Background
Methods
Literature search and study selection
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The publication should provide a clear definition of smoking status into current, former and never-smokers, including baseline characteristics of each group with age as a minimum. In case former smokers were not defined separately, a minimum requisite was that they had to be defined and characterised either as smokers, non-smokers or per definition were excluded from the analysis.
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Both crude and adjusted total mortality rates should be presented. Effect estimates should be provided, and "age" was a minimum requirement as a covariate.
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The length of follow-up should be reported and include at least hospital mortality. Studies reporting only post-discharge mortality were excluded.
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Only English-language original articles were included.
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The study should include > 100 smokers and > 100 non-smokers.
Results
Study categories and adjusted mortality rates
Study | Paradox? | Time symptoms to inclusion | Publ. | Enroll. | Index Event | n | Current (C) n (age) | Former (F) n (age) | Never (N) n (age) | Follow -up | Total mortality | Adjusted mortality rates with 95% confidence interval | ||
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C | F | N | ||||||||||||
Randomised clinical trials in STEMI patients (thrombolytic treatment)
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GUSTO-1 [13] | Yes | 3.2 ± 1.65 h | 1995 | 90 to 93 | STEMI | 40,599 | 17,507 (55) | 11,117 (64) | 11,975 (66) | 30d | 4.0% | 6.7% | 10.3% | OR 1.25 (1.11 to 1.39) N vs. C |
Yes | 3.0 ± 1.6 h | 1993 | 88 to 89 | STEMI | 8,259 | 3,649 (58) | 2,244 (64) | 2,366 (67) | 6 m | 7.7% | 12.1% | 17.6% | OR 1.35 (1.12 to 1.61) N vs. C+F | |
GISSI-2 [23] | No | < 3 h in 70% | 1998 | 88 to 89 | STEMI | 9,694 | 5,151 (57) | 1,932 (64) | 2,611 (68) | In-hosp. | 4.7% | 7.6% | 13.8% | OR 0.80 (0.60 to 1.07) C vs. N OR 0.97 (0.70 to 1.35) F vs. N |
Randomised clinical trials in STEMI patients (invasive treatment)
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CADILLAC [27] | No | < 12 h | 2004 | 97 to 99 | STEMI | 2,082 | 898 (53) | 546 (64) | 638 (65) | 1 y | 2.9% | 3.7% | 6.6% | HR 0.96 (0.52 to 1.76) C vs. N |
Randomised clinical trials in patients with NSTE-ACS (invasive treatment)
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No | < 24 h | 2008 | 01 to 02 | NSTE -ACS | 9,971 | 2,404 (61) | 3,491 (69) | 4,076 (70) | 1 y | 6.5% | 9.1% | 6.7% | HR 1.77 (1.42 to 2.21) C vs. N | |
Multi-centre post-AMI randomised trials
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TRACE [21] | No | 2 to 6 d | 1999 | 90 to 92 | AMI | 6,485 | 3,341 (64) | 1,420 (71) | 1,724 (74) | 3 y | 26 to 27% | 38 to 39% | 42 to 43% | HR 1.04 (0.93 to 1.15) C vs. N |
OPTIMAAL [20] | No | < 10 d | 2004 | 98 to 99 | AMI | 5,475 | 1,832 (62) | 1,867 (69) | 1,776 (71) | 2.7 y | 16.3% | Incl. in C | 19.3% | HR 1.08 (0.93 to 1.25) C+F vs. N |
Single-centre observational studies of patients with AMI
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Mølstad [25] | Yes | NA | 1991 | 82 to 84 | AMI | 484 | 184 (61) | Incl. in N | 456 (70) | 3 m | 11 to 13% | Incl. in N | 32 to 34% | HR 0.62 (0.36 to 1.04) C vs. N+F HR 0.55 (0.33 to 0.93) C vs. N+F |
No | NA | 2004 | 01 to 02 | ACS | 901 | 369 (58) | Incl. in C | 532 (69) | In-hosp. | 2.6% | Incl. in F | 6.6% | OR 0.96 (0.38 to 2.41) C+F vs. N | |
No | NA | 2009 | 04 to 07 | ACS | 1,228 | 450 (58) | Incl. in C | 778 (68) | 6 m | 9.3% | Incl. in C | 13.1% | OR 1.25 (0.61 to 2.54) C+F vs. N | |
No | NA | 2010 | 03 to 07 | NSTEMI | 381 | 103 (63) | Incl. in N | 278 (80) | 1y | 22% | Incl. in N | 27% | HR 2.61 (1.43 to 4.79) C vs. N+F | |
Registries
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No | NA | 1996 | 94 | AMI | 999 | 367 (57) | Incl. in N | 632 (67) | 6 m | 7.9% | Incl. in N | 21.5% | HR 0.84 (0.54 to 1.30) C vs. N+F | |
Andrikopoulos et al. [11] | No | < 24 h | 2001 | 93 to 94 | AMI | 5507 | 3,853 (59) | Excluded | 1,654 (70) | In-hosp. | 7.4% | NA | 14.5% | RR 1.12 (0.86 to 1.44) C vs. N |
NRMI 2 [18] | Yes | NA | 2002 | 94 to 97 | AMI | 297,458 | 72,585 (58) | Incl. in N | 224,871 (72) | In-hosp. | 8.0% | Incl. in N | 16.4% | OR 0.86 (0.83 to 0.90) C vs. N+F |
ARIAM [26] | Yes | < 24 h criterion | 2004 | 95 to 01 | AMI | 17,761 | 5,796 (57) | 3,494 (67) | 8,471 (70) | ICU/CCU | 5.0% | 9.3% | 13.3% | OR 0.77 (0.66 to 0.91) C vs. N |
UAP | 7,795 | 1,721 | 1,950 | 4,124 | ICU/CCU | 0.7% | 1.0% | 1.5% | OR 0.81 (0.48 to 1.36) C vs. N | |||||
