Healthy Skepticism AdWatch

AdWatch illuminates the logical, psychological and pharmacological techniques used in drug advertisements.

August 2004, Australia

Feedback on Micardis Plus (telmisartan plus hydrochlorothiazide) from Boehringer Ingelheim

This report is based on feedback from 52 participants of whom 58% were doctors and 17% pharmacists.

Contents

Summary
Participants
What message was the advertisement sending?
Comments
Plans
Dialogue
Opportunity for further comment

Summary

Our third AdWatch focused on an advertisement for the blood pressure drug Micardis Plus (telmisartan plus hydrochlorothiazide) from Boehringer Ingelheim.

This report is based on feedback from 52 participants of whom 58% were doctors and 17% pharmacists. Of the 52, 63% live in Australia, 8% in the UK and 8% in the USA. 

The advertisement claimed that “In hypertensive patients, the peak incidence of cardiovascular events coincides with early morning blood pressure surges.”  Participants thought the “early morning” was from 05:00 or earlier to 08:00 or earlier. By contrast, according to the references cited in the advertisement, the peak incidence of heart attacks is between 09:00 and 11:00 and peak incidence of stroke is between 08:00 and 10:00.

31 participants got the message that Micardis Plus is more effective at preventing cardiovascular events in the “early morning” than all other antihypertensive drugs. 10 got the message that Micardis Plus is more effective at suppressing the increase in blood pressure in the “early morning” than its components so it may be more effective at preventing cardiovascular events.

There were a wide range of views about whether or not the message from the advertisement was believable but the most common response was that it was “mostly believable”.

After reading our comments on the evidence relevant to the advertising claims most participants judged the message they had received from the advertisement to be unjustified.

Comments addressed to Boehringer Ingelheim included questions, requests for improvement and many criticisms.

Comments addressed to the AdWatch team included requests to continue, questions, and requests for improvement and praise.

Comments about our treatment recommendations included conflicting views about costs, comments about lifestyle change and confessions of lack of knowledge. Some pointed out that our recommendations for uncomplicated hypertension may not apply to complicated hypertension. Some disagreed and others agreed with our recommendations.

Of the 11 participants who prescribed Micardis Plus sometimes or rarely before reading AdWatch on Micardis Plus, 5 planed to prescribe it less often and 6 as often.

Participants

There were 1625 visits to the AdWatch on Micardis Plus webpage during the 49 days from 4 June when it was posted until 22 July 2004 inclusive. This is slightly lower than for the previous AdWatch.

There were 55 participants but 3 did not give permission for their feedback to be included in analysis.  This is a lower number than previously, partly because some feedback was not recorded due to a temporary software glitch.

Almost all participants were health professionals, mostly doctors.

It is possible that some participants are pharmaceutical industry employees who did not disclose that.

Participants’ countries

What message was the advertisement sending?

The Micardis Plus advertisement had a picture of a sleeping man in a bed on railway tracks soon after sunrise. The headline was “Additional power including the early morning danger zone.”

The term “early morning” has a wide range of different meanings but for most participants it means from 05:00 or earlier to 08:00 or earlier. By contrast, according to the references cited in the advertisement, the peak incidence of heart attacks is between 09:00 and 11:00 and peak incidence of stroke is between 08:00 and 10:00.

The messages that participants got from the advertisement (regardless of whether they believed it or not) also varied.

31 participants got the message that Micardis Plus is more effective at preventing cardiovascular events in the “early morning” than all other antihypertensive drugs.

10 got the message that Micardis Plus is more effective at suppressing the increase in blood pressure in the “early morning” than its components so it may be more effective at preventing cardiovascular events.

6 got a message that was somewhere in-between the above.

2 said they got different messages:

Micardis Plus is best (compared with other drugs) reduces early AM BP and by inference is likely to reduce CVS events (which correlate with early AM BP)

This means that if the Drs are prescribing it, they’re getting some great big whopping “gratuities” from the health care/pharmaceutical companies

1 participant was unsure, and wrote:

I get the impression the drug has two actions (undefined) that will let you sleep and wake without having a blood pressure related cardiac event. I don’t feel confident about the information and the image doesn’t make any sense to me either.

