ijcsInternational Journal of Cardiovascular SciencesInt. J. Cardiovasc. Sci.2359-48022359-5647Sociedade Brasileira de CardiologiaN7YY9bqGYCdf8n5GqhHymKnS2359-5647201700050040810.5935/2359-4802.20170069Original ArticlesEffectiveness of Medical and Revascularization Procedures as the Initial Strategy in Stable Coronary Artery Disease: A Cohort StudyFurtadoMariana VargasAraujoGustavo Neves deJostMariana FerreiraAmericoAndre DiasPeruzzoNicolasNasiGuilhermeTeloGuilherme HeidenBorgesFlavia KesslerPolanczykCarisi AnneUniversidade Federal do Rio Grande do SulFaculdade de MedicinaPorto AlegreBrazilFaculdade de Medicina, Universidade Federal do Rio Grande do Sul and Serviço de Cardiologia, Hospital de Clínicas de Porto Alegre, Porto Alegre - BrazilUniversidade Federal do Rio Grande do SulMailing Address: Gustavo Neves de Araujo Ramiro Barcellos, 1891/1002. Postal Code: 9035006, Independência, Porto Alegre, RS - Brazil. E-mail: gustavon.araujo@gmail.com
Author contributions
Conception and design of the research: Furtado MV, Telo GH, Polanczyk CA. Acquisition of data: Furtado MV, Araújo GN, Jost MF, Américo AD, Peruzzo N, Nasi G. Analysis and interpretation of the data: Furtado MV, Araújo GN, Jost MF, Américo AD, Peruzzo N, Telo GH, Borges FK, Polanczyk CA. Statistical analysis: Furtado MV, Araújo GN, Jost MF, Américo AD, Peruzzo N, Nasi G. Obtaining financing: Furtado MV, Telo GH, Polanczyk CA. Writing of the manuscript: Furtado MV, Araújo GN, Jost MF, Borges FK. Critical revision of the manuscript for intellectual content: Furtado MV, Américo AD, Peruzzo N, Nasi G, Telo GH, Borges FK, Polanczyk CA.
Potential Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Sep-Oct20173005408415231120161112201606042017This 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.AbstractBackground:
Coronary artery bypass grafting surgery (CABG) and percutaneous coronary intervention (PCI) are widely-used strategies in the management of stable coronary artery disease (CAD).
Objective:
To evaluate the prognosis of patients with stable CAD initially treated by medical therapy (MT), compared to the patients who were submitted to revascularization procedures.
Methods:
We conducted a prospective cohort study of 560 patients from an outpatient clinic in a tertiary hospital, with a mean follow-up of 5 years. Patients were classified into MT (n = 288), PCI (n = 159) and CABG (n=113) groups according to their initial treatment strategy. Primary endpoints were overall mortality and combined events of death, acute coronary syndrome, and stroke.
Results:
During follow-up, death rates were 11.1% in MT, 11.9% in PCI and 15.9% in CABG patients, with no statistical difference (hazard ratio [HR] for PCI, 1.05; 95% confidence interval [95%CI], 0.59 to 1.84; and HR for CABG, 1.20; 95% CI: 0.68 to 2.15). Combined outcomes occurred more often among patients initially submitted to PCI compared to MT (HR 1.50, 95% CI 1.05 to 2.14), and did not differ between MT and CABG patients (HR 1.24, 95% CI 0.84 to 1.83). Among patients with diabetes (n=198), PCI was the only therapeutic strategy predictive of combined outcomes (HR 2.14; 95% CI 1.25 to 3.63).
Conclusion:
In this observational study of stable coronary artery disease, there was no difference in overall mortality between initial medical therapy or revascularization surgery strategies. Patients initially treated with PCI had greater chance to develop combined major cardiovascular events.
Coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI) are widely used strategies in the management of coronary artery disease (CAD), associated with optimized medical therapy (MT). However, in the last years, evidence has narrowed the indication of revascularization procedures in stable patients, with conflicting results regarding the benefits and impact on mortality when comparing the initial treatment options.1-9 Prior studies have suggested that PCI decreases symptoms without a long-term prognostic effect, even when compared to medical treatment alone.7,8 More recent data reinforced the superiority of CABG in preventing major cardiac events in patients with multivessel disease, especially in patients with more complex coronary artery disease and diabetes.10-12 However, these studies showed similar results between CABG and PCI when patients with less complex disease were evaluated.10,12
Between 2005 and 2008, 166,514 PCIs were performed in Brazil by the Brazilian Public Health System (Sistema Único de Saúde - SUS), an annual average of 41,628 procedures or 22/100,000 inhabitants. Of these, 37% were elective in patients with stable CAD. Drug-eluting stents (DES) are not covered by SUS, and probably a significant proportion of the Brazilian patients do not have optimized medical therapy and access to revascularization procedures, with differences among geographic regions of Brazil.13 Therefore, the results of many clinical trials might not be generalizable to real-world clinical practice.
Even in developed countries, there are gaps in literature regarding the effectiveness of treatment strategies in patients with stable CAD. There are few clinical trials comparing the therapeutic options and this lack of knowledge brings complexity to the decision-making process. The purpose of this study was to evaluate the long-term prognosis of patients with stable CAD treated with medical therapy alone as the initial treatment option, compared with patients submitted to PCI or CABG in a public hospital in Brazil.
MethodsStudy population
This was a prospective cohort study in patients from an outpatient clinic in a tertiary care university hospital in Southern Brazil. Between 1998 and 2011, 560 consecutive patients with stable CAD were enrolled. All patients had documented CAD, which was defined by the presence of at least one of the following: documented history of acute myocardial infarction (AMI), surgical or percutaneous myocardial revascularization, a lesion > 50% in at least one coronary artery assessed by angiography, or the presence of angina and positive noninvasive testing of ischemia.14
Patients were divided into three groups, according to the baseline intervention strategy: MT, PCI, or CABG, which was adopted prior to study enrollment. During follow-up, patients were managed by a multidisciplinary team according to current guidelines and at the discretion of attending physicians. Patients who underwent PCI or CABG during follow-up were identified, although they were analyzed as originally classified. All enrolled patients had complete clinical and laboratory data at baseline, at least three visits and one year of follow-up. This study was approved by the Institutional Research and Ethics Committee.
Follow-up and endpoints
Stable patients were periodically assessed every 3-6 months. At each visit, a standardized register was filled in, which included the current disease history, cardiovascular risk factor control, new cardiac events (including admission data and invasive procedures), laboratory and cardiac exams and pharmacological and non-pharmacological treatment. Relevant comorbidities were evaluated by questionnaire and chart review.
The primary outcomes of interest were death from any cause and occurrence of a major adverse cardiovascular event (MACE), defined as acute coronary syndrome (ACS), stroke and death. Acute coronary syndrome was defined as a hospital admission for chest pain or related symptoms and a discharge diagnosis by a physician of AMI or unstable angina. All-cause mortality and need for revascularization (either surgical or percutaneous) were also assessed.
