Whady Hueb

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.

Background— Despite routine use of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), no conclusive evidence exists that either modality is superior to medical therapy (MT) alone for treating multivessel coronary artery disease with stable angina and preserved ventricular function. Methods and Results— The primary end points were total mortality, Q-wave myocardial infarction, or refractory angina requiring revascularization. The study comprised 611 patients randomly assigned to undergo CABG (n=203), PCI (n=205), or MT (n=203). At the 5-year follow-up, the primary end points occurred in 21.2% of patients who underwent CABG compared with 32.7% treated with PCI and 36% receiving MT alone (P=0.0026). No statistical differences were observed in overall mortality among the 3 groups. In addition, 9.4% of MT and 11.2% of PCI patients underwent repeat revascularization procedures compared with 3.9% of CABG patients (P=0.021). Moreover, 15.3%, 11.2%, and 8.3% of patients experienced nonfatal myocardial infarction in the MT, PCI, and CABG groups, respectively (P<0.001). The pairwise treatment comparisons of the primary end points showed no difference between PCI and MT (relative risk, 0.93; 95% confidence interval, 0.67 to 1.30) and a significant protective effect of CABG compared with MT (relative risk, 0.53; 95% confidence interval, 0.36 to 0.77). Conclusions— All 3 treatment regimens yielded comparable, relatively low rates of death. MT was associated with an incidence of long-term events and rate of additional revascularization similar to those for PCI. CABG was superior to MT in terms of the primary end points, reaching a significant 44% reduction in primary end points at the 5-year follow-up of patients with stable multivessel coronary artery disease.

The Medicine, Angioplasty or Surgery Study (MASS): A prospective, randomized trial of medical therapy, balloon angioplasty or bypass surgery for single proximal left anterior descending artery stenoses

OBJECTIVES This study sought to evaluate, in a prospective and randomized trial, the relative efficacies of three possible therapeutic strategies for patients with a single severe proximal stenosis of the left anterior descending coronary artery and stable angina. BACKGROUND Although percutaneous transluminal coronary angioplasty and coronary artery bypass surgery are often performed in patients with a single proximal stenosis of the left anterior descending coronary artery, it is unclear whether revascularization offers greater clinical benefit than medical therapy alone. METHODS At a single center, 214 patients with stable angina, normal ventricular function and a proximal stenosis of the left anterior descending coronary artery > 80% were randomly assigned to undergo mammary bypass surgery (n = 70), balloon angioplasty (n = 72) or medical therapy alone (n = 72). Angioplasty had to be considered technically feasible in every case. The predefined primary study end point was the combined incidence of cardiac death, myocardial infarction or refractory angina requiring revascularization. RESULTS At an average follow-up period of 3 years, a primary end point had occurred in only 2 patients (3%) assigned to bypass surgery compared with 17 assigned to angioplasty (24%) and 12 assigned to medical therapy (17%) (p = 0.0002, angioplasty vs. bypass surgery; p = 0.006, bypass surgery vs. medical treatment; p = 0.28, angioplasty vs. medical treatment, all by log-rank test). There was no difference in mortality or infarction rates among the groups. However, no patient allocated to bypass surgery needed revascularization, compared with eight and seven patients assigned, respectively, to coronary angioplasty and medical treatment (p = 0.019). Both revascularization techniques resulted in greater symptomatic relief and a lower incidence of ischemia on the treadmill test; however, all three strategies eventually resulted in the abolition of limiting angina. CONCLUSIONS The more aggressive therapeutic approach with initial bypass surgery for patients with a single severe proximal stenosis of the left anterior descending coronary artery is associated with a lower incidence of medium-term adverse events than coronary angioplasty or medical treatment. However, all three strategies resulted in a similar incidence of death and infarction during an average follow-up period of 3 years. This information should be taken into consideration when physicians and patients make therapeutic choices in this setting.

Long-Term Safety and Efficacy of Percutaneous Coronary Intervention With Stenting and Coronary Artery Bypass Surgery for Multivessel Coronary Artery Disease: A Meta-Analysis With 5-Year Patient-Level Data From the ARTS, ERACI-II, MASS-II, and SoS Trials

