According to an analysis, three important classes of active ingredients in antihypertensive drugs are essentially equivalent in the long term. This emerges from an evaluation in which patients were sometimes followed for more than 23 years after the start of a clinical study. Three groups of patients in the original study had received either chlorthalidone, a thiazide-type diuretic, the calcium channel blocker amlodipine, or lisinopril, an angiotensin-converting enzyme (ACE) inhibitor.
“In this secondary analysis of a randomized clinical trial in an adult population with risk factors for high blood pressure and coronary heart disease, the death rate from cardiovascular disease was similar in all three groups,” explains the team led by Jose-Miguel Yamal from the University of Texas Health Science Center in Houston (USA) in the specialist journal “Jama”.
The current study is based on one of the largest studies on the treatment of high blood pressure. The ALLHAT study randomly assigned more than 42,000 patients at 623 medical centers in the United States and Canada between February 1994 and March 2002 to receive a specific drug.
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At that time, the test subjects were at least 55 years old, had slightly or moderately elevated blood pressure and at least one other cardiovascular risk factor (heart attack, diabetes and others). The last follow-up examination took place after an average of 4.9 years. A large amount of data was collected from the patients in order to take into account differences based on gender, age, ethnicity, previous illnesses, cholesterol levels and other characteristics.
The drugs examined in the ALLHAT study work in different ways. A diuretic such as chlorthalidone stimulates the kidneys to excrete more salt, which then removes water from the body; the amount of blood decreases and blood pressure drops. A calcium channel blocker such as amlodipine prevents the muscles in the blood vessel wall from contracting, which typically happens very early in high blood pressure; the larger vessel diameter lowers blood pressure. The protein angiotensin II also constricts the blood vessels, which an ACE inhibitor such as lisinopril prevents.
Yamal and colleagues tracked the study participants until the end of 2017 using medical records from the American health service Medicare. Since around 80 percent of the patients had already died, in many cases they obtained death certificates to determine the cause of death. In this way, they were able to extend the follow-up of 32,804 subjects from the ALLHAT study, some for more than 23 years.
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The mortality rate from cardiovascular disease 23 years after random assignment was 23.7 percent in the group treated with the diuretic chlorthalidone. It was 21.6 percent in the calcium channel blocker group (amlodipine) and 23.8 percent in the ACE inhibitor group (lisinopril). The differences between the values are minimal and could also be random. There were no noticeable differences with regard to gender, ethnicity and numerous other characteristics collected. In addition, there was no evidence that any of the active ingredients increased the risk of cancer.
“The interesting thing about the analysis is the very long follow-up period,” says Markus van der Giet from the Berlin Charité, President of the German Hypertension League. The study shows that none of the types of medication is superior to the other and that there are no unexpected risks with a particular active ingredient after many years. “Basically, the result is a plea for early and careful adjustment of blood pressure,” emphasizes van der Giet.
For Ralf Dechend, researcher at the Charité and the Max Dellbrück Center Berlin and senior physician at the Helios Klinikum Berlin-Buch, the results of the examination offer the opportunity for personalized medicine. “If the active ingredients are equivalent, then the patient can be prescribed the medication that best suits their previous illnesses or that they can best tolerate,” explains Dechend.
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Roland Schmieder, senior physician at Erlangen University Hospital, adds that in the case of heart failure, for example, an ACE inhibitor (or a beta blocker) is usually administered because it also helps against this disease. A calcium channel blocker, however, would be counterproductive in heart failure. If you have diabetes, you should avoid taking a diuretic.
A study presented in Jama in April found that high blood pressure patients may experience far greater improvements by changing their medication than by taking a higher dose. The effects of common medications from different drug classes – thiazide diuretics, ACE inhibitors, angiotensin II antagonists and calcium channel blockers – varied greatly from person to person, with certain patients achieving lower blood pressure with one drug than with another. In addition, for many test subjects, changing medication had a greater effect than doubling the dose of the current medication, reported a team led by Johan Sundström from Uppsala University (Sweden).
A striking feature in the currently presented result, which Yamal and colleagues immediately mitigate, is a 19 percent increased risk of a stroke in the lisinopril group compared to the chlorthalidone group. “After taking into account several comparisons, this increased risk was no longer significant,” write the study authors. Schmieder nevertheless criticizes the fact that this result is highlighted in the specialist article. There is no scientifically reliable evidence that ACE inhibitors increase the risk of stroke. Lowering blood pressure is crucial.
Tension training also lowers blood pressure
Schmieder, one of the authors of the national care guideline “Hypertension” (high blood pressure) and the current European guidelines “Hypertension 2023”, criticizes the “JAMA” study for the fact that the follow-up was only carried out on the basis of medical documents. “It is not known which medications the patients took after the end of the original study, how they lived, what blood pressure they had and there is hardly any other information about the follow-up phase,” emphasizes Schmieder. For this reason, statements like those about ACE inhibitors could be misleading.
The patients’ lifestyle was not examined in the ALLHAT study. Van der Giet, Dechend and Schmieder emphasize the importance of a healthy diet, quitting smoking and sufficient exercise for lowering blood pressure. “When it comes to lifestyle, it is similar to drug treatment: the earlier the lifestyle change takes place and the sooner the blood pressure is sensibly adjusted, the better,” summarizes van der Giet. Schmieder reports that a weight loss of five kilograms lowers systolic blood pressure by an average of ten millimeters of mercury.
What is new is the finding that not only dynamic sports, but also isometric sports, such as tension training in the fitness center, can lower blood pressure, says Schmieder. However, Dechend warns against only relying on exercise and changing your diet to lower blood pressure and avoiding medication. Well-adjusted blood pressure is crucial.
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Just recently, a study, also in “JAMA,” showed that a significant reduction in salt consumption had a blood pressure-lowering effect in three quarters of the 213 participants between the ages of 50 and 75 after just one week. This was true even among patients who were already taking antihypertensive medication. The effect was also independent of age, gender, ethnic group, body mass index and diabetes. The study comes from a group led by Norrina Allen from Northwestern University in Chicago (USA).
According to a World Health Organization (WHO) report presented in September, high blood pressure is a “silent killer” because four out of five sufferers are not properly treated. With better education, diagnosis and treatment, the WHO estimates that 76 million lives could be saved worldwide by 2050. In addition, 120 million strokes and 79 million heart attacks would be prevented.
One in three adults worldwide is affected by high blood pressure, it said. It can lead to strokes, heart attacks, heart and kidney failure and many other diseases. According to the WHO definition, blood pressure of more than 140 over 90 is considered excessive. The risk factors include very salty food, little physical activity and too much alcohol.
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