Dr Curt Furberg (Photo: Larry Husten)

Amsterdam, The Netherlands - Following strong reactions to and sharp criticism of the meta-analysis showing that calcium channel blockers (CCBs) are inferior to other antihypertensive agents in protecting against MI and congestive heart failure (CHF), Dr Curt Furberg (Professor, Public Health Sciences, Wake Forest University Baptist Medical Center, Winston-Salem, NC) the lead investigator of the study, has responded with comments to heartwire that defend his group's research and findings.

Furberg presented the meta-analysis at the 22nd Congress of the European Society of Cardiology in Amsterdam. As previously reported in heartwire, his group's study provoked outrage among other researchers in the field of hypertension. Other experts have questioned not only the findings - which do not tie in with the findings of other meta-analyses or with data from recent clinical trial - but also the scientific basis of the meta-analysis performed by Furberg's group, saying it contains highly selected data from studies that are seriously flawed.

In response, Furberg commented to heartwire as follows: "Our meta-analysis meets the highest scientific standards. The event data are consistent across all 9 trials, including type of CCBs. Four of the 9 trials showed, on their own, statistically significant unfavorable results for the CCBs."

"Our findings are statistically and clinically strong and conclusive. Sensitivity analyses show that exclusion of the smaller trials does not change the overall findings and conclusions."

"Our meta-analysis meets the highest scientific standards. The event data are consistent across all 9 trials, including type of CCBs. Four of the 9 trials showed, on their own, statistically significant unfavorable results for the CCBs."

When reporting his findings in Amsterdam, Furberg declared that, as a result of his group's findings that the CCBs are inferior to other antihypertensive agents, this group of drugs should not be used first-line in the treatment of hypertension. They should only be used as a last resort, in patients not responding or unable to tolerate other agents, and national treatment guidelines should be changed in order to reflect this view. Now, in his comments to heartwire, Furberg notes, "two European countries are already considering changes in their treatment guidelines based on the meta-analysis."

COMMERCIAL IMPLICATIONS

"Our meta-analysis had no external funding as opposed to the WHO-ISH meta-analysis, which is industry-sponsored. We included heart failure as a major event in contrast to the WHO-ISH study. Heart failure is a known serious adverse event of CCBs! The exclusion of this outcome in the WHO-ISH study raises the issue of potential conflict of interest in light of the funding."

Furberg also points out, "Our meta-analysis had no external funding as opposed to the WHO-ISH meta-analysis, which is industry-sponsored. We considered the totality of clinical trial evidence (all randomized trials with more than 200 person-years). Thus, our analysis is more inclusive than the WHO-ISH analysis. Additionally, we included heart failure as a major event in contrast to the WHO-ISH study. Heart failure is a known serious adverse event of CCBs! The exclusion of this outcome in the WHO-ISH study raises the issue of potential conflict of interest in light of the funding."

"The strong reaction to the report, we believe, can be explained by the strength of our findings and the commercial implications," Furberg adds.

The commercial implications are of huge proportions. According to estimates from Lehman Brothers, the world market for antihypertensive drugs is worth a staggering $25 billion, and CCBs account for a large slice of the pie, around $6 billion. In hypertension, they vie for the top billing with ACE inhibitors, which also account for around $6 billion.

However, the CCB market is very fragmented, as many of the drugs are already off-patent and therefore available as generics. The largest product, by far, is amlodipine (Norvasc® - Pfizer), sales of which have topped $3 billion and are still growing. Next is nifedipine (Adalat® - Bayer), which registers sales of approximately $1 billion. Unsurprisingly, Pfizer and Bayer were the two companies that were quick to respond to the latest "bad news" about CCBs to come from Furberg's group.