Arq Bras Cardiol abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC trBGFzFYjrS5hvZDCFxMJKr S0066-782X2015002300410 S0066-782X2015005050088 10.5935/abc.20150088 Original Articles Changes in Medical Management after Coronary CT Angiography Naue Vânia Mairi Camargo Gabriel Sabioni Letícia Roberto Lima Ronaldo de Souza Leão Derenne Maria Eduarda Lorenzo Andréa Rocha de Freire Monica Di Calafiori Azevedo Clério Francisco Filho Resende Elmiro Santos Gottlieb Ilan CDPI - Clínica de Diagnóstico por Imagem Brazil CDPI - Clínica de Diagnóstico por Imagem Mailing Address: Vania Mairi Naue, Rua H, 53, Parque Dez. Postal Code 69050-230, Manaus, AM – Brasil. E-mail: vania_naue@yahoo.com.br, vania_naue@cardiol.com.br

Author contributions

Conception and design of the research: Camargo G, Derenne MR, Resende ES, Gottlieb I; Acquisition of data: Naue VM, Freire MDC, Sabioni LR; Analysis and interpretation of the data: Naue VM, Camargo G, de Lorenzo AR, Lima RSL, Gottlieb I; Statistical analysis: Azevedo Filho CF, Gottlieb I; Writing of the manuscript: Naue VM, Camargo G, Gottlieb I; Critical revision of the manuscript for intellectual content: Gottlieb I.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

 07 08 2015 10 2015 105 4 410 417 23 08 2014 06 05 2015 06 05 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction:

Coronary computed tomography angiography (CCTA) allows for non-invasive coronary artery disease (CAD) phenotyping. There are still some uncertainties regarding the impact this knowledge has on the clinical care of patients.

 Objective:

To determine whether CAD phenotyping by CCTA influences clinical decision making by the prescription of cardiovascular drugs and their impact on non-LDL cholesterol (NLDLC) levels.

 Methods:

We analysed consecutive patients from 2008 to 2011 submitted to CCTA without previous diagnosis of CAD that had two serial measures of NLDLC, one up to 3 months before CCTA and the second from 3 to 6 months after.

 Results:

A total of 97 patients were included, of which 69% were men, mean age 64 ± 12 years. CCTA revealed that 18 (18%) patients had no CAD, 38 (39%) had non-obstructive (< 50%) lesions and 41 (42%) had at least one obstructive ≥ 50% lesion. NLDLC was similar at baseline between the grups (138 ± 52 mg/dL vs. 135 ± 42 mg/dL vs. 131 ± 44 mg/dL, respectively, p = 0.32). We found significative reduction in NLDLC among patients with obstrctive lesions (-18%, p = 0.001). We also found a positive relationship between clinical treatment intensification with aspirin and cholesterol reducing drugs and the severity of CAD.

 Conclusion:

Our data suggest that CCTA results were used for cardiovascular clinical treatment titration, with especial intensification seen in patients with obstructive ≥50% CAD.

 Keywords: Coronary Artery Disease Diagnostic Imaging Atherosclerosis/physiopathology Therapeutics Introduction

Cardiovascular clinical treatment titration in patients without prior diagnosis of coronary artery disease (CAD) is based on patient cardiovascular risk estimated by clinical variables, being generally indicated in patients classified as high risk1.

Coronary computed tomography angiography (CCTA) is generally used with high accuracy2 for obstructive CAD diagnosis and, as it allows three-dimensional evaluation of the wall vessel, it also provides non-obstructive CAD visualization, showing good correlation with intravascular ultrasound3.

The main therapeutic intervention used in patients with atherosclerosis, as a means of primary prevention of ischemic events, are Cholesterol-Lowering Drugs (CLD)4. However, the number needed to treat (NNT) varies according to the studied population and low cardiovascular risk patients benefit less than those at high cardiovascular risk. However, the potential for adverse effects remains similar1, 5, 6. According to the variation of baseline risk, the NNT may vary from 24 to 549 treated patients, for the reduction of an event5.

Studies show that approximately 20% to 30% of asymptomatic patients considered at low cardiovascular risk (event rate less than 10% in ten years) have atherosclerosis in the coronary computed tomography angiography (CCTA)7,8 and it is known that these findings are associated with increased incidence of cardiovascular events, independently from and in addition to the clinical risk factors9, 10. However, it is still uncertain how doctors use the results of CCTA in the clinical treatment titration of their patients.

This study aimed to evaluate the changes in both the prescription and plasma cholesterol levels in the short term, after a CCTA assessment in patients with no prior diagnosis of CAD, according to the severity of CAD found at the examination.

 Methods

A retrospective and analytical cohort was analyzed, and the project was approved by the Research Ethics Committee of HUCFF/FM/UFRJ, under protocol number 27341114.7.0000.5257.

All patients (123) submitted to CCTA between the years 2008 and 2011 in a cardiac imaging laboratory in Rio de Janeiro, with no prior diagnosis of CAD (i.e. without myocardial revascularization history or AMI and no previous CCTA) and had cholesterol measurement recorded at two different times: one up to three months before the CCTA (index measurement), followed by a second sample taken from three to six months after the CCTA (follow-up measurement) were included in this analysis. This period was chosen due to the homogeneity of image acquisition protocols used at that time.

In this institution, a physician from the team performs an interview with the patient prior to the examination, in which information such as anthropometric data, indication for the examination, risk factors, current medications and previous examinations is recorded. Access to the existing clinic database was requested for this study.

The analyzed items were: gender, age, CCTA indication (asymptomatic, typical pain, atypical pain or dyspnea), risk factors (hypertension, diabetes, dyslipidemia, sedentary lifestyle, smoking and family history), medications being used in the index consultation and at the second consultation, such as antiplatelet drugs and Cholesterol-Lowering Drugs (CLD) and the cholesterol levels both at the index and the second consultations. CLD were defined as any drug of the statins or fibrates classes.

Patients whose medical records did not provide the necessary data for this analysis, such as current medication or present risk factors were excluded from the analysis. Additionally patients whose imaging tests had inadequate quality for analysis in three or more coronary segments were also excluded.

The primary outcome of this study was non-LDL cholesterol (NLDLC) reduction after assessment by CCTA in the pre-specified period (three to six months). The NLDLC was considered as the sum of VLDL cholesterol and LDL cholesterol. It was decided to restrict the follow-up to such short period in order to minimize the influence of factors rather than the CCTA outcome on therapeutic decision-making.

As a secondary outcome, the change in medications prescription after the CCTA outcome. was assessed.

CCTA images were acquired using 256-channel devices (BrillianceTIC, Philips Healthcare®, Cleveland, Ohio) or one of the two 64-channel scanners (Brilliance64, Philips Healthcare®, Cleveland, Ohio, SomatomSensation 64, Siemens Healthcare®, Erlangen). For CCTA acquisition, venous and oral beta-blockers were used aiming to reduce HR to less than 60 bpm. Isosorbide dinitrate, 0.4 mg, sublingually was also administered to all patients without contraindications, 3 to 5 minutes prior to image acquisition.