1 had no opinion and one did not answer.

Additional comments included:

Adverts like this could scare some people into using this drug

Also get the message that CVA’s are due to fluctuations in BP rather than BP at rest or average BP, not sure that is right. People who exercise get surges but are protected against cardiovascular events.

While I don’t believe the ad style is justified, the image of peaceful/safe sleep is powerful, and will stay in my mind.

The ad does not contain statistical or clinical outcome data to support its assertions.

Participants were had a wide range of views on the believability of the message that they had taken from the advertisement but the most common response was that it was “mostly believable”.

Comments

After reading our comments on the evidence relevant to the advertising claims most participants judged the message they had received from the advertisement to be unjustified.

22 participants addressed comments to Boehringer Ingelheim including:

Questions

I am unsure whether clear causality has been established between morning hypertension and increased cardiovascular events. Surely the long-term BP control is most important?

i) Has Micardis been tested head-to-head (as opposed to historical data) with other antihypertensives and if so with what results? ii) What is the incidence of serious adverse effects with Micardis plus (for example acute renal failure) compared with patients on one or other component?

Requests for improvement

Get rid of the smoke & mirrors and start dealing with facts.

The message I get from your advertisement has to be proven.

Use statistical and relevant clinical outcome data rather than soft advertisements.

I would prefer information about antihypertensive drugs that is accurate and easy to understand without the need for time-consuming analysis and checking of references.

But mostly criticism

Your ad re Micardis is misleading.

Imagery is over the top, turns me off.

This is a fairly blatant use of scare tactics and is misleading.

Please do not waste money on unproven subliminal messages.

The cited evidence is not evidence for the claims or their implications.

I think this is very unethical and irresponsible advertising. I am appalled.

At the best you are ‘scare-mongerers’ at the worst grubby dollar driven liars.

You have misled me into a false understanding of the response to telmisartan + Hcl.

The observation that the ad is in line with industry practice does not make industry practice good.

29 participants addressed comments to the AdWatch team including:

Requests to continue

Keep up the good work

Questions

When you say “Telmisartan alone reduces the absolute blood pressure but…(etc)”, you’re not talking about Micardis Plus, so how is it applicable?

Answer:

The evidence on this point that BI cited to support their claim about Micardis Plus was a study of telmisartan alone[1] (one of the components of Micardis Plus) We don’t know if the same applies to Micardis Plus or not.  We should have mentioned that.

Do the cited BI references on timing of CVS mortality support their claim?

Answer: BI claimed that “In hypertensive patients, the peak incidence of cardiovascular events coincides with early morning blood pressure surges.”  The answer to the question depends on what you think that ambiguous claim means.  What does the term “early morning” mean to you? As mentioned above the term “early morning” has a wide range of different meanings but for most participants it means from 05:00 or earlier to 08:00 or earlier. According to the studies cited by BI the peak incidence of heart attacks is between 09:00 and 11:00 and peak incidence of stroke is between 08:00 and 10:00. We put more information about this on our more information page.

Whose references do we believe if there is a discrepancy between BI & AdWatch?

We usually use all the references cited by the drug company plus additional references.  Discrepancies between drug company’s claims and our claims can arise because we look at more references and/or because we interpret the evidence differently.  This can occur because we have different roles.  Drug companies’ role is to increase sales so as to increase profits.  Our role is to “Improve health by reducing harm from drug promotion”.  Our core funding is from subscriptions from individuals, mostly doctors and pharmacists.  We have multiple quality improvement systems including requesting and publishing comment from the company responsible for the advertisement so that our readers can decide for themselves.  We seek and respond openly to feedback so that we can detect and correct errors.  If you are unsure about any of our claims please ask us to verify them. Ultimately if you don’t have the time or skills to evaluate the evidence yourself then you have to choose for yourself who to believe.

