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Using some blood pressure medications in the long term may have health risks. svetikd/Getty Images
  • High blood pressure itself can contribute to a heightened risk for several long-term health problems.
  • Managing high blood pressure often involves the use of long-term medications, which may also carry some health risks.
  • A recent study found three medications commonly used to treat high blood pressure all have a similar association with cardiovascular mortality.
  • The results also indicated that angiotensin-converting enzyme (ACE) inhibitors may be associated with an increased risk for stroke.

Long-term management of high blood pressure can improve many areas of health. Sometimes, people can control blood pressure without going on medications. However, several common medications can assist with long-term management.

A recent study published in JAMA Network looked at mortality and several other health outcomes among people taking one of three common medications to manage blood pressure.

In their analysis of over 32,000 participants with high blood pressure, the researchers found similar cardiovascular disease mortality risk regardless of medication type.

However, further analysis of the data showed an 11% increase in risk for fatal and nonfatal stroke associated with taking ACE inhibitors compared with taking diuretics.

The results indicate the need for further research in this area to determine the potential risk of medications like ACE inhibitors.

As defined by the Centers for Disease Control and Prevention (CDC), blood pressure “is the pressure of blood pushing against the walls of your arteries. Arteries carry blood from your heart to other parts of your body.”

When blood pressure gets too high, it can contribute to certain complications like stroke, heart attack, heart failure, or vision loss.

To manage high blood pressure, people can make certain lifestyle changes, such as exercising regularly, cutting down on alcohol, and reducing sodium intake.

Many people with high blood pressure take medication to help keep blood pressure in a healthy range. Three common types of medication used to manage blood pressure are thiazide-type diuretics, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors.

While all of these medications work slightly differently, they can all assist in lowering blood pressure.

This study wanted to look at some long-term effects of taking certain medications for high blood pressure. Because of the study setup, researchers were able to do passive follow-up with participants up to twenty-three years later.

The study was a prespecified secondary analysis of another study, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Researchers were able to include data from 32,804 of these participants.

The participants were age 55 or older, had high blood pressure, and had one or more other coronary heart disease risk factors.

Among participants, researchers looked at several outcomes:

  • Mortality due to cardiovascular disease
  • All-cause mortality
  • Fatal and nonfatal cardiovascular disease combined
  • Morbidity and mortality for coronary heart disease, stroke, cancer, end-stage renal disease, and heart failure

The original trial in question was a double-blind clinical trial where participants received one of three initial medications for high blood pressure: a calcium channel blocker (amlodipine), an ACE inhibitor (lisinopril), or a thiazide-type diuretic (chlorthalidone). The original trial also included participants taking an α-blocker (doxazosin), but this part of the trial ended early.

Dr. Cheng-Han Chen, board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, who was not involved in the study, detailed the three types of medications examined in the study to Medical News Today:

3 types of hypertension drugs studied

“The three types of medications studied in the paperwork to effectively control high blood pressure in different ways. A thiazide-type diuretic works by causing your body to get rid of water and salt, thereby lowering the fluid volume in blood vessels and the resultant pressure in the system. A calcium-channel blocker acts to reduce the calcium entering the blood vessel walls, which in turn relaxes the blood vessels and reduces blood pressure. An angiotensin-converting enzyme (ACE) inhibitor prevents the body from making a certain chemical (Angiotensin II) that constricts blood vessels, and thus relaxes blood vessels and lowers blood pressure.”

For the secondary analysis, researchers were able to go beyond the initial trial period and follow-up through data from the National Death Index, Social Security Administration, and Center for Medicare & Medicaid Services databases.

Study author Jose-Miguel Yamal, Ph.D., associate professor of biostatistics and data science at UTHealth Houston School of Public Health, explained to MNT:

“We sought to determine whether there was a difference in the long-term risk of mortality and morbidity outcomes for older adults with hypertension that were starting with one of three popular antihypertensive treatments: a thiazide-type diuretic, a calcium channel blocker, and an ACE inhibitor.”

“A landmark clinical trial that compared these treatments followed participants up for about five years. We took that group of patients and linked their data with some other administrative datasets, like Medicare, to be able to determine whether they ended up having other outcomes up to 23 years after they started the trial, much longer than what was possible by contacting participants individually,” he continued.

The study’s results found a similar mortality risk due to cardiovascular disease associated with each medication. The results were also similar among the groups for other secondary outcomes.

The main difference was that the ACE inhibitor was associated with an 11% increased risk for fatal and nonfatal hospitalized stroke. This was in comparison to the thiazide-type diuretic.

However, researchers noted that “after accounting for multiple comparisons, this increased risk was no longer significant.” Thus, they believe people should interpret the results cautiously.

“This study reaffirms many of the findings from the original ALLHAT study which informed clinical guidelines. When stroke risk is a major consideration, diuretics and calcium channel blockers have been shown to have better blood pressure control and reduce the risk of stroke compared to ACE inhibitors and this effect persisted well beyond the trial period. Further studies are warranted to confirm these results that include blood pressure medications used in the long-term.”
— Jose-Miguel Yamal

Dr. Rigved Tadwalkar, a board certified cardiologist at Providence Saint John’s Health Center in Santa Monica, CA, who was also not involved in the study, said the study offered “valuable insights” into the long-term effects of antihypertensive medications.

“The most notable observation is the absence of significant differences in cardiovascular disease mortality among patients treated with these three classes of medications over the extended follow-up period of up to 23 years. This suggests that, from a mortality standpoint, these antihypertensive classes are relatively comparable in their long-term efficacy.”
— Dr. Rigved Tadwalkar

This research does have certain limitations.

First, it doesn’t establish a causal relationship between the factors involved. Next, once everything was unblinded, there’s potential for bias, and it’s possible that once participants were unblinded, they may have discontinued medications. The researchers also did not have data on post-trial blood pressure medication use between 2002 and 2006.

After adjustments for multiple comparisons, they found that “none of the analyses were statistically significant.”

The researchers did not follow up on all the participants in the original trial, such as the participants from Canada. They also couldn’t get long-term morbidity follow-up from non-Medicare participants and those using Veterans Affairs services. This may have limited the findings and may make the results less generalizable.

The researchers also did not get laboratory data and blood pressure readings after the original trial completion.

Dr. Tadwalkar noted the following limitations to MNT:

“The next most notable observation is the 11% increased risk of combined fatal and nonfatal hospitalized stroke [for the ACE inhibitor group] compared to [the] diuretics [group]. Nevertheless, this finding needs to be interpreted with caution, considering the potential impact of unmeasured confounding variables and the fact that the study did not have posttrial data on antihypertensive medication use for several years (2002 to 2006).”

“This lack of information raises the possibility of crossover or regression to similar medications, which could have influenced the observed outcomes,” he added.

“All things considered, the findings emphasize the significance of ongoing monitoring and reassessment of antihypertensive regimens, with a focus on tailoring treatment to the specific needs of each patient. Shared decision-making between clinicians and patients is key in this situation, considering the differences in observed outcomes over an extended period of time.”
— Dr. Rigved Tadwalkar