Cost-effectiveness of intensive smoking cessation therapy among patients with small abdominal aortic aneurysms

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1 Cost-effectiveness of intensive smoking cessation therapy among patients with small abdominal aortic aneurysms Kevin Mani, MD, PhD, a,b Anders Wanhainen, MD, PhD, a Jonas Lundkvist, RPh, PhD, c and David Lindström, MD, PhD, d Uppsala, Sweden; London, United Kingdom; and Stockholm, Sweden Introduction: Smoking cessation is one of the few available strategies to decrease the risk for expansion and rupture of small abdominal aortic aneurysms (AAAs). The cost-effectiveness of an intensive smoking cessation therapy in patients with small AAAs identified at screening was evaluated. Methods: A Markov cohort simulation model was used to compare an 8-week smoking cessation intervention with adjuvant pharmacotherapy and annual revisits vs nonintervention among 65-year-old male smokers with a small AAA identified at screening. The smoking cessation rate was tested in one-way sensitivity analyses in the intervention group (range, 22%-57%) and in the nonintervention group (range, 3%-30%). Literature data on the effect of smoking on AAA expansion and rupture was factored into the model. Results: The intervention was cost-effective in all tested scenarios and sensitivity analyses. The smoking cessation intervention was cost-effective due to a decreased need for AAA repair and decreased rupture rate even when disregarding the positive effects of smoking cessation on long-term survival. The incremental cost/effectiveness ratio reached the willingness-to-pay threshold value of 25,000 per life-year gained when assuming an intervention cost of > 3250 or an effect of <1% difference in long-term smoking cessation between the intervention and nonintervention groups. Smoking cessation resulted in a relative risk reduction for elective AAA repair by 9% and for rupture by 38% over 10 years of follow-up. Conclusions: An adequate smoking cessation intervention in patients with small AAAs identified at screening can cost-effectively increase long-term survival and decrease the need for AAA repair. (J Vasc Surg 2011;54: ) Abdominal aortic aneurysm (AAA) is a common and potentially fatal disease with a prevalence of 3% to 5% in elderly men. 1,2 The most efficient manner to decrease the mortality rate in AAA rupture is screening adequately selected cohorts. 2,3 Screening programs are now being implemented in several countries. 4 The most important risk factor for AAA is smoking, which is also a key factor for the expansion of an AAA and for the risk of rupture. 5-7 Approximately 40% to 50% of patients with small AAAs identified by screening are current smokers. 8,9 Smoking cessation is one of the few presently available strategies to decrease the risk for expansion and rupture of small AAAs. 6,7,10 Smoking cessation also improves long-term survival and decreases the risk of cardiovascular disease. 11 Thus, From the Department of Surgical Sciences, Section of Vascular Surgery, Uppsala University, Uppsala a ; the Department of Vascular Surgery, Guy s and St Thomas NHS Foundation Trust, London b ; and the Medical Management Centre, c and Section of Vascular Surgery, Department of Clinical Science and Education, d Karolinska Institutet, Södersjukhuset, Stockholm. This study received financial support from the Swedish Heart and Lung Foundation. Competition of interest: none. Correspondence: Dr Kevin Mani, Department of Vascular Surgery, Uppsala University Hospital, Uppsala, Sweden ( kevin.mani@ surgsci.uu.se). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a competition of interest /$36.00 Copyright 2011 by the Society for Vascular Surgery. doi: /j.jvs smoking cessation improves both general survival and aneurysm outcome. Smoking cessation therapy is relatively more efficient in patients where additional motivational factors are available. This could be exemplified by admittance for coronary heart disease, 12 diagnosis of chronic obstructive pulmonary disease, 13 or in the preoperative setting. 