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Red flags and safety concerns

TL;DR — The harms in hypertension care divide into three kinds, and only one of them is what people expect. Measurement harm: using a regular cuff on an arm needing an extra-large one raised systolic pressure by 19.5 mm Hg (95% CI 16.1–22.9) (Ishigami 2023, PMID 37548984), and 92.4% of home devices sold online in one national marketplace were unvalidated (Picone 2020, PMID 32275193). Treatment harm: meta-analysis of 58 randomised trials and 280,638 participants found antihypertensive treatment associated with acute kidney injury (RR 1.18, 95% CI 1.01–1.39), hyperkalaemia (1.89, 1.56–2.30), hypotension (1.97, 1.67–2.32) and syncope (1.28, 1.03–1.59) — but no association with falls (1.05, 0.89–1.24) (Albasri 2021, PMID 33568342). The falls result matters because fear of falls is the commonest stated reason for undertreating older people, and the concern is not supported at trial level; orthostatic hypotension likewise decreases with intensive treatment (OR 0.93, 95% CI 0.86–0.99) (Juraschek 2021, PMID 32909814). Diagnostic harm: missed secondary causes, unrecognised drug-induced hypertension, and treating asymptomatic inpatient elevation, which is associated with a 28% higher odds of a composite adverse outcome and 90% higher with intravenous agents (Anderson 2023, PMID 37252732).

Measurement error as a safety issue

Error Magnitude Direction of harm
Wrong cuff size (regular on an extra-large arm) +19.5 mm Hg systolic (95% CI 16.1–22.9) Over-diagnosis and over-treatment, concentrated in people with larger arms (Ishigami 2023, PMID 37548984)
Wrong cuff size (regular on a small arm) −3.6 mm Hg (−5.6 to −1.7) Under-treatment (Ishigami 2023, PMID 37548984)
Cuff-size ranges differ between home-device manufacturers Variable A "large" cuff is not standardised across brands (Shahi 2023, PMID 37422909)
Terminal-digit rounding to zero 37.7–41.7% of US readings vs 10–20% expected; worse at first visits, age ≥80 and above threshold Both directions; worst where it changes decisions (Foti 2021, PMID 33246327)
Unvalidated home devices 92.4% of 972 devices sold online in one market; 0% of 532 wrist-band wearables validated Unknown-direction error, cheaper than validated devices (Picone 2020, PMID 32275193)
Attended vs unattended office measurement Pooled 3.66/1.67 mm Hg difference with I² 97%/89% No reliable conversion; SPRINT-derived targets are not directly transferable (Andreadis 2019, PMID 31290085)
Cuffless devices Pooled biases 3.42 and 1.16 mm Hg with I² >87%; precision often unassessed Not fit for diagnosis (Islam 2022, PMID 36713001; Stergiou 2023, PMID 37303198)
Atrial fibrillation Degrades oscillometric accuracy Misclassification (Stergiou 2012, PMID 22914573)

The practical safeguards are: measure arm circumference and select the cuff accordingly, use a validated device (STRIDE-BP-type validation registries), average multiple readings, and confirm any new diagnosis out of the office (USPSTF 2021, PMID 33904861). See definition, measurement and diagnosis.

From 58 trials and 280,638 participants, median 3 years' follow-up (Albasri 2021, PMID 33568342):

Event Summary estimate Note
Falls RR 1.05 (95% CI 0.89–1.24) No association — 7 trials
Acute kidney injury 1.18 (1.01–1.39) 15 trials; heterogeneity reduced when restricted to RAAS-acting drugs
Hyperkalaemia 1.89 (1.56–2.30) 26 trials; likewise RAAS-driven
Hypotension 1.97 (1.67–2.32) 35 trials
Syncope 1.28 (1.03–1.59) 16 trials
All-cause mortality, cardiovascular death, stroke Reduced Myocardial infarction not significantly reduced in this analysis

Trial-specific harms track this: SPRINT reported more hypotension, syncope, electrolyte abnormality and acute kidney injury but not more injurious falls (SPRINT 2021, PMID 34010531); ESPRIT reported excess syncope (HR 3.00, 95% CI 1.35–6.68) without excess hypotension, electrolyte abnormality, injurious fall or acute kidney injury (Liu 2024, PMID 38945140); BPROAD reported more symptomatic hypotension and hyperkalaemia with similar serious adverse events overall (Bi 2025, PMID 39555827); ACCORD-BP reported serious treatment-attributed adverse events in 3.3% versus 1.3% (ACCORD 2010, PMID 20228401). The pooled benefit–harm ledger gives NNT 58 against NNH 55 (Guo 2025, PMID 40902616).

