What is the best blood pressure medication? Types of High Blood Pressure Medications

High blood pressure (hypertension) affects about 1 in 4 adults in Canada. It usually causes no symptoms, but over time it damages the blood vessels and raises the risk of heart attack, stroke, kidney disease and dementia. The good news is that healthy habits and medications can lower blood pressure and prevent these problems. With so many medications available, which one is best for you? This article explains the main types of blood pressure medications, what the latest Canadian guidelines recommend and how your genes can play a role.

What raises blood pressure?

Blood pressure is the force of blood pushing against the walls of your arteries. It goes up when:

• Blood vessels become narrow or stiff, so the heart has to push harder.
• The body holds on to extra salt and water, which increases the amount of fluid in the blood vessels.

A hormone called angiotensin II plays a big part in both. It narrows blood vessels and signals the kidneys to keep salt and water. Most blood pressure medications work by relaxing the blood vessels, removing extra fluid or blocking angiotensin II.

What do the 2025 Canadian guidelines recommend?

The 2025 Hypertension Canada guideline for primary care recommends:

• A diagnosis of high blood pressure at 130/80 or higher, confirmed with proper measurements, including home or 24-hour readings.
• A target top number (systolic pressure) below 130 for most adults on treatment.
• Healthy lifestyle changes for everyone: less salt, more vegetables and fruit, regular physical activity, a healthy weight and limiting alcohol.
• For people who need medication, starting with low doses of two medications, ideally combined in a single pill.

What are the main types of blood pressure medications?

The guideline recommends three main groups of medications as first choices. They lower blood pressure by a similar amount and protect against heart attack and stroke equally well.

1. ACE inhibitors and ARBs

These medications block the effects of angiotensin II, which relaxes the blood vessels and helps the body get rid of extra salt and water. They also protect the kidneys, especially in people with diabetes.

• ACE inhibitors stop the body from making angiotensin II. Examples include ramipril, perindopril, lisinopril and enalapril. A dry cough is a common side effect.
• ARBs (angiotensin receptor blockers) stop angiotensin II from acting on the blood vessels. Examples include candesartan, losartan, telmisartan, irbesartan and valsartan. They rarely cause a cough.

ACE inhibitors and ARBs should not be taken together, and they must be avoided in pregnancy because they can harm the baby. Your prescriber will check your kidney function and potassium levels.

2. Thiazide and thiazide-like diuretics ("water pills")

Diuretics help the kidneys remove extra salt and water in the urine, which lowers the amount of fluid in the blood vessels. Examples include hydrochlorothiazide, chlorthalidone and indapamide. They can lower potassium and sodium levels and make you urinate more often at first.

3. Calcium channel blockers

Calcium channel blockers relax the muscles in the walls of the blood vessels, so the vessels widen. The guideline recommends the long-acting type, such as amlodipine, felodipine and nifedipine extended release. Ankle swelling is a common side effect. Two other calcium channel blockers, diltiazem and verapamil, also slow the heart and are used mostly for heart rhythm problems or chest pain.

Why do most people need two medications?

About 70% of people with high blood pressure need more than one medication to reach their target. Starting with low doses of two medications from different groups works better than a high dose of one, often with fewer side effects. The guideline recommends an ACE inhibitor or ARB combined with either a diuretic or a long-acting calcium channel blocker, ideally in one pill, such as perindopril with indapamide or telmisartan with amlodipine. Taking one pill instead of two also makes it easier to remember your medication. If blood pressure is still high, all three groups can be combined, and spironolactone can be added after that.

When are beta-blockers used?

Beta-blockers, such as metoprolol, bisoprolol and atenolol, slow the heart rate. They lower blood pressure, but they protect against stroke less well than the other groups and cause more side effects such as tiredness. For this reason, they are not a first choice for high blood pressure alone. They are used when there is another reason, such as heart failure, chest pain (angina), a past heart attack or a fast or irregular heartbeat.

Do genes affect blood pressure medications?

For most first-choice blood pressure medications, the choice is based mainly on your age, other health conditions, kidney function, pregnancy plans and side effects. Genes play a bigger role for some heart medications. For example, metoprolol is broken down by the CYP2D6 enzyme. People who are CYP2D6 poor metabolizers have much higher levels of metoprolol and a slower heart rate, and the CPIC guideline recommends starting them on a lower dose and increasing it slowly, or choosing a different beta-blocker.

NAT2 and hydralazine. Hydralazine is an older medication that relaxes the blood vessels. It is used for hard-to-control high blood pressure, for heart failure and during pregnancy. It is broken down by the NAT2 enzyme, and about half of people are NAT2 poor metabolizers (also called slow acetylators). They have higher hydralazine levels, which can lower blood pressure more but also raise the risk of side effects, including drug-induced lupus. The 2025 CPIC guideline gives hydralazine dosing recommendations based on NAT2 results.

