The effects of prescribing varenicline on two-year health outcomes: an observational cohort study using electronic medical records

Abstract

Aims: To investigate whether smokers prescribed varenicline had lower risks of serious ill-health during the 4 years following treatment compared with those prescribed nicotine replacement therapy (NRT).

Design: Observational cohort study of electronic medical records.

Setting: A total of 370 UK general practices sampled from the Clinical Practice Research Datalink.

Participants: A total of 126 718 patients aged 18 and over who were issued smoking cessation prescriptions between 1 September 2006 and 31 March 2014.

Measurements: Our primary outcome was all-cause mortality within 2 years of first prescription as indicated by linked Office of National Statistics data. Our secondary outcomes were cause-specific mortality, all-cause, cause-specific hospitalization, primary care diagnosis of myocardial infarction or chronic obstructive pulmonary disease (COPD), body mass index and attendance rate to primary care within 2 years of first prescription. Risk differences and 95% confidence intervals were estimated by multivariable adjusted regression and propensity score matched regression. We used instrumental variable analysis to overcome residual confounding.

Findings: People prescribed varenicline were healthier at baseline than those prescribed NRT in almost all characteristics, highlighting the potential for residual confounding. Our instrumental variable analysis results found that people prescribed varenicline had a similar risk of mortality at 2 years [risk difference per 100 patients treated = 0.67, 95% confidence interval (CI) = -0.11 to 1.46)] to those prescribed NRT, and there were similar rates of all-cause hospitalization, incident primary-care diagnoses of myocardial infarction and COPD. People prescribed varenicline subsequently attended primary care less frequently.

Conclusions: Smokers prescribed varenicline in primary care in the United Kingdom do not appear to be less likely to die, be hospitalized or experience a myocardial infarction or chronic obstructive pulmonary disease during the following 2 years compared with smokers prescribed nicotine replacement therapy, but they gain more weight and attend primary care less frequently.

Keywords: CPRD; instrumental variables; mortality; myocardial infarction; nicotine replacement therapy; varenicline.

Figure 1

Instrumental variable estimates of the effects of prescribing varenicline versus nicotine replacement therapy on mortality and morbidity during the 2 years following first prescription. Confidence intervals allow for clustering between physicians. Instrumental variable results use seven prior prescriptions, and adjust for year of first prescription, gender and age

Figure 2

The effect of prescribing varenicline on (a) all‐cause, (b) chronic lung disease‐related (ICD J40–44), (c) lung cancer (ICD C34), (d) coronary heart disease (ICD I21–25), (e) pneumonia‐related (ICD J12–18) and (f) cerebrovascular disease (ICD I60–69)‐related mortality during the 4 years following first prescription as indicated via Office of National Statistics mortality records. Linear regression is indicated by , solid line is adjusted for basic confounders, dashed line adjusts for all confounders listed in Table 1 and the instrumental variable results are indicated by ; 95% confidence intervals indicated. Confidence intervals allow for clustering between physicians. The multivariable adjusted results adjust for all the covariates listed in Table 1. Instrumental variable results use seven prior prescriptions. [Colour figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

The effect of prescribing varenicline on (a) all‐cause, (b) chronic lung disease‐related (ICD J40–44), (c) lung cancer (ICD C34), (d) coronary heart disease (ICD I21–25), (e) pneumonia‐related (ICD J12–18) and (f) cerebrovascular disease (ICD I60–69)‐related hospital in‐patient admission during the 4 years following first prescription as indicated via Office of National Statistics death records. Linear regression is indicated by , solid line is adjusted for basic confounders, dashed line adjusts for all confounders listed in Table 1 and the instrumental variable results are indicated by ; 95% confidence intervals indicated. Confidence intervals allow for clustering between physicians. The fully multivariable adjusted results adjust for all the covariates listed in Table 1. Instrumental variable results use seven prior prescriptions. [Colour figure can be viewed at http://wileyonlinelibrary.com]

Figure 4

Effect of prescribing varenicline on (a) weight (kg) and (b) frequency of attendance to primary care during the 4 years following initial prescription. Linear regression is indicated by , solid line is adjusted for basic confounders, dashed line adjusts for all confounders listed in Table 1 and the instrumental variable results are indicated by ; 95% confidence intervals indicated. [Colour figure can be viewed at http://wileyonlinelibrary.com]

Figure 5

Effect of prescribing varenicline on diabetes‐related (ICD E10–14) (a) mortality and (b) in‐patient admission, primary‐care diagnosis of (c) myocardial infarction and (d) chronic obstructive pulmonary disease during the 4 years following initial prescription. Linear regression is indicated by , solid line is adjusted for basic confounders, dashed line adjusts for all confounders listed in Table 1 and the instrumental variable results are indicated by ; 95% confidence intervals indicated. Confidence intervals allow for clustering between physicians. The fully multivariable adjusted results adjust for all the covariates listed in Table 1. Instrumental variable results use seven prior prescriptions. [Colour figure can be viewed at http://wileyonlinelibrary.com]