Introduction
============

Opium abuse has been a major problem in many countries, and there is still a controversy about the effects of opium on coronary artery disease (CAD).  For all the authors espousing the theory that opium usage is beneficial in patients with such diseases as CAD, hypertension, and diabetes mellitus,^[@B1]^ there are those who regard it as a risk factor for coronary heart disease. 

A literature review yields a number of studies on the relationship between opium and coronary artery disease.^[@B2]--[@B10]^ Nevertheless, to our knowledge, there has been no study on the relationship between opium consumption and percutaneous coronary intervention (PCI) outcome.  Given the current paucity of data and persistent controversy, we sought to compare 12 months' major adverse cardiac events (MACE) between two groups of patients undergoing PCI: those with and without opium consumption. 

Methods
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From an initial sample of 2425 patients, 713 females were excluded due to the low prevalence of opium consumption (2.9%) among them.  In addition, the patients who underwent plain old balloon angioplasty (POBA) or had primary procedure and those with incomplete data were excluded.  Totally, 880 patients were excluded from the study ([Figure 1](#F1){ref-type="fig"}), and there remained 1545 male patients who underwent angioplasty in our center between 21^st^ June 2009 and 20th June 2010 and were eligible to be enrolled in this cohort study.  Among these 1545 patients, 350 (22.7%) were addicted to opium. 

![ Study profile, describing the patients' recruitment and allocation steps POBA, Plain old balloon angioplasty](jthc-9-115f1){#F1}

Opium consumption was defined as self-report of opium use during the previous month. 

The outcomes were defined as 12 months' MACE \[cardiac death, non-fatal myocardial infarction, target vessel and target lesion revascularization (TVR and TLR), in-hospital myocardial infarction, coronary artery bypass graft surgery (CABG)\], and 12 months' all-cause mortality.  All deaths were considered cardiac unless documented otherwise. 

All the patients were visited routinely at the first, sixth, and twelfth months after the procedure.  Two trained research nurses contacted the patients who failed to refer to the clinic by telephone. 

The outcomes were defined as 12 months' MACE.  TVR was defined as all PCIs done on the same vessel or CABG.  TLR was defined as repeated revascularization of the target lesion due to ischemia only by PCI. 

The continuous data are described as mean ± standard deviation (SD) and were compared between the patients with and without opium consumption via the Student test or the Mann-Whitney U test.  In [Figure 2](#F2){ref-type="fig"}, the categorical variables are presented through frequencies (percentages) and are compared between the two groups using the chi-squared or the Fischer exact test.  The Kaplan-Meier method was applied to estimate the survivor curves, and the log-rank test was employed to compare the two groups. 

![ The Kaplan Meier survival curves of major adverse cardiac events in the two groups](jthc-9-115f2){#F2}

The effect of opium consumption on MACE was analyzed after adjusting the effect of detected possible confounders, including ejection fraction, diabetes mellitus, and history of myocardial infarction using the Cox proportional hazards model.  For the statistical analyses, the statistical software SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL) was used, and a p value ≤ 0.05 was considered statistically significant. 

Results
=======

The patients were categorized into two groups according to opium consumption history.  One group included 350 (22.7%) patients who consumed opium and the second group consisted of 1195 (77.3%) patients who were not opium users. 

The baseline, clinical, and procedural characteristics of the two study groups are summarized in [Table 1](#T1){ref-type="table"}.  The proportion of the smokers (current and former) was greater in the group with addiction (p value \< 0.001), who was also significantly younger than the group without addiction (55.7 ± 9.2 years vs. 58.4 ± 10.8 years; p value ≤ 0.001).  The two groups had no statistically significant differences in terms of other risk factors, lesions, and procedural characteristics, including hypertension, hyperlipidemia, diabetes mellitus, stent type, and ejection fraction, with the exception of the proportion of the left anterior descending artery as the target vessel and the frequency of diabetes mellitus, both of which were higher in the group without addiction\[723 (60.5%) vs. 175 (50%); p value ≤ 0.001 and 297 (24.9%) vs. 69 (19.7%); p value = 0.047, respectively\]. 

###### 

Characteristics of the patients

                                 Opium consumption   P value           
  ------------------------------ ------------------- ----------------- ----------
  Risk Factors                                                         
    FH                           54/347 (15.6)       184/1189 (15.5)   0.969
    HLP                          195 (55.7)          681 (57)          0.672
    Cigarette smoking                                                  \< 0.001
      No                         60 (17.1)           628 (52.6)        
      Former                     74 (21.1)           224 (18.7)        
      Current                    216 (61.7)          343 (28.7)        
    HTN                          134 (38.3)          518 (43.3)        0.092
    DM                           69 (19.7)           297 (24.9)        0.047
  History of MI                  204/348 (58.6)      656/1187 (55.3)   0.267
  History of PCI                 30 (8.6)            118 (9.9)         0.466
  History of CABG                21 (6)              73 (6.1)          0.94
  Stent Type                                                           0.152
    BMS                          131 (37.4)          411 (34.4)        
    DES                          179 (51.1)          676 (56.6)        
    Mixed                        40 (11.4)           108 (9)           
  Procedural numbers                                                   0.347
    1                            264 (75.4)          868 (72.6)        
    2                            66 (18.9)           270 (22.6)        
    3                            16 (4.6)            50 (4.2)          
    4                            4 (1.1)             7 (0.6)           
  Age (y)                        55.7 (9.2)          58.4 (10.8)       \< 0.001
  BMI (Kg/m^2^)                  26.8 (4.1)          27.2 (4)          0.095
  Abdominal circumference (cm)   98.7 (10.4)         99.9 (9.8)        0.052
  EF (%)                         50.1 (9.4)          49.5 (9.6)        0.269
  RVD mean (mm)                  3.33 (0.49)         3.31 (0.48)       0.534
  Lesion length (mm)             21.12 (9.11)        20.88 (9.1)       0.674
  Type C                         207 (59.1)          689 (57.7)        0.620
  Ostial                         36 (10.3)           134 (11.2)        0.626
  LAD                            175 (50)            723 (60.5)        \< 0.001
  SVG                            9 (2.6)             23 (1.9)          0.455
  Stent diameter (mm)            3.23 (0.45)         3.21 (0.44)       0.609
  Stent length (mm)              22.7 (7.23)         22.59 (6.96)      0.794

