bySanjukta Mondal, Medical Xpress

Treatment plans lowering blood pressure (BP), containing an angiotensin receptor blocker (ARB) had the lowest rates of treatment discontinuation due to side effects. Credit: Thirdman for pexels

TheGlobal Hypertension Reportby the World Health Organization (WHO) revealed that 1.4 billion people were living with hypertension in 2024. Yet, only a little over one in five of those diagnosed have it under control, whether through medication or by managing modifiable health risks. Fear of side effects is a major barrier to effective blood pressure control, often discouraging people from starting medication, accepting higher doses, or staying on treatment for the long term.

Arecent studyinvolving 159,362 participants analyzed which drugs, or combinations of drugs, were most likely to cause side effects and the ones that were easiest for patients to continue.

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Angiotensin II receptor blockers (ARBs) came at the top for having the lowest rates of patients stopping treatment, with fewer treatment withdrawals than even a placebo. Among combinations, the pairing of an ARB with a calcium channel blocker (CCB) was the best tolerated. CCB alone, on the other hand, was significantly more likely to cause side effects, leading to higher discontinuation of medication.

The findings are published inJAMA.

Balancing risks and side effects

High blood pressure, or hypertension, is a condition in which blood exerts excessive pressure against the walls of the arteries, often because these smaller arteries have narrowed. This extra pressure makes the heart work harder than normal, and over time, it can quietly damage both the blood carriers and vital organs. Hence, it is essential to keep it under control via medication and lifestyle changes.

The three most common medications for high BP—ARBs, beta blockers, and CCBs—each work differently to bring the pressure down. ARBs block a hormone that causes blood vessels to narrow, allowing them to relax and blood to flow more freely.

Beta blockers take a different approach, where they slow the heart rate and ease pressure on blood vessel walls, while CCBs keep calcium from entering heart and blood vessel cells, which helps the vessels relax and reduces pressure.

Despite how serious the condition is and the advances in BP medications, studies show that among people newly prescribed antihypertensive medication, about 30% to 80% stop taking it within the first year.

Most of those who discontinue treatment or are hesitant to start it in the first place do so because they do not want to deal with headaches, fatigue, swollen ankles, and other side effects associated with the poor tolerability to blood pressure (BP) medications.

The last two decades haven't seen a comprehensive comparison of how well people tolerate different blood pressure medications and combinations.

Ranking the treatments

In this study, the researchers used the network meta-analysis technique to compare different treatments simultaneously, even if these treatments were never tested against each other in the same trial. They analyzed 716 double-blind, randomized clinical trials where the study durations were at least four to 26 weeks long.

The primary focus was on how often patients stopped their medication altogether because side effects became too much to bear. They also tracked four common side effects that frequently drive people to quit: headaches, dizziness, swelling, and coughing. The data collected were run through statistical models that allowed both direct and indirect comparisons between treatments.

To bring it all together, the team used SUCRA (Surface Under the Cumulative Ranking curve) to create a leaderboard ranking of which drug or combination was best tolerated, which had the most side effects, and which had the highest discontinuation rate.

The results indicated that the best-tolerated combination was an ARB plus a CCB. In fact, ARBs appeared among the four of the five best-tolerated treatment options. On the other hand, people were more likely to stop treatment because of side effects when regimens contained CCBs or combinations like a beta-blocker and a diuretic (increases urine production).

They also found that mostBP medications, except CCBs, were associated with fewer headaches than placebo, possibly because CCBs cause cerebral vasodilation, which can trigger headaches.

Further long-term studies across diverse populations are needed to validate these findings for clinical application. Once confirmed, the data could help doctors tailor blood pressure treatment more effectively by selecting medications that are less likely to cause side effects and more likely to help patients stick to their treatment plans.

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Publication details Nelson Wang et al, Adverse Effects and Treatment Discontinuation of Blood Pressure–Lowering Drugs and Combinations, JAMA (2026). DOI: 10.1001/jama.2026.6214 Mary M. McDermott et al, Minimizing Adverse Effects in Hypertension Treatment, JAMA (2026). DOI: 10.1001/jama.2026.7685 Journal information: Journal of the American Medical Association