Background— Randomized trials that studied clinical outcomes after percutaneous coronary intervention (PCI) with bare metal stenting versus coronary artery bypass grafting (CABG) are underpowered to properly assess safety end points like death, stroke, and myocardial infarction. Pooling data from randomized controlled trials increases the statistical power and allows better assessment of the treatment effect in high-risk subgroups. Methods and Results— We performed a pooled analysis of 3051 patients in 4 randomized trials evaluating the relative safety and efficacy of PCI with stenting and CABG at 5 years for the treatment of multivessel coronary artery disease. The primary end point was the composite end point of death, stroke, or myocardial infarction. The secondary end point was the occurrence of major adverse cardiac and cerebrovascular accidents, death, stroke, myocardial infarction, and repeat revascularization. We tested for heterogeneities in treatment effect in patient subgroups. At 5 years, the cumulative incidence of death, myocardial infarction, and stroke was similar in patients randomized to PCI with stenting versus CABG (16.7% versus 16.9%, respectively; hazard ratio, 1.04, 95% confidence interval, 0.86 to 1.27; P=0.69). Repeat revascularization, however, occurred significantly more frequently after PCI than CABG (29.0% versus 7.9%, respectively; hazard ratio, 0.23; 95% confidence interval, 0.18 to 0.29; P<0.001). Major adverse cardiac and cerebrovascular events were significantly higher in the PCI than the CABG group (39.2% versus 23.0%, respectively; hazard ratio, 0.53; 95% confidence interval, 0.45 to 0.61; P<0.001). No heterogeneity of treatment effect was found in the subgroups, including diabetic patients and those presenting with 3-vessel disease. Conclusions— In this pooled analysis of 4 randomized trials, PCI with stenting was associated with a long-term safety profile similar to that of CABG. However, as a result of persistently lower repeat revascularization rates in the CABG patients, overall major adverse cardiac and cerebrovascular event rates were significantly lower in the CABG group at 5 years.

Ten-Year Follow-Up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II)

Background— This study compared the 10-year follow-up of percutaneous coronary intervention (PCI), coronary artery surgery (CABG), and medical treatment (MT) in patients with multivessel coronary artery disease, stable angina, and preserved ventricular function. Methods and Results— The primary end points were overall mortality, Q-wave myocardial infarction, or refractory angina that required revascularization. All data were analyzed according to the intention-to-treat principle. At a single institution, 611 patients were randomly assigned to CABG (n=203), PCI (n=205), or MT (n=203). The 10-year survival rates were 74.9% with CABG, 75.1% with PCI, and 69% with MT (P=0.089). The 10-year rates of myocardial infarction were 10.3% with CABG, 13.3% with PCI, and 20.7% with MT (P<0.010). The 10-year rates of additional revascularizations were 7.4% with CABG, 41.9% with PCI, and 39.4% with MT (P<0.001). Relative to the composite end point, Cox regression analysis showed a higher incidence of primary events in MT than in CABG (hazard ratio 2.35, 95% confidence interval 1.78 to 3.11) and in PCI than in CABG (hazard ratio 1.85, 95% confidence interval 1.39 to 2.47). Furthermore, 10-year rates of freedom from angina were 64% with CABG, 59% with PCI, and 43% with MT (P<0.001). Conclusions— Compared with CABG, MT was associated with a significantly higher incidence of subsequent myocardial infarction, a higher rate of additional revascularization, a higher incidence of cardiac death, and consequently a 2.29-fold increased risk of combined events. PCI was associated with an increased need for further revascularization, a higher incidence of myocardial infarction, and a 1.46-fold increased risk of combined events compared with CABG. Additionally, CABG was better than MT at eliminating anginal symptoms. Clinical Trial Registration Information— URL: http://www.controlled-trials.com. Registration number: ISRCTN66068876.

Percutaneous Coronary Intervention Outcomes in Patients With Stable Obstructive Coronary Artery Disease and Myocardial Ischemia: A Collaborative Meta-analysis of Contemporary Randomized Clinical Trials

IMPORTANCE Myocardial ischemia in patients with stable coronary artery disease (CAD) has been repeatedly associated with impaired survival. However, it is unclear if revascularization with percutaneous coronary intervention (PCI) to relieve ischemia improves outcomes compared with medical therapy (MT). OBJECTIVE The objective of this study was to compare the effect of PCI and MT with MT alone exclusively in patients with stable CAD and objectively documented myocardial ischemia on clinical outcomes. DATA SOURCES MEDLINE, Cochrane, and PubMed databases from 1970 to November 2012. Unpublished data were obtained from investigators. STUDY SELECTION Randomized clinical trials of PCI and MT vs MT alone for stable coronary artery disease in which stents and statins were used in more than 50% of patients. DATA EXTRACTION For studies in which myocardial ischemia diagnosed by stress testing or fractional flow reserve was required for enrollment, descriptive and quantitative data were extracted from the published report. For studies in which myocardial ischemia was not a requirement for enrollment, authors provided data for only those patients with ischemia determined by stress testing prior to randomization. The outcomes analyzed included death from any cause, nonfatal myocardial infarction (MI), unplanned revascularization, and angina. Summary odds ratios (ORs) were obtained using a random-effects model. Heterogeneity was assessed using the Q statistic and I2. RESULTS In 5 trials enrolling 5286 patients, myocardial ischemia was diagnosed in 4064 patients by exercise stress testing, nuclear or echocardiographic stress imaging, or fractional flow reserve. Follow-up ranged from 231 days to 5 years (median, 5 years). The respective event rates for PCI with MT vs MT alone for death were 6.5% and 7.3% (OR, 0.90 [95% CI, 0.71-1.16); for nonfatal MI, 9.2% and 7.6% (OR, 1.24 [95% CI, 0.99-1.56]); for unplanned revascularization, 18.3% and 28.4% (OR, 0.64 [95% CI, 0.35-1.17); and for angina, 20.3% and 23.3% (OR, 0.91 [95% CI, 0.57-1.44]). CONCLUSIONS AND RELEVANCE In patients with stable CAD and objectively documented myocardial ischemia, PCI with MT was not associated with a reduction in death, nonfatal MI, unplanned revascularization, or angina compared with MT alone.