14,15 Although patients with small AAAs identified in screening programs constitute a population of special interest for smoking cessation therapy, the clinical efficiency and cost-effectiveness of smoking cessation therapy in this group has not been studied. The current study used a Markov simulation model to evaluate the cost and effect of smoking cessation therapy among patients with screening-detected small AAAs. We hypothesized that smoking cessation therapy would be cost-effective in a population with small AAAs by increasing life expectancy and reducing the need for surgical intervention for AAAs. A secondary aim was to identify critical areas where more information is needed to reduce the uncertainty about the effect and cost of smoking cessation among AAA patients. MATERIALS AND METHODS A Markov cohort simulation model was constructed to compare the cost and effect of an intensive smoking cessation intervention with nonintervention among 65-year-old male smokers with a small AAA identified at screening. The Markov cohort simulation model is a common technique in

2 JOURNAL OF VASCULAR SURGERY Volume 54, Number 3 Mani et al 629 Fig 1. Bubble diagram shows the Markov simulation model of a smoking cessation intervention vs nonintervention in a population of 65-year-old male smokers with small abdominal aortic aneurysms (AAAs) identified at screening. health economic evaluations of different health interventions. The technique is based on construction of hypothetic cohorts that are monitored for a predefined period of time. A number of possible health states are defined, and the cohort lifetime is divided into cycles of, for example, 1 year. For each cohort, the costs and effects produced over the studied lifetime are calculated, and the cost-effectiveness of intervention vs nonintervention is evaluated by the difference in effect and cost. The Markov cohort simulation model used in the current study is presented in Fig 1. We assumed that the AAAs found in the studied cohort would have the same composition as those presented in the existing screening trials, with 70% of the aneurysms being in the 3- to 4.4-cm range at detection. 1,16-19 The health care provider s perspective was chosen when evaluating cost-effectiveness, and the cohort was monitored for 20 iterations of 1 year in length (ie, until the age of 85 years). This age cutoff was used because few patients are offered elective AAA repair after the age of 85, and the rates of intact and ruptured AAA repair in the intervention and nonintervention groups were one of the main outcome parameters for this analysis. The model was populated with data based on a literature review and analysis of available data from the Swedish Vascular Registry (Swedvasc) well as from local registries (Table I). One-way sensitivity analyses were performed to identify and evaluate major uncertainties in the current literature. The cost in euros (2009 year value) per life-year gained (LYG) was the main outcome measure, and the cost per quality-adjusted life-year (QALY) was a secondary outcome measure. An incremental cost per effect of 25,000 was regarded as acceptable. The effect of the smoking cessation intervention and actual smoking cessation on the rate of elective AAA repair and rupture among patients with small AAA was calculated based on a Monte-Carlo microsimulation with 100,000 random walks in the Markov model. The model assumed that all individuals would be informed of the AAA and its relationship with smoking and advised to stop smoking, which is the current practice at our institutions. In addition, the individuals could or could not be offered intensive smoking cessation therapy, based on an 8-week smoking cessation intervention that has been proven effective in the perioperative setting (Table II). 15,20 The rate of long-term abstinence from smoking was assumed to vary, based on intervention or nonintervention. Because data have been published on how successful smoking cessation therapy is in this group of patients, different scenarios were tested in an extensive one-way sensitivity analysis, assuming a smoking cessation rate of 22% to 57% in the intervention group (base-case estimated at 33% 14 ) and 3% to 30% in the nonintervention group (base-case estimated at 15%). The wide range of long-term smoking cessation rates tested in the sensitivity analyses was set to reflect smoking cessation rates that could potentially be expected with other forms of interventions, such as including other pharmacologic adjuncts (eg, varenicline), or longer periods of intervention.