Image analysis was performed by a single expert that had broad experience with the method. The coronary plaques were defined as the presence of image with soft tissue density ≥ 1 mm2 compatible with coronary atheromatosis, whereas the degree of luminal stenosis was defined as the ratio between the smallest luminal diameter at the lesion and the reference diameter closest to the lesion.

Patients were classified according to the highest degree of coronary stenosis found, considering: I - no plaque; II - non-obstructive plaques only (< 50% in stenosis); III - at least one obstructive plaque (≥ 50% in stenosis). To measure the cholesterol-lowering effects, a positive CCTA was considered the one with any evidence of coronary atherosclerosis.

Statistical analysis

The following software programs were used for data processing: SPSS version 19.0 and Microsoft Excel 2000© (9.0.2812).

To calculate sample size, we considered a difference of 30% in LDL cholesterol between patients with positive (estimated at 30% of the sample) and negative CCTA (70% of the sample). The estimated "n" was 90 patients for an alpha error of 0.05 and beta of 0.25.

Quantitative data showed normal distribution through the Kolmogorov-Smirnov test with a significance level of 5%. Continuous variables were expressed as mean ± standard deviation and were compared using paired and unpaired Student’s t test, as appropriate. Categorical variables were expressed as amounts and proportions and were compared using the Chi-square and Fisher tests, when appropriate. p values <0.05 were considered significant.

Patients were divided into three groups: without CAD, non-obstructive CAD (< 50% in stenosis) and obstructive CAD (≥ 50% in stenosis). Statistical analysis was carried out for each group separately and the two periods were compared by paired-t test.

 Results

Of a total of 123 patients that had two cholesterol measurements recorded in the proposed time period, 24 were excluded due to incomplete filling out of medical records and two due to poor quality of the images, resulting in 97 patients included in the analysis, of which 67 (69%) were men. The mean age was 64 ± 12 years. Nineteen percent had no risk factor; 15% had only one risk factor; 35% had two or three risk factors; and 31% had four or more risk factors for CAD.

CCTA was performed to assess pain with angina characteristics in 10% of patients; atypical pain in 16%; dyspnea or decreased functional capacity of 23%; and 51% of patients were asymptomatic. The clinical characteristics are described in Table 1. CCTA was normal in 18 (18%) patients, showed no obstructive CAD < 50% in 38 (39%) patients and obstructive CAD ≥ 50% in 42 (43%) patients.

Population characteristics of individuals submitted to CCTA
Variables    
Age (years)   64.2 ± 12
Gender    
  Male 67(69)
  Female 30(31)
Risk Factors    
  Hypertension 57(58)
  DM 23(24)
  DLP 57(58)
  Family history 35(36)
  Smoking 13(13)
  Sedentary life style 17(17)
Indications of CCTA    
  Without pain 50 (51)
  Typical angina 10(10)
  Atypical angina 16(16)
  Dyspnea and exercise intolerance 11(11)

DM: diabetes mellitus; DLP: dyslipidemia; CCTA: Coronary computed tomography angiography

 Cholesterol levels

NLDLC significantly decreased from 136 ± 44 mg/dL in the first to 117 ± 38 mg/dL in the follow-up visit (p = 0.007), a 14% decrease in the average of the general population (Chart 1).

Difference of NLDLC levels pre and post-CCTA when divided into categories according to CAD severity (without CAD, lesions < 50% and lesions ≥ 50%). CAD: coronary artery disease; NLDLC: non-LDL cholesterol.

Between the index and the follow-up visit, the variation in NLDLC in the group with negative CCTA was 4% (137 ± 53 mg/dL to 132 ± 39 mg/dL, p = 0.7), in the group with non-obstructive CCTA was 10% (135 ± 42 mg/dL to 121 ± 39 mg/dL, p = 0.07) and the in group in which CCTA showed obstructive lesions was 18% (130 ± 44 mg/dL to 107 ± 36 mg/dL, p = 0.001). There was no significant difference in NLDLC values between the different groups of CCTA in the index visit (p = 0.3).

Of the 42 individuals that had lesions ≥ 50% in stenosis, 32 (76%) showed LDL values < 100 mg/dL at the second visit (Chart 2).

Changes in the decrease of total cholesterol levels, its fractions and triglycerides, pre and post-CCTA. NLDLC: non-LDL cholesterol; HDL: high-density lipoprotein; NHDL: non-high-density lipoprotein; LDL: low-density lipoprotein; VLDL: very low-density lipoprotein. Medication use

Considering only the 64 (65%) patients that did not use the CLD in the index visit, 28 (43%) started using them after CCTA, when the latter showed at least one coronary segment with lesion (obstructive or not) versus 2 (3%) patients with normal CCTA (p < 0.05). Considering only the 34 patients that used CLD in the index visit, 8 (23%) had negative CCTA (of which 3 discontinued use of CLD) and 5 had at least one coronary segment with lesion (obstructive or not) and discontinued these drugs. Chart 3 illustrates the dynamics between treatment with CLD and CCTA results.

Changes in therapy with cholesterol-lowering drugs, according to CAD severity, demonstrated by CCTA (without CAD, lesions < 50% and lesions ≥ 50%). CAD: coronary artery disease; CLD: chodesterol lowering drugs.

Aspirin use was started after the normal CCTA result in 2 (11%) patients and in 17 (21%) patients with positive CCTA (Chart 4). Importantly, 15 (36%) patients with obstructive lesions were not using any antiplatelet agents on the second visit.

Aspirin prescription as primary preventive therapy, pre and post-CCTA. CAD: Coronary artery disease; ASA: aspirim.

The combined use of aspirin and CLD was started at 0%, 2% and 19% of patients with negative CCTA, with non-obstructive lesions and lesions ≥ 50%, respectively (p = 0.004), and only one of the two drugs alone in 18%, 24% and 38% respectively (p = 0.006).

 Discussion

CAD phenotyping by CCTA has a relevant prognostic impact and improves risk classification for cardiovascular events when compared to the classic risk factors11- 14.

This study allowed to evaluate, in the real world and in the short term, the impact of CCTA results on drug therapy, evaluating trends in cholesterol levels and the use of medications shortly after the CCTA results.

The analysis of this impact on clinical therapy is relevant, as the benefit of antiplatelet agents and CLD is directly associated with the patient’s cardiovascular risk. It has been demonstrated that in an asymptomatic population with zero calcium score, the NNT with aspirin is approximately two thousand individuals to prevent one major cardiovascular event, while the number needed to harm (NNH) is 442 individuals, demonstrating a much greater risk in the prescription of aspirin than its benefits15. A cost-effectiveness analysis showed that the aspirin is only cost-effective in men with clinical risk in ten years greater than 10% and in women when the risk is > 15%16. In our study, aspirin was started in 5% of patients after a completely normal CCTA result, which probably would not be indicated, considering that the annual risk is < 0.1% of combined coronary events9, 16, 17. Conversely, we observed that 22% of patients with positive CCTA (obstructive or not) in our study started aspirin therapy.