Five-Year Follow-Up of a Randomized Comparison Between Off-Pump and On-Pump Stable Multivessel Coronary Artery Bypass Grafting. The MASS III Trial

Background— Coronary artery bypass graft surgery with cardiopulmonary bypass is a safe, routine procedure. Nevertheless, significant morbidity remains, mostly because of the bodys response to the nonphysiological nature of cardiopulmonary bypass. Few data are available on the effects of off-pump coronary artery bypass graft surgery (OPCAB) on cardiac events and long-term clinical outcomes. Methods and Results— In a single-center randomized trial, 308 patients undergoing coronary artery bypass graft surgery were randomly assigned: 155 to OPCAB and 153 to on-pump CAB (ONCAB). Primary composite end points were death, myocardial infarction, further revascularization (surgery or angioplasty), or stroke. After 5-year follow-up, the primary composite end point was not different between groups (hazard ratio 0.71, 95% CI 0.41 to 1.22; P=0.21). A statistical difference was found between OPCAB and ONCAB groups in the duration of surgery (240±65 versus 300±87.5 minutes; P<0.001), in the length of ICU stay (19.5±17.8 versus 43±17.0 hours; P<0.001), time to extubation (4.6±6.8 versus 9.3±5.7 hours; P<0.001), hospital stay (6±2 versus 9±2 days; P<0.001), higher incidence of atrial fibrillation (35 versus 4% of patients; P<0.001), and blood requirements (31 versus 61% of patients; P<0.001), respectively. The number of grafts per patient was higher in the ONCAB than the OPCAB group (2.97 versus 2.49 grafts/patient; P<0.001). Conclusions— No difference was found between groups in the primary composite end point at 5-years follow-up. Although OPCAB surgery was related to a lower number of grafts and higher episodes of atrial fibrillation, it had no significant implications related to long-term outcomes. Clinical Trial Registration— URL: http://www.controlled-trials.com. Unique identifier: ISRCTN66068876.

Coronary Revascularization (Surgical or Percutaneous) Decreases Mortality After the First Year in Diabetic Subjects but not in Nondiabetic Subjects With Multivessel Disease An Analysis From the Medicine, Angioplasty, or Surgery Study (MASS II)

Background— It is currently unknown whether revascularization procedures are associated with an improvement in mortality among diabetic subjects, as compared with a more conservative medical treatment. Methods and Results— In MASS II, a total of 611 patients with stable multivessel coronary disease were randomly assigned to medical treatment, surgery, or angioplasty. From these, 190 patients had diabetes (medical, 75 patients; angioplasty, 56 patients; surgery, 59 patients) and comprised the present study population. Mortality rates were analyzed for the entire 5 years of follow-up. Separate analyzes were also performed for mortality at 2 time intervals: during the first year and after the first year of follow-up. We calculated the probability of death conditional on surviving to the start of the interval analyzed. The cumulative 5-year mortality as well as the mortality during the first year of follow-up was not significantly different among treatment groups, both for diabetic and for nondiabetic subjects. Also, during years 2 to 5, the mortality of the 3 treatment groups was not different for nondiabetic subjects. Among diabetic subjects, however, patients randomized to angioplasty or surgery had a significantly lower mortality between years 2 and 5 than those allocated to medical treatment (P=0.039). Conclusion— Surgery, angioplasty, and medical treatment appear to be associated with similar mortality rates for non-diabetic subjects. For diabetic subjects, however, coronary revascularization (percutaneous or surgical) significantly decreased the risk of death after the first year and up to 5 years, compared with medical treatment alone.

