Chantix should not be withdrawn.

Despite the rising rates of obesity, smoking is still the single leading cause of preventable death in the US.  Quitting smoking is very difficult because one needs to address both the behavioral and pharmacologic aspects of nicotine addiction  Though other agents are available, Chantix or varenicline is the most effective agent to assist in smoking cessation.  This has been proven in several large, randomized clinical controlled trials (RCT's). RCT's are the gold standard when it comes to scientific proof. (More on that in a minute).

Chantix is not without issues.  The main side effect is nausea, which about 30% of users will get.  It is usually mild and usually goes away, though a small percent of people will not tolerate this.  The more recent concern with Chantix was exacerbations of neuropsychiatric symptoms: depression, anxiety, and suicidal ideation.  These side effects were not seen in many of the initial studies, but in later on via reports by doctors and patients after the drug was on the market.  This method is called post-market surveillance. Post-market surveillance is critical in determining drug safety, because rare but serious side effects may not be seen when you only study thousands not millions of patients.  However, unlike RCT's , proving cause and effect can not be determined. In regards to psychiatric symptoms, in the original studies that the Pfizer submitted to the FDA, Chantix had few interactions and did not show any. However, because Pfizer compared Chantix to bupropion (the only other pill indicated for smoking cessation, but also used for depression), patients with mental illness were purposely excluded from the study. (See more about this in Where's the Good News about Chantix? and More FDA warnings should not be cause for worry.) In fact, since these warnings first appeared, further studies seem to indicate that just stopping smoking, not necessarily Chantix, can cause these problems.  Furthermore, warnings were not just added to Chantix but also to bupropion. Regardless or whether symptoms like depression or even suicidal thoughts is linked to Chantix or stopping smoking, doctors and patients should be aware of this concern for any patient quitting tobacco. 

Now we have a new concern regarding Chantix causing cardiovascular events.  The initial concern was raised by the FDA in their review of a study of 700 patients with known cardiovascular disease randomized to Chantix or placebo. Though Chantix was far more effective in helping these patients with known heart disease quit tobacco, there was a small number of increased cardiovascular events, more in the Chantix group than placebo. The total number of events was 28 in the Chantix group vs. 17 in the placebo.  The study was not designed to show whether or not this number was statistically significant (was really true), but the FDA added a warning to Chantix' label.

However, a new study raises questions about Chantix and people without heart disease.  This is being blasted all over the media.  The Wall Street Journal reports "Drug Tied to Heart Risks."  The New York Times reports "Study Links Smoking Drug to Cardiovascular Problems."  ABC News states "Chantix: Quit Smoking, But Risk Your Heart?" All of them have similar language to the ABC news site stating:


Study authors looked at 14 past studies of Chantix and found that overall, people on the drug had a 72 percent increased risk of being hospitalized with a heart attack or other serious heart problems when compared with those taking a placebo.


That seems pretty bad! Unless, of course, you look at the actual data. The new study is a meta-analysis of studies looking at patients on Chantix without cardiovascular disease.  The study is from the Canadian Medical Association Journal.  They looked at data from 14 RCT's 8216 participants. They found that Chantix was associated with a significantly increased risk of serious adverse cardiovascular events compared with placebo on 1.06% [52/4908] in varenicline group compared to  0.82% [27/3308] in placebo group.  In other words, the absolute difference between Chantix and placebo is 0.24% or 24/10,000. This sounds a lot less scary than 72% increase (relative increase) being reported in the media.  It is also very, very important to note that the technique used to derive these numbers is a statistical technique, a meta-analysis, which is not nearly as rigorous as an RCT.  Meta-analysis are designed to ask questions, not to answer them.  ( I have blogged previously about the pros and cons of meta-analysis). Furthermore, even patients without a history of cardiovascular disease who smoke, have a risk for cardiovascular disease, which is why they need to stop in the first place.

Bottom Line: One must always question 1) the results of a meta-analysis because it has many limitations and 2) any non-RCT, especially a meta-analysis, with a very small absolute risk (i.e. 0.24%) especially if the authors/journalists are trumpeting a large relative risk (i.e. 72%) and  also 3) take into account the context of the situation, i.e. the single best agent we have available for the leading preventable cause of death in the United States, might possibly have an associated very small increase in heart disease in smokers that will likely have a much greater risk of heart disease if they don't stop smoking. While I agree more research is needed, and warnings about a possibly increased cardiovascular risk are not inappropriate, pulling Chantix from the market would be a huge mistake.

Cigarette Taxes Apparently Work

Not to be negative about public health educational campaigns, which I believe are important, but the two major factors that have led to the decline in US smokers over the past decade are most attributable two two things: smoking bans and taxes on cigarettes. When it becomes difficult to smoke in public places and expensive do to so anywhere, people are more motivated to quit.
An article in the NY Times today caught my attention: In Japan, Pfizer Is Short of Drug to Help Smokers. The focus of the article regards how Pfizer was a little unprepared for the excessive demand of the smoking cessation drug Chantix (called Champix in Japan and elsewhere) when the Japanese government imposed a cigarette tax.

