Spin doctors soft pedal data on antihypertensives

The results of a major study that compared different classes of antihypertensives have drug company spin doctors working overtime. It's no easy job to save market share for expensive antihypertensive drugs when headlines read “When Cheaper Is Also Better,” as one did in the New York Times on 19 December 2002.

The “antihypertensive and lipid lowering to prevent heart attack trial” (ALLHAT), published in the 18 December issue of JAMA (2002;288;2981-97), shows that calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors used to treat hypertension were no better than a diuretic. In some instances they were not quite as safe—even though they were substantially more expensive.

But the spin doctors are swinging into action to counter the clear message of ALLHAT that cheaper is better, even if that means just playing it down. Kevin Brode, vice president of sales and marketing at marketRx, a firm that provides strategic marketing information to the pharmaceutical industry, isn't too worried about who the winner will be. “Doctors say they'll change their prescribing habits after a negative study,” he said, “but their prescription behaviour tends not to bear this out.”

Why not? “The reality is no one promotes a diuretic,” said Mr Brode. “So you've got one study that says yes, you should [use a diuretic], then starting the day after, you've got a $10bn [£6.2bn; €9.5bn] industry . . . and 55 promotional events . . . for an ACE inhibitor coming back in and saying ‘Here’s why my ACE inhibitor is safe and here's why you should be using this.' I mean, it's promotion. Can ALLHAT stand up to that?”

Mr Brode, despite his rosy predictions regarding sales, didn't challenge the ALLHAT results, saying instead: “Great data. Very solid. Didn't surprise anybody . . . but nobody's promoting diuretics.”

But if Dr Curt Furberg, chair of the ALLHAT steering committee, has his way, that won't be the case. He and other ALLHAT staff are staying on to disseminate the data. He says that expensive calcium channel blockers and ACE inhibitors may be costing an excess of $8bn to $10bn—without providing any benefit to patients, and in some instances adding more risk.

Why was so much money wasted for so many years on drugs that weren't as good? Dr Furberg says, “We just didn't know.” But why didn't they know?

The practice of testing new medicines against placebo, rather than against the best treatment available, has contributed to a general lack of knowledge. But spin doctoring clearly triumphed when a head-to-head comparison provided at least one answer. In March 2000 the ALLHAT researchers halted the α blocker arm of the trial when it was found that doxazosin (Cardura) was inferior to a diuretic. Patients on Cardura, dubbed a “miracle drug” by a Pfizer executive, experienced a 25% higher rate of cardiovascular disease and twice the rate of congestive heart failure as patients on a diuretic, results published in the 19 April 2000 issue of JAMA show.

Pfizer, aware of the results before publication, launched a sophisticated damage control campaign in early 2000. Sales of Cardura, estimated at $800m (£500m;€760m) worldwide in 2000, continued virtually unaffected by the study for the rest of the year.

Just how Pfizer managed this feat is revealed by internal drug company documents filed in January 2001 as part of a “citizen's petition” against Pfizer. The plan included using an outside research agency to study doctors' awareness of the ALLHAT results. When the agency found that “knowledge of the trial's preliminary results is minimal for all specialties,” they took steps to avoid sullying that lack of awareness.

Pfizer decided not to issue a public statement about the ALLHAT results because doing so “would likely draw more media attention to the situation.” They instructed their drug reps to provide information about ALLHAT “only when asked.” Finally, two enterprising Pfizer employees were praised as “quite brilliant” for “sending their key doctors to sightsee” during a presentation at the annual American College of Cardiology conference in California in 2000. The doctors, from Italy, were brought to California by Pfizer. The tour, according to the Pfizer email praising the reps, kept the doctors from attending Dr Furberg's presentation of the ALLHAT results.

But Pfizer was not alone in blunting the response to ALLHAT results. The American College of Cardiology (ACC) issued an alert in March 2000 urging doctors to “discontinue use” of Cardura. However, another Pfizer memo dated 28 March 2000 and stamped “confidential” says that Pfizer was “successful in getting the ACC to agree to a clarification” of the ACC press release. The “clarification” that the ACC agreed upon replaced its initial press release on the ACC website within just hours of the original posting and changed the recommendation that Cardura be discontinued to a much milder recommendation that doctors “reassess” its use. It may have added to Pfizer's standing with the ACC that Pfizer has contributed more than $500 000 (£312 000; €474 000) annually to the college in recent years.