The proportion of patients that initiated therapy with CLD has increased significantly as the severity of CAD increased (normal CCTA = 12%; non-obstructive CAD = 24%; CAD ≥ 50% = 43%), demonstrating that in the real world there is an agreement between therapy intensity and the severity of CAD lesions. There was no reduction in NLDLC in patients with normal CCTA, which occurred in patients with obstructive lesions ≥ 50%. There was a NLDLC decrease trend in patients with non-obstructive lesions, and these data are corroborated by other studies 9, 15, 18, 19. Among the 42 patients with obstructive CAD ≥ 50%, 12 (29%) maintained the prescription of statin and/or aspirin and 24 (57%) started the use of the two drugs or added one of the two to previous therapy, after the CCTA result, corroborating the results of other published studies19- 23.

A meta-analysis24 involving 170,000 patients showed that a 1-mmol/L decrease in LDL cholesterol was able to reduce the risk of cardiovascular events by 20%. We observed in this study that 28 (29%) showed LDL decrease > 1 mmol/L, which implies a reduction of cardiovascular risk in this group.

The reduction in all lipid fractions, except HDL, demonstrates not only the potent LDL-lowering effect of the CLD, as well as reductions more related to changes in dietary habits, as demonstrated by the reduction in triglycerides 1, 4, 19.

Of all patients considered at high risk by CCTA (lesion ≥ 50%), 32 (76%) reached the LDL target <100 mg/dL. This result contrasts with the data collected by Vacanti et al.25in a Brazilian population, in which it was found that only 30% of patients had LDL values within the Guideline’s targets.

The stratification of cardiovascular risk made by visualization of coronary atherosclerosis has previously demonstrated to have greater impact on medication adherence and change in clinical management than the risk stratification by clinical scores20, 21, 26- 29. The results of this study indirectly corroborate that, showing patients with higher atherosclerotic disease severity have higher reduction in cholesterol levels.

Hulten et al.26 recently addressed the impact of CCTA findings on drug therapy in a study that evaluated 2,839 patients with a mean follow-up of 3.6 years, and found that after the CCTA examination there was an increase in the prescription of aspirin even in the group without CAD (10-46% vs. 17%-72% vs. 25%-89%, p = 0.001). This study also found statin prescription intensification after the CCTA results. After the CCTA results, 36% of patients without CAD were using CLD and 18% had been prescribed therapy intensification; in patients with non-obstructive lesions < 50%, 72% were using CLD and in 42%, prescription intensified occurred; in patients with lesions > 50% in stenosis, of the total 90% in use of statin, there was an intensification of 63%.

Among the assessed patients, two of them are especially illustrative for the analysis of the results. The first one, aged 54, had fatigue on moderate exertion, hypertension and did not use statins or aspirin. He had NLDLC of 201 mg/dL in the index visit. The CCTA disclosed 50% -70% lesion in the middle third of the Anterior Descending Artery (ADA). In the follow-up assessment, the patient was using aspirin and CLD and the NLDLC had decreased to 140 mg/dL. The second patient, aged 66 years, had atypical chest pain, diabetes, dyslipidemia, was hypertensive and sedentary, was using aspirin and CLD in the index visit had a NLDLC of 120 mg/dL. The CCTA disclosed a 50% -70% lesion in the proximal third of the ADA. At the second assessment, the NLDLC had decreased to 100 mg/dL with medication maintenance. The two patients were at high risk for cardiovascular events, but in the second case, there was not so marked decrease in NLDLC values, probably because the patient was already undergoing medical treatment and the medication was only optimized after CCTA the result.

Study limitations

Some limitations should be considered in our study, which was observational and retrospective, performed at a single diagnostic imaging center, with two CTs of different manufacturers, with a relatively small sample. Because we selected patients with two sequential cholesterol measurements, there may have been some selection bias, preferably excluding patients that had not started treatment with CLD and therefore had no clinical need to collect a new blood sample for lipid level measurement. Therefore, the results are more relevant for the analysis of factors involved in the prescription of antiplatelet agents and CLD than for the lack of their indication.

 Conclusions

The severity of CAD positively correlated with the decrease in cholesterol levels and more frequent prescription of antiplatelet agents and CLD. These data suggest that the CCTA result can influence drug treatment approach in the short term in the real world.

Sources of Funding

There were no external funding sources for this study.

Study Association

This article is part of the thesis of master submitted by Vânia Mairi Naue, from Universidade Federal de Uberlândia.

