Sep 16, 2009

Comparison of antihypertensive drugs: best proof of benefit offered by diuretics

In general, diuretics should be used in preference to any other antihypertensive drug class when it comes to preventing complications

Diuretics can be the best and the first choice for many patients in the treatment of high blood pressure. This is the conclusion of the final report of the Institute for Quality and Efficiency in Health Care (IQWiG) published on 16 September 2009. The Institute addressed the question of how far the benefit from the therapy is dependent on which individual drug was first used in the treatment.

Lowering high blood pressure can prevent complications such as strokes, kidney disease or heart disease, and extend life. Studies show that this can be done particularly with the help of antihypertensive drugs. However, it is still unclear whether there are differences between different antihypertensive drugs. The Federal Joint Committee (G-BA) therefore commissioned IQWiG to carry out a comparative investigation on the potential advantages and disadvantages of antihypertensive drugs used up till now.

Five drug classes under the microscope

The final report compares the benefit of 5 drug classes approved in Germany for the treatment of high blood pressure: diuretics (particularly thiazide diuretics), beta blockers, ACE inhibitors, calcium antagonists and angiotensin-II antagonists. However, the benchmark for benefit was not lowering blood pressure but rather the risk of its complications. From the patients' viewpoint, the effects on the following outcomes are particularly important: besides extended life span, the most important are the prevention of heart disease, strokes, other cardiovascular diseases and kidney damage. Additional aspects are health-related quality of life, patient satisfaction or the frequency of hospitalizations. Adverse drug effects were also investigated.

Only trials with a comparable treatment regimen were included

Essential hypertension is the term given to increased blood pressure with no recognizable cause. In about half of these patients, a therapy with only one drug (monotherapy) is sufficient to control blood pressure. In the remaining patients, a second or even a third drug must be combined. It therefore seems sensible to start patients on a therapy with a single drug first and only add a second (or third) drug afterwards if required.

In order to ensure a fair comparison, the report only includes randomized, controlled trials in which the patient groups only received a single representative of the 5 drug classes at first and which could then be compared when the drugs were added at a later stage.

Eight out of a total of 10 possible comparisons are included in trials

Overall, the scientists were able to include 16 trials in the assessment. However, direct comparator trials with all other groups were not available for every drug class and for all research questions. The thiazide diuretics and calcium antagonists were the most thoroughly investigated. The least amount of data was available for the angiotensin-II antagonists.

Diuretics superior in some respects

As far as preventing complications was concerned, diuretics were never worse but sometimes better than all other drug classes, and in individual aspects, such as the prevention of heart failure, heart attacks and strokes, even better to some extent. According to IQWiG Director, Peter Sawicki, "Overall, thiazide diuretics can be considered the therapy of first choice." He explains, "As long as there are no special reasons contraindicating these drugs in a patient, it is worthwhile starting treatment with one of these diuretics, for example, chlortalidone."

Report preparation procedure

IQWiG published the preliminary results in the form of the preliminary report, 2.0 version, in September 2008 and interested parties were invited to submit comments. When the comments stage ended, the preliminary report was revised and sent as a final report to the contracting agency, the Federal Joint Committee, at the end of July 2009. Documentation of the written comments and minutes of the oral debate are published in a separate document simultaneously with the final report. The report was produced in collaboration with external experts.

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