Being in the business section, the focus is on sales and Pfizer's handling of the situation. However, I am much more interested in the impact of the Japanese cigarette tax on behavior. Japan has a much high smoking rate than in the US. In 2009, about 40% of Japanese men smoked, compared to about 24% of US males. The Japanese tax started in October of this year. Prior to this, the rate of smokers in Japan decreased by about 2%. The tax increased the cost of a pack of cigarettes from about $3.60 US dollars to $4.80. Prior to the tax, ad campaigns sponsored by Pfizer, led to sales of Chantix to 70,000 patients a month in August, which more than doubled to 170,000 patients in September (just before the tax) and continued to grow in October (the NY times article talks about how Pfizer had to suspend prescriptions to new patients because they couldn't make enough Chantix fast enough to keep pace with demand).

The bottom line is that cigarette taxes have been effective in the US, and seem to quite effective in Japan based on excess demand for Chantix and a significant drop in Japanese smokers prior to the tax. With our economy still not in the best shape, health care costs escalating, and respiratory illness now rising to the 3rd leading cause of death in the US, we should consider increasing cigarette taxes even more.

Why Barack Obama should come clean about his smoking and what he can do to quit

As a physician I believe that your personal health should be private. I can certainly understand why the American people would want the right to know about a potential presidential candidate's health prior to an election. However, afterwards, the health of a President, unless life threatening should probably remain private. That said, the President recently had a complete physical and the results of that physical are now public. In addition to knowing the President's blood pressure and cholesterol numbers, we now also know according to a New York Time's report (President in ‘Excellent Health,’ Routine Checkup Finds) that President Barack Obama continues to smoke. Though I still believe that health should be a private matter for patients, even if that patient happens to be the President, since our President has chosen to reveal his health information, I think that he should officially come clean about how much he smokes. According to the New York Times report, all we know is that he doesn't smoke on a daily basis, but rather smokes infrequently. In June, the President was quoted as saying, “Have I fallen off the wagon sometimes? Yes. Am I a daily smoker, a constant smoker? No.”

Tobacco smoke in the US is an important matter. It is currently the single leading cause of preventable death and accounts for billions of dollars in health care costs. Given our current health care crisis, including the escalating costs of health care, I think it would be important for the President to discuss the burden of tobacco in this country as well as his own struggle in quitting cigarette smoking.

Now as far as what the President can do, a lot depends on how much he smokes. My guess is that he probably smokes a few cigarettes a few days a week during stressful times. If this is the case, then withdrawal is likely a minimal concern, and his nicotine consumption is probably just reinforcing this very bad habit. If that is the case, stress management techniques are probably the best way to quit. I advise patients who smoke only a few cigarettes a day to think about what else they can do to manage their stress besides smoking. For example, taking a walk, reading a book, meditation, prayer, etc. Something that is relaxing and reduces stress. Certainly our President is under a lot of stress and one can understand why he would need some sort of stress relieving activity. Smoking cigarettes is obviously not the best way to reduce stress.

If the President does smoke more than just a few cigarettes a day, the current guidelines recommend that most patients benefit from pharmacotherapy (medication). Nicotine replacement in the form of lozenges, gum or the patch have been effective in doubling quit rates. Even more effective than nicotine replacement are pills, specifically buproprion or Chantix (Varenicline). Recently there's been some concern about safety issues regarding Chantix, ( see More FDA warnings should not be cause for worry. and Where's the Good News about Chantix? ) initially brought up by the FDA. However, these safety concerns have not seemed to have panned out, and more recent studies seem to indicate that Chantix is very safe given certain precautions, specifically worsening of mental conditions. Patients using any form of a medication should be aware that quitting cigarettes (with or without medication) can worsen underlying mental health conditions, such as depression or anxiety.

In addition, I have blogged previously about Electronic Cigarettes , which I have received a number of comments (also see More on Electronic Cigarettes or E-cigs ). I think those who responded are mostly e-cigarette users that have misunderstood my objections to e-cigarettes. My objection is not that I am opposed to the existence of electronic cigarette. It's more that e-cigarettes are not regulated, so 1) their safety cannot be completely ascertained and 2) they are being promoted as a smoking cessation treatment, which they have not proven to do. E-cigarettes are likely a healthier alternative to tobacco smoke, but should be regulated by the FDA since they do contain nicotine. I'm also bothered that electronic cigarettes are sold in our shopping malls, and can potentially be purchased by children. Electronic cigarettes are probably less carcinogenic, than tobacco cigarettes. However, nicotine itself has unhealthy effects, and the goal of smoking cessation should be getting off nicotine completely. All of the treatments for smoking cessation such as the patch and the gum and even the pills are only supposed to be used for short periods of time, usually three months to no more than 6 months. Electronic cigarettes might be safer replacement for tobacco cigarettes, but are not designed to get patients off of nicotine. Generally, most of the nicotine replacement products work by giving patients a continuous supply of nicotine, and eventually weaning that level down once the patient has been off tobacco cigarettes for a few weeks. For example, with the nicotine gum or lozenge, you don't take a piece of gum every time you crave a cigarette. Rather, you use the gum continuously throughout the day, starting with about 15 pieces per day eventually decreasing the number. Theoretically, the electronic cigarette could be used in that manner, but by just replacing a tobacco cigarette, you are not addressing the behavioral issues related to smoking cessation. So, while I believe that electronic cigarettes may be safe, I also believe they should be regulated by the FDA and should not (until proven) be used or promoted as smoking cessation agents.


