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8.6.2 Other devices

Most device-based therapies investigated for BP-lowering therapy in hypertension have been aimed at modulating the autonomic nervous system activity (baroreflex activation therapy, endovascular baroreflex amplification therapy, and carotid body ablation).560 Cardiac neuromodulation therapy aims to lower left ventricular preload by variably altering the atrioventricular interval using a dual-chamber, rate-responsive, implantable pulse generator in patients indicated for implantation or replacement of a dual-chamber pacemaker.591,592 Some, though not all, of these devices have shown promising results in non-randomized, single-arm studies. A sham-controlled trial investigating central iliac arteriovenous stent anastomosis was terminated early after longer-term follow-up data indicated an increase in heart failure in the stent group.561 Therefore, the use of these device-based therapies is not recommended for routinely treating hypertension until further evidence regarding their safety and efficacy becomes available (see Supplementary data online).

8.7 Unintended and potentially harmful

consequences of blood pressure lowering and implications for treatment targets 8.7.1. Adverse effects of blood pressure-lowering medications 8.7.1.1. Symptomatic adverse effects BP-lowering medications have multiple side effects, which may be more common in females.536,593,594 Although generally well tolerated, common side effects include headaches, cough, dizziness or light-headedness, diarrhoea or constipation, fatigue, ankle swelling, and erectile problems, depending on the drug class (see Supplementary data online, Table S9).536,550,593–597 In randomized trials of adults aged >60 years, the overall rate of symptomatic BP-lowering drug withdrawal was higher than the rate of placebo withdrawal (approximately 15% vs. 5%).593 A systematic review, which included 280 638 participants in 58 RCTs, reported no evidence for an increased relative risk of falls in those taking BP-lowering drugs.550 There was, however, an increased relative risk of mild hyperkalaemia, acute kidney injury, hypotension, and syncope. Furthermore, very frail adults were excluded from BP-lowering trials, which is relevant because such patients are more prone to adverse effects and polypharmacy (see Supplementary data online).596

8.7.1.2 Renal effects

A systematic review reported an increased risk of acute kidney injury and hyperkalaemia associated with BP-lowering treatment.550 Analyses of outcomes by specific drug class showed that drugs affecting the RAAS were more likely to be associated with acute kidney injury and hyperkalaemia.550 Patients with significant CKD tend to be excluded from RCTs.137,545,598 It is important to remember these exclusion criteria, and that patients with CKD are more likely to suffer from resistant hypertension, when extrapolating the results of more intensive BP lowering to patients with moderate-to-severe CKD (see Section 9).599

8.7.1.3 Erectile dysfunction

Older classes of BP-lowering drugs (including diuretics, beta-blockers, and centrally acting medications) are associated with erectile dysfunction.600 However, newer classes have neutral effects.601

Angiotensin receptor antagonists may have beneficial effect on erectile function.602

8.7.2 Pill burden and non-adherence

More intensive treatment of elevated BP and hypertension may be associated with an increased risk of polypharmacy and pill burden, which are themselves associated with non-adherence.603,604 Single-pill, fixeddose drug combinations can help to reduce pill burden and are recommended to improve adherence (refer to Section 8.3.4). Increased intensity of BP lowering (while ultimately cost reducing in terms of CVD reduction)605 can also result in higher upfront direct and indirect healthcare costs, with more people requiring medication and higher demand for technology-based adherence strategies, which can be challenging to implement, especially in resource-poor settings.604

8.7.3 Potentially harmful consequences of blood

pressure lowering for frail older people Unintended consequences of BP lowering (hypotension, syncope, falls) can be hazardous for frail older people in particular.606 Retrospective studies have shown that adults aged >75 years from the general population, who would have met the criteria for inclusion in the Systolic Blood Pressure Intervention Trial (SPRINT), had a rate of injurious falls and syncope that was nearly five times that of the standard care group in the trial. This suggests that healthy participant bias may have contributed to the findings of SPRINT and other similar BP-lowering trials, and that the results may not fully generalize to older adults in more routine clinical care.607 Patients’ functional ability should be considered in addition to age to help negate any unintended consequences of BP lowering in a frailer cohort. Despite their chronological age, older patients with hypertension who are fit and can independently carry out activities of daily living will benefit from guideline-directed treatment similar to younger cohorts.131 However, tailoring treatment targets and treatment plans for frail older patients is necessary to avoid unintended consequences. This should include assessing frailty, including cognitive status, risk of falls, propensity for symptomatic orthostatic hypotension, polypharmacy, and other comorbid conditions.608,609 Of note, and as detailed in Section 9, some data indicate a benefit of more intensive BP-lowering on cognitive function.523,610,611 For those with loss of function but preserved activities of daily living, a more detailed geriatric assessment is required to explore the risks and benefits of treatment, as well as considerations for tailoring therapeutic strategies where appropriate. For patients who are both functionally impaired and unable to carry out activities of daily living, the therapeutic goals of hypertension treatment should be personalized, and medications discontinued where appropriate (see Section 9.3).596

8.7.4 Clinical inertia in blood pressure lowering

The fear of serious adverse events with BP-lowering medications is often cited as a reason for clinical inertia, although the evidence to date from meta-analyses of RCTs suggests these side-effect concerns may be exaggerated.550,612 However, RCTs often select populations with less frailty and multimorbidity who are more likely to tolerate treatment.613 Consequently, fewer adverse effects might be reported than would be expected in the general population. It remains up to individual clinicians to initiate shared decision-making with each patient, especially patients in vulnerable groups and those who have experienced previous adverse events, weighing up potential benefits against risks of treatment.614,615 Downloaded from academic.oup.com/eurheartj/article/45/38/3912/7741010 by guest on 07 October 2026