Pulmonary function after coronary artery bypass surgery

Coronary artery bypass graft surgery (CABG) adversely affects pulmonary function tests (PFTs). Although several previous studies have addressed these changes, none has measured the forced vital capacity (FVC) on a daily basis. The purpose of the present study was to assess serial changes in the FVC following CABG and to identify factors that may influence these changes. The FVC was obtained pre- and daily postoperatively (1-10 days) in 120 patients. Fifty-one patients received saphenous vein grafts (SVG group) while 69 received at least one internal mammary artery graft in addition to SVG (IMA group). On the first postoperative day, the FVC decreased to 33% of the pre-operative value in the SVG group and to 29% in the IMA group. The spirometry gradually improved, but after 10 days, the FVC remained reduced (SVG, 70%; IMA, 60%). Although the decreases in FVC tended to be greater in the IMA group, there was no significant difference in the two groups (P = 0.27). The changes in FVC were not significantly related to age (P = 0.48), smoking history (P = 0.65), anesthesia (P = 0.38) or pump time (0.09). From this study, it is concluded that after CABG, there is a significant worsening of the pulmonary function. The nadir of FVC occurs immediately after surgery and improves gradually thereafter. However, on the tenth postoperative day, the FVC still remains more than 30% below pre-operative values. Since there is only a slight tendency for patients undergoing IMA grafting to have larger decreases in their pulmonary function, patients with ventilatory impairment should not be excluded from IMA grafting.

Factors related to the selection of surgical versus percutaneous revascularization in diabetic patients with multivessel coronary artery disease in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial.

OBJECTIVES We evaluated demographic, clinical, and angiographic factors influencing the selection of coronary artery bypass graft (CABG) surgery versus percutaneous coronary intervention (PCI) in diabetic patients with multivessel coronary artery disease (CAD) in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial. BACKGROUND Factors guiding selection of mode of revascularization for patients with diabetes mellitus and multivessel CAD are not clearly defined. METHODS In the BARI 2D trial, the selected revascularization strategy, CABG or PCI, was based on physician discretion, declared independent of randomization to either immediate or deferred revascularization if clinically warranted. We analyzed factors favoring selection of CABG versus PCI in 1,593 diabetic patients with multivessel CAD enrolled between 2001 and 2005. RESULTS Selection of CABG over PCI was declared in 44% of patients and was driven by angiographic factors including triple vessel disease (odds ratio [OR]: 4.43), left anterior descending stenosis >or=70% (OR: 2.86), proximal left anterior descending stenosis >or=50% (OR: 1.78), total occlusion (OR: 2.35), and multiple class C lesions (OR: 2.06) (all p < 0.005). Nonangiographic predictors of CABG included age >or=65 years (OR: 1.43, p = 0.011) and non-U.S. region (OR: 2.89, p = 0.017). Absence of prior PCI (OR: 0.45, p < 0.001) and the availability of drug-eluting stents conferred a lower probability of choosing CABG (OR: 0.60, p = 0.003). CONCLUSIONS The majority of diabetic patients with multivessel disease were selected for PCI rather than CABG. Preference for CABG over PCI was largely based on angiographic features related to the extent, location, and nature of CAD, as well as geographic, demographic, and clinical factors. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305).

TCF7L2 Polymorphism rs7903146 Is Associated with Coronary Artery Disease Severity and Mortality

Background TCF7L2 polymorphisms have been consistently associated with type 2 diabetes mellitus in different populations and type 2 diabetes mellitus is a major risk factor for cardiovascular disease, especially coronary artery disease. This study aimed to evaluate the association between TCF7L2 polymorphism rs7903146 and coronary artery disease in diabetic and non-diabetic subjects. Methods and Results two populations were studied in order to assess severity of coronary artery disease and cardiovascular events incidence. Eight-hundred and eighty nine subjects who were referred for cardiac catheterization for coronary artery disease diagnosis were cross-sectionally evaluated for coronary lesions (atherosclerotic burden) and 559 subjects from the MASS-II Trial were prospectively followed-up for 5 years and assessed for major cardiovascular events incidence. As expected, rs7903146 T allele was associated with diabetes. Although diabetic patients had a higher prevalence of coronary lesions, no association between TCF7L2 genotype and coronary lesions was found in this subgroup. However, non-diabetic individuals carrying the T allele were associated with a significantly higher frequency of coronary lesions than non-diabetic non-carriers of the risk allele (adjusted OR  = 2.32 95%CI 1.27–4.24, p = 0.006). Moreover, presence of multi-vessel coronary artery disease was also associated with the CT or TT genotypes in non-diabetics. Similarly, from the prospective sample analysis, non-diabetics carrying the CT/TT genotypes had significantly more composite cardiovascular end-points events than CC carriers (p = 0.049), mainly due to an increased incidence of death (p = 0.004). Conclusions rs7903146 T allele is associated with diabetes and, in non-diabetic individuals, with a higher prevalence and severity of coronary artery disease and cardiovascular events. name of registry site (see list below), registration number, trial registration URL in brackets. Clinical Trial Registration Information Medicine, Angioplasty, or Surgery Study (MASS II): Unique identifier: ISRCTN66068876.