Beta-blockers: Bashed for too Long

19. September 2013

They save lives, but things have not worked out best for their reputation: beta blockers are feared because of numerous side effects – unfairly, as a new study is able to show. But does this apply for all cardiovascular diseases?

Whether high blood pressure, coronary heart disease, heart attack, arrhythmias or heart failure: beta-blockers have long found their place among valued medications, but are sometimes frowned upon because of their side effects. These include arrhythmias, asthma attacks, bradycardia, depressed mood, blood sugar fluctuations, circulatory disorders, hypercholesterolaemia, fatigue and erectile dysfunction. Little wonder that despite their proven benefits doctors sometimes prescribe the medication with hesitation. Patients are also shocked by the listed undesirable effects – and without ado they shelve these essential medications and stop taking them. With beta-blockers the compliance rate is comparatively low, a matter associated both with the low-level distress of cardiovascular diseases and the accompanying metre-long leaflets full of listed associated side effects.

Five out of 33

Anthony J. Barron from the National Heart and Lung Institute at Imperial College London wanted to know more. Together with colleagues, he initiated a meta-analysis of randomised double-blind trials involving cases of heart failure. He found six works in the literature on carvedilol and one or two studies each respectively on bisoprolol, bucindolol, metoprolol and nebivolol. The starting point was the idea to critically scrutinise all 33 of the U.S. Food and Drug Administration’s (FDA) listed side effects. To their great surprise only five side effects occurred significantly more often in comparison to a placebo. These are bradycardia, intermittent claudication (Claudication intermittens), diarrhea, hyperglycaemia and dizziness. Some effects were just as often detected whether under a verum or placebo, such as weight increases, hypotension, impotence, fatigue or syncope. In addition, some side effects were able to be shown to occur even more frequently with placebos than with beta-blockers themselves. The authors mention among these chest pain, depression, heart failure, insomnia or tachycardia. Where adverse reactions occurred, patients in the placebo group discontinued taking their preparation more frequently than in the verum group. Therefore according to Anthony J. Barron, some side effects can be traced back to nocebo effects or to the underlying disease. The researchers would even like to see more intensive discussion about the five confirmed forms of malaise in relation to possible causes.

Questionable indications

In his work, Barron points to two important indications of beta-blockers: Using the appropriate agents cardiologists succeed in significantly reducing the morbidity and mortality of their heart failure patients. Beta-blockers are used In atrial fibrillation cases as well, but without improving the prognosis. Professor Dr. Dirk Jan van Veldhuisen from the University Hospital Groningen has examined whether the agents also have an impact, should both diseases occur together – which is not a rare situation in practice. For his meta-analysis, he assessed work on bisoprolol, carvedilol, metoprolol and nebivolol. Van Veldhuisen found four placebo-controlled randomised trials, namely CIBIS-II, MERIT-HF, SENIORS, and investigations by the U.S. Carvedilol Heart Failure Study Group. Using these, data was available on a total of 8,680 heart failure patients. In 1,677 cases cardiologists additionally diagnosed atrial fibrillation. With atrial fibrillation plus heart failure, beta-blockers did not bring added value in terms of mortality, whereas patients with sinus rhythm had a significant survival gain. Other parameters such as the hospitalisation rate also improved only with normal neural networks. The authors conclude that the positive effects of beta-blockers in heart failure – about a 35 percent reduction in mortality – remain limited to patients with sinus rhythm. Anyone who suffers from congestive heart failure with atrial fibrillation gets no benefit from the medications.

Customise guidelines?

However, further prospective studies would be useful in order to examine the phenomenon more closely. One problem: with all four beta-blockers, patent protection has long expired. Where funding for the work should come from remains an open question. The topic is of interest, because beta-blockers have varied effects. For bucindolol, in a subset of the BEST study there are indications that patients with heart failure plus atrial fibrillation benefit from the medication. According to van Veldhuisen the only way remaining at present is to continue on with the use of beta-blockers. Nevertheless, physicians should critically review the medication and adjust things if necessary. Medical specialists’ societies, in updating their guidelines, will also draw from more recent work.

Protection from chemotherapy

Beta-blockers can yet do even more: they protect the heart against adverse effects of chemotherapy. Following the existence of ample evidence from animal experiments, Australian scientists working under Professor Dr. Thomas H. Marwick at the Menzies Research Institute, Hobart, went on a search for suitable publications. They found 14 observational studies or randomised trials involving 2015 subjects. ACE inhibitor, beta-blockers, statins and dexrazoxane were used as cardioprotection – mostly before, rarely after chemotherapy treatment. Using the medications, it was possible to reduce negative consequences by nearly 70 percent: While there were 304 cardiac events in the control groups, there were only 83 in the groups using drug prophylaxis. For each of the four drugs the effect was significantly better than without cardioprotection. Marwick points to the great potential of these drugs, but calls for prospective studies.

Old medication – new impulse

One conclusion: beta-blockers have already been available on the market since the 1960s. Nevertheless, they still hold quite some surprises in store. The work of Barron, Marwick and van Veldhuisen point to further potential but also to the limitations of these agents. Which innovations will find their way into practice will be seen in a few years.

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