3 630 Mani et al JOURNAL OF VASCULAR SURGERY September 2011 Table I. Probabilities and costs in Markov simulation model Parameter Probability or cost in basecase Tested range References Age, years Age at screening Rate of long-term smoking cessation, % Intervention , 14, 36, 37 Nonintervention , 14, 36, 37 Rate of smoking cessation after AAA repair, % Yearly risk of i-aaa repair, % Smokers % 1, 6, 7, Former smokers % 1, 6, 7, Yearly risk of rupture, % Smokers 1% 0.6%-1.5% 1, 7, Former smokers 0.6% 0.3%-1% 1, 7, Rate of rupture undergoing AAA repair, % 50% 30-70% 1, Rupture mortality, % 79% 71-84% 1, 16, 17, 27, 28 Peri-op mortality i-aaa repair, % 2.7% 25; current analysis Former smokers 2.1 Current smokers 3.4 Relative mortality Smokers , 22, 26 Former smokers , 22, 26 Reduced QALY among smokers, % 0% 0-4% 34 Cost of smoke intervention, health care system, , 15, 21, 37 Cost of i-aaa repair, 24,108 10%-50% higher cost for smokers 29 Cost of ruptured AAA repair, 1.5 cost of elective repair cost of elective repair 30, 31 Cost of pre-op AAA surveillance, Cost of post-op follow-up, AAA, Abdominal aortic aneurysm; i-aaa, intact abdominal aortic aneurysm; QALY, quality-adjusted life-year. Table II. Details of planned smoking cessation intervention and costs of intervention for 8 weeks Program Estimated costs, a Motivational counselling 122 b Professionally trained counselor (nurse), cognitive behavioral methods, weekly faceto-face consultations for the first month, then weekly by phone in the last month Self-help material Free Written information about smoking cessation, telephone number to a hotline providing smoking cessation advice Adjuvant pharmacotherapy 103 Individual nicotine replacement therapy, estimated cost for 8 weeks: patches, chewing gum, or microtabs Total cost 225 a Costs estimated from Hejblum et al 21 (2009) recalculated to 2009 values. b Including Fagerström scoring of nicotine dependence and testing of CO in expired air. The cost of the smoking cessation intervention was calculated at 225 per individual based on cost and resources in previous interventions. 14,15,21 In the sensitivity analysis, a minimum cost limit of 122 was tested (assuming that the cost of adjuvant pharmacotherapy would not be covered within the smoking cessation intervention), as well as a maximum cost limit of 1463 (assuming a 52-week smoking cessation intervention with relapse support). A high percentage of smokers quit smoking after AAA repair (35% according to the UK Small Aneurysm Trial 22 ), which was factored into the model (Table I). A literature review was used to estimate the annual risk of elective AAA repair, rupture, and death for current and former smokers (Table I). The annual rupture rate after screening was estimated at 0.8% based on previous screening studies 1,16-18 and was adjusted based on smoking status according to data from the UK Small Aneurysm Trial, with an adjusted hazard ratio for rupture of 0.59 for previous smokers compared with current smokers 7 (Table I). The overall rate of intact AAA (i-aaa) repair was estimated at 3.9% per year, 19 assuming surgical intervention when the aneurysm expands to a maximum diameter of 5.5 cm. The rate of i-aaa repair was adjusted for smoking status using data from previous studies on increased expansion rate of small AAAs among smokers. 6,23,24 In the base case, current smokers were assumed to have a 15% to 20% increased risk of i-aaa repair compared with previous smokers because of the difference in growth rate (Table I). The overall perioperative mortality rate was estimated at 2.7% after i-aaa repair based on the Swedvasc Registry 2009, 25 which also showed that 53% of all intact AAA repairs were performed with endovascular AAA repair (EVAR). Perioperative mortality was estimated to be equal in the current and former smoker groups in the base case. Data on the effect of smoking status on the perioperative mortality rate after AAA repair was not available in the literature and was therefore calculated from original data from the Swedvasc Registry in a logistic regression model. In this model, 8663 i-aaa repairs registered in the Swed-

4 JOURNAL OF VASCULAR SURGERY Volume 54, Number 3 Mani et al 631 Table III. Base-case cost and effect of smoking cessation intervention per person Variable Nonintervention Intervention Difference Cost, Smoking cessation intervention Pre-op follow-up of small AAA Intact AAA repair Ruptured AAA repair Follow-up after AAA repair Total cost 13,692 13, Effect Life years Quality-adjusted life-years AAA, Abdominal aortic aneurysm. vasc registry 26 from 1987 to 2005 were analyzed, including patient age, operation year, operation method (open repair or EVAR) and smoking status (smoker vs nonsmoker or former smoker). The adjusted odds ratio for perioperative mortality for smokers was 1.6 compared with nonsmokers or former smokers. To test for the effect of a potential difference in perioperative mortality after i-aaa repair between current and former smokers in the sensitivity analysis, a perioperative mortality rate of 2.1% was assumed for former smokers vs 3.4% for current smokers. Overall mortality after AAA rupture was estimated at 79%, based on studies performed during a period when open repair was performed for ruptured AAA. 1,16,17,27,28 Cost of AAA repair, including cost of postoperative follow-up, was established using data from our institution 29 and a literature review 30,31 and was estimated to be the same in smokers and former smokers in the base case. The cost of repair was derived from mixed use of open surgical and endovascular repair of AAAs in a populationbased setting, 29 assuming that approximately half of the patients would undergo open repair and half EVAR for intact AAA. The postoperative cost included the cost of all clinical follow-up, imaging, reoperations, and reinterventions. 