Which blood pressure medications have the fewest side effects?
The analysis included 716 clinical studies with more than 159,000 participants. The researchers compared important groups of blood pressure-lowering medications, including ACE inhibitors, ARBs, beta blockers, calcium channel blockers, and thiazide diuretics. The key question was how often patients stopped their treatment because of side effects.
Key takeaways at a glance
- ARBs (sartans) were among the best-tolerated blood pressure medications in the analysis.
- The combination of an ARB and a calcium channel blocker performed best.
- Four of the top five therapies included an ARB.
- ACE inhibitors can be effective, but they may cause a dry, irritating cough in some people.
- Calcium channel blockers can make fluid retention in the feet and ankles more likely.
- Do not stop blood pressure medication on your own. If you notice side effects, ask a doctor to clarify whether switching or adjusting the treatment makes sense.
Why tolerability of blood pressure medications is so important
High blood pressure usually needs treatment for many yearsoften for the rest of your life. To keep the therapy working long term, you have to take your medicines regularly. This is a common problem: when unpleasant side effects occur, some people stop their blood pressure medications on their own or take them only irregularly.
This can be risky. If blood pressure stays too high over the long term, the risk of heart attack, stroke, heart failure, and kidney damage increases. Thats why its not just important how strongly a medication lowers blood pressure. It also needs to fit into everyday life and be as well tolerated as possible.
You can also find an overview of different drug groups in the article High blood pressure medications.
Which blood pressure medications were compared?
For the study, the five most important groups of blood pressure medications and various combinations were compared:
- ACE inhibitors, for example ramipril, enalapril, or lisinopril
- ARBs (sartans), for example candesartan, valsartan, or losartan
- beta blockers, for example metoprolol or bisoprolol
- calcium channel blockers, also called calcium antagonists, for example amlodipine or nifedipine
- Thiazide diuretics, for example hydrochlorothiazide or chlorthalidone
The researchers mainly looked at how often patients stopped their treatment because of side effects. This is especially important in everyday practice: a medicine can only protect you if its taken regularly.
Which blood pressure medications were best tolerated?
The most noticeable finding of the study: medicines from the ARB group were overall among the best-tolerated blood pressure medications. In the analyzed studies, patients stopped an ARB treatment even less often due to side effects than participants who only received placebo.
The combination of an ARB and a calcium channel blocker performed particularly well. It was the best-tolerated therapy among those studied. Overall, four of the five highest-ranked treatments included an ARB.
Treatments that were more often discontinued due to side effects in this analysis included calcium channel blockers as the only therapy, ACE inhibitors in combination with calcium channel blockers, and beta blockers in combination with thiazide diuretics.
Blood pressure medications in comparison: Tolerability and typical side effects
| Drug group | Examples | Tolerability in the study | Typical possible side effects |
|---|---|---|---|
| ARBs (sartans) | Candesartan, Valsartan, Losartan | Very good; comparatively rare treatment discontinuation due to side effects | Depending on the patient, for example dizziness or tiredness may occur |
| ARB + calcium channel blocker | for example valsartan + amlodipine | Best tolerability among the therapies studied | Watch for possible side effects from both drug groups |
| ACE inhibitors | Ramipril, Enalapril, Lisinopril | Proven, but not the top performer in tolerability | A dry, irritating cough is a typical side effect |
| Calcium channel blockers | Amlodipine, Nifedipine | As a single therapy, more often discontinued than some other groups | Fluid retention, especially in the feet and ankles |
| Beta blockers | Metoprolol, Bisoprolol | No top position; combination with a thiazide diuretic was less favorable | Depending on the patient, tiredness, a slower pulse, or reduced exercise capacity may occur |
| Thiazide diuretics | Hydrochlorothiazide, Chlortalidone | Tolerability depends on the patient and the combination | More frequent urination or changes in certain blood values may occur |
ARBs: especially well tolerated in the analysis
ARBs, also called angiotensin II receptor blockers, showed especially good tolerability in the study. They were discontinued comparatively rarely due to side effects. Combinations that included an ARB also often achieved good results.
However, this doesnt mean ARBs are automatically the best choice for everyone. Your medical history, kidney function, existing conditions, and other medications always need to be considered.
ACE inhibitors: proven, but a dry cough is possible
ACE inhibitors are well-established blood pressure medications and are used very often. A typical side effect, however, is a dry, irritating cough. Some patients tolerate it well, while others find the cough so bothersome that switching the active ingredient should be discussed.
The study also found that combining an ACE inhibitor with a calcium channel blocker more often led to treatment discontinuation due to side effects than placebo.
Calcium channel blockers: effective, but more frequent fluid retention
Calcium channel blockers can lower blood pressure effectively. At the same time, fluid retention occurred more frequently among themespecially in the feet and ankles. As a single therapy, calcium channel blockers were discontinued more often due to side effects in the study than some other drug groups.
This doesnt mean calcium channel blockers are generally poorly tolerated. Many people do well with them. The deciding factor is whether symptoms occur, how strong they are, and whether a different dose or combination might be better suited.
Beta blockers and thiazide diuretics: depends on the patient and the combination
Beta blockers overall did not rank at the top for tolerability. In the study, the combination of a beta blocker and a thiazide diuretic performed particularly poorly. This combination was among the treatments that were discontinued more often due to side effects.
Thiazide diuretics, sometimes also referred to in everyday language as water pills for blood pressure, can be useful depending on the patient and the combination. However, tolerability in the study strongly depended on which other active ingredient they were combined with.
