Effect on CCBs from latest Furberg attack - limited, at least so far

New York, NY - Pharmaceutical companies marketing calcium channel blockers (CCBs) for use in hypertension do not seem unduly concerned about the latest attack on this class of drug coming from Dr Curt Furberg (Wake Forest University Baptist Medical Center, Winston-Salem, NC) and colleagues.

As previously reported by heart wire , in August 2000 Furberg's group reported a new meta-analysis that suggested CCBs were inferior to other antihypertensive drugs in protecting against the risk of MI and congestive heart failure (CHF). As a result of this finding, and because the CCBs are expensive, Furberg declared that the CCBs should not be used as first-line drugs in hypertension, but rather used only as a "last resort." The story was picked up and featured prominently in the US media, making it onto the front page of the Wall Street Journal, and was also covered by the New York Times and Time magazine. Furberg was also featured on several TV news programs, citing his group's estimates of the many thousands of Americans that are needlessly suffering MI and CHF as a result of taking CCBs instead of other antihypertensives.

As manufacturers of the best-selling CCB product, amlodipine (Norvasc®), and as the US marketers of another, nifedipine (Procardia® XL), Pfizer was on the frontline fielding the fallout. The immediate casualties were patients taking these drugs and their physicians, and the publicity led to a huge amount of anxiety, says Dr Bruce Beckerman (Medical Director, Cardiovasculars, Pfizer Inc). "The main concern was drug safety, and we had to reassure both patients and physicians that the drugs are safe," he says. In fact, safety wasn't an issue in this latest attack on the CCBs, although it had been 5 years ago when the same group of academics raised concerns that this class of agents may be harmful; this time round, the researchers were questioning clinical effectiveness. "But people don't understand all the issues behind the latest headlines, and the danger is that they will stop taking drug therapy for an asymptomatic disorder," Beckerman said. His marketing colleague, Patrick Holmes, refused to speculate on what effect the latest news would have on patient and physician confidence in the CCBs, and ultimately on the sales of these drugs.

Both Pfizer executives criticized the coverage the story received in the general press. "This is a story that was promulgated in the lay media," says Holmes - so far there is no scientific publication of this meta-analysis, and no abstract from the meeting where the data was presented, as it was added at a late stage to a Hot Line session.

"The only information we have comes from press reports," says Beckerman, "which leaves us in a very difficult position - we have to respond to patient concerns without access to data." He also pointed out that none of the lay press had carried any rebuttals to the Furberg findings, and so "there was no balance in any of the reports," he complained. This is despite the fact that Furberg's findings are hotly disputed by many experts in the field of hypertension, and do not tie in with the findings of two other meta-analyses which are awaiting publication, as reported in heart wire .

Both Pfizer executives sounded more than a little exasperated by the whole situation, and said it raises serious questions about the way in which new findings are reported: "Whatever happened to the peer review process?"

In stark contrast to what happened in the US, the general media in Europe did not cover the Furberg story, even though the findings were presented during the European Society of Cardiology meeting in Amsterdam. Amazingly, at one company contacted - Knoll in Germany, manufacturers of the original CCB, verapamil (Securon® SR) - the press officer was unaware of the controversy that had been raging on the other side of the Atlantic, but said there were no worries about the product and no negative impact on sales.

Also in Germany, Bayer - manufacturers of nifedipine (Adalat®) - said it was keeping a close eye on the story, but reported only a few inquiries from patients and doctors. When asked about the reaction to the new findings within the company, Dr Michael Diehl said "We are confident that further analyses like the WHO/ISH meta-analysis will shed light on the highly disputable results from Furberg's group." He also added that "the fact that media are alerted prior to discussion within the scientific community and prior to peer-reviewed publication is worrisome."

Another manufacturer of a top-selling CCB, AstraZeneca in Sweden, which markets felodipine, said that it could not comment on the latest findings, as the full data have not been made generally available and have not been subjected to independent review. But medical affairs manager Ingrid Warnoid commented: "we have been here before."

Five years ago, Warnoid noted, when Furberg's group questioned the safety of CCBs, the company had trawled through all of its safety data from clinical trials, re-examining each individual adverse reaction report, in order to examine the issue, and found no indication that felodipine increases mortality or the incidence of cardiovascular events, and found a trend to fewer events with felodipine as compared with placebo. Since then, two further large clinical trials have been carried out - the Hypertension Optimal Treatment (HOT) study and the ongoing STOP-2 study - and neither of these have "given any indication that there is anything to worry about," she said.

A feeling of déj vu was also reported by a senior PR executive - who has been working on behalf of companies marketing CCBs for some time - who spoke "off the record" to heart wire . However, he said, this time the situation is somewhat different in that the drugs involved are so much older, and are either nearing the end of their natural product life cycle or are already off-patent. Last time round, the CCBs were still growing in terms of sales, and the Furberg controversy over safety coincided with a flattening of the sales curve. Although the rate of growth was probably slowing down anyway, within industry it is widely felt that the controversy contributed towards this, he said. "In fact, there are many in the industry who believe that it is the reason why the CCBs didn't realize their full commercial potential."

By now, however, interest in the CCBs has waned somewhat, the PR executive continued. The focus in research has since turned towards the renin-angiotensin system, and drugs like the ACE inhibitors and the newer angiotensin-antagonists are in the spotlight. CCBs are slowly becoming "yesterday's drugs," he believes. While sales of several of these products are still riding high, they are expected to fall off gradually as cheaper generic versions become available; eg the recent US launch of the first generic version of nifedipine from Biovail. However, this will be a gradual and natural decay, he believes - having talked with both industry and opinion leaders on both sides of the Atlantic since the story broke in August, he says he is convinced that the latest attack from Furberg and colleagues is no death threat.

However, the story's not finished yet. Rumor has it that the Furberg meta-analysis will be published in the Lancet, with timing to coincide with further airing of the data at the forthcoming American Heart Association meeting in November 2000.

Furberg stands by his group's findings, and expects a furor when the results are published. He says the strong reactions to his findings so far are driven by commercial considerations, and says "if there was nothing of substance in our findings, there wouldn't have been such a strong reaction."

Heartwire from Medscape © 2000 

Cite this: Effect on CCBs from latest Furberg attack - limited, at least so far - Medscape - Oct 04, 2000.