Statistical Analyses
Continuous variables were expressed as mean ± 1 Standard Deviation (SD) and non-continuous ones were expressed as median and interquartile range (IQR) and were compared using paired t-test or the Wilcoxon signed-rank test, as appropriate. Categorical data were presented as frequencies and were compared by Qui-square or Fisher's exact test. All tests were two-sided. Long-term outcomes were compared for those who initially underwent medical treatment, with the outcomes for those who underwent CABG and PCI, irrespective of stent type. The primary analysis evaluated the time to the first MACE. Survival curves were derived by Kaplan-Meier analysis and compared using log-rank tests. Multivariate Cox analyses were used to compare event-free survival among groups. In the multivariate analyses, parameters that were clinically or significantly associated with main outcomes were included in the models. Outcomes were adjusted for gender, age, diabetes, smoking, ventricular dysfunction, chronic kidney disease and presence of comorbidities such as peripheral vascular disease, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), liver disease and cancer. Variables that had any effect on the variable of interest were selected by the manual and stepwise method (p < 0.10). All data were analyzed using SPSS program (version 11.0.0; SPSS, Chicago, Illinois, USA) and P values less than 0.05 were considered significant.
Results
The mean follow-up of the study was 5.1 years. Of the 560 patients, 288 (51.4%) were initially managed with MT, 159 (28.4%) with PCI and 113 (20.2%) with CABG. Baseline characteristics of patients according to the management strategy are shown in Table 1. Patients in the PCI group were more likely to have previous AMI than the other two groups. Patients in the CABG group had more hypertension, dyslipidemia, left ventricular dysfunction and, as expected, greater proportion of patients with three-vessel coronary disease.
Baseline Characteristics of the Patients
Total n = 560
MT n = 288
PCI n = 159
CABG n = 113
p Value
Age, years
62 ± 11
62 ± 11
61 ± 12
63 ± 10
0.16
Male
329 (58.8)
170(59)
85 (53.5)
74 (65.5)
0.14
Diabetes Mellitus
198 (35.4)
110 (38.2)
47 (29.6)
41 (36.3)
0.18
Hypertension
438 (78.2)
226 (78.5)
114 (71.7)
98 (86.7)
0.01
Dyslipidemia
355 (63.4)
178 (61.8)
96 (60.4)
81 (71.7)
0.05
Smoking (current)
83 (14.8)
45 (15.6)
31 (19.5)
7 (6.2)
0.02
Smoking (previous)
264 (47.1)
132 (45.8)
67 (42.1)
65 (57.5)
0.02
Myocardial infarction
289 (51.6)
130 (45.1)
108 (67.9)
51 (45.1)
< 0.001
Cerebrovascular disease
58 (10.4)
33 (11.5)
15 (9.4)
10 (8.8)
0.67
Renal failure
86 (15.4)
36 (12.5)
25 (15.7)
25 (22.1)
0.06
LVEF (%)
54 ± 13
55 ± 14
54 ± 13
50 ± 11
0.01
LVEF < 50%
188 (33.6)
94 (32.6)
43 (27)
51 (45.1)
< 0.01
Three-vessel disease
81 (14.5)
30 (17.3)
14 (10.8)
37 (41.6)
< 0.001
Data are expressed as mean ± Standard Deviation or as a number (%).
P-values were obtained through chi-square test for categorical variables and Student's t-test for continuous variables.
MT: medical therapy; PCI: percutaneous coronary intervention; CABG: coronary artery bypass grafting; LVEF: left ventricular ejection fraction.
All-cause mortality occurred in 69 patients (12.3%), with an annual mortality incidence of 2.5%/year (13 events/year). The cumulative survival rates for patients assigned to each group were 89% for MT, 88% for PCI, and 84% for CABG (p = 0.82). During follow-up, 115 patients (20.5%) underwent PCI and 56 patients (10%) underwent CABG. The rate of events and comparisons between groups are shown in Table 2. Patients from PCI and CABG groups had more ACS (22.6% and 23.9% respectively) when compared with MT group (14.9%, p = 0.04). On the other hand, the rate of CABG revascularization during the follow-up was higher in the MT (14.2%) and PCI (6.9%) groups when compared to CABG (3.5%) (p < 0.01).
Primary and secondary outcomes
Total n = 560
MT n = 288
PCI n = 159
CABG n = 113
p Value
Combined Outcomes
168 (30)
77 (26.7)
52 (32.7)
39 (34.5)
0.21
Death
69 (12.3)
32 (11.1)
19 (11.9)
18 (15.9)
0.41
ACS
106 (18.9)
43 (14.9)
36 (22.6)
27 (23.9)
0.04
Stroke
14 (2.5)
9 (3.1)
5 (3.8)
0
0.16
Cardiovascular death
40 (7.1)
23 (9)
7 (4.4)
10 (8.8)
0.27
Heart failure
24 (4.3)
10 (3.5)
6 (3.8)
8 (7.1)
0.26
Subsequent revascularization*
PCI
115 (20.5)
54 (18.8)
37 (23.3)
24 (21.2)
0.51
CABG
56 (10)
41 (14.2)
11 (6.9)
4 (3.5)
< 0.01
Data are expressed as total number of events (%).
P-values were obtained through Fisher's exact test for categorical variables.
Some patients had a nonfatal myocardial infarction or stroke before their subsequent death, so the number of combined events is lower than the sum of each single event. In the survival analyses, the time until the first event was used.
Values represent the first revascularization procedure in patients who were originally assigned to the medical therapy group.
At the end of follow-up, there was no significant difference in adjusted mortality between groups (hazard ratio [HR] for the PCI group, 1.05; 95% confidence interval [CI], 0.59 to 1.84; and HR for the CABG group, 1.20; 95% CI 0.68 to 2.15), with virtually identical survival curves (Figure 1A). In the multivariate Cox-model analysis, age, male gender, diabetes, and cerebrovascular disease were predictive of overall mortality (Table 3). Considering the occurrence of combined major events, PCI was independently associated with worse prognosis (HR 1.50, 95% CI 1.05 to 2.14), with no difference between MT and CABG (HR 1.24, 95% CI 0.84 to 1.83) (Figure 1B). Ventricular dysfunction, diabetes and cerebrovascular disease were also predictive of major events (Table 3).
Multivariate analyses comparing event-free survival between groups, adjusted for clinical parameters
Unadjusted probability of event-free survival in patients in the MT, CABG, and treatment groups, adjusted for clinical parameters. A: overall mortality; B: combined events of death, myocardial infarction, and stroke; C: revascularization.
Both groups of MT and PCI were more likely to require further revascularization (PCI or CABG) during the follow-up, after the multivariate analysis (HR =1.55, 95% CI 1.01 to 2.41 and HR = 1.85, 95% CI 1.13 to 3.02, respectively) (Figure 1C). The median time to subsequent revascularization was 32 months (IQR - 11 to 79) in the MT, 32 months (IQR - 8 to 79) in PCI and 38 months (IQR - 24 to 83) in the CABG group (P=0.019). Ventricular dysfunction and diabetes were also predictive of additional revascularization and previous acute myocardial infarction was inversely associated with this outcome (Table 3).
Subgroup analyses
We also analyzed rates of combined major events in patients with diabetes and three-vessel coronary disease, factors identified as determinants in the choice of therapy in patients with stable CAD. There was no significant difference in outcome between initial management strategy in patients with 3-vessel coronary disease (HR = 1.22, 95% CI 0.36 to 4.15 in the PCI group and HR = 1.05, 95%, CI 0.40 to 2.73 in the CABG group). However, in patients with diabetes, the PCI group was predictor of combined major events in the multivariate analyses (HR = 2.14, 95% CI 1.26 to 3.63).
