Lisinopril is the most popular medication for high blood pressure in the United States, with over 76 million prescriptions filled in 2023 alone. That makes it the fourth most prescribed drug in the country, all categories included. But lisinopril isn’t the only widely used option. Amlodipine and losartan are close behind, and each works differently in the body.
The Three Most Prescribed Blood Pressure Drugs
Lisinopril, amlodipine, and losartan dominate the prescription landscape for high blood pressure. All three became significantly more popular after losing patent exclusivity, which made generic versions available at a fraction of the original cost. Insurance formularies then began listing them as preferred options in their respective classes, pushing prescribing rates even higher.
Lisinopril is an ACE inhibitor. It works by blocking an enzyme your body uses to produce a hormone called angiotensin II, which tightens blood vessels. Without that hormone constricting things, your vessels relax and blood pressure drops. Amlodipine is a calcium channel blocker. It prevents calcium from entering the muscle cells of your blood vessel walls, which keeps those walls from squeezing tight. Losartan is an ARB (angiotensin receptor blocker), which blocks the same vessel-tightening hormone that lisinopril targets, just at a different point in the process.
All three belong to the four classes of first-line blood pressure drugs recommended by the American Heart Association and American College of Cardiology in their 2025 guidelines. The fourth class is thiazide diuretics, which lower blood pressure primarily by reducing fluid volume and preventing a compensatory rise in that same vessel-tightening hormone.
Why Losartan Has Surged in Popularity
Losartan’s rise is one of the more dramatic trends in blood pressure treatment. Prescription fills jumped from 7 million in 2010 to 46 million in 2021. The trigger was its patent expiring in 2010, which opened the door to cheap generics. Before that, valsartan and combination ARB products were more commonly prescribed within the class. After 2014, losartan took over as the most-used ARB in the country.
Medicare Part D also played a role. When the program launched in 2006, beneficiaries who previously had no prescription coverage were 40% more likely to start using blood pressure medications. The biggest jump was in ARB use specifically, with a 53% increase in the odds of filling an ARB prescription. As losartan’s price dropped, insurance companies increasingly listed it as their preferred ARB, steering both doctors and patients toward it with lower out-of-pocket costs.
How Side Effects Differ Between Them
The most notable side effect of lisinopril is a persistent dry cough. In user-reported data, nearly 29% of people taking lisinopril mention cough as a side effect. This is a well-known class effect of all ACE inhibitors, and it’s a major reason many patients switch to an ARB like losartan, which works on the same hormonal pathway without triggering the cough.
Amlodipine’s signature side effect is swelling, particularly in the ankles and feet, reported by about 14% of users. Fluid pooling in the lower legs happens because the drug relaxes blood vessels so effectively that some fluid leaks into surrounding tissue. Headaches, dizziness, and fatigue show up with both medications at roughly similar rates, ranging from 5% to 13% depending on the symptom.
Losartan tends to be the best tolerated of the three, which is part of its appeal. It lacks the cough problem of ACE inhibitors and the swelling issue of calcium channel blockers. For patients who tried lisinopril and couldn’t tolerate the cough, losartan is often the next step.
Why Your Doctor Might Choose One Over Another
Cost, tolerability, and your other health conditions all factor into which medication you end up on. Lisinopril remains a default starting point for many doctors because it’s extremely cheap, taken once daily, and has decades of safety data behind it. If you also have heart failure or kidney disease from diabetes, ACE inhibitors offer protective benefits beyond just lowering blood pressure.
Race and ethnicity can influence the choice. Black patients tend to have a smaller average blood pressure response to ACE inhibitors, ARBs, and beta blockers compared to white patients. Thiazide diuretics and calcium channel blockers like amlodipine produce stronger average responses in Black patients. For this reason, current guidelines recommend that most Black patients with hypertension start on combination therapy, often pairing a calcium channel blocker or diuretic with another agent, rather than relying on a single drug.
Age matters too. Calcium channel blockers like amlodipine are effective across age groups but are particularly useful in older adults who tend to have stiffer arteries. If you have other conditions like frequent migraines or an elevated heart rate, your doctor might lean toward a different class entirely, like a beta blocker, even though it’s not among the top first-line recommendations for blood pressure alone.
Single Drug vs. Combination Therapy
Many people assume they’ll take one pill and their blood pressure will reach a healthy range. In practice, a large portion of people with hypertension need two or more medications from different classes to get adequate control. The 2025 guidelines reflect this reality, recommending combination therapy as a starting point for anyone whose blood pressure is more than 20/10 mmHg above their goal or who has stage 2 hypertension.
The drugs are often combined strategically. Pairing an ACE inhibitor like lisinopril with a thiazide diuretic works particularly well because the diuretic causes a hormonal response that the ACE inhibitor blocks, making both drugs more effective together than either would be alone. Similarly, adding a diuretic to amlodipine helps counteract the ankle swelling that amlodipine can cause. Many of these combinations are available as a single pill, which simplifies things if you end up needing more than one medication.