Typical side effects of blood pressure medications
Side effects can vary depending on the drug group, dose, age, existing conditions, and other medications. The following complaints are especially commonly discussed:
ACE inhibitors:
A dry, irritating cough is a well-known side effect. Typical examples of ACE inhibitors are ramipril, enalapril, or lisinopril.
Calcium channel blockers:
Fluid retention can occur particularly in the feet and ankles. A commonly used active ingredient is amlodipine.
Many blood pressure medications:
Dizziness can occur especially at the beginning of treatment. This is often because blood pressure is dropping and the body needs time to adjust to lower values.
Beta blockers:
Some patients report tiredness, a slower pulse, or reduced physical stamina. Whether this is relevant depends a lot on the individual situation.
Thiazide diuretics:
Depending on the active ingredient and dose, you may have to urinate more often or notice changes in certain blood values. Thats why medical check-ups can be important.
There was also an interesting point: Among most blood pressure medications, headaches tended to decrease. This could be related to the fact that a better-controlled blood pressure itself causes fewer complaints.
Tolerability overview
Very well tolerated in the analysis:
✓ ARB + calcium channel blocker
✓ ARB alone
✓ Other combinations with an ARB
Moderate tolerability:
○ ACE inhibitors
○ Beta blockers
○ Thiazide diuretics
More frequent treatment discontinuation due to side effects:
⚠ Calcium channel blockers alone
⚠ ACE inhibitors + calcium channel blockers
⚠ Beta blockers + thiazide diuretics
Limitations of the study: No blanket treatment recommendation for everyone
The results show clear differences in tolerability among various blood pressure medications. However, they do not mean that ARBs are automatically the best choice for every patient.
Its also important: the analysis is based on short-term studies with follow-up periods of 4 to 26 weeks. The average observation time was 8.6 weeks. Long-term side effects, individual existing conditions, kidney function, other medications, and personal risks must be considered by a doctor.
So the study evaluates average tolerability in clinical trials. It does not replace an individual treatment decision.
What does this mean for patients?
The results show: blood pressure medications differ not only in how they work, but also in how well they are tolerated. In this analysis, ARBs in particular performed well.
But this does not mean that all patients should automatically take an ARB. The treatment that is best for you depends on many factors. These include, for example, age, existing conditions, kidney function, other medications, other illnesses, and individual risks.
Thats why its important: do not stop blood pressure medications on your own. If you notice side effects, ask your doctor to clarify them. Often, a better-tolerated solution can be found by switching the active ingredient, adjusting the dose, or changing the combination.
For more information, see the article Tips for dealing with high blood pressure medications.
How to document side effects better for your doctor visit
If you suspect that a blood pressure medication isnt suiting you well, you should note your symptoms as specifically as possible. Helpful details include the date and time, measured blood pressure values, pulse, the medicines you took, and the symptoms you observed.
This makes it easier for the doctor to judge at your appointment whether the symptoms could be related in time to a new dose, a new active ingredient, or a combination.
A blood pressure diary can help you keep measurements and medication intake organized and spot changes more easily.
With the BloodPressureDB App, you can document blood pressure readings, pulse, and medications and review them in a clear way for your doctors appointment.
Frequently asked questions about blood pressure medications and side effects
Which blood pressure medications have the fewest side effects?
In the JAMA analysis, ARBs were especially well tolerated. The best result was for the combination of an ARB and a calcium channel blocker. Still, the right treatment always depends on the individual situation.
Are ARBs better tolerated than ACE inhibitors?
In the analysis, fewer patients stopped ARBs due to side effects. ACE inhibitors are also proven blood pressure medications, but they can cause a dry, irritating cough more often.
Are there blood pressure medications without side effects?
No. Even well-tolerated blood pressure medications can cause side effects. The key is to find a medicationor combinationthat works and is as well tolerated as possible in everyday life.
What can you do if Ramipril causes coughing?
A dry, irritating cough is a known side effect of ACE inhibitors like ramipril. Patients should not stop the medication on their own, but discuss with a doctor whether switching is sensible.
What to do about fluid retention from Amlodipine?
Fluid retention in the feet or ankles can occur with calcium channel blockers like amlodipine. Here too, a doctor should check whether the dose, the active ingredient, or the combination can be adjusted.
Is it okay to simply stop blood pressure tablets because of side effects?
No. Stopping suddenly can be risky because blood pressure may rise again. Side effects should be documented and discussed with your doctor as soon as possible.
Conclusion
Side effects are an important reason why people stop their blood pressure therapy. The current analysis shows there are clear differences between drug groups. ARBs and ARB-based combinations were especially well tolerated. The combination of an ARB and a calcium channel blocker performed best.
If you dont tolerate your blood pressure medications well, dont stop them on your owntalk to your doctor about possible alternatives.
Sources
- Wang N, Van Der Hoorn S, Pant R, et al. Adverse Effects and Treatment Discontinuation of Blood Pressure-Lowering Drugs and Combinations: A Network Meta-Analysis. JAMA. 2026;335(24):2135-2145. doi:10.1001/jama.2026.6214. https://jamanetwork.com/journals/jama/fullarticle/2849512
- aponet.de: Large hypertension study: ARBs do best when it comes to side effects.https://www.aponet.de/artikel/grosse-bluthochdruck-studie-sartane-schneiden-bei-nebenwirkungen-am-besten-ab-33499
Author Sabine Croci is a certified medical assistant with many years of experience in internal medicine and cardiology practices as well as in outpatient care. Since 2015 she has led the editorial team at BloodPressureDB. With additional qualifications as a paramedic, first responder, and training in various therapy and emergency areas, she provides well-founded, practical, and reliably reviewed information.
