The aim of this analysis was to assess the effect of body mass index (BMI) on 1-year outcomes in patients enrolled in a contemporary percutaneous coronary intervention trial comparing a sirolimus-eluting stent with a durable polymer to a biolimus-eluting stent with a biodegradable polymer. A total of 1,707 patients who underwent percutaneous coronary intervention were randomized to treatment with either biolimus-eluting stents (n = 857) or sirolimus-eluting stents (n = 850). Patients were assigned to 1 of 3 groups according to BMI: normal (<25 kg/m 2 ), overweight (25 to 30 kg/m 2 ), or obese (>30 kg/m 2 ). At 1 year, the incidence of the composite of cardiac death, myocardial infarction, and clinically justified target vessel revascularization was assessed. In addition, rates of clinically justified target lesion revascularization and stent thrombosis were assessed. Cox proportional-hazards analysis, adjusted for clinical differences, was used to develop models for 1-year mortality. Forty-five percent of the patients (n = 770) were overweight, 26% (n = 434) were obese, and 29% (n = 497) had normal BMIs. At 1-year follow-up, the cumulative rate of cardiac death, myocardial infarction, and clinically justified target vessel revascularization was significantly higher in the obese group (8.7% in normal-weight, 11.3% in overweight, and 14.5% in obese patients, p = 0.01). BMI (hazard ratio 1.47, 95% confidence interval 1.02 to 2.14, p = 0.04) was an independent predictor of stent thrombosis. Stent type had no impact on the composite of cardiac death, myocardial infarction, and clinically justified target vessel revascularization at 1 year in the 3 BMI groups (hazard ratio 1.08, 95% confidence interval 0.63 to 1.83, p = 0.73). In conclusion, BMI was an independent predictor of major adverse cardiac events at 1-year clinical follow-up. The higher incidence of stent thrombosis in the obese group may suggest the need for a weight-adjusted dose of clopidogrel.
The purpose of this study was to assess the effect of body mass index (BMI) on the clinical outcomes of patients who participated in the Limus Eluted From a Durable vs Erodable Stent Coating (LEADERS) trial, which randomized patients to percutaneous coronary intervention (PCI) with either a sirolimus-eluting stent (with a durable polymer) or a biolimus-eluting stent (with a biodegradable polymer).
Methods
The LEADERS trial was a multicenter European trial that enrolled a total of 1,707 patients, who were randomized to PCI with a biolimus-eluting stent (n = 857) with a biodegradable polymer or a sirolimus-eluting stent (n = 850) with a durable polymer from November 27, 2006, to May 18, 2007. Details of the study have been described previously.
Briefly, selection criteria were broad, reflecting routine clinical practice. Patients with chronic stable coronary artery disease or acute coronary syndromes, including ST elevation myocardial infarction (MI), were eligible for enrollment if they had ≥1 lesion with ≥50% diameter stenosis and reference vessel diameters of 2.25 to 3.5 mm. There were no limits to the numbers of treated lesions or vessels or to lesion length and no exclusion of patients on the basis of co-morbidities or age. Specific exclusion criteria included known allergy to acetylsalicylic acid, clopidogrel, heparin, stainless steel, sirolimus, biolimus, or contrast material; planned surgery within 6 months of PCI, unless dual-antiplatelet therapy could be maintained throughout the perisurgical period; pregnancy; participation in another trial before reaching the primary end point; and inability to provide informed consent. The study complied with the Declaration of Helsinki and was approved by all institutional ethics committees. All patients provided written informed consent for participation in this trial. Before or at the time of the procedure, patients were given ≥75 mg of acetylsalicylic acid, a 300- to 600-mg loading dose of clopidogrel, and unfractionated heparin in a dose of ≥5,000 IUs, or 70 to 100 IU/kg. The use of glycoprotein IIb/IIIa antagonists was left to the discretion of the operator. All patients were discharged on acetylsalicylic acid ≥75 mg/day for life and clopidogrel 75 mg/day for ≥12 months. In the case of intercurrent revascularization procedures needing stent implantation, treating cardiologists were encouraged to use study stents.