Are you owned and operated by Merck/Medco????

We have never had any contact with Merck/Medco.  We have campaigned against misleading drug promotion by MSD.

The commentary above is difficult to interpret, how do we differentiate most and least optimistic, for example?

See requests for improvement below.

Requests for improvement

The wording of the most/least optimistic interpretations is confusing. The interpretation is a take away ‘message’ and I think it would therefore be better expressed as a statement rather than a question.

We struggled with how to word this. Our aim was to develop a measure of the range of messages that people take from advertisements. We guessed the most positive/optimistic/upbeat/pro-the-promoted-drug reasonable message that people could take from the advertisement and its reasonable opposite. Then we wanted participants to let us know if their interpretation of either of the advertisement was similar to either the most optimistic or least optimistic message or somewhere inbetween or different (including more extreme in either direction).

(We would like to have something equivalent to 90% confidence intervals for data and an indication of the dispersion and skew.)

Because our guesses about the most and least optimistic interpretations were only hypotheses, for which we were seeking confirmation, we expressed them as questions. Our impression is that what we did has worked ok for most participants.  However we would appreciate any suggestions for improving the wording.  Please use the suggestion box at the bottom of this page.

Most comments addressed to AdWatch were praise

Thanks

Good choice.

We don’t deserve praise for choice of topic because this topic was chosen at random.

Another very good review, well done

I have hypertension, and so this is quite personal to me - I find it really useful

Good - simple and easy to understand with the back up depth for those who want it.

Very good contribution as it saves me doing all the hard work of assessing the claims!

Thank you for helping me to learn how to critique pharmaceutical promotional materials. Seeing the information offered in an ad is incomplete, emotional, and obscured by the images and small typefaces is instructive.

Thank you again for the good analysis of a drug adv. Hopefully it will also make other drug company look at your analysis and hopefully not do the same.

On going vigilance to ensure scientific data is correctly interpreted and marketed is enabling.

31 participants commented on our recommendations for treating uncomplicated hypertension in Australia including:

Conflicting views about costs

Too much emphasis on cost

Costs per year very informative

The more physicians and patients know what the price/effectiveness ratio of pharmaceuticals really is the better.

When there are no clear advantages of one drug over another on effectiveness, adverse effects or convenience then costs become important considerations.  Wasting money on expensive drugs reduces resources that could be spent elsewhere in the health system for example on emergency departments and healthy lifestyle interventions.  Advertisements rarely provide comparative information about costs so we feel it is useful for AdWatch to fill the gap.

Comments about lifestyle change

More effort should be given to lifestyle changes

Life style Changes are always beneficial with or without medication. Getting Patients to realise this is another matter.

The promotional skills of the pharmaceutical and advertising industry would be better used if focused on helping achieve lifestyle changes.

Confessions of lack of knowledge

I assume chlorthalidone must be a diuretic, my understanding was that this class was first line drug treatment

Correct.

I graduated in 2002 and have never heard of chlorthalidone! Is it similar in efficacy/price to indapamide?

Your medical school let you and your patients down.  There is no comparative evidence to show if one if better than the other.  We favored chlorthalidone because there is stronger evidence (eg ALLHAT ) that chlorthalidone is at least as good as more expensive non-thiazide blood pressure drugs than there is for the other thiazide type drugs.  However I am not aware of any head-to-head comparisons to show if any thiazide type drugs have clinically significant benefits over the others.  The best we have is indirect comparisons (by meta-analysis) between chlorthalidone and non-chlorthalidone diuretics that suggest no significant difference in major outcomes. (Psaty BM, Lumley T, Furberg CD.  Meta-analysis of health outcomes of chlorthalidone-based vs nonchlorthalidone-based low-dose diuretic therapies.  JAMA 2004; 292: 43-44 Medline)