 References 1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-97. Expert in Panel on Detection.Evaluation, and Treatment of High Blood Cholesterol Adults Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) JAMA 2001 285 19 2486 2497 2. Dewey M, Vavere AL, Arbab-Zadeh A, Miller JM, Sara L, Cox C, et al. Patient characteristics as predictors of image quality and diagnostic accuracy of MDCT compared with conventional coronary angiography for detecting coronary artery stenoses: CORE-64 Multicenter International Trial. AJR Am J Roentgenol. 2010;194(1):93-102. Dewey M Vavere AL Arbab-Zadeh A Miller JM Sara L Cox C Patient characteristics as predictors of image quality and diagnostic accuracy of MDCT compared with conventional coronary angiography for detecting coronary artery stenoses: CORE-64 Multicenter International Trial AJR Am J Roentgenol 2010 194 1 93 102 3. Leber AW, Knez A, von Ziegler F, Becker A, Nikolaou K, Paul S, et al. Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography: a comparative study with quantitative coronary angiography and intravascular ultrasound. J Am Coll Cardiol. 2005;46(1):147-54. Leber AW Knez A von Ziegler F Becker A Nikolaou K Paul S Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography: a comparative study with quantitative coronary angiography and intravascular ultrasound J Am Coll Cardiol 2005 46 1 147 154 4. Stone NJ, Robinson J, Lichtenstein AH, Merz CNB, Blum CB, Eckel RH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S1-45. Erratum in: Circulation. 2014;129(25 Suppl 2):S46-8. Stone NJ Robinson J Lichtenstein AH Merz CNB Blum CB Eckel RH American College of Cardiology/American Heart Association Task Force on Practice Guidelines 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Circulation 2014 129 25 2 S1 45 5. Blaha MJ, Budoff MJ, DeFilippis AP, Blankstein R, Rivera JJ, Agatston A, et al. Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study. Lancet. 2011;378(9792):684-92. Blaha MJ Budoff MJ DeFilippis AP Blankstein R Rivera JJ Agatston A Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study Lancet 2011 378 9792 684 692 6. National Institute for Health and Care Excellence (NICE). Statins for the prevention of cardiovascular events. London; 2015. [Accessed in 2014 May 10]. Available from: http://www.publications.nice.org.UK/statins-for-the-prevention-of-cardiovascular-events-7a94 National Institute for Health and Care Excellence (NICE) Statins for the prevention of cardiovascular events London 2015 2014 May 10 Available from: http://www.publications.nice.org.UK/statins-for-the-prevention-of-cardiovascular-events-7a94 7. Choi EK, Choi SI, Rivera JJ, Nasir K, Chang SA, Chun EJ, et al. Coronary computed tomography angiography as a screening tool for the detection of occult coronary artery disease in asymptomatic individuals. J Am Coll Cardiol. 2008;52(5):357-65. Choi EK Choi SI Rivera JJ Nasir K Chang SA Chun EJ Coronary computed tomography angiography as a screening tool for the detection of occult coronary artery disease in asymptomatic individuals J Am Coll Cardiol 2008 52 5 357 365 8. Greenland P, Smith SC Jr, Grundy SM. Improving coronary heart disease risk assessment in asymptomatic people: role of traditional risk factors and noninvasive cardiovascular tests. Circulation. 2001;104(15):1863-7. Greenland P Smith SC Jr Grundy SM Improving coronary heart disease risk assessment in asymptomatic people: role of traditional risk factors and noninvasive cardiovascular tests Circulation 2001 104 15 1863 1867 9. Min JK, Shaw LJ, Devereux RB, Okin PM, Weinsaft JW, Russo DJ, et al. Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality. J Am Coll Cardiol. 2007;50(12):1161-70. Min JK Shaw LJ Devereux RB Okin PM Weinsaft JW Russo DJ Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality J Am Coll Cardiol 2007 50 12 1161 1170 10. Min JK, Dunning A, Lin FY, Achenbach S, Al-Mallah M, Budoff MJ, et al; CONFIRM Investigators. Age-and sex-related differences in all-cause mortality risk based on coronary computed tomography angiography findings: results from the International Multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: an international multicenter registry) of 23,854 patients without known coronary artery disease. J Am Coll Cardiol. 2011;58(8):849-60. Min JK Dunning A Lin FY Achenbach S Al-Mallah M Budoff MJ CONFIRM Investigators Age-and sex-related differences in all-cause mortality risk based on coronary computed tomography angiography findings: results from the International Multicenter CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: an international multicenter registry) of 23,854 patients without known coronary artery disease J Am Coll Cardiol 2011 58 8 849 860 11. Gottlieb I, Mansur Filho J, Costa Lima JA. Estratificação de risco cardiovascular no paciente assintomático por tomografia computadorizada cardíaca de múltiplos detectores. Rev SOCERJ. 2006;19(4):339-46. Gottlieb I Mansur J Filho Costa Lima JA Estratificação de risco cardiovascular no paciente assintomático por tomografia computadorizada cardíaca de múltiplos detectores Rev SOCERJ 2006 19 4 339 346 12. Schlett CL, Banerji D, Siegel E, Bamberg F, Lehman SJ, Ferencik M, et al. Prognostic value of CT angiography for major adverse cardiac events in patients with acute chest pain from the emergency department: 2-year outcomes of the ROMICAT trial. JACC Cardiovasc Imaging. 2011;4(5):481-91. Schlett CL Banerji D Siegel E Bamberg F Lehman SJ Ferencik M Prognostic value of CT angiography for major adverse cardiac events in patients with acute chest pain from the emergency department: 2-year outcomes of the ROMICAT trial JACC Cardiovasc Imaging 2011 4 5 481 491 13. Prazeres CE, Cury RC, Carneiro AC, Rochitte CE. Angiotomografia de coronárias na avaliação da dor torácica aguda na sala de emergência. Arq Bras Cardiol. 2013;101(6):562-9. Prazeres CE Cury RC Carneiro AC Rochitte CE Angiotomografia de coronárias na avaliação da dor torácica aguda na sala de emergência Arq Bras Cardiol 2013 101 6 562 569 14. Shareghi S, Ahmadi N, Young E, Gopal A, Liu ST, Budoff MJ. Prognostic significance of zero coronary calcium scores on cardiac computed tomography. J Cardiovasc Comput Tomogr. 2007;1(3):155-9. Shareghi S Ahmadi N Young E Gopal A Liu ST Budoff MJ Prognostic significance of zero coronary calcium scores on cardiac computed tomography J Cardiovasc Comput Tomogr 2007 1 3 155 159 15. Miedema MD, Duprez DA, Misialek JR, Blaha MJ, Nasir K, Silverman MG, et al. Use of coronary artery calcium testing to guide aspirin utilization for primary prevention: estimates from the multi-ethnic study of atherosclerosis. Circ Cardiovasc Qual Outcomes. 2014;7(3):453-60. Miedema MD Duprez DA Misialek JR Blaha MJ Nasir K Silverman MG Use of coronary artery calcium testing to guide aspirin utilization for primary prevention: estimates from the multi-ethnic study of atherosclerosis Circ Cardiovasc Qual Outcomes 2014 7 3 453 460 16. Greving JP, Buskens E, Koffijberg H, Algra A. Cost-effectiveness of Aspirin treatment in the primary prevention of cardiovascular disease events in subgroups based on age, gender, and varying cardiovascular risk. Circulation. 2008;117(22):2875-83. Greving JP Buskens E Koffijberg H Algra A Cost-effectiveness of Aspirin treatment in the primary prevention of cardiovascular disease events in subgroups based on age, gender, and varying cardiovascular risk Circulation 2008 117 22 2875 2883 17. Sarwar A, Shaw LJ, Shapiro MD, Blankstein R, Hoffmann U, Cury RC, et al. Diagnostic and prognostic value of absence of coronary artery calcification. JACC Cardiovasc Imaging. 2009;2(6):675-88. Sarwar A Shaw LJ Shapiro MD Blankstein R Hoffmann U Cury RC Diagnostic and prognostic value of absence of coronary artery calcification JACC Cardiovasc Imaging 2009 2 6 675 688 18. Schwartz J, Allison MA, Rifkin DE, Wright CM. Influence of patients' coronary artery calcium on subsequent medication use patterns. Am J Health Behav. 2012;36(5):628-38. Schwartz J Allison MA Rifkin DE Wright CM Influence of patients' coronary artery calcium on subsequent medication use patterns Am J Health Behav 2012 36 5 628 638 19. Nasir K, McClelland RL, Blumenthal RS, Goff DC Jr, Hoffmann U, Psaty BM, et al. Coronary artery calcium in relation to initiation and continuation of cardiovascular preventive medications. The Multi-Ethnic Study of Atherosclerosis (MESA). Circ Cardiovasc Qual Outcomes. 2010;3(3):228-35. Nasir K McClelland RL Blumenthal RS Goff DC Jr Hoffmann U Psaty BM Coronary artery calcium in relation to initiation and continuation of cardiovascular preventive medications. The Multi-Ethnic Study of Atherosclerosis (MESA) Circ Cardiovasc Qual Outcomes 2010 3 3 228 235 20. Xavier HT, Izar MC, Faria Neto JR, Assad MH, Rocha VZ, Sposito AC; Sociedade Brasileira de Cardiologia. V Diretriz brasileira de dislipidemias e prevenção da aterosclerose. Arq Bras Cardiol. 2013;101(4 Supl.1):1-22. Xavier HT Izar MC Faria JR Neto Assad MH Rocha VZ Sposito AC Sociedade Brasileira de Cardiologia. V Diretriz brasileira de dislipidemias e prevenção da aterosclerose Arq Bras Cardiol 2013 101 1 1 22 21. McEvoy JW, Blaha MJ, Nasir K, Yoon YE, Choi EK, Cho IS, et al. Impact of coronary computed tomographic angiography results on patient and physician behavior in a low-risk population. Arch Intern Med. 2011;171(14):1260-8. McEvoy JW Blaha MJ Nasir K Yoon YE Choi EK Cho IS Impact of coronary computed tomographic angiography results on patient and physician behavior in a low-risk population Arch Intern Med 2011 171 14 1260 1268 22. LaBounty TM, Devereux RB, Lin FY, Weinsaft JW, Min JK. Impact of coronary computed tomographic angiography findings on the medical treatment and control of coronary artery disease and its risk factors. Am J Cardiol. 2009;104(7):873-7. LaBounty TM Devereux RB Lin FY Weinsaft JW Min JK Impact of coronary computed tomographic angiography findings on the medical treatment and control of coronary artery disease and its risk factors Am J Cardiol 2009 104 7 873 877 23. Blankstein R, Murphy MK, Nasir K, Gazelle GS, Batlle JC, Al-Mallah M, et al. Perceived usefulness of cardiac computed tomography as assessed by referring physicians and its effect on patient management. Am J Cardiol. 2010;105(9):1246-53. Blankstein R Murphy MK Nasir K Gazelle GS Batlle JC Al-Mallah M Perceived usefulness of cardiac computed tomography as assessed by referring physicians and its effect on patient management Am J Cardiol 2010 105 9 1246 1253 24. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al; Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-81. Baigent C Blackwell L Emberson J Holland LE Reith C Bhala N Cholesterol Treatment Trialists' Collaboration Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials Lancet 2010 376 9753 1670 1681 25. Vacanti LJ, Santos SC, Fujita AM, Lima DS, Lopes AF, Vetorazi R, et al. A baixa taxa de obtenção da meta do LDL- colesterol numa população de baixa renda. Arq Bras Cardiol. 2005;85(3):162-5. Erratum in: Arq Bras Cardiol. 2005;85(4):302. Vacanti LJ Santos SC Fujita AM Lima DS Lopes AF Vetorazi R A baixa taxa de obtenção da meta do LDL- colesterol numa população de baixa renda Arq Bras Cardiol 2005 85 3 162 165 26. Hulten E, Bittencourt MS, Singh A, O'Leary D, Christman MP, Osmani W, et al. Coronary artery disease detected by coronary computed tomographic angiography is associated with intensification of preventive medical therapy and lower low-density lipoprotein cholesterol. Circ Cardiovasc Imaging. 2014;7(4):629-38. Hulten E Bittencourt MS Singh A O'Leary D Christman MP Osmani W Coronary artery disease detected by coronary computed tomographic angiography is associated with intensification of preventive medical therapy and lower low-density lipoprotein cholesterol Circ Cardiovasc Imaging 2014 7 4 629 638 27. Cheezum MK, Hulten EA, Smith RM, Taylor AJ, Kircher J, Surry L, et al. Changes in preventive medical therapies and CV risk factors after CT angiography. JACC Cardiovasc Imaging. 2013;6(5):574-81. Cheezum MK Hulten EA Smith RM Taylor AJ Kircher J Surry L Changes in preventive medical therapies and CV risk factors after CT angiography JACC Cardiovasc Imaging 2013 6 5 574 581 28. Rozanski A, Gransar H, Shaw LJ, Kim J, Miranda-Peats L, Wong ND, et al. Impact of coronary artery calcium scanning on coronary risk factors and downstream testing the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) prospective randomized trial. J Am Coll Cardiol. 2011;57(15):1622-32. Rozanski A Gransar H Shaw LJ Kim J Miranda-Peats L Wong ND Impact of coronary artery calcium scanning on coronary risk factors and downstream testing the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) prospective randomized trial J Am Coll Cardiol 2011 57 15 1622 1632 29. Taylor AJ, Bindeman J, Feuerstein I, Le T, Bauer K, Byrd C, et al. Community- based provision of statin and aspirin after the detection of coronary artery calcium within a community-based screening cohort. J Am Coll Cardiol. 2008;51(14):1337-41. Taylor AJ Bindeman J Feuerstein I Le T Bauer K Byrd C Community- based provision of statin and aspirin after the detection of coronary artery calcium within a community-based screening cohort J Am Coll Cardiol 2008 51 14 1337 1341 Mudanças no Manejo Clínico após Angiotomografia Coronariana Naue Vânia Mairi Camargo Gabriel Sabioni Letícia Roberto Lima Ronaldo de Souza Leão Derenne Maria Eduarda Lorenzo Andréa Rocha de Freire Monica Di Calafiori Azevedo Clério Francisco Filho Resende Elmiro Santos Gottlieb Ilan Clínica de Diagnóstico por Imagem Brazil CDPI - Clínica de Diagnóstico por Imagem Correspondência: Vania Mairi Naue, Rua H, 53, Parque Dez. CEP 69050-230, Manaus, AM – Brasil. E-mail: vania_naue@yahoo.com.br, vania_naue@cardiol.com.br

