) represents a novel, fascinating therapeutic strategy that allows for selective reduction in the production of a specific protein through RNA interference. In the cardiovascular (CV) field, several siRNAs have been developed in the last decade. Inclisiran has been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) circulating levels with a reassuring safety profile, also in older patients, by hampering proprotein convertase subtilisin/kexin type 9 (PCSK9) production. Olpasiran, directed against apolipoprotein(a) mRNA, prevents the assembly of lipoprotein(a) [Lp(a)] particles, a lipoprotein linked to an increased risk of ischemic CV disease and heart valve damage. Patisiran, binding transthyretin (TTR) mRNA, has demonstrated an ability to improve heart failure and polyneuropathy in patients with TTR amyloidosis, even in older patients with wild-type form. Zilebesiran, designed to reduce angiotensinogen secretion, significantly decreases systolic and diastolic blood pressure (BP). Thanks to their effectiveness, safety, and tolerability profile, and with a very low number of administrations in a year, thus overcoming adherence issues, these novel drugs are the leaders of a new era in molecular therapies for CV diseases.

Chronic obstructive pulmonary disease (COPD) and heart failure (HF) often coexist. Moreover, elderly patients suffering from HF have a higher incidence of COPD, which further complicates their clinical condition. Indacaterol/glycopirronium has shown benefits in the treatment of COPD, with few cardiologic adverse effects. We evaluated the safety and efficacy of this therapy in patients with history of HF. We enrolled 56 patients with a history of HF (New York Heart Association [NYHA] classes II and III) and stable COPD. We evaluated blood samples, clinical assessment, echocardiograms and basal spirometry at baseline and after 6 months of therapy with indacaterol/glycopirronium. In addition, the number of re-hospitalizations during the treatment period was evaluated. The treatment was well tolerated. Brain natriuretic peptide (BNP) levels were significantly reduced compared with baseline (p < 0.001) after 6 months of treatment, and a higher percentage of patients improved their clinical status compared with baseline (p < 0.001). Minor changes were noted in the hemodynamic and metabolic parameters. Significant improvements in the echocardiographic parameters were noted in HF with reduced ejection fraction (HFrEF) patients. All respiratory parameters (forced expiratory volume in 1 s [FEV1], FEV1/forced vital capacity [FVC] ratio and COPD Assessment Test [CAT] scores) improved significantly (p < 0.001). No hospitalizations owing to HF or COPD exacerbation occurred. One patient died of respiratory failure. Indacaterol/glycopirronium was well-tolerated and effective in the treatment of COPD in this cohort of patients with a history of HF. Further studies are needed to clarify whether this compound can have a direct role in improving overall cardiovascular function.

Background and Aim: Insulin resistance (IR), often associated with visceral adiposity, contributes to the development of dyslipidemia and hypertension through various mechanisms. IR bio-anthropometric indices, such as triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C), triglyceride-glucose index (TyGi), TyGi-Body mass index (TyGi-BMI), TyGi-Waist circumference (TyGi-WC), lipid accumulation product (LAP), visceral adiposity index (VAI), and metabolic score for insulin resistance (METS-IR), correlate with hypertension risk and poor blood pressure control when assessed via office blood pressure (OBP). However, their associations with 24-hour ambulatory BP (ABP) and antihypertensive therapy remain unclear. This study examines the relationships between IR indices and ABP in outpatients without diabetes. Methods: This cross-sectional study included 1,336 outpatients undergoing ABP monitoring. IR indices were calculated, and antihypertensive therapy was assessed by medication count and treatment intensity score (TIS). After log-transformation and centering of the IR indexes, logistic regression models analysed associations between IR and uncontrolled 24-hour ABP. Following a likelihood ratio test, restricted cubic spline (RCS) analyses were performed to model the non-linear relationship between the IR indexes and the odds of uncontrolled 24-hour blood pressure (BP). Results: The cohort (mean age: 54.9 years, 58.3% male, mean BMI: 27.4 kg/m²) showed median values of TG/HDL-C 2.07, TyGi-BMI 234.9, TyGi-WC 832.8, LAP 41.4, VAI 71.3, and METS-IR 41. Uncontrolled ABP (64.2%) was more prevalent in younger males with higher IR indices. METS-IR and TyGi-BMI were independently associated with uncontrolled ABP. Conclusions: METS-IR and TyGi-BMI were associated with uncontrolled ABP, independently of treatment status, sex, and age. These indices, derived from widely available parameters, provide practical tools for identifying patients with an increased risk of hypertension in real-life clinical settings.

(2020). Are monotherapies still valuable to the treatment of hypertension?. Expert Opinion on Pharmacotherapy. Ahead of Print.