29 The long-term mortality rate was calculated from a previous analysis of long-term survival among AAA patients in the Swedvasc registry (standardized mortality ratio of 1.4 for AAA patients compared with a healthy population adjusted for age, sex, and calendar year). 26 This value was adjusted for the difference in survival between current and previous smokers, with an adjusted hazard ratio of death of 1.25 for current smokers with AAA compared with former smokers with AAA. 22 Data from the general Swedish population were used to estimate the QALYs gained within the Markov model. 32 The QALY levels were estimated at 0.88 QALYs gained per lived year for ages 65 to 69 years, 0.77 for ages 70 to 79, and 0.63 for ages 80 to The QALY in the base case was assumed to be equal for current and previous smokers. 33 In the sensitivity analysis, the QALY of smokers was assumed to be 4% lower than the QALY of former smokers. 34 The Markov model was analyzed in a base case with the parameter values summarized in Table I. The uncertainty of the included parameters was tested in a one-way sensitivity analysis, where each parameter was varied (one at a time) within a tested range to evaluate the effect of the uncertainty in this parameter on the overall health economic evaluation of the smoking cessation intervention. All tested ranges for the parameters are presented in Table I. In addition to this sensitivity analysis, two specific scenarios were tested in the model: 1. To focus on the effect of smoking cessation on AAAspecific mortality, the model was evaluated when disregarding the effect of smoking cessation on long-term survival; that is, all parameters were equal in the intervention and nonintervention group except for the cost of the intervention, the smoking cessation rate, and the rate of elective AAA repair and rupture among current vs former smokers. 2. To focus on the effect of smoking cessation on general survival, the model was evaluated when focusing only on the difference in long-term survival; that is, assuming that all parameters were equal in the intervention and nonintervention group except the long-term survival rate of current vs former smokers. Statistical analysis was done using SPSS 16.0 software (SPSS, Chicago, Ill), and the health-economic evaluation was done with TreeAge-Pro 2007 software (TreeAge Software Inc, Williamstown, Mass). The Swedish Consumer Price Index was used to convert all costs to 2009 values. A discount rate of 3% (based on the Swedish standard) was used for both costs and health outcomes. No ethical approval was required for this study. RESULTS Base-case health economic evaluation. In a basecase analysis, the per-person cost of the intervention was 84, and the health gain in the intervention group was life-years, resulting in an incremental cost/effectiveness ratio of 674/LYG (Table III). The gain in QALYs in the intervention group was per person in base case, with a cost/effectiveness ratio of 924/QALY gained. The cost of the smoking cessation intervention was partly out-

5 632 Mani et al JOURNAL OF VASCULAR SURGERY September 2011 Table IV. One-way sensitivity analysis of Markov model per person Parameter a Assumption Cost difference, b Difference in LY Cost/LYG, Base-case Cost of intervention, Dominated ,657 Rate of long-term smoking cessation, % Intervention Dominated Nonintervention Dominated Smoking cessation rate post-aaa repair, % Yearly risk of i-aaa repair, % Smokers Dominated Former smokers Dominated Yearly risk of rupture, % Smokers Former smokers Rate of rupture undergoing AAA repair, % Rupture mortality Perioperative mortality i-aaa repair, % Former smokers Smokers Relative mortality Smokers Dominated Former smokers Cost of i-aaa repair, smokers, % Dominated Dominated Cost of ruptured AAA repair, 1.3 i-aaa i-aaa Dominated Cost of pre-op AAA surveillance, Cost of post-op follow-up, AAA, Abdominal aortic aneurysm; i-aaa, intact abdominal aortic aneurysm; LY, life year; LYG, life-year gained. a Each parameter is presented with the lower margin of the sensitivity analysis in the first row and the higher margin in the second row. b Compared with nonintervention. weighed by the reduced cost of AAA repair due to the lower AAA expansion and rupture rate after the smoking cessation intervention (Table III). Sensitivity analyses. The smoking cessation intervention was cost-effective in all scenarios of the one-way sensitivity analyses, and intervention was the dominant strategy in several scenarios (Table IV). The cost-effectiveness of the intervention reached the willingness-to-pay threshold value of 25,000/LYG only when assuming an intervention cost of 3250 or an effect of 1% difference in long-term smoking cessation between the intervention and nonintervention groups (Fig 2). A 4% reduction in the QALY value for smokers resulted in an increase of the incremental effect to QALYs per person and a cost/ effectiveness ratio of 573/QALY gained. In the two additional scenarios tested, the smoking cessation intervention was the dominant strategy when focusing on the AAA disease-related health gains and disregarding the effect of smoking cessation on long-term survival. Although the positive effect of the intervention was lower when disregarding the effect on long-term survival (0.039 LYG per person), the smoking cessation intervention resulted in an overall cost saving in this scenario due to the lower cost of AAA repair and follow-up (overall 7 lower cost after intervention vs nonintervention). When disregarding the AAAspecific effect of smoking cessation in scenario 2, the intervention was still cost-effective, at an incremental cost/ effectiveness ratio of 3674 per LYG (cost 315 and effect LYG per person) due to the beneficial effect of smoking cessation on long-term survival.

