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Too high: Older drugs work well for hypertension, new medications show little innovation

In this piece in a series on high blood pressure, Randall Stafford, MD, PhD, outlines the most common medications used to treat blood pressure.

Doctors can choose from more than 200 medications to treat hypertension, a primary risk factor for stroke and heart attack. But only a few, mostly older, generic drugs are commonly used, making prescription costs lower than for many other chronic diseases. This is a trade-off — new drugs often have higher costs, but can sometimes offer improvements or reduce side effects.

Here is a quick and easy guide to improve your understanding of the five most common drugs, used by the majority of patients.

  • The most commonly used drug is hydrochlorothiazide or HCTZ (which is used by 22 percent of hypertension patients, according to QuintilesIMS). It’s a diuretic, which causes the kidneys to increase urination. This results in a lower volume of fluid in the bloodstream, which reduces blood pressure. It or its cousin drug, chlorthalidone, are preferred first drugs because they work well for most patients.
  • Equally common is lisinopril, a drug in the angiotensin converting enzyme inhibitor (ACEI) family (most end in “-pril”). It interferes with a chemical signal in the body that would otherwise increase blood pressure.
  • Amlodipine, which is used by 17 percent of hypertension patients, is a calcium channel blocker. It lowers blood pressure by partially preventing calcium from traveling into cells, which prevents blood vessels from narrowing and raising blood pressure.
  • A drug class closely related to ACEIs are angiotensin receptor blockers or ARBs, which interfere with the same chain of reactions as ACEIs. The most commonly used ARB, losartan, is taken by 10 percent of patients. Usually, ACEIs are prescribed first because of their well-established record, but are replaced by ARBs if side effects occur.
  • Unlike the other classes, beta blockers are not a great blood pressure drug for everyone. They work best for people with heart disease because they slow the heart rate and reduce blood pressure. Metoprolol, used by 8 percent of hypertension patients, is the leading beta-blocker (most end in “-olol”).

Let’s revisit Margaret, who was introduced in a previous post: She is a 53-year-old with high blood pressure. When first treated, she was prescribed the drug lisinopril, which blocks the tightening of blood vessels. Even with gradual dosage increases, her blood pressure remained too high. Her increasing weight made her hypertension harder to treat. Her physician then added a second medication, amlodipine, which relaxes blood vessels. Her blood pressure was controlled for a time, although she had some side effects, including ankle swelling. At her last visit, Margaret’s blood pressure was up again and her doctor was considering adding a third, new drug, hydrochlorothiazide (HCTZ).

HCTZ, lisinopril, and amlodipine are effective drugs often used together. Most people require two or three different medications to fully control blood pressure (just like Margaret). Occasionally, patients require even more drugs.

The three top drugs are low cost older drugs. HCTZ, first available in 1959, costs pharmacies only $4.29 for one patient’s annual supply. Lisinopril (introduced in 1987 and costs pharmacies $6.33 per year per patient) and amlodipine (introduced in 1992 and costs pharmacies $5.66 per year per patient) are also inexpensive.

There are newer drugs, but they aren’t breakthroughs. Many resemble existing medications or are simply combinations of already available drugs. For most patients, they are not worth their significant extra cost. For example, azilsartan, a new angiotensin receptor blocker introduced in 2011, costs a pharmacy $2,000 per year per patient.

This lack of innovation from drug companies is concerning given the huge burden of disease caused by inadequately treated high blood pressure. For now, the older drugs are the best drugs, but very often must be combined with each other.

This is second piece in a five-part series on "Too high" blood pressure, created for those with high blood pressure and their family and friends. Future articles will discuss drug side effects, the power of lifestyle changes, and appropriate blood pressure targets. Some data in this series come from QuintilesIMS. For additional information, please contact rstaff@stanford.edu.

Randall Stafford, MD, PhD, a professor of medicine and director of the Program on Prevention Outcomes and Practices, practices primary care internal medicine at Stanford. He is developing practical strategies to improve how physicians and consumers approach chronic disease treatment and prevention.

Previously: Too high: Despite drugs, blood pressure rates continue to soar in the United States  
Photo by qimono

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