Current medical research and opinion
-
Most patients with schizophrenia need life-long treatment. There is therefore a continued need for effective and tolerable treatment options. A 2-monthly LAI formulation of aripiprazole, Aripiprazole 2-Month Ready-to-Use 960 mg (Ari 2MRTU 960) has recently been approved in the US. ⋯ Some of these advantages become more pronounced with longer injection intervals. Additional advantages of longer injection intervals are more room for non-medication-related communication between healthcare professionals and patients, patient and physician preferences, reduced caregiver burden, and easier transitioning from inpatient to outpatient treatment. Taken together, since aripiprazole may be a good treatment choice for many patients based on its favorable safety and tolerability profile, and given the advantages of LAI treatment over oral treatment and the advantages of reduced dosing frequency, Ari 2MRTU 960 may become an important treatment option for many clinically stable patients with schizophrenia.
-
The benefits of improved clinical outcomes through blood pressure (BP) reduction have been proven in multiple clinical trials and meta-analyses. The new (2023) guideline from the European Society of Hypertension (ESH) includes β-blockers within five main classes of antihypertensive agents suitable for initiation of antihypertensive pharmacotherapy and for combination with other antihypertensive agents. This is in contrast to the 2018 edition of ESH guidelines that recommended β-blockers for use primarily in patients with compelling indications such as cardiovascular comorbidities, e.g. coronary heart disease, heart failure. ⋯ Hypertension management guidelines support for the use of combination therapies for almost all patients with hypertension, ideally within a single-pill combination to optimise adherence to therapy. Where a β-blocker is prescribed, the inclusion of a dihydropyridine calcium channel blocker within a combination regimen is rational. These agents together reduce both peripheral and central BP, which epidemiological studies have shown is important for reducing the burden of premature morbidity and mortality associated with uncontrolled hypertension, especially strokes.
-
Heart failure (HF) is associated with disabling symptoms, poor quality of life, and a poor prognosis with substantial excess mortality in the years following diagnosis. Overactivation of the sympathetic nervous system is a key feature of the pathophysiology of HF and is an important driver of the process of adverse remodelling of the left ventricular wall that contributes to cardiac failure. Drugs which suppress the activity of the renin-angiotensin-aldosterone system, including β-blockers, are foundation therapies for the management of heart failure with reduced ejection fraction (HFrEF) and despite a lack of specific outcomes trials, are also widely used by cardiologist in patients with HF with preserved ejection fraction (HFpEF). ⋯ Moreover, β-blockers also reduce mortality in the setting of HF occurring alongside common comorbid conditions, such as diabetes, CKD (of any severity), and COPD. Higher doses of β-blockers are associated with better clinical outcomes in populations with HF, so that ensuring adequate titration of therapy to their maximal (or maximally tolerated) doses is important for ensuring optimal outcomes for people with HF. In principle, a patient with HF could have combined treatment with a β-blocker, renin-angiotensin-aldosterone system inhibitor/neprilysin inhibitor, mineralocorticoid receptor antagonist, and a SGLT2 inhibitor, according to tolerability.
-
β-blockers are a heterogeneous class, with individual agents distinguished by selectivity for β1- vs. β2- and α-adrenoceptors, presence or absence of partial agonist activity at one of more β-receptor subtype, presence or absence of additional vasodilatory properties, and lipophilicity, which determines the ease of entry the drug into the central nervous system. Cardioselectivity (β1-adrenoceptor selectivity) helps to reduce the potential for adverse effects mediated by blockade of β2-adrenoceptors outside the myocardium, such as cold extremities, erectile dysfunction, or exacerbation of asthma or chronic obstructive pulmonary disease. According to recently updated guidelines from the European Society of Hypertension, β-blockers are included within the five major drug classes recommended as the basis of antihypertensive treatment strategies. Adding a β-blocker to another agent with a complementary mechanism may provide a rational antihypertensive combination that minimizes the adverse impact of induced sympathetic overactivity for optimal blood pressure-lowering efficacy and clinical outcomes benefit.
-
Cardioselective β-blockade is generally well tolerated in practice and contraindications to this therapy are uncommon. β-blockers are a diverse therapeutic class, and their individual tolerability profiles are influenced strongly by their pharmacodynamic effects across different adrenergic receptors. Bisoprolol, probably the β-blocker with the highest selectivity for blockade of β1- vs. β2-adrenoceptors, does not block β2-adrenoceptors to an appreciable extent at doses in therapeutic use. ⋯ Starting with a low dose and titrating upwards carefully is important for optimising the tolerability of a β-blocker. Most people with hypertension will receive combination antihypertensive therapy in practice, and the low-dose combination therapy approach provides a useful strategy for optimising the efficacy and tolerability of a regimen that includes a β-blocker, compared with up-titrating an existing monotherapy.