Orthostatic hypotension is not a reason to avoid treatment. Individual-participant meta-analysis of 18,466 participants and 127,882 follow-up visits found intensive treatment lowered the odds of orthostatic hypotension (OR 0.93, 95% CI 0.86–0.99), with no interaction by pre-randomisation orthostatic hypotension; the authors state explicitly that orthostatic hypotension should not be a reason to avoid or de-escalate treatment (Juraschek 2021, PMID 32909814). A 2025 companion analysis of 31,124 participants and 315,497 standing measurements found orthostatic hypertension in 17% and also modestly reduced by intensive treatment (OR 0.93, 0.90–0.96) (Juraschek 2025, PMID 40132860). Management of coexisting hypertension and orthostatic hypotension has been reviewed (Rajesh 2026, PMID 42033492), and deprescribing effects on orthostatic symptoms examined in TONE (Juraschek 2022, PMID 34718403).

Where harm does concentrate is frailty and institutional care. Antihypertensive treatment-associated serious adverse events rise with age and frailty (Sheppard 2023, PMID 37075078); initiation was associated with fracture risk in nursing-home residents (Dave 2024, PMID 38648065) and with falls and other serious events in people with dementia (Fujiwara 2025, PMID 40961130). This is the population in which the trial-level reassurance about falls does not obviously transfer, because these people were not in the trials. See special populations.

Over-treatment in specific settings

  • Hospitalised patients with asymptomatic elevation. Intensive inpatient treatment: composite adverse outcome OR 1.28 (95% CI 1.18–1.39), rising to 1.90 (1.65–2.19) with intravenous agents, consistent across frailty and prior-pressure strata (Anderson 2023, PMID 37252732). Treated inpatients had more acute kidney injury (10.3% vs 7.9%) and myocardial injury (1.2% vs 0.6%) with no blood-pressure interval in which treatment looked better (Rastogi 2021, PMID 33369614). As-needed medication: acute kidney injury HR 1.23 (1.18–1.29), rapid systolic fall 1.5-fold more likely, composite of MI/stroke/death 1.69-fold higher (Canales 2025, PMID 39585709). See hypertensive emergencies.
  • At hospital discharge. Intensification of the outpatient regimen at discharge in older adults is associated with harm and does not improve subsequent control (Anderson 2018, PMID 30209052; Rastogi 2021, PMID 33369614).
  • Referring hypertensive urgency to hospital. No difference in major adverse cardiovascular events at 7 days, 30 days or 6 months, but more admissions (Patel 2016, PMID 27294333).
  • Very low diastolic pressure. Diastolic <60 mm Hg carried adjusted odds of 2.2 for elevated high-sensitivity troponin versus 80–89 mm Hg, predicted progressive troponin rise and incident coronary events, most pronounced at systolic ≥120 mm Hg (McEvoy 2016, PMID 27590090). This is an observational signal, not a trial result — see risk and outcomes.

Drugs and substances that raise blood pressure

Systematically under-elicited, and a common cause of apparent resistance and of malignant hypertension (Grossman 2012, PMID 22195528; Foy 2019, PMID 31655781; Lovell 2017, PMID 28451850; Jurca 2016, PMID 27671491):

  • NSAIDs (including over-the-counter), COX-2 inhibitors
  • Combined oral contraceptives; some hormone therapies
  • Sympathomimetic decongestants; stimulants; cocaine and amphetamines
  • VEGF-pathway inhibitors and other antiangiogenic oncology drugs — a recognised trigger of hypertensive emergency (Boulestreau 2024, PMID 38658108); polygenic risk has been studied for bevacizumab-induced hypertension (Quintanilha 2022, PMID 35527502)
  • Calcineurin inhibitors, glucocorticoids, erythropoiesis-stimulating agents
  • Serotonin–noradrenaline reuptake inhibitors (Azizi 2026, PMID 41870448)
  • Licorice, excessive alcohol (Roerecke 2017, PMID 29253389)

Missed diagnoses

Missed diagnosis Why it is missed Signal
Primary aldosteronism Screening keyed to resistant hypertension; aldosterone-renin ratio has poor sensitivity and negative predictive value Present in 11.3–22.0% across the pressure spectrum (Brown 2020, PMID 32449886); Endocrine Society now suggests universal screening (Adler 2025, PMID 40658480)
Non-adherence Self-report and pharmacy data understate it 31.2% pooled in apparent resistance (Durand 2017, PMID 28777133)
White-coat effect Office-only measurement ~37.5% of apparent resistance (Azizi 2026, PMID 41870448)
Masked hypertension / masked asleep hypertension Normal office readings Estimated 13.3% of US adults have isolated masked asleep hypertension (Li 2021, PMID 33112362)
Phaeochromocytoma Episodic symptoms attributed to anxiety Metanephrines; germline testing (Pacak 2015, PMID 25716634)
Coarctation, recurrent or residual Resting pressure may be normal Exercise-induced hypertension post-repair (Correia 2013, PMID 24239395; Panzer 2022, PMID 35282025)
Obstructive sleep apnoea Not asked about CPAP lowers pressure in the uncontrolled (Pengo 2025, PMID 39401854)