Discussion
The present study reports the results of a cohort from an outpatient clinic in a tertiary care university hospital in Southern Brazil. Developing countries are characterized by a limited access to therapies and difficulties in incorporating new technologies, where the gap in applying the results of clinical trials is even more evident.
National and international guidelines for the management of patients with stable CAD recommend revascularization with CABG for symptomatic patients with unprotected left main coronary artery disease, 3-vessel disease with or without proximal left anterior descending artery disease or 2-vessel disease with proximal left anterior descending artery (Class I recommendation). For the same patients, PCI has a Class IIa recommendation to improve survival. However, all revascularization recommendations to improve survival are based on level of evidence B or C.14-16 Guidelines emphasize the importance of using a Heart Team approach to decide which therapy is best for each patient, demonstrating that the optimal therapeutic strategy in stable CAD patients is not straightforward.15
The Second Medical, Angioplasty, or Surgery Study (MASS II) was the first randomized clinical trial with stable multivessel CAD that compared the 3 current therapeutic strategies: PCI with bare-metal stents versus CABG versus MT alone.9 The 5-year and 10-year follow-up data showed no differences in overall mortality between the groups. CABG was superior to MT and PCI for the combined endpoints of AMI, additional revascularization and mortality.17,18 Our study results were consistent with MASS II findings regarding overall mortality and subsequent revascularization, suggesting that the initial strategy with MT can be considered, while acknowledging that during a long-term follow-up a revascularization procedure may be necessary. However, the MASS II 10-year follow-up showed a higher incidence of AMI in MT and PCI compared to CABG patients, which demonstrates the better prognosis of surgical patients.18
The lack of difference in mortality between MT and PCI strategies in our study corroborate the findings of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial which showed death rates of 7.6% in PCI group and 8.3% in MT group.8 The COURAGE nuclear substudy, however, observed a graded relationship between risk of events and the extent and severity of residual ischemia in the end of follow-up. In addition, revascularization with PCI resulted in a more effective reduction of ischemia than MT alone. Although not evidenced by the clinical trial, a pragmatic interpretation of these data indicates revascularization for patients with more than 10% of ischemia during stress testing.19 Our study did not evaluate data from stress testing and did not consider the degree of ischemia in the analysis, limiting the ability to identify a subgroup of patients with worse prognosis in the MT group. On the other hand, a sub-analysis of the STICH trial showed that in patients with CAD with severe left ventricular dysfunction (ejection fraction ≤ 35%), inducible myocardial ischemia did not identify patients with worse prognosis or those with greater benefit from CABG revascularization over MT alone.20
Similar results concerning overall mortality were observed in the BARI 2D trial, in which cumulative survival did not differ significantly between the revascularization (88.3%) and MT groups (87.8%, p = 0.97).11 These rates are very similar to those found in our study. However, we observed a worse prognosis in the PCI group when combined events were analyzed, especially in the subgroup of diabetic patients. This difference may be attributable to the use of bare-metal stents in our patients (the option available at the public health system in our country), as opposed to the wide use of drug-eluting stents in BARI 2D. The significantly reduced major cardiovascular events in patients who were selected to undergo CABG when compared to MT differ from our results.
The FREEDOM Trial showed that the combined events of death, AMI and stroke occurred more frequently in patients who underwent PCI compared to CABG (26.6% vs. 18.7%, respectively).12 These findings are consistent with the ARTS,21 CARDia22 and SYNTAX (subgroup analysis)10 trials, where higher rates of major adverse cardiovascular events were observed in diabetic patients assigned to undergo PCI, rather than CABG. Similar to our results, revascularization rates were significant in the PCI group. Likewise, a recent meta-analysis of six randomized trials using contemporary therapy strategies compared CABG and PCI with DES.23 Although there were no significant differences in death or AMI rates at 1 or 2 years, these differences were evident after 5 years of follow-up, favoring CABG.
The subgroup analysis performed in our patients with three-vessel disease showed no difference in combined events between initial management strategies. Although multivessel disease is considered a complex CAD, results of the SYNTAX trial demonstrated the importance of estimating lesion severity, and showed that major cardiac events did not significantly differ between PCI and CABG in patients with low SYNTAX score.10 The present study did not measure coronary disease complexity, limiting its ability to provide comparative data regarding better optimum revascularization strategy for multivessel-disease patients. In a large North-American observational study, patients older than 65 years with multivessel CAD had a better long-term survival when submitted to CABG, when compared to patients who underwent PCI.24 Similar results were found in a pooled database of three large randomized trials that compared long-term outcomes between these groups,25 showing lower rates of AMI and repeated revascularization in patients with multivessel or left main CAD and previous AMI. We have also demonstrated a worse prognosis in PCI group in overall patients, but could not show any differences in the multivessel-disease subgroup.
Our study had limitations inherent to observational studies. Moreover, it used data from a single center in a reference hospital, in which the results may not be generalized. However, our results represent the real-world practice in a public health system.
Conclusion
The present study shows that stable CAD patients who are initially treated with medical therapy instead of coronary revascularization have similar rates of death from any cause and major cardiovascular events compared to those initially treated invasively.
Sources of Funding
This study was funded by FIPE - Fundo de Financiamento à Pesquisa e Eventos - HCPA.
Study Association
This article is part of the thesis of Doctoral submitted by Mariana Vargas Furtado, from Universidade Federal do Rio Grande do Sul.
