Interpretation of Class 2b, Level B-R Recommendation
The guideline suggests that varenicline might be a better choice than bupropion or NRT for smoking cessation in patients with CCD based on one randomized controlled trial.
Understanding the Recommendation Classification
The Class 2b designation means this is a weak recommendation where the benefit-to-risk balance is uncertain and the intervention "may be considered" rather than "should be used" 1. This reflects equipoise in the evidence, indicating that varenicline is a reasonable option but not definitively superior enough to warrant a stronger recommendation 1.
The Level B-R (Randomized) evidence designation indicates the recommendation is based on moderate-quality evidence from randomized controlled trials, but importantly, no head-to-head trials directly compared these agents specifically in CCD patients 1. The guideline explicitly states that "no trials have compared various agents with each other in patients with CCD" 1.
Why the Other Options Are Incorrect
Option 2 (Epidemiological Studies) - Incorrect
- The Level B-R designation specifically indicates randomized controlled trials, not epidemiological studies 1
- Epidemiological studies would be classified as Level B-NR (non-randomized) or Level C (observational) 1
Option 3 (Strong Recommendation) - Incorrect
- Class 2b is explicitly a weak recommendation ("may be considered"), not a strong one 1
- A strong recommendation would be Class 1 ("is recommended" or "should") 1
- The phrase "should be the drug of choice" contradicts the uncertain benefit-to-risk balance inherent in Class 2b 1
Option 4 (Multiple High-Quality Trials) - Incorrect
- While meta-analyses show varenicline superiority in general populations (5 trials vs bupropion, 8 trials vs NRT), no direct comparative trials exist specifically in CCD patients 1
- The word "preferentially" implies stronger guidance than Class 2b provides 1
- "Multiple, high-quality clinical trials" would typically warrant Class 1, Level A evidence 1
Clinical Context
The evidence shows varenicline has higher abstinence rates than comparators in general populations (RR 1.39 vs bupropion, RR 1.25 vs NRT) 1, and one dedicated cardiovascular safety trial in 714 stable CVD patients demonstrated efficacy without increased cardiovascular events 2. However, the lack of direct head-to-head comparisons specifically in CCD patients, combined with the need to consider "patients' previous experiences, preferences, and comorbidities," justifies the weaker Class 2b recommendation 1.