The primary end point of this post hoc analysis was the composite of cardiac death, MI, and clinically justified target vessel revascularization (TVR) at 12 months. The definition of cardiac death included any death due to an immediate cardiac cause (e.g., MI, low-output heart failure, fatal arrhythmia); procedure-related deaths, including those related to concomitant treatment; unwitnessed death; and death of unknown cause. MI was defined according to the electrocardiographic criteria of the Minnesota code manual or by a measured level of creatinine kinase 2 times the upper limit of normal, with a positive concentration of either creatine kinase-MB or troponin I or troponin T. TVR was defined as any repeat percutaneous intervention or surgical bypass of any segment within the entire major coronary vessel proximal and distal to a target lesion, including upstream and downstream branches and the target lesion itself. Target lesion revascularization was defined as a repeat revascularization due to a stenosis within the stent or within a 5-mm border proximal or distal to the stent. Stent thrombosis was defined according to the Academic Research Consortium definitions.
A revascularization was regarded as clinically justified if the stenosis of the treated lesion was ≥50% of the luminal diameter on the basis of quantitative coronary angiography in the presence of ischemic signs or symptoms or if the diameter stenosis was ≥70% irrespective of the presence or absence of ischemic signs or symptoms.
The National Heart, Lung, and Blood Institute and the World Health Organization have introduced a weight classification for BMI that is calculated by dividing a patient’s weight in kilograms by that patient’s height in square meters. According to this classification, patients with BMIs of 18.5 to 24.9 kg/m 2 were considered normal, those with BMIs of 25 to 30 kg/m 2 were considered overweight, and those with BMIs >30 kg/m 2 were considered obese. Patients enrolled in the sirolimus- and biolimus-eluting stent arms of the LEADERS trial were stratified into 3 subgroups according to their BMIs: normal (BMI <25 kg/m 2 ), overweight (BMI 25 to 30 kg/m 2 ), and obese (BMI >30 kg/m 2 ).
Continuous variables are expressed as mean ± SD and categorical variables as absolute and relative values. Comparisons among groups were performed by analysis of variance for independent samples; for variables measured repeatedly within a patient, the covariance structure was taken into account by the use of PROC MIXED in SAS (SAS Institute Inc., Cary, North Carolina). The Cochran-Armitage test for trend was used for comparisons of categorical data. For variables measured repeatedly within a patient, the covariance structure was taken into account by the use of PROC GENMOD.
The Kaplan-Meier method was used to estimate the event-free survival rate, and the differences among groups were assessed using the log-rank test. Cox proportional-hazards analysis, adjusted for clinical differences, was used to develop models for 30-day and 1-year mortality. The following variables were included in the models: BMI, diabetes, multivessel disease, stent type, age, hypertension, and dyslipidemia. A collinearity test on the explanatory variables included in the models was performed. Statistical analysis was performed using SAS by a dedicated statistician. All p values are 2 sided, and p <0.05 was considered statistically significant.
Results
Data on 1,701 patients who underwent PCI with biolimus-eluting stents (n = 854) and sirolimus-eluting stents (n = 847) were available for complete analysis. Forty-five percent of the patients (n = 770) were overweight, 26% (n = 434) were obese, and 29% (n = 497) had normal BMIs. Baseline clinical characteristics of all patients are listed in Table 1 . Of note, there was a significantly higher incidence of diabetes, hypertension, and dyslipidemia in the overweight and obese groups compared to the normal BMI group. The collinearity analysis showed no significant interrelations among the clinical variables (condition index <30).
