Millions Abandon Third Blood Pressure Drug Within a Year, Global Study Finds

A sweeping analysis of real-world medical records from six countries has revealed a troubling and surprisingly consistent pattern in the treatment of hypertension that is harder to control: the majority of patients who are prescribed a third blood pressure medication stop taking it within a year, even though many of them have not reached their blood pressure targets. The findings, drawn from the multinational EnligHTN observational cohort study and published in the journal Advances in Therapy, offer one of the most detailed pictures to date of what actually happens after clinicians intensify treatment in patients who are already taking two antihypertensive drugs from different classes.

The research team, led by Jesper N. Bech of the University Clinic in Nephrology and Hypertension at Gødstrup Hospital and Aarhus University in Denmark, together with colleagues from the United Kingdom, the United States, Germany, Spain, Israel, and Denmark, extracted data from de-identified electronic medical records, insurance claims, and national health registries covering the years 2018 through 2023, and through 2024 for Denmark. Their study population comprised 64,501 adults with diagnosed hypertension who had been maintained on a stable two-drug regimen and then initiated a third antihypertensive medication, a step that clinicians interpret as treatment intensification in patients whose blood pressure remains above goal. The third medication fell into one of six commonly prescribed classes: angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, beta-blockers, diuretics, or mineralocorticoid receptor antagonists.

The headline result is stark. Across countries and drug classes, between 54 percent and 100 percent of patients had discontinued their third medication within 12 months of starting it, and between 67 percent and 100 percent had done so within 24 months. In most countries, the median time to discontinuation was remarkably short, ranging from just 0.1 to 0.5 years, meaning that half of patients in many cohorts had abandoned the new drug within roughly two to six months. Denmark stood out as the exception, with discontinuation rates of 54 to 67 percent at one year and median persistence of 0.5 to 0.8 years, a difference the investigators suggest may partly reflect differences in how Danish physicians prescribe and dispense medications, with prescriptions commonly issued for 100 days or more.

Adherence told a similarly sobering story. The researchers measured adherence using the proportion of days covered, a pharmacoepidemiological standard that tracks how much of a follow-up period a patient actually has medication available based on prescription fills and dispensations. Median adherence to the third drug declined steadily over time, and the proportion of patients achieving the conventional threshold of more than 80 percent adherence at six months was 66 to 79 percent in Denmark but only 8 to 52 percent elsewhere. By 24 months, the picture in most countries had deteriorated further. Notably, adherence and persistence patterns were broadly similar across the six drug classes within each country, suggesting that the problem is less about which particular medication is chosen and more about systemic factors governing how patients engage with complex multidrug regimens.

The blood pressure outcomes raise equally difficult questions. Among the subset of patients with recorded blood pressure measurements at 12 months, only 23 to 50 percent in the United States, 35 to 66 percent in the United Kingdom, 42 to 55 percent in Germany, 57 to 70 percent in Spain, 63 to 89 percent in Israel, and 35 to 71 percent in Denmark had blood pressure below their country-specific target, which was 130/80 mmHg in the United States and 140/90 mmHg everywhere else. Median reductions in systolic blood pressure over the first year were modest, ranging from essentially zero for some drug classes in some countries to around 14 mmHg for calcium channel blockers at best. At 24 months, many patients showed no meaningful improvement, and some experienced worsening systolic pressures relative to baseline.

Perhaps most striking was what the medication data revealed about dosing behavior. When the investigators plotted daily dose categories and discontinuation across the first 365 days after the index prescription, they found that up-titration to higher doses was uncommon. Patients overwhelmingly started on low or usual doses and stayed there, even as a substantial proportion remained above their blood pressure targets. In some cases, prescriptions fell below licensed doses altogether: at least half of patients receiving the mineralocorticoid receptor antagonist spironolactone in the UK, USA, and Spain were dispensed 25 mg or less, below the 50 mg threshold generally considered the licensed starting dose for hypertension, and a similar pattern appeared for eplerenone. The authors interpret this combination of low starting doses, minimal up-titration, and high discontinuation as a signature of therapeutic inertia, the well-documented clinical phenomenon in which providers fail to intensify treatment despite evidence that a patient’s condition remains uncontrolled.

The clinical stakes of this gap are considerable. Hypertension is the leading modifiable risk factor for cardiovascular and renal disease worldwide, and meta-analyses indicate that every 10 mmHg reduction in systolic blood pressure lowers the risk of major cardiovascular events by roughly 20 percent. Yet globally, only about one in five people with hypertension achieves guideline-recommended blood pressure control. Patients who require multiple medications and still fail to reach target face elevated risks of stroke, ischemic heart disease, heart failure, chronic kidney disease, diabetes, and death. The EnligHTN analysis also showed that many of these patients carried substantial comorbid disease at baseline: the prevalence of heart failure ranged from 2 to 56 percent across cohorts, chronic kidney disease from 14 to 84 percent, and type 2 diabetes from 8 to 38 percent, conditions that complicate blood pressure management both biologically and pharmacologically.

The authors are careful to note important limitations. Discontinuation was inferred from prescribing and dispensing records rather than direct measurement of medication intake, so the estimates reflect loss of observed treatment continuity rather than definitive proof that patients stopped taking their pills; gaps may also reflect clinician-directed strategy changes or incomplete data capture. Blood pressure measurements were missing for a majority of patients at follow-up, ranging from 50 to 90 percent at the 12- and 24-month time points, so control rates describe only those patients with documented monitoring and may not generalize to the full cohort. The setting in which readings were taken could not always be determined, leaving open the possibility of white-coat or pseudo-resistant effects, and some prescribed doses may have been intended for indications other than hypertension.

Even with those caveats, the scale and consistency of the findings across six distinct healthcare systems carry a clear message. High discontinuation, suboptimal adherence, and therapeutic inertia converge to leave many patients with harder-to-control hypertension undertreated and unprotected. The study’s authors argue that the field needs two parallel advances: adherence-focused strategies that reduce pill burden and support patients in staying on therapy, and new classes of antihypertensive agents that are better tolerated and more effective at targeting the underlying pathophysiology in patients who do not respond adequately to existing drugs. With newer pharmacological options entering the hypertension landscape, the real-world treatment patterns documented by EnligHTN provide a crucial benchmark against which any genuine improvement in persistence, adherence, and blood pressure control will have to be measured.

Subject of Research: Real-world antihypertensive medication adherence, discontinuation, and blood pressure control in patients with harder-to-control hypertension

Article Title: Antihypertensive Medication Patterns in Patients with Hypertension that is Harder to Control: Insights from the EnligHTN Study

Article References: Bech, J. N., McCormack, T., Bhalla, V., Ben Dor, N. R., Segura, J., Hougaard Christiansen, S., Andersen, I. T., Erhard, C., Rhodes, K. M., Norris, T., Coto, E., & Weil, J. (2026). Antihypertensive Medication Patterns in Patients with Hypertension that is Harder to Control: Insights from the EnligHTN Study. Advances in Therapy. https://doi.org/10.1007/s12325-026-03771-5

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03771-5

Keywords: hypertension, antihypertensive medications, medication adherence, blood pressure control, treatment discontinuation, therapeutic inertia, EnligHTN study, real-world evidence, observational cohort study, treatment persistence, cardiovascular risk, polypharmacy