Adwatch on Micardis Plus: More information

What message is the advertisement sending?

Headline

It has been well understood, since at least the time when the ancient Greek oracle stories were first told, that it is common for people to interpret ambiguous statements to mean what they hope for.  

“NEW” could apply to the drug or to evidence about the drug or both.  Using the word “new” has been shown to add to the effectiveness of advertising.[1]  It appeals to doctors’ desire to keep up and prove to themselves and others that they are not burnt out.  Unfortunately, few new drugs turn out to be better than older ones.[2] [The author of reference 2, Joel Lexchin, is a member of Healthy Skepticism Inc.]

“ADDITIONAL POWER” is also ambiguous.  It is qualified with an asterisk but most people only take in the pictures and headlines of advertisements[3] so footnote disclaimers can make advertising misleading.[4]  

Problems with use of the word “power” and the use of foot note disclaimers were discussed in our Dialogue with AstraZeneca about Nexium.

“EARLY MORNING DANGER ZONE” is vague.  The meaning is partially clarified by the picture. 

For some readers the term “DANGER ZONE” may evoke images of the doctor as rescuer like the 1960s TV Thunderbirds racing to the “danger zone” to rescue people from mortal peril in just in the nick of time.

Picture

The picture is a middle aged man asleep on railway tracks within about half an hour after sunrise.  In Australia sunrise is between 05:03 in Perth in midsummer and 07:43 in Hobart in midwinter.[5]  

Being hit by a train usually results in severe injury or death.[6]

The advertising copy

“In hypertensive patients, the peak incidence of cardiovascular events coincides with early morning blood pressure surges.^1-3”  The term “surges” could be understood as “increases” or as “increases, peaks and decreases”.  The term “coincides” does not claim causation but it is common to think that association indicates causation because it often does.  Such thinking leaves us vulnerable to being mislead when A is associated with B without causation.

“Powerful 24-hour blood pressure control, including the last hours of the dosing period.^4,5  New MICARDIS PLUS:  Additional BP control compared to monotherapy for a broad range of patients who need greater BP reductions.⁶”  The comparator is not specified so could be any or all blood pressure drugs.

“*Additional efficacy of the combination of MICARDIS and hydrochlorothiazide (HCTZ) versus the individual components.⁶”  This is the footnote disclaimer that qualifies the headline.  There is no indication that it qualifies the sentences except that it has the same reference.

A)  Is this the most positive reasonable interpretation?

Blood pressure increases, peaks then decreases before people wake up.  That causes a peak in the incidence of heart attacks and strokes before people wake up.  There is new evidence that Micardis is more effective than other interventions* for preventing heart attacks and strokes before people wake up and take their next blood pressure pill.  Micardis Plus achieves this by providing “powerful 24- hour blood pressure control” that completely suppresses the blood pressure peak.

* Most people only take in the headlines and pictures of most advertisements so could interpret the “Additional power” claim to refer to superiority compared to any or all other blood pressure interventions.  However the footnote disclaimer in the advertisement qualifies that claim to apply only to superiority for the combination in Micardis Plus over the individual components.

B) Is this the least positive reasonable interpretation?

Blood pressure increases and there is a peak in the incidence of heart attacks and strokes in the early morning.  Micardis Plus is more effective than its components alone at reducing the increase in blood pressure in the morning.  Consequently Micardis Plus may reduce the rate of heart attacks and strokes.

Is the message justified by the evidence cited in the advertisement?

1a.  Does hypertension increase, peak then decrease before people wake up?

Answer 1a:  No.  Blood pressure increases slowly before people wake.  The most rapid increase and the peak occur later.

Blood pressure is lowest from 01:00 to 04:00 then increases slowly.  After 07:00 blood pressure increases more rapidly to peak at 09:00.[7]

1b.  Does hypertension increase in the early morning?

Answer 1b:  Yes but it continues to increase until around 10:00.

2a.  Is there a peak in the incidence of cardiovascular events before people wake up?

Answer 2a: No.  Most of the peak in the incidence of cardiovascular events occurs after people have woken up.

The peak incidence of heart attacks is between 09:00 and 11:00.[8]

The peak incidence of stroke is between 08:00 and 10:00.[9]

2b.  Is there a peak in the incidence of cardiovascular events in the early morning?

Answer 2a: No.  The peak incidence of cardiovascular events is between 08:00 and 11:00.

4a.  Is Micardis Plus more effective than other drugs for preventing heart attacks and strokes?

Answer 4.  Unknown.  The impact of Micardis Plus on heart attacks and stokes has not been tested.

4b. Is Micardis Plus more effective than its components alone at reducing the increase in blood pressure in the morning? 

Answer 4b.  Unknown.  Micardis Plus is more effective than its components alone at reducing absolute blood pressure in the morning.[10]  However, the references cited in the advertisement do not include a study comparing the effect of Micardis Plus vs its components alone on the increase in blood pressure in the morning.

5a.  Does Micardis Plus completely suppresses the morning blood pressure peak?

5a.  Unknown.  The relevant study cited in the advertisement was of telmisartan alone vs valsartan alone.[11]  That study found that telmisartan does not completely suppress the blood pressure peak. 

Telmisartan reduces absolute blood pressure but the magnitude of reduction does not increase and may diminish slightly towards the end of the 24 hour dosing period. Consequently the magnitude of increase of blood pressure in the morning is not reduced and may be slightly enlarged.5

5a.  Does Micardis Plus reduce the increase in blood pressure in the morning?

5a.  Unknown.  The relevant study cited in the advertisement found that telmisartan alone does not reduce and may slightly enlarge the relative increase in blood pressure in the morning. 

6.  Is there new evidence that Micardis Plus is superior in any way to interventions other than its components alone?

Answer 6.  No such evidence is cited in the advertisement.

AdWatch's current recommendation for Australia

We recommend chlorthalidone because it is best supported by evidence including the ALLHAT trial.[12]  However we are not aware of any trials of chlorthalidone vs similar drugs so we do not know if it is the best in its class or not.