6 JOURNAL OF VASCULAR SURGERY Volume 54, Number 3 Mani et al 633 with 9% at 10 years of follow-up (absolute reduction from 30.4% to 27.7%) and 4% at 20 years (from 41.5% to 39.8%), as well as their risk of rupture, with 38% at 10 years (from 7.2% to 4.5%) and 34% at 20 years (from 10.0% to 6.6%). Fig 2. Incremental cost-effectiveness of a smoking cessation intervention based on (A) the cost of the intervention and (B) the effect of the intervention in the difference in smoking cessation rates after intervention compared with nonintervention. B, Simulation was performed when assuming a smoking cessation rate of 15% with no intervention and 16% to 50% with intervention. However, the result of the simulation was equal when assuming a lower or higher start rate (eg, 5% smoking cessation with no intervention and 6% to 40% with intervention, or 25% with no intervention and 26%-60% with intervention). LYG, Life-year gained. Effect of smoking cessation intervention on surgical volume and rupture. Fig 3, A and B describes the rate of elective AAA repair and rupture at 5, 10, 15, and 20 years after smoking cessation intervention as per base case assumptions of 33% smoking cessation in the intervention group and 15% smoking cessation in the nonintervention group. Fig 3, C and D describes the effect of full smoking cessation on risk of elective AAA repair and rupture when assuming 100% smoking cessation at intervention compared with no smoking cessation. Without intervention, 41.4% of patients underwent elective AAA repair after the aneurysm reached a size of 5.5 cm. In summary, the smoking cessation intervention had a small effect on the total surgical volume of elective AAA repair but resulted in a 6% reduction in rupture rate during a 20-year period, for an absolute reduction from 9.6% to 9.0%. Patients who stopped smoking at the intervention reduced their risk of elective AAA repair, DISCUSSION As screening programs for AAAs are being implemented in several countries, an increasing number of current smokers with a small AAA will be included in aneurysm surveillance programs. The current report underlines the importance of an adequate smoking cessation intervention in these patients to cost-effectively increase long-term survival and decrease the need for AAA repair. The association between AAAs and smoking is stronger than for any other cardiovascular disease 9 and makes smoking cessation in this population crucial. Despite important uncertainties in the Markov model used in the current study, the cost-effectiveness of the smoking cessation intervention in this setting is undisputable in the sensitivity analysis. Several studies have established the correlation between smoking and AAA expansion and rupture, 6,7,24 indicating significantly higher AAA expansion and rupture rate among smokers compared with former smokers. However, the exact effect of smoking cessation on the need for AAA repair and rupture has not been studied. We believe that the assumptions regarding the effect of smoking cessation on AAA expansion and rupture rate used in the current model are conservative. Even when assuming a much smaller effect of smoking cessation on the rate of i-aaa repair or rupture in the one-way sensitivity analysis, intervention was highly costeffective. Because it is difficult to appreciate how much of the long-term survival benefit of smoking cessation is due to the decreased risk of AAA-related mortality, there is a risk of double accounting of the effect of smoking cessation when improved long-term survival and decreased AAA mortality are both included in the model. Therefore, the two scenarios were tested where each of these effects was evaluated separately. Interestingly, the effect of smoking cessation on the need for i-aaa repair and rupture was per se cost-saving to the health care provider when disregarding the effect on long-term survival. The positive effect of smoking cessation on long-term survival actually resulted in an increase in cost in the current model, because longer survival was associated with a higher cost for follow-up. Evaluation of QALYs gained after intervention is affected by uncertainties in the QALY of patients with small AAAs as well as the change in QALY due to smoking cessation. Although gain in QALY is most probably lower than LYG in the current population, the smoking cessation intervention is still cost-effective. The smoking cessation intervention had a very small effect on the rate of elective AAA repair over time but had a larger effect on the rate of rupture. The effect of the smoking cessation intervention on elective repair and rupture was highly dependent of the success rate of the inter-