References1 Pursnani S, Korley F, Gopaul R, Kanade P, Chandra N, Shaw RE, et al. Percutaneous coronary intervention versus optimal medical therapy in stable coronary artery disease: a systematic review and meta-analysis of randomized clinical trials. Circ Cardiovasc Interv. 2012;5(4):476-90.PursnaniSKorleyFGopaulRKanadePChandraNShawREPercutaneous coronary intervention versus optimal medical therapy in stable coronary artery disease: a systematic review and meta-analysis of randomized clinical trialsCirc Cardiovasc Interv2012544764902 Serruys P, Daemen J, Morice MC, De Bruyne B, Colombo A, Macaya C, et al. Three-year follow-up of the ARTS-II- sirolimus-eluting stents for the treatment of patients with multivessel disease. EuroIntervention. 2008;3(4):450-9.SerruysPDaemenJMoriceMCDe BruyneBColomboAMacayaCThree-year follow-up of the ARTS-II- sirolimus-eluting stents for the treatment of patients with multivessel diseaseEuroIntervention2008344504593 Rodriguez A, Bernardi V, Navia J, Baldi J, Grinfeld L, Martinez J, et al. Argentine randomized study: coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II): 30 days results and one-year follow-up results. J Am Coll Cardiol. 2001;37(1):51-8. Erratum in: J Am Coll Cardiol. 2001;37(3):973-4.RodriguezABernardiVNaviaJBaldiJGrinfeldLMartinezJArgentine randomized study: coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II): 30 days results and one-year follow-up resultsJ Am Coll Cardiol20013715158Erratum in: J Am Coll Cardiol. 2001;37(3):973-44 Booth J, Clayton T, Pepper J, Nugara F, Flather M, Sigwart U, et al; SoS Investigators. Randomized, controlled trial of coronary artery bypass surgery versus percutaneous coronary intervention in patients with multivessel coronary artery disease: six-year follow-up from the Stent or Surgery Trial (SoS). Circulation. 2008;118(4):381-8.BoothJClaytonTPepperJNugaraFFlatherMSigwartUSoS InvestigatorsRandomized, controlled trial of coronary artery bypass surgery versus percutaneous coronary intervention in patients with multivessel coronary artery disease: six-year follow-up from the Stent or Surgery Trial (SoS)Circulation200811843813885 Hannan EL, Wu C, Walford G, Culliford AT, Gold JP, Smith CR, et al. Drug-eluting stents vs. coronary-artery bypass grafting in multivessel coronary disease. N Engl J Med. 2008;358(4):331-41.HannanELWuCWalfordGCullifordATGoldJPSmithCRDrug-eluting stents vs. coronary-artery bypass grafting in multivessel coronary diseaseN Engl J Med200835843313416 Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, et al; SYNTAX Investigators. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Eng J Med. 2009;360(10):961-72. Erratum in: N Engl J Med. 2013;368(6):584.SerruysPWMoriceMCKappeteinAPColomboAHolmesDRMackMJSYNTAX InvestigatorsPercutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery diseaseN Eng J Med200936010961972Erratum in: N Engl J Med. 2013;368(6):5847 Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, et al; COURAGE Trial Research Group. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356(15):1503-16.BodenWEO'RourkeRATeoKKHartiganPMMaronDJKostukWJCOURAGE Trial Research GroupOptimal medical therapy with or without PCI for stable coronary diseaseN Engl J Med200735615150315168 Shaw LJ, Berman DS, Maron DJ, Mancini GB, Hayes SW, Hartigan PM, et al; COURAGE Investigators. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation. 2008;117(10):1283-91.ShawLJBermanDSMaronDJManciniGBHayesSWHartiganPMCOURAGE InvestigatorsOptimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudyCirculation200811710128312919 Hueb W, Soares PR, Gersh BJ, César LA, Luz PL, Puig LB, et al. The Medicine, Angioplasty, or Surgery Study (MASS-II): a randomized, controlled clinical trial of three therapeutic strategies for multivessel coronary artery disease: one-year results. J Am Coll Cardiol. 2004;43(10):1743-51.HuebWSoaresPRGershBJCésarLALuzPLPuigLBThe Medicine, Angioplasty, or Surgery Study (MASS-II): a randomized, controlled clinical trial of three therapeutic strategies for multivessel coronary artery disease: one-year resultsJ Am Coll Cardiol200443101743175110 Mohr FW, Morice MC, Kappetein, Feldman TE, Ståhle E, Colombo A, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet. 2013;381(9867):629-38.Mohr FWMorice MCKappeteinFeldman TEStåhle EColombo ACoronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trialLancet2013381986762963811 Frye RL, August P, Brooks MM, Hardison RM, Kelsey SF, MacGregor JM, et al; BARI 2D Study Group. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med. 2009;360(24):2503-15.FryeRLAugustPBrooksMMHardisonRMKelseySFMacGregorJMBARI 2D Study GroupA randomized trial of therapies for type 2 diabetes and coronary artery diseaseN Engl J Med2009360242503251512 Farkou ME, Domanski M, Sleeper LA, Siami FS, Dangas G, Mack M, et al; FREEDOM Trial Investigators. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012;367(25):2375-84.FarkouMEDomanskiMSleeperLASiamiFSDangasGMackMFREEDOM Trial InvestigatorsStrategies for multivessel revascularization in patients with diabetesN Engl J Med2012367252375238413 Piegas LS, Haddad N. Percutaneous coronary intervention in Brazil: results from the Brazilian Public Health System. Arq Bras Cardiol. 2011;96(4):317-24.PiegasLSHaddadNPercutaneous coronary intervention in Brazil: results from the Brazilian Public Health SystemArq Bras Cardiol201196431732414 Guimarães JI, César LA, Mansur AP, Armaganijan D, Amino JG, Souza AC, et al; Sociedade Brasileira de Cardiologia. Diretriz de angina estável. Arq Bras Cardiol. 2004;83(supl 2):6-44.GuimarãesJICésarLAMansurAPArmaganijanDAminoJGSouzaACSociedade Brasileira de CardiologiaDiretriz de angina estávelArq Bras Cardiol200483supl 264415 Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, et al; American College of Cardiology Foundation; American Heart Association Task Force on Practice Guidelines; American College of Physicians; American Association for Thoracic Surgery; Preventive Cardiovascular Nurses Association.; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2012;60(24):e44-164.FihnSDGardinJMAbramsJBerraKBlankenshipJCDallasAPAmerican College of Cardiology FoundationAmerican Heart Association Task Force on Practice GuidelinesAmerican College of PhysiciansAmerican Association for Thoracic SurgeryPreventive Cardiovascular Nurses Association.Society for Cardiovascular Angiography and InterventionsSociety of Thoracic Surgeons2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic SurgeonsJ Am Coll Cardiol20126024e4416416 Wijns W, Kolh P, Danchin N, Di Mario C, Falk V, Folliguet T, et al; Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS); European Association for Percutaneous Cardiovascular Interventions (EAPCI) . Guidelines on myocardial revascularization. Eur Heart J. 2010;31(20):2501-55.WijnsWKolhPDanchinNDi MarioCFalkVFolliguetTTask Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)European Association for Percutaneous Cardiovascular Interventions (EAPCI)Guidelines on myocardial revascularizationEur Heart J201031202501255517 Hueb W, Lopes NH, Gersh BJ, Soares P, Machado LA, Jatene FB, et al. Five-year follow-up of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease. Circulation. 2007;115(9):1082-9.HuebWLopesNHGershBJSoaresPMachadoLAJateneFBFive-year follow-up of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery diseaseCirculation200711591082108918 Hueb W, Lopes NH, Gersh BJ, Soares PR, Ribeiro EE, Pereira AC, et al. Ten-year follow-up of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease. Circulation. 2010;122(10):949-57.HuebWLopesNHGershBJSoaresPRRibeiroEEPereiraACTen-year follow-up of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery diseaseCirculation20101221094995719 Shaw LJ, Berman DS, Maron DJ, Mancini GB, Hayes SW, Hartigan PM, et al; COURAGE Investigators. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial nuclear substudy. Circulation. 2008;117(10):1283-91.ShawLJBermanDSMaronDJManciniGBHayesSWHartiganPMCOURAGE InvestigatorsOptimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial nuclear substudyCirculation2008117101283129120 Panza JA, Holly TA, She L, Pellikka PA, Velazquez EJ, Lee KL, et al. Inducible myocardial ischemia and outcomes in patients with coronary artery disease and left ventricular dysfunction. J Am Coll Cardiol. 2013;61(18):1860-70.PanzaJAHollyTASheLPellikkaPAVelazquezEJLeeKLInducible myocardial ischemia and outcomes in patients with coronary artery disease and left ventricular dysfunctionJ Am Coll Cardiol201361181860187021 Serruys PW, Ong AT, van Herwerden LA, Sousa JE, Jatene A, Bonnier JJ, et al. Five-year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease: the final analysis of the Arterial Revascularization Therapies Study (ARTS) randomized trial. J Am Coll Cardiol. 2005;46(4):575-81.SerruysPWOngATvan HerwerdenLASousaJEJateneABonnierJJFive-year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease: the final analysis of the Arterial Revascularization Therapies Study (ARTS) randomized trialJ Am Coll Cardiol200546457558122 Kapur A, Hall RJ, Malik IS, Qureshi AC, Butts J, de Belder M, et al. Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients: 1-year results of the CARDia (Coronary Artery Revascularization in Diabetes) trial. J Am Coll Cardiol. 2010;55(5):432-40.KapurAHallRJMalikISQureshiACButtsJde BelderMRandomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients: 1-year results of the CARDia (Coronary Artery Revascularization in Diabetes) trialJ Am Coll Cardiol201055543244023 Fanari Z, Weiss SA, Zhang W, Sonnad SS, Weintraub WS. Comparison of percutaneous coronary intervention with drug eluting stents versus coronary artery bypass grafting in patients with multivessel coronary artery disease: meta-analysis of six randomized controlled trials. Cardiovasc Revasc Med. 2015;16:70-77.FanariZWeissSAZhangWSonnadSSWeintraubWSComparison of percutaneous coronary intervention with drug eluting stents versus coronary artery bypass grafting in patients with multivessel coronary artery disease: meta-analysis of six randomized controlled trialsCardiovasc Revasc Med201516707724 Weintraub WS, Grau-Sepulveda MV, Weiss JM, O'Brien SM, Peterson ED, Kolm P, et al. Comparative effectiveness of revascularization strategies. N Engl J Med. 2012;366(16):1467-76.WeintraubWSGrau-SepulvedaMVWeissJMO'BrienSMPetersonEDKolmPComparative effectiveness of revascularization strategiesN Engl J Med2012366161467147625 Chang M, Lee CW, Ahn JM, Cavalcante R, Sotomi Y, Onuma Y, et al. Coronary artery bypass grafting versus drug-eluting stents implantation for previous myocardial infarction. Am J Cardiol. 2016;118(1):17-22.ChangMLeeCWAhnJMCavalcanteRSotomiYOnumaYCoronary artery bypass grafting versus drug-eluting stents implantation for previous myocardial infarctionAm J Cardiol201611811722Artigos OriginaisEfetividade da Terapia Medicamentosa e dos Procedimentos de Revascularização como Estratégia Inicial na Doença Arterial Coronariana Estável: Estudo de CoorteFurtadoMariana VargasAraujoGustavo Neves deJostMariana FerreiraAmericoAndre DiasPeruzzoNicolasNasiGuilhermeTeloGuilherme HeidenBorgesFlavia KesslerPolanczykCarisi AnneFaculdade de Medicina, Universidade Federal do Rio Grande do Sul e Serviço de Cardiologia, Hospital de Clínicas de Porto Alegre, Porto Alegre - BrasilCorrespondência: Gustavo Neves de Araujo Ramiro Barcellos, 1891/1002. CEP: 9035006, Independência, Porto Alegre, RS - Brasil. E-mail: gustavon.araujo@gmail.com
Contribuição dos autores
Concepção e desenho da pesquisa: Furtado MV, Telo GH, Polanczyk CA. Obtenção de dados: Furtado MV, Araújo GN, Jost MF, Américo AD, Peruzzo N, Nasi G. Análise e interpretação dos dados: Furtado MV, Araújo GN, Jost MF, Américo AD, Peruzzo N, Telo GH, Borges FK, Polanczyk CA. Análise estatística: Furtado MV, Araújo GN, Jost MF, Américo AD, Peruzzo N, Nasi G. Obtenção de financiamento: Furtado MV, Telo GH, Polanczyk CA. Redação do manuscrito: Furtado MV, Araújo GN, Jost MF, Borges FK. Revisão crítica do manuscrito quanto ao conteúdo intelectual importante: Furtado MV, Américo AD, Peruzzo N, Nasi G, Telo GH, Borges FK, Polanczyk CA.
Potencial Conflito de Interesse
Declaro não haver conflito de interesses pertinentes.
ResumoFundamento:
A cirurgia de revascularização miocárdica (CRM) e a intervenção coronária percutânea (ICP) são estratégias amplamente utilizadas no manejo da doença arterial coronariana (DAC) estável.
Objetivo:
Avaliar o prognóstico de pacientes com DAC estável inicialmente tratada com terapia médica (TM), em comparação com os pacientes submetidos a procedimentos de revascularização.
Métodos:
Estudo prospectivo de coorte com 560 pacientes ambulatoriais de um hospital terciário com seguimento médio de 5 anos. Os pacientes foram classificados nos grupos TM (n = 288), ICP (n = 159) e CRM (n = 113) de acordo com sua estratégia inicial de tratamento. Os desfechos primários foram mortalidade global e eventos combinados de morte, síndrome coronária aguda e AVC.
Resultados:
Durante o seguimento, as taxas de mortalidade foram de 11,1% em TM, 11,9% em ICP e 15,9% em pacientes submetidos à CRM, sem diferença estatística (Hazard Ratio [HR] para ICP, 1,05; Intervalo de Confiança de 95% [IC95%], 0,59 a 1,84; e HR para CRM, 1,20; IC95%, 0,68 a 2,15). Os desfechos combinados ocorreram com maior frequência entre os pacientes inicialmente submetidos à ICP em relação à TM (HR 1,50, IC 95% 1,05 a 2,14) e não diferiram entre TM e CRM (HR 1,24, IC95% 0,84 a 1,83). Entre os pacientes com diabetes (n = 198), a ICP foi a única estratégia terapêutica preditiva de desfechos combinados (HR 2,14; IC 95%: 1,25 a 3,63).
Conclusão:
Neste estudo observacional de doença arterial coronariana estável, não houve diferença na mortalidade global entre as estratégias iniciais de terapia médico ou de cirurgia de revascularização. Os pacientes inicialmente tratados com ICP tiveram maior chance de desenvolver eventos cardiovasculares maiores combinados.
Palavras-chave:Doença da Artéria Coronariana/cirurgiaRevascularização MiocárdicaConduta do Tratamento MedicamentosoIntervenção Coronária PercutâneaEstudos de CoortesIntrodução
A cirurgia de revascularização miocárdica (CRM) e a intervenção coronária percutânea (ICP) são estratégias amplamente utilizadas no tratamento da doença arterial coronariana (DAC) associadas à terapia médica (TM) otimizada. No entanto, nos últimos anos, evidências reduziram a indicação dos procedimentos de revascularização em pacientes estáveis, com resultados conflitantes em relação aos benefícios e impacto na mortalidade quando comparados às opções iniciais de tratamento.1-9 Estudos prévios sugeriram que a ICP diminui os sintomas sem efeito prognóstico a longo prazo, mesmo quando comparada ao tratamento médico isolado.7,8 Dados mais recentes reforçaram a superioridade da CRM na prevenção de eventos cardíacos maiores em pacientes com doença multiarterial, especialmente em pacientes com doença arterial coronariana mais complexa e diabetes.10-12 No entanto, esses estudos mostraram resultados similares entre a CRM e a ICP quando pacientes com doenças menos complexas foram avaliados.10,12
Entre 2005 e 2008, 166.514 ICPs foram realizadas no Brasil pelo Sistema Único de Saúde (SUS), com média anual de 41.628 procedimentos ou 22/100.000 habitantes. Desses, 37% foram eletivos em pacientes com DAC estável. Os stents farmacológicos (SF) não são cobertos pelo SUS, e provavelmente uma proporção significativa dos pacientes brasileiros não têm terapia medicamentosa otimizada e acesso aos procedimentos de revascularização, com diferenças entre as regiões geográficas do Brasil.13 Portanto, os resultados de muitos ensaios clínicos podem não ser generalizáveis para a prática clínica do mundo real.