Data are presented as n (%) or proportion (%)

FH, Family history; HLP, Hyperlipidemia; MI, Myocardial infarction; HTN, Hypertension; DM, Diabetes mellitus; PCI, Percutaneous coronary intervention; CABG, Coronary artery bypass graft; BMI, Body mass index; EF, Ejection fraction; RVD, Reference vessel diameter; LAD, Left anterior descending; SVG, Saphenous vein graft

Overall, 64 (4.1%) patients had MACE during the 12 months' follow-up.  The results demonstrated that opium consumption had no statistically significant effect on total MACE over the 12-month period.  The unadjusted hazard of one year's MACE in the group with addiction versus the group without addiction was 0.704 (95%CI: 0.367 -- 1.347; p value = 0.289).  After adjustment for the detected potential confounders, i.e. ejection fraction (EF), diabetes mellitus (DM), and history of non-fatal myocardial infarction, this measure was changed to 0.715 (95%CI: 0.372 -- 1.371; p value = 0.312).  The different components of MACE, including TVR, TLR, CABG, mortality, and non-fatal myocardial infarction, were not statistically different between the two groups as well ([Table 2](#T2){ref-type="table"}). 

###### 

Comparison of clinical 12 months' outcomes between the opium consumption and control groups

                        Opium consumption   Log-rank test p value   
  --------------------- ------------------- ----------------------- -------
  MACE                  11 (3.1)            53 (4.4)                0.286
  TVR                   9 (2.6)             27 (2.3)                0.75
  TLR                   3 (0.9)             11 (0.9)                0.909
  CABG                  5 (1.4)             11 (0.9)                0.421
  Non-fatal MI          3 (0.9)             14 (1.2)                0.617
  All-cause mortality   2 (0.6)             20 (1.7)                0.144
  Cardiac death         2 (0.6)             14 (1.2)                0.337

MACE, Major adverse cardiac event; TVR, Target vessel revascularization; TLR, Target lesion revascularization; CABG, Coronary artery bypass graft; MI, Myocardial infarction

Discussion
==========

The results from the present study revealed that the preoperative use of opium in patients undergoing PCI was not correlated with a significant difference in the 12 months' outcome. [ Table 1](#T1){ref-type="table"} depicts the clinical, lesion, and procedural characteristics of the two study groups. 

Given the established effects of cigarette smoking on CAD, we did not exclude cigarette smokers from the final analysis.  What is more, other studies have reported the difficulty of focusing solely on non-cigarette smoking opium consumers.^[@B2],\ [@B3],\ [@B5]^ We, therefore, adjusted cigarette smoking and other possible confounders in the present study. 

A retrospective study by Sadeghianet al.^[@B4]^ on 2405 patients and a case-control study by Masoomiet al.^[@B11]^ concluded that opium consumption was an independent risk factor for CAD.  One study demonstrated a relationship between opium consumption and outcome of myocardial infarction.^[@B12]^ Mohammadi and colleagues^[@B13]^ posited the atherogenic effects of opium in animal models.  The results of one study showed that opium increased the risk of CAD in opium users by raising the serum levels of lipids.^[@B14]^ In contrast, Fatemi et al.^[@B15]^ showed that serum lipids were decreased by opium use. 

In our study, there was no significant difference in the rate of hyperlipidemia between the two groups.  This finding is echoed by another study conducted in our hospital insofar as it reported no significant effect of opium on lipid levels.^[@B6]^ Shirani et al.^[@B6]^ studied 1339 patients candidated for CABG in their retrospective investigation and reported that opium was not cardioprotective.  Another study carried out in 2005 found no relationship between opium and myocardial infarction.^[@B16]^ Be that as it may, there are other studies that do not chime in with our results.  Prominent among this group of studies is the one by Marmer et al. ,^[@B15]^ (2004) who studied the effect of opium among autopsy samples and showed a decreased CAD rate and its consequences.  In the present study, the rate of previous myocardial infarction was not different between the two groups. 

The similarity in terms of patient characteristics between the two groups in our study may support the notion that opium consumption in patients undergoing PCI most probably does not influence cardiac risk factors and coronary angioplasty outcome. 

The present study was a historical cohort analysis of data in a single referral center.  Moreover, data collected on opium usage were self-reported and information on the duration, dosage, and route of opium consumption was not available.  Furthermore, the impurity of opium in use, which is an issue of significance, was not taken into consideration in the current study. 

Conclusion
==========

Pre-procedural opium consumption in patients undergoing PCI was not associated with its 12 months' outcome.  Our results showed that opium consumption did not correlate with MACE.  Our study may generalize the invalidity of the popular belief regarding the potential beneficial effects of opium usage on CAD.  Well-designed randomized clinical trials will help us to assess more accurately how opium use affects the outcomes of PCI. 

Although the withdrawal effects in post-cardiac procedure CAD patients have yet to be investigated, it may be advisable for this group of patients to postpone quitting opium to a later time. 

The authors are indebted to Dr. Sepideh Sarookhani and Miss Mahboobeh Rahimi for their sincere collaboration.  This study was approved and was supported by Tehran Heart Center, Tehran University of Medical Sciences.