7 634 Mani et al JOURNAL OF VASCULAR SURGERY September 2011 Fig 3. Proportion of patients who have (A) undergone elective abdominal aortic aneurysm (AAA) repair or who have (B) experienced rupture after a smoking cessation intervention compared with nonintervention. Proportion of patients who have (C) undergone elective AAA repair or who have (D) experienced rupture after smoking cessation at intervention compared with continued smoking. vention in long-term smoking cessation. The effect was highest early on and diminished with time. This was because a larger proportion of the smokers in the Markov model underwent elective repair or experienced rupture early on, and a larger proportion of the nonsmokers remained at risk for events over time. In the base case, the increased rate of smoking cessation after intervention would only result in 0.6% of the patients avoiding rupture and 0.3% of the patients avoiding elective repair during a 20-year period. The statistical significance of this reduction cannot be evaluated with the current model, but the clinical relevance of this reduction would be highly marginal, and the effect on the burden of AAA repairs would be negligible. From the patient s perspective, however, the current study indicates that a decision to quit smoking can result in a 30% to 40% reduction in the risk of AAA rupture over a 10- to 20-year perspective. This information can be important when motivating patients with small AAAs to stop smoking. The effectiveness of a smoking cessation intervention is based on the additional rate of individuals who quit smoking compared with usual care. The spontaneous smoking cessation rate without further assistance is approximately 2% to 7%. 8,35 In the current study, a base-case smoking cessation rate of 15% was assumed in the nonintervention group, based on the spontaneous smoking cessation rate in patients in the preoperative setting and in patients with a coronary artery event. 12,14,36,37 The success rate increases when the intervention includes information on the health effects of smoking, motivational counseling, strategies for successful cessation, information on changes in behavior and exercise, prevention of relapses and different drugs, including nicotine replacement therapy (NRT), bupropion, and varenicline. 8 The absolute risk reduction of intervention compared with nonintervention is an 18% to 28% higher abstinence rate. 12,14,36,37 In the current report, an absolute difference of 18% in the smoking cessation rate was assumed between nonintervention and intervention in the base case. This was derived from the 1-year follow-up of a recent randomized trial of patients undergoing benign general and orthopedic operations. 14 In comparison, our group of screened patients with AAAs will have a new diagnosis of a life-threatening disease, they are an average of almost 10 years older, and consists of only men. These three factors are generally positive factors for success in smoking cessation. 13,38 There are some indications of possible psychologic stress and depression after the diagnosis of AAA or after AAA repair that could potentially negatively influence the effectiveness of a smoking cessation intervention. However, studies of smoking cessation among patients with a recent coronary event or AAA repair have found a significant quit rate in these groups. 12,26 Randomized trials have also shown that varenicline may be even more effective in achieving abstinence than NRT, 39 and therefore, a more effective and more expensive intervention was also tested in the sensitivity analyses. The base-case analysis was, however, derived from previous studies of smoking cessation interventions that did not include other forms of adjuvant pharmacotherapy, and thus analyzed the cost and effect of smoking cessation intervention with NRT only. Interestingly, the incremental cost/

8 JOURNAL OF VASCULAR SURGERY Volume 54, Number 3 Mani et al 635 effectiveness ratio for smoking cessation intervention was below the expected willingness-to-pay threshold, even when assuming a cost of up to 3250 per patient for the intervention, or when assuming only a 1% higher smoking cessation rate after intervention compared with nonintervention (regardless of the actual rates of smoking cessation in the groups; Fig 2). Currently, the cost of NRT is not covered by the health care provider within the Swedish health care system. If the cost of the NRT were borne by the patients, the intervention would be even cheaper to the health care provider. This study indicates that a smoking cessation intervention in patients with small AAAs could include the cost of NRT, or other adjuvant pharmacotherapy, and would remain cost-effective despite the higher cost of the intervention. Uncertainties in the long-term smoking cessation rate after intervention as well as the exact effect of smoking cessation on the AAA expansion rate, and the rate of elective AAA repair and rupture, would affect the result of the current analysis. Currently, these variables would have to be based on previous studies of similar populations, although