Contribuição dos autores

Concepção e desenho da pesquisa: Camargo G, Derenne MR, Resende ES, Gottlieb I; Obtenção de dados: Naue VM, Freire MDC, Sabioni LR; Análise e interpretação dos dados: Naue VM, Camargo G, de Lorenzo AR, Lima RSL, Gottlieb I; Análise estatística: Azevedo Filho CF, Gottlieb I; Redação do manuscrito: Naue VM, Camargo G, Gottlieb I; Revisão crítica do manuscrito quanto ao conteúdo intelectual importante: Gottlieb I.

Potencial conflito de interesse

Declaro não haver conflito de interesses pertinentes.

 Resumo Fundamento:

A Angiotomografia Coronariana (AngioTC Cor) permite a fenotipagem de Doença Arterial Coronariana (DAC) de forma não invasiva. Ainda há incertezas sobre o impacto que esse conhecimento promove no tratamento clínico do paciente.

 Objetivo:

Avaliar se a fenotipagem da DAC por AngioTC Cor influencia na tomada de decisão sobre o início da terapêutica cardiovascular e seu impacto nos níveis séricos de colesterol não HDL (CNHDL).

 Métodos:

Foram analisados pacientes consecutivos sem diagnóstico prévio de DAC que realizaram AngioTC Cor entre os anos 2008 e 2011 e que possuíam duas dosagens seriadas de colesterol até três meses antes da AngioTC Cor, e de três a seis meses após.