| Variable | BMI (kg/m 2 ) | p Value | ||
|---|---|---|---|---|
| <25 (n = 497) | 25–30 (n = 770) | >30 (n = 434) | ||
| Women | 142 (29%) | 170 (22%) | 117 (27%) | 0.49 |
| Mean BMI (kg/m 2 ) | 23.0 ± 1.7 | 27.4 ± 1.4 | 33.1 ± 3.0 | NA |
| Age (years) | 65.9 ± 10.9 | 64.6 ± 10.5 | 63.1 ± 10.8 | <0.05 |
| Acute coronary syndromes | 288 (58%) | 412 (53%) | 240 (55%) | 0.38 |
| Stable angina pectoris | 157 (32%) | 274 (36%) | 156 (36%) | 0.15 |
| Previous PCI | 163 (33%) | 298 (39%) | 163 (38%) | 0.12 |
| Previous MI | 153 (31%) | 265 (34%) | 135 (31%) | 0.86 |
| Hypertension (≥165/95 mm Hg) | 324 (65%) | 565 (73%) | 357 (82%) | <0.05 |
| Diabetes mellitus | 73 (15%) | 181 (23%) | 160 (37%) | <0.05 |
| Peripheral vascular disease | 45 (9%) | 54 (7%) | 34 (8%) | 0.46 |
| Hypercholesterolemia (>190 mg/dl) | 299 (60%) | 525 (68%) | 316 (73%) | <0.05 |
| Current smokers | 134 (27%) | 162 (21%) | 122 (28%) | 0.79 |
Angiographic baseline and periprocedural characteristics are listed in Table 2 . The rate of total occlusions was significantly higher in the obese patients. The Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score was not significantly different among the 3 BMI groups.
| Variable | BMI (kg/m 2 ) | p Value | ||
|---|---|---|---|---|
| <25 (n = 497) | 25–30 (n = 770) | >30 (n = 434) | ||
| Left anterior descending | 241 (48%) | 382 (50%) | 198 (46%) | 0.41 |
| Left circumflex | 156 (31%) | 253 (33%) | 151 (35%) | 0.27 |
| Right | 195 (39%) | 296 (38%) | 163 (38%) | 0.60 |
| Left main | 7 (1%) | 21 (3%) | 6 (1%) | 0.95 |
| Coronary total occlusion | 89 (18%) | 147 (19%) | 107 (25%) | <0.05 |
| In-stent restenosis | 8 (8%) | 19 (13%) | 6 (7.%) | 0.95 |
| Lesion length (mm) | 14.7 (13.8–15.6) | 14.5 (13.8–15.2) | 16.0 (15.0–16.9) | 0.06 |
| Minimal luminal diameter (mm) | 0.94 (0.91–0.98) | 0.95 (0.92–0.98) | 0.87 (0.82–0.91) | <0.05 |
| Stenosis (%) | 63 (62–65) | 63 (62–64) | 67 (65–69) | <0.05 |
| SYNTAX score | 13.6 ± 8.9 | 13.4 ± 8.4 | 12.8 ± 8.9 | 0.18 |
| No. of treated lesions | 1.44 ± 0.71 | 1.49 ± 0.73 | 1.39 ± 0.67 | 0.41 |
| No. of stents | 1.93 ± 1.21 | 1.91 ± 1.17 | 1.88 ± 1.21 | 0.53 |
At 1-month clinical follow-up, BMI was an independent predictor of clinically justified percutaneous TVR (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09 to 3.09, p = 0.04) and target lesion revascularization (HR 1.75, 95% CI 1.03 to 2.96, p = 0.04). The cumulative incidence of cardiac death, MI, and clinically justified TVR at 1 month was higher in obese patients (4.6% in normal-weight patients, 5.2% in overweight patients, and 7.8% in obese patients, p = 0.04).
One-year Kaplan-Meier survival curves are shown in Figure 1 . The 1-year cumulative rate of cardiac death, MI, and clinically justified TVR was significantly higher in the obese group (8.7% in normal-weight patients, 11.3% in overweight patients, and 14.5% in obese patients, p = 0.01). The 1-year cumulative rate of MI was significantly higher in the obese group (4.2% in normal-weight patients, 4.5% in overweight patients, 7.6% in obese patients, p = 0.04) ( Table 3 ).