Mesmo em países desenvolvidos, existem lacunas na literatura sobre a eficácia das estratégias de tratamento em pacientes com DAC estável. Existem poucos ensaios clínicos comparando as opções terapêuticas e essa falta de conhecimento causa complexidade no processo de tomada de decisão. O objetivo desse estudo foi avaliar o prognóstico a longo prazo de pacientes com DAC estável tratada com terapia médica como opção inicial de tratamento, em comparação com pacientes submetidos à ICP ou CRM em um hospital público no Brasil.
MétodosPopulação do estudo
Trata-se de um estudo de coorte prospectivo realizado em pacientes ambulatoriais de um hospital universitário de nível terciário do sul do Brasil. Entre 1998 e 2011, foram admitidos 560 pacientes consecutivos com DAC estável. Todos os pacientes tinham DAC documentada, definida conforme a presença de pelo menos um dos seguintes itens: histórico documentado de infarto agudo do miocárdio (IAM), revascularização miocárdica percutânea ou cirúrgica, lesão > 50% em pelo menos uma artéria coronária avaliada por angiografia, ou presença de angina e teste não-invasivo positivo de isquemia.14
Os pacientes foram divididos em três grupos, de acordo com a estratégia de intervenção basal, adotada antes da inclusão nesse estudo: TM, ICP ou CRM. Durante o acompanhamento, os pacientes foram tratados por uma equipe multidisciplinar de acordo com as diretrizes atuais e a critério dos médicos assistentes. Os pacientes submetidos à ICP ou CRM durante o seguimento foram identificados, embora eles tenham sido analisados de acordo com sua classificação original. Todos os pacientes incluídos no estudo tinham dados clínicos e laboratoriais completos no início do estudo, pelo menos três consultas e um ano de seguimento. Esse estudo foi aprovado pelo Comitê de Ética e Pesquisa Institucional.
Seguimento e desfechos
Pacientes estáveis foram periodicamente avaliados a cada 3 a 6 meses. Em cada visita, foi preenchido um formulário padronizado, o qual incluiu o histórico corrente da doença, controle de fatores de risco cardiovascular, novos eventos cardíacos (incluindo dados de admissão e procedimentos invasivos), exames laboratoriais e cardíacos e tratamento farmacológico e não-farmacológico. As comorbidades relevantes foram avaliadas através de questionário e revisão de prontuários.
Os desfechos de interesse primários foram morte por qualquer causa e ocorrência de um evento cardiovascular adverso maior (ECAM), definido como síndrome coronária aguda (SCA), acidente vascular cerebral e morte. A síndrome coronária aguda foi definida como admissão hospitalar causada por dor torácica ou sintomas relacionados e um diagnóstico médico na alta hospitalar de IAM ou angina instável. Também foram avaliadas a mortalidade por todas as causas e a necessidade de revascularização (cirúrgica ou percutânea).
Análise estatística
As variáveis contínuas foram expressas como média ± 1 desvio-padrão (DP) e as não-contínuas foram expressas como mediana e intervalo interquartil (IIQ) e foram comparadas utilizando-se o teste t pareado ou o teste de postos com sinais de Wilcoxon, conforme apropriado. Os dados categóricos foram apresentados como frequências e foram comparados pelo teste Qui-quadrado ou teste exato de Fisher. Todos os testes foram bicaudais. Resultados de longo prazo foram comparados entre aqueles inicialmente submetidos a tratamento médico, com os resultados daqueles submetidos à CRM e ICP, independentemente do tipo de stent. A análise primária avaliou o tempo até o primeiro ECAM. As curvas de sobrevivência foram obtidas através da análise de Kaplan-Meier e comparadas utilizando teste de postos com sinais. Análises multivariadas de Cox foram utilizadas para comparar a sobrevida livre de eventos entre os grupos. Nas análises multivariadas, os parâmetros clínicos ou significativamente associados aos principais desfechos foram incluídos nos modelos. Os resultados foram ajustados para sexo, idade, diabetes, tabagismo, disfunção ventricular, doença renal crônica e presença de comorbidades, como doença vascular periférica, doença cerebrovascular, doença pulmonar obstrutiva crônica (DPOC), doença hepática e câncer. As variáveis que tiveram algum efeito sobre a variável de interesse foram selecionadas pelo método manual e pelo método stepwise (p < 0,10). Todos os dados foram analisados utilizando-se o programa SPSS (versão 11.0.0, SPSS, Chicago, Illinois, EUA) e os valores de P inferiores a 0,05 foram considerados significativos.
Resultados
O seguimento médio do estudo foi de 5,1 anos. Dos 560 pacientes, 288 (51,4%) foram inicialmente tratados com TM, 159 (28,4%) com ICP e 113 (20,2%) com CRM. As características basais dos pacientes de acordo com a estratégia de manejo são mostradas na Tabela 1. Os pacientes no grupo ICP mostraram maior probabilidade de apresentar IAM prévio do que os dos outros dois grupos. Os pacientes do grupo CRM tinham mais hipertensão, dislipidemia, disfunção ventricular esquerda e, como esperado, maior proporção de pacientes com doença coronariana triarterial.
Características basais dos pacientes
Total n = 560
TM n = 288
ICP n = 159
RM n = 113
p valor
Idade, anos
62 ± 11
62 ± 11
61 ± 12
63 ± 10
0,16
Sexo masculino
329 (58,8)
170(59)
85 (53,5)
74 (65,5)
0,14
Diabetes Melito
198 (35,4)
110 (38,2)
47 (29,6)
41 (36,3)
0,18
Hipertensão
438 (78,2)
226 (78,5)
114 (71,7)
98 (86,7)
0,01
Dislipidemia
355 (63,4)
178 (61,8)
96 (60,4)
81 (71,7)
0,05
Tabagismo (atual)
83 (14,8)
45 (15,6)
31 (19,5)
7 (6,2)
0,02
Tabagismo (prévio)
264 (47,1)
132 (45,8)
67 (42,1)
65 (57,5)
0,02
Infarto do miocárdio
289 (51,6)
130 (45,1)
108 (67,9)
51 (45,1)
< 0,001
Doença cerebrovascular
58 (10,4)
33 (11,5)
15 (9,4)
10 (8,8)
0,67
Insuficiência renal
86 (15,4)
36 (12,5)
25 (15,7)
25 (22,1)
0,06
FEVE (%)
54 ± 13
55 ± 14
54 ± 13
50 ± 11
0,01
FEVE <50%
188 (33,6)
94 (32,6)
43 (27)
51 (45,1)
< 0,01
Doença triarterial
81 (14,5)
30 (17,3)
14 (10,8)
37 (41,6)
< 0,001
Os dados são expressos como média ± desvio padrão ou como número (%).
