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米心臓協会が薬物の心不全への影響について報告：海外専門家コメント

米国の心臓協会（American Heart Association）は、心不全を引き起こしたり悪化させたりする可能性のある薬物についての報告を行いました。論文中には、薬物とリスクの大小、エビデンスの信頼度などについての一覧表が掲載されており、たとえば、頭痛などでよく服用される非ステロイド系鎮痛薬（NSAIDs）は「リスク大、エビデンスランクB」、メトホルミン（糖尿病治療薬）「リスク大、エビデンスランクC」、ドキサゾシ（降圧薬）「リスク中等度、エビデンスランクB 」などとなっています。論文は7月11日付のCirculationに掲載。この件についての専門家コメントをお送りします。

【論文情報】

http://circ.ahajournals.org/content/early/2016/07/11/CIR.0000000000000426

翻訳は迅速さを優先しております。ご利用の際には必ず原文をご確認ください。

Prof Sir Munir Pirmohamed

David Weatherall Chair of Medicine, University of Liverpool, and Vice President Clinical, British Pharmacological Society

新しい内容の報告ではありませんが、心不全と薬物についてのよい分析だと思います。もちろん、患者の薬物感受性、年齢、合併疾患などを考慮して薬を処方する必要がありますが、必要最低量を必要最短で使うということが最も重要でしょう。高齢化にともなって服用する薬が増えると、思わぬ薬剤と薬剤の相互作用で心不全を起こすこともあります。薬物間の相互作用についての研究を進めていくことも重要だと思います。

原文

“The AHA has published a very thorough analysis of drugs that can either cause or exacerbate heart failure.  This is an important document which provides up-to-date information in this clinically significant area in one place.  This is not new evidence but a synthesis of evidence that is already available in the literature, and is based on sound pharmacological principles.

“There are of course many different mechanisms and many different drugs involved, and prescribing in susceptible individuals should take into account the age of the patient, any other comorbidities and other drugs that the patient is taking.

“As with any other area, the key issues are (a) to use the lowest dose of the drug for the shortest period of time; (b) to be aware of the potential for the drug to cause or exacerbate heart failure and monitor patients for the occurrence of new symptoms of heart failure; (c) to get a thorough drug history before patients are started on any new drugs, including a history of herbal medications to minimise drug-drug interactions; and (d) to ensure that patients do not stop drugs of their own accord, but always consult with their doctor about the drugs they are taking and any associated adverse effects.

“As our population demographics change, with an aging population, we need to be especially aware of the potential for drug-drug interactions and drug-disease interactions which can lead to heart failure.  Further research in this area will be important to ensure that we can identify these complex interactions in a timely manner in the future.”

Prof Tony Fox

Professor of Pharmaceutical Medicine　King's College London

どの薬剤も一般的に使われているもので、心不全との関連の複雑さと注意の必要性を示すものとなっています。ハーブについては毒性がよくわかっていないものもあります。心不全患者は、主治医に服用している薬剤をすべて知っておいてもらう、主治医に相談せずにハーブを含む新たな薬剤を服用しない、副作用かなと思ったら症状が軽くても主治医に相談するといったことを守ってください。

原文

“Today’s American Heart Association statement on drugs, herbals and heart failure draws attention to the importance and complexity of these drugs and this disease.  The drugs that the statement mentions are also commonly used in the UK and the rest of Europe.

“Heart failure almost never occurs as a single disease.  The trade-offs and interplay between drugs, heart failure, and its complications requires regular review when treating a patient.  For example, in someone who has arthritis as well as heart failure, is it worth trying a dose of ibuprofen (an over the counter pain killer) that could cause a small amount of fluid retention, but which may improve the patient’s physical activity, and will that ability to exercise help overall?

“Sodium (salt) is generally bad for patients with heart failure. The amounts that can be taken, and also avoided, in food are huge.  These amounts in food are generally much bigger than those found in tablets.  Once again, a small amount of sodium in a tablet has always to be weighed against the benefit that the tablet may create.