| Variable | BMI (kg/m 2 ) | HR | 95% CI | p Value | ||
|---|---|---|---|---|---|---|
| <25 (n = 497) | 25–30 (n = 770) | >30 (n = 434) | ||||
| Death | 15 (3%) | 22 (2.9%) | 18 (4.1%) | 1.23 | 0.85–1.78 | 0.27 |
| Cardiac death | 11 (2.2%) | 14 (1.8%) | 16 (3.7%) | 1.4 | 0.91–2.16 | 0.13 |
| Myocardial infarction | 21 (4.2%) | 35 (4.5% | 33 (7.6%) | 1.36 | 1.01–1.82 | <0.05 |
| Q-wave myocardial infarction | 4 (0.8%) | 3 (0.4%) | 4 (0.9%) | 1.25 | 0.55–2.84 | 0.6 |
| Non-Q-wave myocardial infarction | 18 (3.6%) | 32 (4.2%) | 29 (6.7%) | 1.34 | 0.98–1.83 | 0.07 |
| All revascularizations | 33 (6.6%) | 77 (9.9%) | 43 (9.9%) | 1.25 | 0.98–1.59 | 0.07 |
| Percutaneous | 25 (5%) | 70 (9.1%) | 40 (9.2%) | 1.27 | 1.0–1.62 | <0.05 |
| Surgical | 9 (1.8%) | 11 (1.4%) | 6 (1.4%) | 0.71 | 0.42–1.22 | 0.22 |
| All target vessel revascularization | 32 (6.4%) | 76 (9.9%) | 43 (9.9%) | 1.17 | 0.93–1.46 | 0.18 |
| Percutaneous target vessel revascularization | 25 (5%) | 70 (9.1%) | 40 (9.2%) | 1.27 | 1.0–1.62 | <0.05 |
| Surgical target vessel revascularization | 8 (1.6%) | 10 (1.3%) | 6 (1.4%) | 0.77 | 0.44–1.35 | 0.36 |
| Clinically justified target vessel revascularization | 21 (4.2%) | 56 (7.3%) | 33 (7.6%) | 1.24 | 0.95–1.62 | 0.11 |
| Clinically justified percutaneous target vessel revascularization | 18 (3.6%) | 54 (7%) | 31 (7.1%) | 1.3 | 0.99–1.71 | 0.06 |
| Clinically justified surgical target vessel revascularization | 4 (0.8%) | 4 (0.5%) | 5 (1.2%) | 0.97 | 0.45–2.08 | 0.93 |
| All target lesion revascularization | 22 (4.4%) | 62 (8.1%) | 35 (8.1%) | 1.24 | 0.96–1.60 | 0.10 |
| Percutaneous target lesion revascularization | 19 (3.8%) | 59 (7.7%) | 33 (7.6%) | 1.29 | 0.99–1.68 | 0.06 |
| Surgical target lesion revascularization | 4 (0.8%) | 7 (0.9%) | 5 (1.2%) | 0.97 | 0.49–1.94 | 0.94 |
| Clinically justified target lesion revascularization | 15 (3%) | 50 (6.5%) | 28 (6.5%) | 1.3 | 0.97–1.73 | 0.08 |
| Clinically justified percutaneous target lesion revascularization | 14 (2.8%) | 48 (6.2%) | 26 (6%) | 1.32 | 0.98–1.77 | 0.07 |
| Clinically justified surgical target lesion revascularization | 2 (0.4%) | 3 (0.4%) | 5 (1.2%) | 1.3 | 0.52–3.24 | 0.57 |
| Composite of cardiac death, myocardial infarction, and clinically justified target vessel revascularization | 43 (8.7%) | 87 (11.3%) | 63 (14.5%) | 1.28 | 1.05–1.57 | <0.05 |
| Composite of cardiac death, myocardial infarction, and clinically justified target lesion revascularization | 37 (7.4%) | 81 (10.5%) | 59 (13.6%) | 1.33 | 1.08–1.63 | <0.05 |
| Composite of death, myocardial infarction, and clinically justified target vessel revascularization | 47 (9.5%) | 92 (11.9%) | 65 (15%) | 1.25 | 1.03–1.52 | <0.05 |
| Composite of death and myocardial infarction | 31 (6.2%) | 51 (6.6%) | 47 (10.8%) | 1.37 | 1.07–1.75 | <0.05 |
| Composite of cardiac death and myocardial infarction | 27 (5.4%) | 45 (5.8%) | 45 (10.4%) | 1.44 | 1.11–1.87 | <0.05 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
