Randomized controlled clinical trials have shown a reduction in heart failure (IC) of the 50% or more with antihypertensive treatment1. The mechanisms for the prevention of HF are explained by the prevention of myocardial infarction, prevention and regression of left ventricular hypertrophy (WHI) during antihypertensive treatment or prevention of arrhythmias, mainly atrial fibrillation with rapid ventricular rate based on coronary artery disease or LVH. Prevention of LVH and its regression are important objectives for antihypertensive treatment and have an important impact on the prevention of HF.2. At the moment, treatment of hypertension (HT), including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (BARRIER), beta blockers (BBs), calcium channel blockers and thiazide/thiazide-like diuretics, can be used for the prevention of HF (recommendation I A)1.
In patients with HT and HF with reduced ejection fraction (FEr), It is recommended to combine drugs with documented benefits in the results, including ACEIs (ARAII if they are not tolerated), or replace them with sacubitril/valsartan, BBs, mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter inhibitors 2 (SGLT2i), if they are not contraindicated and are well tolerated (recommendation I A)1. In patients with HF with preserved ejection fraction (FEp), treating HT with all major classes of antihypertensive medications (ECAi or ARAII, BBs, CCBs and similar thiazide/thiazide diuretics), as well as with the SGLT2i, regardless of the presence of type diabetes 2, are currently recommended (recommendation I A)1. In patients with HFpEF, particularly in the lower HFpEF spectrum, both replacement of an RAS inhibitor with sacubitril/valsartan and treatment with an MRA (spironolactone) can be considered (recommendation II B)1.
The role of SRA in HT has long been evaluated through its inhibition with consistently good clinical results compared to other antihypertensive compounds available for the treatment of HT and HF.. A large study that evaluated the association between the use of ACEIs, ARAII or inhibitors in RAS (non-RASi) and cardiovascular events in an unselected national HT cohort (n = 2.025.849 patients) found that the use of ACEIs and ARBs was associated with a decreased risk of myocardial infarction, ischemic stroke, atrial fibrillation, HF and deaths from all causes, compared to non-RASi users3. Therefore, at the moment, classical RAS inhibitors are the recommended first-line antihypertensive treatment to start in most patients, as a single agent or in combination, both in HT and in HFrEF and HFpEF (recommendation I A)1.
However, It is reported that until 60% of patients with HT have poor adherence to conventional pharmacology4. The side/adverse effects of conventional pharmacology are abundant (tos, angioedema, enteropathy, Erectile dysfunction, among others) and have the potential to diminish the therapeutic results of prescribed treatments. As expected, Patients with good adherence to antihypertensive medications have shown a lower incidence and risk of experiencing general and specific cardiovascular events compared to those with poor adherence.. Given these limitations, a new pharmacology needs to be found, that is not only effective in controlling HT, but also, to reduce or limit target organ damage in HT and HF. The development of new targeted drugs that are not associated with side/adverse effects and formulated in delivery systems capable of providing prolonged release, could improve short-term results, promoting adherence and providing long-term benefits4.
Peptide drugs constitute a predominant class of new biopharmaceuticals that have reached the market in recent years.. However, therapeutic peptides have multiple disadvantages, such as limited oral bioavailability, the short half-life, rapid elimination from the body and susceptibility to biological conditions (For example, Acid pH and enzymolysis). Therefore, high peptide doses and dosing frequencies are required for effective patient treatment5. Besides, oral administration, due to physiological aspects (gastric emptying), limits the possibility of achieving longer responses 24-48 hours depends critically on repetitive and brief administration, which limits its therapeutic effectiveness. Innovations in pharmaceutical formulations have substantially improved the delivery of therapeutic peptides by providing the following advantages: extended release, precise dose administration, retention of biological activity and improvement of patient compliance. Among the new strategies, micro/nano particles (lipid-based, polymers, porous silicon, silica and stimuli-responsive materials), hydrogels (sensitive to stimuli), particle/hydrogel composites and scaffolds (natural or synthetic) have emerged as important possibilities5.
References
- Mancia G, Kreutz r, Brunström m, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens. 2023;41:1874-2071.
- Kasiakogias A, Rosei EA, Camafort M, et al. Hypertension and heart failure with preserved ejection fraction: position paper by the European Society of Hypertension. J Hypertens 2021; 39:1522–1545.
- Park CS, Kim B, Rhee TM, et al. Association between renin-angiotensin-aldosterone system blockade and clinical outcomes in patients with hypertension: real-world observation from a nationwide hypertension cohort. Clin Res Cardiol. 2023;112:1577-1586.
- Bring, Briere JB, Zhuc L, et al. Impact of poor medication adherence on clinical outcomes and health resource utilization in patients with hypertension and/or dyslipidemia: systematic review. Expert Rev Pharmacoecon Outcomes Res. 2024;24:143-154.
- Zangabad PS, Rezvani ZA, Tong Z, et al. Recent Advances in Formulations for Long-Acting Delivery of Therapeutic Peptides. ACS Appl. Bio Mater. 2023, 6, 9, 3532–3554.