medication with statins and agents to reduce blood pressure may have changed in recent years, potentially affecting expansion and rupture rate of AAAs. However, as shown in the one-way sensitivity analysis, the costeffectiveness of a smoking cessation intervention is very robust, even when varying these variables within a reasonable range. In the future, it would be desirable to monitor these parameters in the expanding population of patients with small AAAs identified at screening. The current analysis focuses on the effects of smoking cessation on AAA-related mortality and morbidity and disregards several of the other cost-and-effect benefits of smoking cessation. The analysis does not account for the reduction in postoperative morbidity that will follow from preoperative smoking cessation. Abstinence from smoking 4 to 8 weeks before surgery dramatically reduces the number of postoperative complications. 15,20 In addition, the model did not include the cost-saving effect of smoking cessation in the reduced need for general cardiovascular and pulmonary medication and care. Because the health care provider s perspective was chosen for the analysis, the actual reduction in the cost of cigarettes for the patients was not regarded in the model. These factors would all increase the cost-effectiveness of the smoking cessation intervention, and it is probable that a smoking cessation intervention in this patient group would even be cost-saving to the society and the patient when all the benefits of smoking cessation are included. The current analysis is also affected by the limitations of the one-way sensitivity analysis, which does not evaluate the effect of variation in several variables on cost-effectiveness. The current analysis assumed that approximately half of the patients who underwent intact AAA repair would be treated with an endovascular technique. Although this assumption was not part of the Markov model per se, the perioperative mortality data and cost data used in the model were from the Swedvasc Registry and a population-based study where the rate of EVAR was approximately 50%. 25,29 The increasing rate of EVAR could affect perioperative mortality rates after intact and ruptured AAA repair as well as the cost of AAA repair and follow-up. As shown in the sensitivity analysis in Table IV, the intervention strategy was cost-effective regardless of variations in perioperative mortality, rupture mortality, cost of AAA repair, and cost of follow-up after AAA repair. The costs and health effects of the smoking cessation intervention were only analyzed up to the age of 85 years in the studied cohort. An intentional cutoff at 85 years was set because few patients after this age are offered elective AAA repair. Monitoring the cohort until 100 years of age or death would have resulted in a somewhat larger health effect, which potentially would have been set off by a higher cost due to longer follow-up. In addition, a longer follow-up of the patients in the current Markov model, which assumed a stable annual rupture and i-aaa repair rate regardless of age, would be misleading because the model would overestimate the number of elective and rupture repairs performed in patients with very old age ( 85 years) compared with reality. A dynamic model with varying repair rates based on age could theoretically address this issue. However, this was not regarded as realistic because no data are currently available in the literature on how the AAA repair rate varies with age. This analysis supports the allocation of adequate resources to set up efficient smoking cessation initiatives in conjunction with AAA screening programs. It could also be argued that the cost of NRT, pharmacotherapy, and counseling should be fully subsidized for these patients due to the favorable cost-effectiveness of smoking cessation interventions in patients with small AAAs. CONCLUSIONS A smoking cessation intervention among patients with small AAAs was highly cost-effective in a Markov model due to the beneficial effect of smoking cessation on AAA expansion and rupture, even when disregarding the positive effects of smoking cessation on long-term survival. Evidence-based smoking cessation programs should thus be part of the health care intervention package offered to all AAA patients. AUTHOR CONTRIBUTIONS Conception and design: KM, AW, JL, DL Analysis and interpretation: KM, AW, JL, DL Data collection: KM, DL Writing the article: KM, DL Critical revision of the article: KM, AW, JL, DL Final approval of the article: KM, AW, JL, DL Statistical analysis: KM, JL Obtained funding: KM, AW Overall responsibility: KM REFERENCES 1. 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Screening for abdominal aortic aneurysm among patients referred to the vascular laboratory is cost-effective. Eur J Vasc Endovasc Surg 2010;39: Submitted Dec 5, 2010; accepted Feb 20, 2011.