Current medical research and opinion
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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.
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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.
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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.
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Stable angina, one manifestation of chronic coronary syndrome (CCS), is characterised by intermittent episodes of insufficient blood supply to the myocardium, provoking symptoms of myocardial ischaemia, particularly chest pain. These attacks usually occur during exercise or stress. Anti-ischaemic drugs are the mainstay of pharmacologic management of CCS with symptoms of angina. β-blockers reduce heart rate and myocardial contractility, thus reducing myocardial oxygen consumption. ⋯ Current management guidelines include β-blockers as a first-line management option for most patients with CCS and symptoms of myocardial ischaemia, alongside dihydropyridine calcium channel blockers (CCB). The presence of comorbid angina and heart failure is a strong indication for starting with a β-blocker. β-blockers are also useful in the management of angina symptoms accompanied by a high heart rate, hypertension (with or without a renin-angiotensin-aldosterone-system [RAS] blocker or CCB), or microvascular angina (with a RAS blocker and a statin). A β-blocker is not suitable for a patient with low heart rate (<50 bpm), although use of a β-blocker may be supported by a pacemaker if the β-blocker is strongly indicated) and should be used at a low dose only in patients with low blood pressure.
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Cardiovascular disease (CVD) remains the most prevalent cause of premature death worldwide. It had been suspected for decades that increased activity of the sympathetic nervous system (SNS) might play a pathogenetic role in the development and progression of hypertension, heart failure (HF) and CVD. The use of microneurographic techniques to directly assess the SNS has allowed this field to advance considerably in recent years. ⋯ Sympathetic overactivity also drives increased cardiovascular risk in the settings of obesity, metabolic syndrome, chronic kidney disease and obstructive sleep apnoea, among other conditions. Thus, sympathetic overactivity is an important factor that drives patients through the CVD continuum, from the early appearance of cardiovascular risk factors, to impairments of the structure and function of components of the heart and arteries, to established CVD, and ultimately to a life-threatening cardiovascular event. A deeper understanding of the role of sympathetic overactivity in the pathogenesis of CVD and HF will support the optimization of therapeutic interventions for these conditions.