ALLHAT study

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The ALLHAT study ( Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ) is one of the largest and most important studies on the treatment of high blood pressure .

Between February 1994 and March 2002, around 40,000 patients with mild to moderately high blood pressure were enrolled at 623 centers in North America . The design was randomized and double-blind . In contrast to many other drug studies, a new therapeutic agent was not tested against a placebo , but an older standard therapy was compared with three newer ones.

research object

The aim of the study was to find out whether newer blood pressure medications such as the ACE inhibitor lisinopril , the calcium antagonist amlodipine or the α-receptor blocker doxazosin help prevent fatal heart disease and non-fatal heart attacks as well or better as the older and much cheaper thiazide diuretic Chlortalidone .

In another randomized, but not blinded partial study (ALLHAT-LLT), around 20,000 patients from the ALLHAT collective were examined to determine whether treatment with a statin ( pravastatin ) could reduce all-cause mortality compared to the standard treatment at the time , if cholesterol was only slightly increased .

Study population

Study participants were women and men aged 55 and over with arterial hypertension (grade I or II) and an additional cardiovascular risk factor such as previous heart attack , left ventricular (in the left ventricle ) hypertrophy , type 2 diabetes , current nicotine abuse , low HDL cholesterol below 35 mg / dl or other arteriosclerotic diseases. Patients who had been hospitalized for heart failure or who had a left ventricular ejection fraction below 35 percent were excluded from participation.

Study arms

The 42,418 study participants were randomly assigned to the control group with chlortalidone (12.5–25 mg / day) or the three alternative treatment groups ( amlodipine 2.5–10 mg / day, lisinopril 10–40 mg / day, doxazosin 2–8 mg / day ) assigned. If available, previous blood pressure medication was discontinued at the start of the study and therapy with one of the four study drugs began.

In the course of the disease , the additional administration of atenolol , clonidine , reserpine or dihydralazine was allowed if the blood pressure was insufficiently reduced . The doxazosin arm was closed early in 2000 after the heart failure rate in this group was twice as high as in the chlortalidone arm and strokes had also occurred significantly more frequently .

Statistical analysis

The primary endpoint of the study was the number of fatal heart disease and non-fatal myocardial infarction . The statistical evaluation was carried out using an intention-to-treat analysis . Secondary endpoints were all-cause mortality, stroke , heart disease in particular (including cardiovascular death and myocardial infarction, cardiac catheterization or hospitalization for angina pectoris ) and cardiovascular disease in general ( coronary artery disease , stroke, angina pectoris with and without hospitalization, heart failure , PAD ).

Results

After the doxazosin arm had to be prematurely terminated, only 33,357 patients from the remaining three study arms were included in the final analysis of results. The mean observation time was 4.9 years. 2956 patients died of heart disease or had a non-fatal heart attack . There was no decisive difference between chlortalidone, lisinopril and amlodipine. Overall mortality was also not different in the three main arms.

The systolic blood pressure values ​​after five years in the amlodipine and lisinopril groups were significantly higher than in the chlortalidone group. In contrast, the diastolic blood pressure values ​​were significantly lower after five years with amlodipine. Heart failure occurred much more frequently in the amlodipine arm than in patients on chlortalidone. When compared to lisinopril, chlorthalidone was clearly superior in preventing cardiovascular disease, stroke and heart failure.

Conclusion

The most important result of the ALLHAT study was that in patients over 55 years of age, newer blood pressure drugs are not superior to the older and cheaper thiazide diuretic chlortalidone. On the contrary, doxazosin, lisinopril and amlodipine were even inferior in terms of preventing certain secondary diseases of high blood pressure. With the ACE inhibitor and the calcium antagonist, cardiac insufficiency requiring treatment was much more common . The doxazosin arm even had to be stopped prematurely as a result. However, it has also been shown that treatment with lisinopril or amlodipine does not differ from chlortalidone with regard to all- cause mortality, mortality from myocardial infarction and the incidence of non-fatal myocardial infarctions.

discussion

The evaluation of the study results remains controversial. While it is undisputed that chlortalidone showed the most beneficial effect in the study population, the question of the transferability of the results to high blood pressure patients in general is still the subject of discussion. While the broad use of cheap thiazide diuretics (mainly hydrochlorothiazide in Germany ) is desirable from a health policy perspective , there are also good arguments for the other groups of substances examined. ACE inhibitors such as lisinopril are used as a primary substance in diabetes patients because of their additional nephroprotective effect; doxazosin is still justified as a second and third choice.

literature

Web links

Individual evidence

  1. ↑ Allhat study on the treatment of high blood pressure . ( Memento from January 16, 2008 in the Internet Archive ) mdr.de