Statin therapy in patients with Mild to Moderate Coronary Stenosis by 64-slice Multidetector Coronary Computed Tomography Hyo Eun Park 1, Eun-Ju Chun 2, Sang-Il Choi 2, Soyeon Ahn 2, Hyung-Kwan Kim 3, Yong-Jin Kim 3, Dong-Ju Choi 2, Dae-Won Sohn 3, *Goo-Yeong Cho 2 1 Healthcare System Gangnam Center, Seoul National University Hospital 2 Seoul National University Bundang Hospital 3 Seoul National University Hospital
Disclosure : None
Statin-a panacea? Dyslipidemia = a major risk factor for coronary heart disease Statin recommended for primary and secondary prevention in patients who are at risk of MI, stroke and death form cardiovascular causes Reduce rates of first occurrence and recurrence of coronary heart disease by about 20-40%
Beneficial effect of statin
Statin effect from previous trials Lancet 2010;376:1670-81
Statin effect from previous trials Lancet 2010;376:1670-81
Study population What is known.. Statin is beneficial in patients with known cardiovascular disease or with cardiovascular risk factors What is unknown.. Role of statin in asymptomatic patients with documented mild to moderate coronary artery stenosis? Is statin beneficial in patients without significant coronary artery disease?
Aim To investigate the effect of statin therapy in patients with documented mild to moderate coronary artery stenosis detected by 64-slice multidetector computed tomography, compared to those without statin therapy.
Methods Study design: retrospective observational study CT performed for screening purpose on patients demand at Health Promotion Center, Seoul National University Bundang Hospital Past medical history and current medications derived from medical questionnaires
Study Population 13,513 Asymptomatic subjects 2,055 subjects Exclusion 1. Epicardial stenosis = 0% or 70% 2. Lt main stenosis 50% 3. History of PCI or CABG 4. Follow up loss 5. Prior use of statin therapy 6. Blooming artifact Exclusion CT guided admission (n = 103) 1,952 subjects (statin user = 751, non-user = 1201 ) Propensity score matching : Age, % stenosis, CACS, total cholesterol, TG, HDL, LDL, BUN/Cr, FBS, HbA1c, SBP, and DBP 1286 subjects (statin user = 643, non-user = 643 )
Main outcome measures Primary end point First major cardiovascular event defined as cardiac death and acute coronary syndrome Secondary end point First major cardiovascular event defined as cardiac death, acute coronary syndrome and stroke
Baseline characteristics Before propensity score matching After propensity score matching Statin user Statin non-user Statin user Statin non-user n=751 n=1201 n=643 n=643 Male, n(%) 511 (68.0%) 927 (77.2%) 450 (70.0%) 457 (71.1%) Age, yrs 63±10 59±11 62±10 62±11 SBP, mmhg 129±19 124±16 128±17 128±18 DBP, mmhg 76±11 76±11 76±11 77±11 BMI, kg/m 2 24.8±3.0 24.5±2.9 24.7±3.0 24.5±3.1 HTN, n(%) 492 (65.5%) 591 (49.2%) 412 (64.1%) 414 (64.4%) DM, n(%) 398 (53.0%) 583 (48.5%) 350 (54.4%) 354 (55.1%) Coronary CT CACS Degree of stenosis, % 142±294 (IQR 2-133) 36±17 (IQR 20-50) 91±220 (IQR 0-66) 28±45 (IQR 20-35) 139±300 (IQR 1-131) 34±16 (IQR 20-40) 132±277 (IQR 5-132) 33±16 (IQR 20-40) *Matched parameters: age, sex, presence of hypertension and diabetes mellitus, systolic and diastolic blood pressure, serum fasting glucose, total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, coronary artery calcium score and degree of epicardial coronary artery stenosis
Baseline characteristics Lipid profiles at baseline Before propensity score matching After propensity score matching Statin user Statin non-user Statin user Statin non-user n=751 n=1201 n=643 n=643 T. cholesterol, mg/dl 218±41 204±36 215±39 212±37 Triglyceride, mg/dl 163±111 146±85 159±91 154±91 HDL-cholesterol, mg/dl 51±12 51±12 51±12 52±12 LDL-cholesterol, mg/dl 119±30 110±26 117±29 116±27 HbA1C, % 6.3±1.2 6.1±1.0 6.2±1.1 6.2±1.1 Lipid profiles at last follow up Total cholesterol,mg/dl 172±36 189±37 172±36 191±39 Triglyceride, mg/dl 141±80 143±88 139±70 149±97 HDL-cholesterol, mg/dl 52±24 51±12 50±12 51±12 LDL-cholesterol, mg/dl 86±28 104±27 87±28 104±28
Cardiovascular outcome Median follow up duration: 26 months Event Statin users Statin non-users Cardiac death 0 1 Acute coronary syndrome 7 8 CVA 10 13
Event-free survival Kaplan-Meier Survival Analysis for primary endpoint: cardiovascular death or ACS Statin user Statin non-user p=0.375 Time to event (days)
Event-free survival Kaplan-Meier Survival Analysis for secondary endpoint: cardiovascular death, ACS or CVA Statin user Statin non-user p=0.196 Time to event (days)
Subgroup analysis Age Sex DM HTN 60 yrs >60 yrs Female Male No Yes No Yes Coronary artery stenosis 50% >50% CACS <0.1 0.1 Triglyceride Total Cholesterol LDL-Cholesterol HDL-Cholesterol 150mg/dL >150mg/dL 200mg/dL >200mg/dL 100mg/dL >100mg/dL 50mg/dL >50mg/dL Aspirin use
Result There was no significant difference between statin users vs. statin non-users for both primary and secondary end point Subgroup analyses also show that there is no significant benefit of statin therapy in patient subgroups (overall OR 0.78, 95% CI 0.29-2.09)
Conclusion Statin therapy in patients with mild to moderate coronary artery stenosis on 64-slice MDCT has no beneficial effect in reducing adverse cardiovascular events. Use of statin in patients with mild to moderate coronary artery stenosis should be based on standard risk stratification methods using current guidelines such as NCEP/ATP-III, rather than image-oriented evaluation of atherosclerosis.
Limitations Specific subtypes of statins and dosages were not investigated Not only the statin users, but also statin non-users had significant reduction in total cholesterol and LDLcholesterol levels at follow up Since the current study population includes a significant portion of hypertensive and diabetic patients, we should be careful in extrapolating the result to the general population.
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Event-free survival Cox-regression survival analysis for primary endpoint with covariates adjusted Statin user Statin non-user p=0.149 Time to event (days) Adjusted covariates: Age, sex, HTN/DM, systolic and diastolic BP, glucose, cholesterol, TG, HDLcholesterol, LDL-cholesterol, CACS, % stenosis
Event-free survival Cox-regression survival analysis for secondary endpoint with covariates adjusted Statin user Statin non-user p=0.072 Time to event (days) Adjusted covariates: Age, sex, HTN/DM, systolic and diastolic BP, glucose, cholesterol, TG, HDLcholesterol, LDL-cholesterol, CACS, % stenosis