“The warnings about ‘herbal’ medicines, almost all of which are not medicine at all, are especially good.  With rare exceptions, we know little about the toxicity of these unregulated products, and there is next-to-no evidence for any benefit, either. Ephedra, in particular, is a well-known poison in patients both with and without heart disease because of its effects on blood pressure.  Goldenseal, St John’s wort and other herbal materials interfere with the patient’s enzymes that handle other drugs.  This can cause an overdose even though the patient is still correctly taking exactly the same number of tablets as was prescribed.  Just because it is ‘herbal’ does not automatically mean it is safe, and not just in heart failure, either.  Even Shakespeare knew about that: Romeo and Juliet die after taking a herbal poison.

“While heart failure patients should not be alarmed, this statement emphasises a few common sense things. 1. Make sure your doctor knows about ALL of the drugs that you take INCLUDING all herbal remedies.  2. Do not start taking some new drug or herbal medicine without checking with your doctor first.  3. Be alert for mild adverse effects, and tell your doctor about them BEFORE they get any worse.  4. Check with your doctor before you stop taking a drug that has been prescribed.  5. NEVER change the dose that you have been prescribed (in particular, it is wrong to believe that if one tablet does you good then two will make you feel even better).”

Prof Stephen Evans

Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine

報告内容については、私がすでに知っていたものばかりですが、各薬剤と心不全との関連についてのエビデンスの信頼度は高くないように思います。一定条件のもとで得られた結果ではなく、先行研究による知見を集めたものだからです。ただし、医師は薬剤の毒性、相互作用について明確に認識する必要があります。患者にとっては、何か不安があったら医師か薬剤師に相談することが何よりも重要です。

原文

Is this statement based on good quality research?

“The strength of evidence for many of the drugs is rather weak. Many of the associations from observational data may be explained by the patients who are treated with the drugs of interest being at higher risks of heart failure for reasons other than the drugs they are given. For many drugs, the effects are based on randomised trials and the possibility of false-positive findings is markedly reduced.

 Are the conclusions in the statement backed up by solid data?

“They all have data as far as I can tell, but some of the data is not as certain as the authors imply.

Did we already know about these potential adverse effects / interactions for the drugs listed?

“As far as I can tell, all of these adverse effects were known before. This paper and guideline brings together data that were scattered across many other places. In most instances (I have not had time to check them all), there are warnings of these effects in the product information available to prescribers and patients.

How does this statement fit with the existing evidence?

“Generally it reflects current beliefs.

Are all these drugs used commonly in the UK?

“The great majority of these drugs (again I have not checked them all in detail so it may be all of them) are used in the UK.

Have the authors accounted for confounders?  Are there important limitations to be aware of?

“The authors do not seem to have done original research on these drugs generally, but they have relied on original investigators to deal with confounders. In some instances, the adjustments made may have been inadequate.

What are the implications in the real world?

“Doctors do need to be aware of the potential for adverse effects of many medicines, and also of the potential for interactions, even with common medicines.“In most instances doctors will have correctly assessed the benefit/harm balance for an individual patient, but with people taking a large number of drugs this can be very difficult. 

Should people stop taking their medications?

“People should never be advised to stop their medicines on the basis of what is here; they should consult their doctor, or at least their pharmacist if they have concerns. In many instances the effects are not large and they are not described in terms of their magnitude in many cases – rates are absent from Table 1. "Major" refers to the type of adverse event that is affected, not how large the effect is for an individual.

 Does this mean NSAIDs like ibuprofen can cause heart failure?

“NSAIDs can contribute to heart failure and this knowledge of the cardiac effects of NSAIDs has been shown previously in a large meta-analysis published in The Lancet in 20131.”

1 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778977/]

Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769-779.

 

上記以外のコメントは下記を参照。

http://www.sciencemediacentre.org/expert-reaction-to-american-heart-association-statement-about-drugs-and-heart-failure/

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