Drug-specific cautions

  • ACE inhibitors, ARBs and direct renin inhibitors are contraindicated in pregnancy (fetal renal toxicity). This is absolute; women of childbearing potential taking them should have a plan. See hypertension in pregnancy.
  • Dual renin-angiotensin blockade (ACE inhibitor plus ARB) increases hypotension, syncope and renal dysfunction with no outcome benefit (ONTARGET 2008, PMID 18378520).
  • Mineralocorticoid receptor antagonists cause hyperkalaemia; PATHWAY-2 recorded potassium >6.0 mmol/L on one occasion in 6 of 285 spironolactone-treated patients despite eligibility restrictions (Williams 2015, PMID 26414968), and the 2026 review restricts spironolactone initiation to eGFR ≥45 mL/min/1.73 m² and potassium ≤4.5 mmol/L (Azizi 2026, PMID 41870448). Potassium monitoring after initiation is imperfect in practice (Raebel 2010, PMID 20087674), and hyperkalaemia recurs in identifiable high-risk groups (Adelborg 2019, PMID 31226134). Non-steroidal mineralocorticoid receptor antagonists and potassium binders alter but do not remove this constraint (Pandey 2022, PMID 35713973; Gregg 2023, PMID 36264349).
  • Potassium-enriched salt substitutes plus RAAS blockade or a mineralocorticoid receptor antagonist. SSaSS largely excluded people at high hyperkalaemia risk and found no excess hyperkalaemia events in those enrolled (rate ratio 1.04, 95% CI 0.80–1.37) (Neal 2021, PMID 34459569), but the combination in CKD is untested; two trials now address it directly (see clinical trials landscape). Cochrane review notes the same gap (Brand 2022, PMID 35944931).
  • Thiazides: hypokalaemia (6.0% with chlorthalidone vs 4.4% with hydrochlorothiazide in a 13,523-patient pragmatic trial), hyponatraemia, hyperuricaemia and gout, glucose intolerance (Ishani 2022, PMID 36516076; Black 2008, PMID 18000186).
  • Abrupt withdrawal. Withdrawal of antihypertensive therapy can precipitate hypertensive crisis, classically described in renovascular hypertension (Strauss 1977, PMID 578267) and as a rebound phenomenon with agents used in coronary disease (Laham 1979, PMID 231311). Non-adherence is the commonest precipitant of malignant hypertension (Boulestreau 2024, PMID 38658108). Planned deprescribing under supervision is a different matter and was safe over 12 weeks in OPTIMISE (Sheppard 2020, PMID 32453368).

Recognition: when severe elevation is an emergency

Severe elevation plus any of: new neurological deficit or encephalopathy, chest pain, tearing back pain, acute breathlessness or pulmonary oedema, oliguria or rapidly rising creatinine, new grade III–IV retinopathy, or pregnancy beyond 20 weeks with headache, visual change or right-upper-quadrant pain. Without such features, the evidence favours oral therapy and outpatient follow-up over emergency referral (Patel 2016, PMID 27294333; Boulestreau 2024, PMID 38658108). See hypertensive emergencies.

Open questions

  • Does the absence of a falls association at trial level (Albasri 2021, PMID 33568342) hold in nursing-home and dementia populations, where observational data suggest harm? (Dave 2024, PMID 38648065; Fujiwara 2025, PMID 40961130)
  • If orthostatic hypotension is reduced by intensive treatment (Juraschek 2021, PMID 32909814), why does clinical practice still treat it as a contraindication?
  • What is the hyperkalaemia risk of salt substitution combined with RAAS blockade and a mineralocorticoid receptor antagonist in CKD? (Neal 2021, PMID 34459569; Brand 2022, PMID 35944931)
  • Would mandating validated devices and cuff-size selection change population blood-pressure distributions measurably? The 2026-09-01 searches located measurement-accuracy and implementation studies but no measurement-quality intervention trial with a clinical endpoint (Ishigami 2023, PMID 37548984; Picone 2020, PMID 32275193).
  • Three observational studies agree that treating asymptomatic inpatient hypertension is harmful; the equipoise for a randomised trial is explicit (Canales 2025, PMID 39585709) — why has none been done?

References

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