However there is a big difference in price. According to http://web.archive.org/web/20051217051348/http://www1.health.gov.au/pbs/index.htm currently in Australia the price of 30 days treatment is:

Pointing out that our recommendations for uncomplicated hypertension may not apply to complicated hypertension. I’m not sure about the advice for diabetics - I would still go for an ACE inhibitor first ACE inhibitors may be preferable to beta-blockers in diabetics and fall in price as more come off patent Although good in theory I have difficulty with propranolol for diabetics, asthmatics and those who feel weary on it. Our recommendations were limited to uncomplicated high blood pressure because we wanted to to keep them simple so as to focus is on evaluation of advertising. It is better to avoid beta-blockers for people who have asthma.  However some asthmatics may be able to take small doses of atenolol without harm. (Ellis ME, Sahay JN, Chatterjee SS, Cruickshank JM, Ellis SH. Cardioselectivity of atenolol in asthmatic patients. Eur J Clin Pharmacol. 1981;21(3):173-6. Medline) By contrast case against beta-blockers for diabetics is not as strong as is widely believed.  The most relevant evidence that I am aware of is the UKPDS 39 trial which compared 358 hypertensive diabetics on atenolol vs 400 on captopril and found that neither “drug has any specific beneficial or deleterious effect”.  (Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group. BMJ. 1998 Sep 12;317(7160):713-20.  Full text ) Disagreements with our recommendations Six lines seem too explicit to me. Why not: 2nd line = diuretic or ß-blocker. 3rd line = rest. That would have been easier for us but less helpful when people have to choose between the lesser drugs.  Also, we wanted to make the point that A2 blockers such as Micardis are 6th line therapy. In line with the evidence, but who gives diuretics first, even the cardiologists don’t, so what hope have we! I do!  I have been using thiazides first line in general practice for over 20 years. Anyone who values randomised controlled trial evidence above peer pressure or deference to cardiologists is likely to prefer thiazides. (Cardiologists may lack relevant expertise in general practice, evidence based medicine, clinical pharmacology, pharmacovigilance, epidemiology, public health and health economics.) Interesting - in the UK we use bendrofluazide 2.5mg 1st line alongside advice on lifestyle. As mentioned above: We favored chlorthalidone because there is stronger evidence that it is at least as good as more expensive non-thiazide blood pressure drugs (eg ALLHAT ) than there is for the other thiazide type drugs.  However I am not aware of any head-to-head comparisons to show if any thiazide type drugs have clinically significant benefits over the others. I thought:  * most hypertensives are uncontrolled on one pill The definition of what is “uncontrolled” blood pressure is arbitrary. However it is true that no drug alone is strong enough to “control” hypertension in all people. The current consensus is to add drugs in the expectation that lower blood pressure is better.  There is much observation evidence supporting that idea. However, except for diabetics, there is no RCT evidence on whether using more than one pill is better than one. The only study of intensity of blood pressure control for non-diabetics that I am aware of is the HOT study. That study showed a trend for harm with lower blood pressure in the non-diabetic subgroup. There were more deaths and cardiovascular events in the most intense treatment group (where the aim was diastolic <80 and the achieved mean diastolic was 81.1) vs the least intense treatment group (where the aim was diastolic <90 and the achieved mean diastolic was 85.2). This key finding was not mentioned by the authors but the information can be extracted from the tables by subtracting the results for the diabetic subgroup from the total. This was discussed briefly in Therapeutics Letter, issue 27, November - December 1998 and in more a little more detail in the July/August 2000 Healthy Skepticism International News. I conclude that no one knows how intensively to treat hypertension but the limited evidence suggests not aiming to go below diastolic 90. Because we don’t know it is reasonable to go along with the consensus as far as getting diastolics down to 90. However pushing reluctant patients to accept polypharmacy that causes immediate adverse effects in the hope of long term benefits is not justified by currently available evidence. * perindopril was a cheaper ACEI than ramipril No. According to http://www1.health.gov.au/pbs/index.htm the current prices in Australia for a pack of 30 are:

  * combination medication (reducing pill numbers) was one of the few proven ways to improve medication adherence Correct.   * “uncomplicated” HTN is often uninvestigated HTN; many GP’s do not do urine urine albumin:creatinine ratios annually or at all Correct. To be convinced that we should test albumin:creatinine ratios I would need to see evidence that treating people differently on the basis of this test produced enough benefit to be cost effective. This depends on several factors including how common are adverse albumin:creatinine ratios? and how accurate is the test?    * HTN with proteinuria is a powerful indication for ACEI (or ARBs) as first line therapy - their effectiveness is most cost-effectively augmented by using a thiazide combination pill   * as a nephrologist, I spend all my time retarding CRF progression - combination ACEI/ARB/thiazide is my most powerful & effective tool (see COOPERATE trial, Lancet 2003) To attempt to confirm or deny these claims is beyond our focus on an advertisement targeting GPs. (See an emergency physician’s comments about ACE inhibitors as a cause of acute renal failure below.) I thought Beta blockers would come after ACEI in HTN. We are not aware of any evidence of superiority of either for uncomplicated hypertension but beta-blockers are cheaper. I think that efficacy of thiazides as first line therapy is no longer regarded as being as good as ACEI/A2RB. That is widely believed. It is further evidence for the effectiveness of promotion by drug companies. However there is no convincing evidence of superiority of ACE inhibitors or A2 blockers over thiazide type drugs. The ANBP2 and ALLHAT trials have been used to support opposing opinions but there is probably little difference between ACE inhibitors and thiazides except that the latter are much cheaper so should be used first line. Further reading: Turnbull F, Neal B. Resolving the differences between ACE inhibitors and diuretics - ALLHAT and ANBP2. Australian Prescriber 2004;27:98-101 Davis BR, Furberg CD, Wright JT Jr, Cutler JA, Whelton P; ALLHAT Collaborative Research Group. ALLHAT: setting the record straight. Ann Intern Med. 2004 Jul 6;141(1):39-46. I am not happy about blanket recommendations especially when people react differently to drugs. That is why we included many choices in our list. If drugs at the top of the list are unsuitable for an individual then try one further down. I am well aware re guidelines to have diuretics 1 st line, but in reality find this not a good way to go clinically due to Na, Mg and K effects, gout, glucose effects and variable effect in reaching target BPs All antihypertensive drugs have adverse effects. Clinical experience is not an accurate way to reach conclusions about which drugs have more and/or worse adverse effects overall. The clinical trial evidence suggests that adverse effects of low dose thiazide type drugs are no worse than with other antihypertensive drugs. Agreement with our recommendations Straightforward and easy to follow seems very realistic and sensible reasonable and accord with other opinion I have read eg NPS info. makes sense I agree. The Standard Treatment Guidelines for Hypertension serve as excellent guidelines for rational treatments. Allhat was convincing, looks right to me. I don’t know the relative proportions of prescribing so its difficult to know, but as an emergency physician I see acute renal failure (usually reversible) every week & in a busy dept, most days in elderly people who are on ACE inhibitors & get an intercurrent illness. Combination with diuretics increases that risk. Indapamide seems to be the diuretic most likely to be at fault when there are significant electrolyte imbalances.

Plans

Before participants read AdWatch on Micardis Plus

Micardis Plus

Having read AdWatch on Micardis Plus, participants planed to prescribe, take or recommend Micardis Plus

Of the 11 participants who prescribed Micardis Plus sometimes or rarely before reading AdWatch on Micardis Plus, 5 planed to prescribe it less often and 6 as often.

Dialogue

16 participants wanted their name to be sent with their feedback to pharmaceutical companies and regulatory agencies.  We also understand that many people have compelling reasons for keeping their participation in AdWatch confidential.  All participants’ feedback will be kept confidential unless permission is given for disclosure. We will write to BI soon.  If there is no progress then we will write to Medicines Australia.

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