IBERICA [15] | Yes | < 12 h in 82% | 2007 | 97 to 98 | AMI | 7,796 | 3,057 (56) | 1,730 | 2,839 (65) | 28 d | 8.9% | 16.9% | 20.1% | OR 0.57 (0.42 to 0.78) C vs. N |
GRACE [19] | No | NA | 2005 | 99 to 02 | ACS | 19,325 | 5,276 (57) | 5,691 (67) | 8,358 (71) | In-hosp. | 3.3% | 4.5% | 6.9% | OR 1.01 (0.80 to 1.27) C vs. N |
Randomised controlled trials (RCT) in patients treated with fibrinolysis for STEMI
RCT in STEMI treated with percutaneous coronary intervention (PCI)
RCT of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) subjected to invasive management
Multi-centre post-AMI studies from RCTs
Single centre observational studies of patients with AMI
Registries
Confounding factors included in the adjusted analyses
Study | Baseline and clinical characteristics | Reperfusion and medication |
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Studies supporting the existence of a smoker's paradox | ||
Mølstad [25] | Age, atrial fibrillation, s-creatinine, s-potassium | None |
Barbash et al. [12] | Age, sex, MI site, diabetes, previous MI, antecedent angina, hypertension, hypotension at entry, Killip class, body mass index, hypercholesterolemia, family history of CAD | Time to lysis |
GUSTO-1 [13] | Age, sex, systolic blood pressure, Killip class, heart rate, MI site, previous MI, previous CABG, height, diabetes, hypertension, cerebrovascular disease | Time to lysis, type of thrombolytic treatment |
NRMI 2 [18] | Age, sex, MI site, previous MI, previous CABG, weight, diabetes, hypertension, hypercholesterolemia, family history of CAD, black race, other race, previous heart failure, previous PTCA, previous stroke, Q vs. non-Q, | Any reperfusion therapy, aspirin first 24 hours, any heparin, intravenous nitroglycerine, beta-blocker, i.v. lidocaine, i.v. magnesium, ACE-inhibitor, calcium channel blocker, other anti-thrombin, other antiplatelet |
ARIAM [26] | Age, Killip class, MI site, diabetes, Q-wave, non-Q-wave with ST elevation, non-Q-wave with ST decent | None |
IBERICA [15] | Age, sex, MI site, previous MI, diabetes, hypertension, previous angina, spline function for symptoms monitoring, cardiogenic shock or acute pulmonary oedema, severe arrhythmias | Thrombolysis, primary angioplasty, aspirin, beta-blocker |
Studies not supporting the existence of a smoker's paradox
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Gottlieb et al. [17] | Age, sex, systolic blood pressure < 100 mmHg, heart rate > 100/min, Killip class ≥ 2, anterior MI, diabetes, hypertension, previous MI, previous angina, Q-wave MI, family history of CAD, CHF during index hospitalization, atrial fibrillation during hospitalization | Thrombolytic therapy, invasive coronary procedures |
GISSI-2 [23] | Age, sex, Killip class, MI site, hypertension, diabetes, previous angina, body mass index, number of leads with ST elevation | Time to lysis |
TRACE [21] | Age, sex, body mass index, COPD, previous angina, previous MI, hypertension, family history of CAD, CHF, wall motion index, Q wave anterior MI | Thrombolytic treatment |
Andrikopoulos et al. [11] | Age, sex, diabetes, hypertension, previous MI | Thrombolytic treatment |
OPTIMAAL [20] | Age, sex, COPD, cerebrovascular accidents, diabetes, hypercholesterolemia, hypertension, previous MI, Killip Class, Q wave MI, MI site, peripheral vascular disease | Thrombolytic treatment, discharge medication |
Bettencourt et al. [14] | Age, sex | None |
GRACE [19] | Age, sex, geographical region, previous angina, previous MI, previous PCI/CABG, hypertension, diabetes, hyperlipidemia, chronic heart failure, Killip class, blood pressure, heart rate | Thrombolytic treatment, catheterization, PCI, CABG, aspirin, UFH, LMWH, Glycoprotein IIb/IIIa inhibitor, ACE-inhibitor, calcium channel blocker, beta-blocker, statin |
CADILLAC [27] | Age, sex, Killip class ≥ 2, MI site, previous MI, previous CABG, diabetes, hypertension, hypercholesterolemia, LAD culprit vessel, triple vessel disease, baseline TIMI 0 or 3 | Stent randomization, abciximab randomization, time from MI to ER, time from ER to first balloon |
SYNERGY [24] | Age, gender, creatinine clearance, heart rate, history of CHF, diabetes, baseline rales, ST depression on baseline ECG, weight, peripheral vascular disease, Killip class 3 or 4, No positive biomarkers at randomization, T-wave inversion on baseline ECG | Enoxaparin vs. UFH |
Gaspar et al. [16] | Age, left ventricular dysfunction, Killip class > 1, ST-elevation ACS | None |
Aune et al. [7] | Age, s-creatinine, previous left ventricular systolic dysfunction, interaction term (current smoking/strategy) | Invasive strategy, aspirin, statin |