 Resultados:

Um total de 97 pacientes foram incluídos, sendo 69% homens, idade média de 64 ± 12 anos. A AngioTC Cor revelou que 18 (18%) pacientes não tinham lesões detectáveis, 38 (39%) tinham lesões não obstrutivas < 50%, e 41 (42%) tinham ao menos uma lesão obstrutiva ≥ 50%. As medidas de CNHDL basal foram similares entre os grupos, (138 ± 52 mg/dL vs. 135 ± 42 mg/dL vs. 131 ± 44 mg/dL, respectivamente, p = 0,32). Observou-se redução significativa do CNHDL apenas no grupo com lesões obstrutivas ≥ 50% (-18%, p = 0,001). Observa-se ainda relação entre a intensificação do tratamento clínico com AAS e drogas redutoras de colesterol proporcional à gravidade da DAC pela AngioTC Cor.

 Conclusão:

Esses dados sugerem que o resultado da AngioTC Cor foi utilizado para a titulação terapêutica de pacientes com DAC, sendo o tratamento intensificado especialmente em DAC obstrutiva ≥ 50%.

 Palavras-chave: Doença arterial coronariana Diagnóstico por Imagem Terapêutica Aterosclerose/fisiopatologia Introdução

A titulação terapêutica cardiovascular em pacientes sem o diagnóstico prévio de Doença Arterial Coronariana (DAC) é baseada no risco cardiovascular do paciente estimado mediante variáveis clínicas, sendo indicada geralmente em pacientes classificados em alto risco1.

A Angiotomografia Coronariana (AngioTC Cor) é geralmente utilizada com alta acurácia2 para o diagnóstico de DAC obstrutiva, e por permitir avaliação tridimensional da parede do vaso, também propicia a visualização de DAC não obstrutiva, apresentando boa correlação com o ultrassom intravascular3.

A principal intervenção medicamentosa utilizada em pacientes com diagnóstico de aterosclerose, como forma de prevenção primária de eventos isquêmicos, são as Drogas Redutoras do Colesterol (DRC)4. Porém, o Número Necessário para Tratar (NNT) varia muito de acordo com a população estudada, e pacientes de baixo risco cardiovascular têm menor benefício do que aqueles em alto risco cardiovascular. No entanto, o potencial para efeitos adversos permanece semelhante1, 5, 6. De acordo com variação do risco basal, o NNT pode variar de 24 a 549 pacientes tratados, para a redução de um evento5.

Estudos revelam que cerca de 20% a 30% dos pacientes assintomáticos considerados como de baixo risco cardiovascular (taxa de eventos inferior a 10% em dez anos) apresentam aterosclerose na angiotomografiacoronariana (AngioTC Cor)7, 8 e sabe-se que esses achados estão associados ao aumento da incidência de eventos cardiovasculares, independentemente e adicionalmente aos fatores de risco clínico9, 10. Todavia, ainda é incerto como os médicos usam os resultados da AngioTC Cor na titulação terapêutica clínica de seus pacientes.

Neste artigo buscou-se avaliar as mudanças tanto na prescrição quanto nos valores de colesterol plasmático em curto prazo, após um exame de AngioTC Cor, em pacientes sem diagnóstico prévio de DAC, de acordo com a gravidade da DAC encontrada.

 Métodos

Foi analisada uma coorte retrospectiva e analítica, tendo sido o projeto aprovado pelo comite de ética em pesquisa do HUCFF/FM/UFRJ, sob o número de protocolo 27341114.7.0000.5257.

Foram incluídos todos (123) os pacientes que realizaram AngioTC Cor entre os anos 2008 e 2011 em um laboratório de imagem cardíaca no Rio de Janeiro, sem diagnóstico de DAC prévia (i.e. sem história de revascularização miocárdica ou IAM e sem AngioTC Cor prévia) e que tinham dosagem de colesterol registrada em dois momentos distintos: sendo uma até três meses antes da AngioTC Cor (dosagem índice), seguida de uma segunda amostra colhida de três a seis meses após a AngioTC Cor (dosagem de seguimento). Esse período foi escolhido devido à homogeneidade dos protocolos de aquisição de imagem utilizados à época.

Nessa instituição, um médico da equipe faz uma entrevista com o paciente antes da realização do exame, na qual registra informações como: dados antropométricos, indicação do exame, fatores de risco, medicações em uso e exames prévios. Para este estudo foi solicitado acesso ao banco de dados existente na clínica.

Os itens analisados foram: gênero, idade, indicação de AngioTC Cor (assintomáticos, dor típica, dor atípica ou dispneia), fatores de risco (hipertensão, diabetes, dislipidemia, sedentarismo, tabagismo e história familiar), medicações em uso na visita índice e na segunda visita como antiagregantes plaquetários e Drogas Redutoras de Colesterol (DRC) e os níves de colesterol tanto na visita índice como na segunda visita.

As DRC foram definidas como qualquer droga das classes das estatinas ou fibratos.

Foram excluídos da análise os pacientes cujos prontuários não forneciam os dados necessários para essa análise, como a medicação em uso ou fatores de risco presentes. Além desses, foram excluídos também pacientes cujas imagens apresentavam qualidade inadequada para análise em três ou mais segmentos coronarianos.

O desfecho principal deste estudo foi a redução do colesterol não HDL (CNHDL) após a realização do exame de angiotomografia de coronárias no período pré- especificado (três a seis meses). O CNHDL foi considerado como a soma do colesterol VLDL e do colesterol LDL. Optou-se por restringir o seguimento a um prazo tão curto para minimizar a influência de fatores alheios ao resultado da AngioTC Cor na decisão terapêutica dos pacientes.

Como desfecho secundário foi avaliada a mudança na prescrição de medicações após o resultado da AngioTC Cor.

As imagens da AngioTC Cor foram realizadas em equipamentos de 256 canais (BrillianceTIC, a Philips Healthcare®, Cleveland, Ohio) ou um dos dois tomógrafos de 64 canais (Brilliance64, Philips Healthcare®, Cleveland, Ohio, SomatomSensation 64, Siemens Healthcare®, Erlangen). Para a aquisição da AngioTC Cor foram utilizados betabloqueadores orais e venosos com o objetivo de reduzir a FC para menos de 60 bpm. Administrou-se ainda dinitrato de isossorbida, 0,4 mg por via sublingual, para todos os pacientes sem contraindicações, 3 a 5 minutos antes da aquisição da imagem.

A análise das imagens foi feita por um único examinador especialista e experiente no método. As placas coronarianas foram definidas como a presença de imagem com densidade de partes moles ≥ 1 mm2 compatível com ateromatose coronariana, e o grau de estenose luminal definido como a relação entre o menor diâmetro luminal na lesão e o diâmetro de referência mais próximo da lesão.

Os pacientes foram classificados de acordo com o maior grau de estenose coronariana encontrada consideramdo-se: I - nenhuma placa; II - apenas placas não obstrutivas (< 50% em estenose); III - pelo menos uma placa obstrutiva (≥ 50% em estenose). Para medida dos efeitos de redução de colesterol, uma AngioTC Cor positiva foi aquela com qualquer evidência de aterosclerose coronariana.