Os valores de p foram obtidos através do teste do qui-quadrado para as variáveis categóricas e do teste t de Student para as variáveis contínuas.
TM: terapia medicamentosa; ICP: intervenção coronária percutânea; RM: revascularização miocárdica; FEVE: fração de ejeção do ventrículo esquerdo.
A mortalidade por todas as causas ocorreu em 69 pacientes (12,3%), com incidência anual de mortalidade de 2,5% ao ano (13 eventos/ano). As taxas de sobrevivência acumuladas para os pacientes atribuídos a cada grupo foram 89% para TM, 88% para ICP e 84% para CRM (p = 0,82). Durante o seguimento, 115 pacientes (20,5%) foram submetidos à ICP e 56 pacientes (10%) foram submetidos à CRM. A taxa de eventos e as comparações entre os grupos estão mostradas na Tabela 2. Os pacientes dos grupos ICP e CRM apresentaram maior incidência de SCA (22,6% e 23,9%, respectivamente) quando comparados ao grupo TM (14,9%, p = 0,04). Por outro lado, a taxa de cirurgia de revascularização miocárdica durante o seguimento foi maior nos grupos TM (14,2%) e ICP (6,9%) quando comparados com o grupo CRM (3,5%) (p < 0,01).
Desfechos primários e secundários
Total n = 560
TM n = 288
ICP n = 159
RM n = 113
p valor
Desfechos combinados
168 (30)
77 (26,7)
52 (32,7)
39 (34,5)
0,21
Morte
69 (12,3)
32 (11,1)
19 (11,9)
18 (15,9)
0,41
SCA
106 (18,9)
43 (14,9)
36 (22,6)
27 (23,9)
0,04
AVC
14 (2,5)
9 (3,1)
5 (3,8)
0
0,16
Morte cardiovascular
40 (7,1)
23 (9)
7 (4,4)
10 (8,8)
0,27
Insuficiência cardíaca
24 (4,3)
10 (3,5)
6 (3,8)
8 (7,1)
0,26
Revascularização subsequente*
ICP
115 (20,5)
54 (18,8)
37 (23,3)
24 (21,2)
0,51
RM
56 (10)
41 (14,2)
11 (6,9)
4 (3,5)
< 0,01
Os dados são expressos como número total de eventos (%).
Os valores de p foram obtidos através do teste exato de Fisher para variáveis categóricas.
Alguns pacientes tiveram infarto do miocárdio não-fatal ou acidente vascular cerebral antes de sua morte subsequente, portanto, o número de eventos combinados é menor do que a soma de cada evento. Nas análises de sobrevivência, foi utilizado o tempo até o primeiro evento.
Os valores representam o primeiro procedimento de revascularização em pacientes que foram originalmente tratados com terapia medicamentosa
Ao final do seguimento, não houve diferença significativa na mortalidade ajustada entre os grupos (hazard ratio [HR] para o grupo ICP, 1,05, intervalo de confiança de 95% [IC95%], 0,59 a 1,84 e HR para o grupo CRM, 1,20; IC 95% 0,68 a 2,15), com curvas de sobrevivência virtualmente idênticas (Figura 1A). Na análise multivariada do modelo de Cox, idade, sexo masculino, diabetes e doença cerebrovascular foram preditores de mortalidade global (Tabela 3). Considerando a ocorrência de eventos maiores combinados, a ICP foi associada independentemente com pior prognóstico (HR 1,50, IC 95% 1,05 a 2,14), sem diferença entre TM e CRM (HR 1,24, IC 95% 0,84 a 1,83) (Figura 1B). Disfunção ventricular, diabetes e doença cerebrovascular também foram preditivos de eventos maiores (Tabela 3).
Análises multivariada comparando a sobrevida livre de eventos entre os grupos, ajustada para os parâmetros clínicos
Desfecho
HR
IC95%
p
Morte
Idade
1,04
1,01 - 1,07
0,005
Sexo masculino
2,17
1,14 - 4,13
0,018
Diabetes
2,22
1,28 - 3,86
0,005
Doença cerebrovascular
5,07
2,89 - 8,90
< 0,001
Insuficiência renal
1,65
0,93 - 2,91
0,086
Morte, infarto do miocárdio e acidente vascular cerebral
Disfunção ventricular esquerda
1,43
1,06 - 1,95
0,022
Diabetes
1,58
1,16 - 2,15
0,004
Doença cerebrovascular
1,73
1,16 - 2,59
0,008
Grupo ICP
1,50
1,05 - 2,14
0,026
Grupo RM
1,24
0,84 - 1,83
0,270
Revascularização
Disfunção ventricular esquerda
1,46
1,05 - 2,05
0,025
Diabetes
1,88
1,37 - 2,59
< 0,001
Infarto do miocárdio prévio
0,58
0,42 - 0,82
0,002
Grupo ICP
1,85
1,13 - 3,02
0,015
Grupo terapia medicamentosa
1,55
1,01 - 2,41
0,049
HR: Hazard Ratio; IC95%: intervalo de confiança de 95%; ICP: intervenção coronária percutânea; RM: revascularização do miocárdio
Probabilidade não-ajustada de sobrevivência livre de eventos nos pacientes dos grupos de tratamento com TM, RM e ICP, ajustado para parâmetros clínicos. A: mortalidade global; B: eventos combinados de morte, infarto do miocárdio e acidente vascular cerebral; C: revascularização.
Ambos os grupos TM e ICP apresentaram maior probabilidade de necessitar revascularização adicional (ICP ou CRM) durante o seguimento, após a análise multivariada (HR = 1,55, IC95% 1,01 a 2,41 e HR = 1,85, IC95% 1,13 a 3,02, respectivamente) (Figura 1C). A mediana do tempo até a revascularização subsequente foi de 32 meses (IIQ: 11 a 79) na TM, 32 meses (IIQ 8 a 79) na ICP e 38 meses (IIQ 24 a 83) no grupo CRM (p = 0,019). Disfunção ventricular e diabetes também foram preditivos de revascularização adicional, e o infarto agudo do miocárdio prévio foi inversamente associado com esse desfecho (Tabela 3).
Análises de subgrupos
Analisamos também as taxas de eventos combinados maiores em pacientes com diabetes e doença coronariana triarterial, fatores identificados como determinantes na escolha da terapia em pacientes com DAC estável. Não houve diferença significativa no desfecho entre a estratégia de manejo inicial em pacientes com doença coronariana triarterial (HR = 1,22, IC 95% 0,36 a 4,15 no grupo ICP e HR = 1,05, IC 95% 0,40 a 2,73 no grupo CRM). No entanto, em pacientes com diabetes, o grupo PCI foi preditor de eventos maiores combinados nas análises multivariadas (HR = 2,14; IC 95% 1,26 a 3,63).