CYP3A4 and calcium channel blockers. Amlodipine, felodipine, nifedipine, diltiazem and verapamil are broken down mainly by the CYP3A4 and CYP3A5 enzymes. Natural differences in these genes may change drug levels and blood pressure response, although study results are mixed. Drug interactions also matter: medications that block CYP3A4, such as clarithromycin and some antifungals, and grapefruit juice can raise the levels of these medications and cause low blood pressure, dizziness or ankle swelling.

Genes may also help explain why diuretics work better for some people than others. A genome-wide study linked variants near the YEATS4 gene to how much blood pressure dropped with hydrochlorothiazide, and a follow-up study confirmed that people with one YEATS4-region variant had a larger drop in blood pressure with hydrochlorothiazide, but not with the beta-blocker atenolol. These findings are not yet used to guide prescribing, but they show how genes may one day help choose the right blood pressure medication from the start.

Genes also matter for many other medications that people with high blood pressure often take, such as blood thinners, cholesterol medications, painkillers and antidepressants. Some of these can interact with blood pressure medications or raise blood pressure themselves; for example, anti-inflammatory painkillers such as ibuprofen can raise blood pressure and reduce the effect of blood pressure medications.

How can a pharmacogenetic test help?

A Pillcheck test reports CYP2D6, NAT2, CYP3A4, CYP3A5 and other genes, and shows how they affect metoprolol, hydralazine, calcium channel blockers and many other heart and blood pressure-related medications, including blood thinners such as clopidogrel and warfarin, and cholesterol medications such as statins. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. A Pillcheck pharmacist reviews your results together with all your medications, checks for interactions and recommends safer options and doses to discuss with your prescriber.

Read also: How does managing your blood pressure reduce your risk of dementia?

Summary

• The 2025 Canadian guideline defines high blood pressure as 130/80 or higher and sets a target top number below 130 for most adults.
• Healthy lifestyle changes are recommended for everyone with high blood pressure.
• The first-choice medications are ACE inhibitors or ARBs, thiazide-type diuretics and long-acting calcium channel blockers.
• Most people should start with low doses of two medications, ideally in one pill.
• Beta-blockers are used mainly when there is another heart condition; CYP2D6 poor metabolizers may need a lower dose of metoprolol.
• NAT2 affects hydralazine, and CYP3A4 and CYP3A5 genes and drug interactions affect calcium channel blockers such as amlodipine.
• A pharmacogenetic test and pharmacist review can help make all your medications safer.

Frequently asked questions

What is the best blood pressure medication?

There is no single best medication for everyone. For most people, the guideline recommends starting with an ACE inhibitor or ARB combined with either a diuretic or a long-acting calcium channel blocker, ideally in one pill. Your prescriber will choose based on your age, health conditions, side effects and pregnancy plans.

Why does my ACE inhibitor make me cough?

A dry cough is a common side effect of ACE inhibitors such as ramipril. If it bothers you, your prescriber can switch you to losartan or valsartan, which rarely cause a cough.

Why did my doctor prescribe two medications at once?

Most people need more than one medication to reach their target. Low doses of two medications work better and often cause fewer side effects than a high dose of one.

Are beta-blockers good for high blood pressure?

They lower blood pressure but are not a first choice unless you also have heart failure, angina, a past heart attack or a heart rhythm problem.

Can my genes affect my blood pressure medication?

Yes, for some medications. CYP2D6 poor metabolizers have much higher levels of metoprolol and may need a lower dose, NAT2 poor metabolizers have higher levels of hydralazine, and CYP3A4 and CYP3A5 affect calcium channel blockers such as amlodipine. Genes also affect many other medications that people with high blood pressure often take.

References

Goupil R, Tsuyuki RT, Santesso N, et al. Hypertension Canada guideline for the diagnosis and treatment of hypertension in adults in primary care. CMAJ. 2025;197(20):E549-E564.

Duarte JD, Thomas CD, Lee CR, et al. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy. Clin Pharmacol Ther. 2024;116(4):939-947.

Eadon MT, Hein DW, Andersen MA, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for NAT2 Genotype and Hydralazine Therapy. Clin Pharmacol Ther. 2025;118(6):1430-1436.

Zhang YP, Zuo XC, Huang ZJ, et al. CYP3A5 polymorphism, amlodipine and hypertension. J Hum Hypertens. 2014;28(3):145-149.

Turner ST, Bailey KR, Fridley BL, et al. Genomic association analysis suggests chromosome 12 locus influencing antihypertensive response to thiazide diuretic. Hypertension. 2008;52(2):359-365.

Duarte JD, Turner ST, Tran B, et al. Association of chromosome 12 locus with antihypertensive response to hydrochlorothiazide may involve differential YEATS4 expression. Pharmacogenomics J. 2013;13(3):257-263.

Image used under the Creative Commons 2.0 License, photo taken by Quinn Dombrowski.