Análise estatística

Foram utilizados os seguintes softwares para o tratamento dos dados: SPSS versão 19.0 e Microsoft® Excel 2000© (9.0.2812).

Para o cálculo do tamanho amostral consideramos uma diferença de 30% no colesterol LDL entre os pacientes com AngioTC Cor positiva (estimada em 30% da amostra) e negativa (70% da amostra). Para um erro alfa de 0,05 e beta de 0,25, o n calculado foi de 90 pacientes.

Os dados quantitativos apresentam distribuição normal por meio do teste Kolmogorov-Smirnov ao nível de 5% de significância. Variáveis contínuas foram expressas como média ± desvio padrão e foram comparadas pelo teste t de Student pareado e não pareado conforme apropriado. Variáveis categóricas foram expressas como contagens e proporções e foram comparadas usando-se o chi-quadrado e teste de Fisher, quando apropriado. Valores de p < 0,05 foram considerados significativos.

Os pacientes foram separados em três grupos: sem DAC, DAC não obstrutiva (< 50% em estenose) e DAC obstrutiva (≥ 50% em estenose). A análise estatística foi feita para cada grupo em separado, comparando os dois momentos pelo t-pareado.

 Resultados

De um total de 123 pacientes que tinham o registro de duas verificações de colesterol na janela de tempo proposta, 24 foram excluídos por preenchimento incompleto do prontuário e dois devido a má qualidade das imagens, resultando em 97 pacientes incluídos na análise, dos quais 67 (69%) eram homens. A idade média foi 64 ± 12 anos. Dezenove por cento não tinham nenhum fator de risco; 15% tinham apenas um fator de risco; 35% tinham dois ou três fatores de risco; e 31% tinham quatro ou mais fatores de risco para DAC.

A AngioTC Cor foi realizada para avaliar dor com características anginosas em 10% dos pacientes; dor atípica em 16%; dispneia ou redução da capacidade funcional em 23%; e 51% dos pacientes eram assintomáticos. As características clínicas estão descritas na tabela 1.

Característica populacionais dos individuos submetidos a AngioTC Cor
Variáveis    
Idade (anos)   64,2 ± 12
Gênero    
  Masculino 67(69)
  Feminino 30(31)
Fatores de Risco    
  HAS 57(58)
  DM 23(24)
  DLP 57(58)
  História familiar 35(36)
  Tabagismo 13(13)
  Sedentarismo 17(17)
Indicações da AngioTC Cor    
  Sem dor 50 (51)
  Angina típica 10(10)
  Angina atípica 16(16)
  Dispneia e intolerancia ao exercício 11(11)

HAS: hipertensão arterial sistêmica; DM: diabete melito; DLP: dislipidemia; AngioTCCor: angiotomografia coronariana.

A AngioTC Cor foi normal em 18 (18%) pacientes, apresentou DAC não obstrutiva < 50% em 38 (39%) pacientes e DAC obstrutiva ≥ 50% em 42 (43%) pacientes.

Níveis de colesterol

O CNHDL diminuiu significativamente de 136 ± 44 mg/dL na visita índice para 117 ± 38 mg/dL no seguimento (p = 0,007) uma queda de 14% na média da população geral (Gráfico 1).

Diferença nos nives de CNHDL pré e pós-AngioTC Cor, quando separados em categorias de acordo com a severidade da DAC (sem DAC, lesões < 50% e lesões ≥ 50%). DAC: doença arterial coronariana; CNHDL: colesterol não HDL.

Entre a visita índice e o seguimento, a variação no CNHDL no grupo com AngioTC Cor negativa foi de 4% (137 ± 53 mg/dL para 132 ± 39 mg/dL, p = 0,7), no grupo com AngioTC Cor não obstrutiva foi de 10% (135 ± 42 mg/dL para 121 ± 39 mg/dL, p = 0,07) e no grupo no qual a AngioTC Cor demonstrou lesão obstrutiva foi de 18% (130 ± 44 mg/dL para 107 ± 36 mg/dL, p = 0,001). Não houve diferença significativa nos valores de CNHDL entre os diferentes grupos de AngioTC Cor na visita índice (p = 0,3).

Dos 42 indivíduos que apresentavam lesões ≥ 50% em estenose, 32 (76%) atingiram valores de LDL inferiores a 100 mg/dL na segunda visita (Gráfico 2).

Mudanças na redução dos niveis de coleterol total, suas frações e de triglicerideos, pré e pós-AngioTC Cor. CNHDL: colesterol não HDL; HDL: lipoproteína de alta densidade; NHDL: lipoproteína não HDL; LDL: lipoproteína de baixa densidade; VLD: lipoproteína de muito baixa densidade. Uso de medicações

Considerando-se apenas os 64 (65%) indivíduos que não usavam DRC na visita índice, 28 (43%) começaram a usá-las depois da AngioTC Cor, quando essa evidenciou pelo menos um segmento coronariano com lesão (obstrutiva ou não), versus 2 (3%) pacientes com AngioTC Cor normal (p < 0,05). Considerando-se apenas os 34 pacientes que faziam uso de DRC na visita índice, 8 (23%) tiveram AngioTC Cor negativa (dos quais 3 interromperam as DRC), e 5 tiveram pelo menos um segmento coronariano com lesão (obstrutiva ou não) e descontinuaram essas drogas. O Gráfico 3 ilustra a dinâmica entre a terapêutica com DRC e os resultados da AngioTC Cor.

Mudanças na terapia com drogas redutoras de colesterol, de acordo com a severidade da DAC, demonstrada por AngioTC Cor (sem DAC, lesões < 50% e lesões ≥ 50%). DAC: doença arterial coronariana; DRC: drogas redutoras de colesterol.

O uso de AAS foi iniciado após o resultado da AngioTC Cor normal em 2 (11%) dos pacientes e em 17 (21%) dos pacientes com AngioTC Cor positiva (Gráfico 4). Importantemente, 15 (36%) dos pacientes com alguma lesão obstrutiva não estavam usando nenhuma droga antiagreganteplaquetária na segunda visita.

Prescrição de AAS como terapia preventiva primaria, pré e pós-AngioTC Cor. DAC: doença arterial coronariana; AAS: aspirina.

O uso combinado de AAS e DRC foi iniciado em 0%, 2% e 19% dos pacientes com AngioTC Cor negativa, com lesões não obstrutivas e lesões ≥ 50%, respectivamente (p = 0,004), e apenas uma das duas drogas isoladamente em 18%, 24% e 38% respectivamente (p = 0,006).

 Discussão

A fenotipagem da DAC pela AngioTC Cor tem relevante impacto prognóstico e melhora a classificação de risco para eventos cardiovasculares quando comparado com os fatores de risco clássicos11- 14.

