Pfizer has come out strongly in favour of the benefits of Chantix following the publication of a meta-analysis which claims the smoking cessation treatment significantly increases the risks of cardiovascular problems.

The study, described in the Canadian Medical Association Journal, claims that healthy, middle-aged smokers who take Chantix (varenicline), also known as Champix, have a 72% increased risk of being hospitalised with a heart attack or other serious cardiovascular problems compared to those taking a placebo. Researchers on the Johns Hopkins Medical Institutions-led study came to this conclusion after analysing 14 clinical trials involving more than 8,200 healthy people taking the drug or a placebo.

The meta-analysis claims that whereas the number of people who died in each group was the same (seven), the increased risk of a major harmful cardiovascular event was 72% in the varenicline arms. The authors also note that none of the studies followed people for longer than a year and the average age of participants was less than 45 and the majority were men.

Modest increase in helping smokers quit

The authors claim that Chantix has been shown to modestly increase the chances of a successful quit attempt, compared to unassisted smoking cessation attempts. However overall, they note, the majority of smokers who quit "do so without any pharmaceutical assistance at all".

Sonal Singh of the Johns Hopkins University School of Medicine and lead author of the research, said that "people want to quit smoking to reduce the risk of cardiovascular disease but in this case they're taking a drug that increases the risk for the very problems they're trying to avoid".

He noted that Chantix already carries a boxed warning because of its association with suicidal thoughts and behaviours, adding that "we notified the US Food and Drug Administration of our cardiovascular safety concerns with Chantix earlier this year". Last month, the agency announced that on the basis of a 700-person study, people with existing heart disease who use varenicline have a slightly increased risk of a heart attack or other cardiovascular event.

Now Prof Singh's study suggests Champix substantially increased the risk of a serious cardiovascular event even among smokers without heart disease. "I think our new research shifts the risk-benefit profile of varenicline," he says and "people should be concerned. They don't need Chantix to quit and this is another reason to consider avoiding Chantix altogether."

Prof Singh and other colleagues who worked on the meta-analysis from Wake Forest University School of Medicine and the University of East Anglia in the UK, emphasise the need to quit smoking, but suggest Champix may not be the right drug to kick the habit. He says questions about the drug's cardiovascular disease risks have been raised since varenicline went on the market in 2006, but no study has clarified the magnitude of these risks to the extent found in the new study. The FDA used a 'fast-track' review process in allowing varenicline to be sold in the USA and Prof Singh would like regulators to take a new look.

Reliability concerns

Pfizer hit back by saying that "the reliable science" on varenicline involving over 14 trials with more than 7,000 smokers "demonstrate the importance of the medicine as an effective and appropriate treatment option for adult smokers wanting to quit".

Saying that it stands behind the benefit/risk profile of Chantix, the company expressed concerns about the reliability of the meta-analysis related "to the appropriateness of the authors' measure of cardiovascular risk, or composite endpoint, which combines events that do not share a common biological cause; the manner in which cardiovascular events were counted and classified; and a small number of events, which forms the authors' conclusions".

Pfizer adds that the authors themselves acknowledge that the cardiovascular risk “estimates are imprecise owing to the low event rates.” The US giant adds that "notwithstanding these reliability concerns, the difference of 72% reported in the Singh analysis also needs to be put into appropriate context", ie the actual difference in cardiovascular event rates reported in this analysis was less than one quarter of 1% (1.06% with varenicline versus 0.82% with placebo).

US giant plans own meta-analysis

Pfizer added that it is discussing with the FDA a protocol to conduct a meta-analysis of its clinical trial data to help further evaluate the cardiovascular safety of Chantix, which had first-quarter sales of $233 million, up 32%. This will "address a number of limitations in the Singh analysis", the firm notes, as  it will be based on "a more reliable composite endpoint to measure cardiovascular risk, as well as a validated process to classify, or adjudicate, cardiovascular events that are part of the composite endpoint".

Gail Cawkwell, vice president of medical affairs at Pfizer, said the company's scientists and doctors "continuously evaluate the benefits and risks of its medicines, including Chantix". She added that the currently available safety data, including a pooled analysis of 7,375 people trying to quit smoking, "do not support an increased cardiovascular risk associated with Chantix.”