Varenicline Not Linked With CVD or Psychiatric Risk in New Analysis

September 10, 2015

DUSSELDORF, GERMANY — A new analysis of smokers using different aids to help them quit found the use of varenicline (Chantix/Champix, Pfizer) did not result in any significant neuropsychiatric or cardiovascular risks compared with nicotine-replacement therapy[1].

In fact, compared with nicotine-replacement therapy, the use of varenicline was associated with a 20% lower risk of ischemic heart disease and a significant 34% lower risk of depression and a 44% lower risk of self-harm.

"We noted no evidence of any increased risk of cardiovascular or neuropsychiatric adverse events in smokers using varenicline or bupropion when compared with [nicotine-replacement therapy] users," write Dr Daniel Kotz (Heinrich Heine University, Dusseldorf, Germany) and colleagues. "On the contrary, some events were associated with a reduced risk, including the events with the highest noted incidences (ie, depression and ischemic heart disease)."

The researchers report the use of varenicline was also associated with significantly lower risks of cerebral infarction, heart failure, and developing an arrhythmia.

The results of the retrospective cohort study are published in the Lancet: Respiratory Medicine.

Boxed warning

Varenicline was approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for smoking cessation in 2006, but postmarketing reports raised concerns about the drug's cardiovascular safety. A 2011 meta-analysis published in CMAJ, one that included 8200 participants, showed the use of varenicline increased the risk of serious cardiovascular events by 72% compared with placebo (1.06% event rate in varenicline vs 0.82% in the placebo arm). This led to a warning about potential cardiovascular risks in the FDA label for varenicline.

Similarly, the FDA and EMA issued warnings about the potential for neuropsychiatric symptoms, including changes in behavior, agitation, depression, suicidal ideation, and attempted/completed suicide, based on postmarketing data. In fact, as Kotz and colleagues point out in their review, the FDA was sufficiently concerned about varenicline it issued a boxed warning in 2009 about the risk of neuropsychiatric events.

In this latest analysis, Kotz and colleagues identified 51,450 patients who received a prescription for varenicline, 106,759 for nicotine-replacement therapy, and 6557 for bupropion, another agent that is used to help people quit smoking. Nicotine-replacement therapy was used as the reference group, as it is presumed by regulatory agencies not to carry any risks, say the investigators. A follow-up period of 6 months was chosen, as this is the typical treatment duration for the drugs.

Varenicline significantly reduced the risks of multiple cardiovascular disease end points compared with nicotine-replacement therapy, the exception being peripheral vascular disease (odds ratio 0.95; 95% CI 0.73–1.23). Bupropion also reduced the risks of ischemic heart disease, cerebral infarction, arrhythmia, and depression compared with nicotine but had no effect on heart failure, peripheral vascular disease, or self-harm end points.

The patients were young, just 38 years old in the varenicline and bupropion arms and 40 years old in the nicotine-replacement group. As such, the incidence of ischemic heart disease was low, at 6% in the nicotine-replacement arm and 3% in varenicline- and bupropion-treated patients. Rates of previous depression were higher, with more than one-third of participants reporting previous depression. One in 10 had harmed themselves in the past.

"Although this study could not rule out adverse reactions that do not get recorded in general practice records, the findings have clear implications for the safety warnings for varenicline and for clinical practice," according to Kotz and colleagues. "They suggest an opportunity for physicians to prescribe varenicline more broadly, even for patients with comorbidities, thereby helping more smokers to quit successfully than do at present."

Kotz received grant support from Pfizer for a smoking-cessation study outside of this submitted work. Disclosures for the coauthors are listed in the paper.

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