O presente estudo permitiu avaliar, no mundo real e em curto prazo, as consequências do resultado da AngioTC Cor na terapêutica medicamentosa, avaliando-se as tendências nos níveis de colesterol e o uso de medicações pouco tempo após o resultado da AngioTC Cor.

A análise desse impacto na terapêutica clínica é relevante, pois o benefício dos antiangregantes e das DRC está diretamente relacionado ao risco cardiovascular do paciente. Já foi demonstrado que em uma população assintomática com escore de cálcio zero, o NNT com AAS é de aproximadamente dois mil indivíduos para prevenir um evento cardiovascular maior, enquanto o número necessário para causar dano (NNH) é de 442 indivíduos, demonstrando-se um risco na prescrição do AAS muito maior do que o benefício em fazê-lo15. Uma análise de custo-efetividade demonstrou que o AAS só é custo-eficaz em homens com risco clínico em dez anos superior a 10% e em mulheres quando o risco é superior a 15%16. Em nosso estudo o AAS foi iniciado em 5% dos pacientes após AngioTC Cor completamente normal, o que provavelmente não estaria indicado dado o risco anual ser < 0,1% de eventos coronarianos combinados9, 16, 17. Conversamente, observamos que 22% dos pacientes com AngioTC Cor positiva (obstrutiva ou não) em nosso estudo iniciou AAS.

A proporção de pacientes que iniciaram a terapia com DRC aumentou significativamente à medida que aumentou a gravidade da DAC (AngioTC Cor normal = 12%; DAC não obstrutiva = 24%; DAC ≥ 50% = 43%), demonstrando que no mundo real há concordância entre intensidade terapêutica e gravidade das lesões da DAC. Não houve redução no CNHDL entre os pacientes com AngioTC Cor normal o que ocorreu os pacientes com lesões obstrutivas ≥ 50%. Houve tendência de redução do CNHDL nos pacientes com lesões não obstrutivas, dados esses corroborados em outros estudos9, 15, 18, 19. Entre os 42 pacientes que apresentaram DAC obstrutiva, ≥ 50%, 12 (29%) mantiveram a prescrição de estatina e/ou AAS e 24 (57%) iniciaram o uso dos dois medicamentos ou acrescentaram um dos dois à terapêutica prévia, após o resultado da AngioTC Cor, corroborando os resultados de outros estudos publicados19- 23.

Uma meta-análise24 envolvendo 170 mil pacientes demonstrou que queda no LDL colesterol de 1 mmol/L seria capaz de reduzir o risco de eventos cardiovasculares em 20%. Observamos neste estudo que 28 (29%) tiveram um queda do LDL superior a 1 mmol/L, o que implica redução do risco cardiovascular nesse grupo.

A redução em todas as frações de lípides, com exceção do HDL, demonstra não apenas o potente efeito redutor de LDL das DRC, como também reduções mais relacionadas à mudanças nos hábitos alimentares, como a demonstrada pela redução dos triglicérides1, 4, 19.

Do total de pacientes considerados em alto risco pela AngioTC Cor (lesão ≥ 50%), 32 (76%) atingiram a meta de LDL < 100 mg/dL. Esse resultado se contrapõe com dados levantados por Vacanti e cols.25numa população brasileira na qual foi verificado que apenas 30% dos pacientes apresentavam valores de LDL dentro das metas da Diretriz.

A estratificação do risco cardiovascular feita pela visualização da aterosclerose coronariana já demostrou anteriormente ter maior impacto na aderência medicamentosa e mudança de conduta clínica do que a estratificação de risco por escores clínicos20, 21, 26- 29. Os resultados do presente estudo corroboram isso de forma indireta, ao demonstrar-se que pacientes com maior gravidade de doença aterosclerótica apresentam maior redução nos níveis de colesterol.

Hulten e cols.26 recentemente abordaram o impacto dos resultados da AngioTC Cor sobre a terapêutica medicamentosa em um estudo que avaliou 2.839 pacientes com média de seguimento de 3,6 anos e verificaram que após o exame de Angio TC Cor houve aumento da prescrição de AAS mesmo no grupo sem DAC (10-46% vs. 17% - 72% vs. 25% - 89%, p = 0,001). Este estudo também encontrou intensificação da prescrição de estatina após o resultado da Angio TC Cor. Após o resultado da angiotomografia, 36% dos pacientes sem DAC estavam em uso de DRC e em 18% havia sido prescrita intensificação da terapêutica; nos pacientes que apresentavam lesões não obstrutivas < 50%, 72% estavam em uso de DRC e em 42% ocorreu intensificação da prescrição; nos pacientes com lesões superiores a 50% em estenose, do total de 90% em uso de estatina, houve intensificação em 63%.

Entre os pacientes avaliados dois são especialmente ilustrativos para a análise dos resultados. Um deles, com 54 anos, referia cansaço aos moderados esforços, era hipertenso e não usava estatina nem AAS. Apresentava CNHDL de 201 mg/dL na visita índice. A AngioTC Cor revelou lesão de 50%-70% no terço médio da Artéria Descendente Anterior (ADA). Na avaliação de seguimento, o paciente estava em uso de AAS e DRC e o CNHDL havia baixado para 140 mg/dL. Outro paciente de 66 anos, com dor torácica atípica, diabético, dislipidêmico, hipertenso e sedentário, estava em uso de AAS e DRC na visita índice e CNHDL de 120 mg/dL. A AngioTC Cor revelou lesão de 50%-70% no terço proximal da ADA. O CNHDL na segunda avaliação baixou para 100 mg/dL com manutenção das medicações. Os dois pacientes apresentavam alto risco para eventos cardiovasculares, porém no segundo caso não houve queda tão acentuada nos valores de CNHDL provavelmente porque o paciente já estava em tratamento clínico e só otimizou a medicação após o resultado da AngioTC Cor.

Limitações do estudo

Algumas limitações devem ser consideradas no nosso estudo, o qual foi observacional e retrospectivo, realizado em um único centro de diagnóstico por imagem, com dois tomógrafos de empresas diferentes com amostra relativamente pequena. Por termos selecionado, a priori, pacientes com duas medidas sequenciais de colesterol, pode ter havido algum viés de seleção, excluindo-se preferencialmente pacientes que não iniciaram tratamento com DRC e que, portanto, não tiveram necessidade clínica de coleta de nova amostra de sangue para aferição de lípides. Portanto, os resultados têm maior importância na análise dos fatores envolvidos na prescrição dos antiagregantes plaquetários e DRC, do que na não indicação das mesmas.

 Conclusões

A gravidade da DAC se correlacionou positivamente com a queda das taxas de colesterol e com prescrição mais frequente de antiagregantes plaquetários e DRC. Esses dados sugerem que o resultado da AngioTC Cor pode influenciar a conduta terapêutica medicamentosa a curto prazo no mundo real.

Fontes de financiamento

O presente estudo não teve fontes de financiamento externas.

Vinculação acadêmica

Este artigo é parte de Dissertação de Mestrado de Vânia Mairi Naue pela Universidade Federal de Uberlândia.