The President could also call 1-800 QUIT NOW. This is a 24/7 support line designed to help patients quit tobacco products. It is free and fully funded by money from this tobacco settlements. This program can be used use in conjunction with treatment from your health care provider as well as with medication, nicotine replacement and other smoking cessation techniques.


Bottom Line: While I do believe the President's health is a personal matter, since he has come out admitting that he is still smoking cigarettes despite his promises to our First Lady, I believe that he should admit to exactly how much he still smokes as well as further discuss his own personal struggles with his addiction. This will hopeful bring additional attention to the problem of cigarette smoking, which remains the single leading cause of preventable death in our country.

Prescription Drugs: Risk vs. Benefit vs Cost- The Chantix Example

When a physician prescribes a medication, a patient generally wants the most effective medication, with the least amount of side effects, that won't cost a lot of money. Unfortunately, this is often not the case. When determining which medication is right for you, all things need to be balanced. Obviously, for people with good prescription coverage and/or substantial wealth, cost likely does not play into the picture. However, for most patients, decisions need to be made. Should a patient take a generic medication that might not work as well or have potentially more side effects, but will cost substantially less than the branded medication? The choice is not always easy.

The Chantix example

I have posted several times about Chantix here, here, here, and here. The main reasons for these postings was due to the fact that the media (and some organizations) in my opinion were blowing out of proportion the risk of side effects of a very useful medication for the single leading preventable cause of death in our country.

Now, we have data in that seems to confirm that Chantix is the most effective agent available in the United States for smoking cessation. For those of you not familiar with the Cochrane group, they are international and free of any commercial bias. They review all data available in a systematic way, and are considered by most as some of the most unbiased and highest level of evidence available for therapeutics. The Cochrane review for Chantix (varenicline) is now in, and states that compared to placebo, nicotine replacement or bupropion (Wellbutrin, Zyban), that Chantix is the most effective agent, essentially doubling to tripling your chances of successfully quitting cigarettes.

Soon after Chantix had been on the market, reports of worsening of neuropsychiatric symptoms (depression, anxiety, suicidal ideation) surfaced, and the FDA took notice. Unfortunately, they went very public with this and the media had a field day scaring a lot of patients. In the original studies, patients with underlying depression and anxiety were purposefully excluded. Yet, patients with mental health disorders are much more likely to be smokers. We also know that stopping smoking, even without medication, can cause a worsening of these symptoms. In their final analysis, the FDA stated that it was not entirely clear whether Chantix was responsible for some of these adverse events. They appropriately added language to the drug information (package insert) to warn doctors and patients to look out for these side effects. This is a good thing, because even if Chantix is not the causative agent, it serves as a reminder that stopping smoking can cause worsening of neuropsychiatric symptoms.

Thus, the issue becomes efficacy vs. safety. Should you take a medication that is the most effective agent to help you stop smoking and risk a potential side effect that you could become depressed or even suicidal? One also has to consider the risks of NOT taking the drug. If I don't take Chantix, for example, and continue smoking, I am at risk for a lot of major problems! Given that it is unclear that Chantix has any more or less risk than other agents or no agents at all, in my opinion, since smoking increases risks for things like cancer, heart attack and stroke; in this case risk is outweighed by benefit.

Probably more troublesome is efficacy vs. cost. Chantix trumped bupropion (wellbutrin, zyban) and nicotine replacement (patch, gum, etc.). However, bupropion is generic and for most patients with prescription coverage, a relatively low out of pocket expense. Nicotine replacement is not covered by insurance, and thus the patch, gum or lozenge is a high out of pocket expense. Finally, many insurances still do not cover Chantix, and when covered the co-pay can be high. Thus, do you take the medicine is that is likely to be the most effective, but pay more, or do you try the generic which will likely work, though possibly not as well?

It would be great if all medicines were covered and at low costs to patients, worked incredibly well with virtually no side effects. However, in general this is just not the case. Many generics work just as well if not better than newer more expensive drugs. However, this is not always the situation. Furthermore, sometimes more effective drugs come to market but with increased risk. Doctors and patients must weigh cost, benefit, and risk with each prescription. Every patient's situation will be different. Thus, when being prescribed a new drug you need to take all of these into account.

Here are some questions to ask:
1. What are the side effects of the drug, and what is the chance that I will get these side effects?
2. What are the benefits of this drug, and how much and how likely will I benefit if I take this drug?
3. What are the risks if I don't take this drug, and how likely am I to get these consequences?
4. Are there alternatives available for this drug? If so, what would my out of pocket costs be for each one?
5. What are the differences in risk and benefits between all my options, including not taking any medication?