Discussão
O presente estudo relata os resultados de uma coorte de um ambulatório de um hospital universitário de nível terciário do Sul do Brasil. Os países em desenvolvimento são caracterizados por um acesso limitado a terapias e dificuldades na incorporação de novas tecnologias, onde a lacuna na aplicação dos resultados dos ensaios clínicos é ainda mais evidente.
As diretrizes nacionais e internacionais para o manejo de pacientes com DAC estável recomendam revascularização com CRM para pacientes sintomáticos com doença não-protegida da artéria coronária esquerda principal, doença triarterial com ou sem doença da artéria descendente anterior esquerda proximal ou doença biarterial com artéria descendente anterior esquerda proximal (Classe de recomendação I). Para os mesmos pacientes, a ICP tem uma Classe de recomendação IIa para melhora da sobrevida. No entanto, todas as recomendações de revascularização para melhorar a sobrevivência são baseadas no nível de evidência B ou C.14-16 As diretrizes enfatizam a importância de se usar uma abordagem da Equipe Cardíaca para decidir qual terapia é a melhor para cada paciente, demonstrando que a estratégia terapêutica ideal em pacientes com DAC estável não é simples.15
O estudo Second Medical, Angioplasty, or Surgery Study (MASS II) foi o primeiro ensaio clínico randomizado com DAC estável multiarterial que comparou as três estratégias terapêuticas atuais: ICP com stents convencionais versus CRM versus TM isolada.9 Os dados de seguimento de 5 e 10 anos não mostraram diferenças na mortalidade global entre os grupos. A CRM foi superior à TM e à ICP para os desfechos combinados de IAM, revascularização adicional e mortalidade.17,18 Os resultados do nosso estudo foram consistentes com os achados do estudo MASS II em relação à mortalidade geral e revascularização subsequente, sugerindo que a estratégia inicial com TM pode ser considerada, reconhecendo-se que durante um acompanhamento de longo prazo um procedimento de revascularização pode ser necessário. No entanto, o seguimento de 10 anos do estudo MASS II mostrou uma maior incidência de IAM na TM e ICP em comparação aos pacientes submetidos à CRM, o que demonstra o melhor prognóstico dos pacientes cirúrgicos.18
A ausência de diferença de mortalidade entre as estratégias TM e ICP corrobora as descobertas do estudo Clinical Outcomes Utilizing Revascularizationand Aggressive Drug Evaluation (COURAGE), que mostrou taxas de mortalidade de 7,6% no grupo ICP e 8,3% no grupo TM.8 O subestudo nuclear do estudo COURAGE, no entanto, observou uma relação graduada entre o risco de eventos e a extensão e gravidade da isquemia residual ao final do seguimento. Além disso, a revascularização com ICP resultou em uma redução mais efetiva da isquemia do que a TM de forma isolada. Embora não evidenciada pelo estudo clínico, uma interpretação pragmática desses dados indica revascularização para pacientes com mais de 10% de isquemia durante o teste de estresse.19 Nosso estudo não avaliou dados de testes de estresse e não considerou o grau de isquemia na análise, limitando a capacidade de identificar um subgrupo de pacientes com pior prognóstico no grupo TM. Por outro lado, uma sub-análise do estudo STICH mostrou que, em pacientes com DAC com disfunção ventricular grave (fração de ejeção ≤ 35%), a isquemia miocárdica induzível não identificou pacientes com pior prognóstico ou aqueles com maior benefício da CRM sobre a TM isoladamente.20
Resultados semelhantes em relação à mortalidade global foram observados no estudo BARI 2D, no qual a sobrevida cumulativa não diferiu significativamente entre os grupos de revascularização (88,3%) e TM (87,8%, p = 0,97).11 Essas taxas são muito semelhantes às encontradas em nosso estudo. No entanto, observou-se um pior prognóstico no grupo ICP quando eventos combinados foram analisados, especialmente no subgrupo de pacientes diabéticos. Essa diferença pode ser atribuída ao uso de stents convencionais em nossos pacientes (a opção disponível no sistema público de saúde de nosso país), em oposição à ampla utilização de stents farmacológicos no estudo BARI 2D. Os eventos cardiovasculares maiores, significativamente reduzidos em pacientes selecionados para submeter-se à CRM em comparação com TM, diferem dos nossos resultados.
O estudo FREEDOM mostrou que os eventos combinados de morte, IAM e acidente vascular encefálico ocorreram com maior frequência em pacientes que foram submetidos à ICP em comparação com CRM (26,6% vs. 18,7%, respectivamente).12 Estes resultados são consistentes com os estudos ARTS,21 CARDia22 e SYNTAX (análise de subgrupos),10 nos quais taxas mais elevadas de eventos cardiovasculares adversos maiores foram observadas em pacientes diabéticos submetidos à ICP em vez da CRM. Semelhante aos nossos resultados, as taxas de revascularização foram significativas no grupo ICP. Do mesmo modo, uma meta-análise recente de seis estudos randomizados utilizando estratégias de terapia contemporânea comparou a CRM e a ICP com SFs.23 Embora não houvesse diferenças significativas nas taxas de morte ou IAM em 1 ou 2 anos, essas diferenças foram evidentes após 5 anos de acompanhamento, favorecendo a CRM.
A análise de subgrupos realizada em nossos pacientes com doença triarterial não mostrou diferença nos eventos combinados entre as estratégias de manejo inicial. Embora a doença multiarterial seja considerada uma DAC complexa, os resultados do estudo SYNTAX demonstraram a importância de estimar a gravidade das lesões e mostraram que os eventos cardíacos maiores não diferiram significativamente entre ICP e CRM em pacientes com baixo escore SYNTAX.10 O presente estudo não mediu a complexidade da doença coronariana, limitando sua capacidade de fornecer dados comparativos sobre a melhor estratégia de revascularização para pacientes com doença multiarterial. Em um grande estudo observacional norte-americano, pacientes com mais de 65 anos com DAC multiarterial tiveram uma melhor sobrevivência em longo prazo quando submetidos à CRM em comparação com pacientes submetidos à ICP.24 Resultados similares foram encontrados em um pool de dados obtidos de três grandes estudos randomizados que compararam resultados em longo prazo entre esses grupos,25 mostrando taxas mais baixas de IAM e revascularização repetida em pacientes com DAC multiarterial e de artéria coronária esquerda principal e IAM prévio. Demonstramos também um pior prognóstico no grupo ICP em pacientes em geral, mas não conseguimos demonstrar diferenças no subgrupo de doença multiarterial.
Nosso estudo teve limitações inerentes aos estudos observacionais. Além disso, utilizou dados de uma única instituição em um hospital de referência, e assim os resultados não podem ser generalizados. Entretanto, nossos resultados representam a prática clínica no mundo real em um sistema de saúde pública.
Conclusão
O presente estudo mostra que os pacientes com DAC estável que são inicialmente tratados com terapia médica em vez de revascularização coronária têm taxas semelhantes de morte por qualquer causa e eventos cardiovasculares maiores, quando comparados com aqueles inicialmente tratados de forma invasiva.
Fontes de Financiamento
O presente estudo foi financiado por FIPE - Fundo de Financiamento à Pesquisa e Eventos - HCPA.
Vinculação Acadêmica
Este artigo é parte de tese de Doutorado de Mariana Vargas Furtado pela Universidade Federal do Rio Grande do Sul.