|BOOKS AND TRIALS
|Year : 2016 | Volume
| Issue : 1 | Page : 31-33
Recent trials in cardiology: Newer evidence in management of coronary artery disease
Gagandeep Singh Wander MD, DM
Department of Cardiology, Medanta The Medicity, Gurgaon, Haryana, India
|Date of Web Publication||14-Jun-2016|
Gagandeep Singh Wander
Department of Cardiology, Medanta - The Medicity, Sector 38, Gurgaon - 122 001, Haryana
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Wander GS. Recent trials in cardiology: Newer evidence in management of coronary artery disease
. J Clin Prev Cardiol 2016;5:31-3
We discuss few recent trials in the management of coronary artery disease with the potential to change our everyday clinical practice. Recent evidence has again shown the absence of survival benefit over long-term in stable ischemic heart disease patients who undergo percutaneous coronary artery intervention (PCI). At the same time, simultaneous control of multiple risk factors in diabetics has been found to decrease cardiovascular morbidity and mortality. Diabetics also seem to benefit from extending the duration of clopidogrel treatment >12 months regarding very late death or myocardial infarction (MI). Single stage PCI in non-ST-segment MI patients with the multivessel disease has been found to be not only safe but also superior to multistaged PCI regarding repeat coronary revascularization. However, ranolazine has been found to be ineffective in angina relief in patients who have incomplete revascularization after PCI.
| Effect of PCI on Long-term Survival in Patients with Stable Ischemic Heart Disease|| |
Clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial: 15 years follow-up
Sedlis SP, Hartigan PM, Teo KK, Maron DJ, Spertus JA, Mancini GB, et al. Effect of PCI on long-term survival in patients with stable ischemic heart disease. N Engl J Med 2015;373:1937-46.
Percutaneous coronary intervention (PCI) has been shown to increase survival rates in patients with acute ST-segment elevation myocardial infarction (MI) and among patients with non-ST-segment elevation MI. However in patients with stable ischemic heart disease, although PCI relieves angina and reduces the extent of myocardial ischemia, but trials have not shown a survival benefit. Between June 1999 and January 2004, in COURAGE trial 2287 patients with stable ischemic heart disease were randomly assigned to an initial management strategy of optimal medical therapy alone (medical-therapy group) or optimal medical therapy plus PCI (PCI group) and there was no significant difference in the rate of survival during a median follow-up of 4.6 years. The investigators now report the rate of survival among the patients who were followed for up to 15 years.
The investigators obtained permission from the patients at the Department of Veterans Affairs (VA) sites and some non-VA sites in the United States to use their social security numbers to track their survival after the original trial period ended. They also searched the VA national Corporate Data Warehouse and the National Death Index for survival information and the dates of death from any cause.
Extended survival information was available for 1211 patients (53% of the original population). The median duration of follow-up for patients at the sites that permitted survival tracking was 11.9 years (range, 0-15). A total of 561 deaths (180 during the follow-up period in the original trial and 381 during the extended follow-up period) occurred: 284 deaths (25%) in the PCI group and 277 (24%) in the medical-therapy group (adjusted hazard ratio, 1.03; P = 0.76).
During an extended follow-up of up to 15 years in COURAGE trial, there was no difference in survival between an initial strategy of PCI plus medical therapy and medical therapy alone in patients with stable ischemic heart disease.
| Comprehensive Cardiovascular Risk Factor Control Improves Survival. The BARI 2D Trial|| |
Bittner V, Bertolet M, Barraza Felix R, Farkouh ME, Goldberg S, Ramanathan KB, et al. Comprehensive cardiovascular risk factor control improves survival: The BARI 2D trial. J Am Coll Cardiol 2015;66:765-73.
It is unclear that achievement of multiple risk factors goals through protocol guided intensive medical therapy is feasible and associated with improved survival and lower cardiovascular event rates among patients with coronary heart disease and type 2 diabetes mellitus (DM). This aim of the study was to quantify the relationship between achieved goals in the bypass angioplasty investigation revascularization 2 diabetes (BARI 2D) trial and cardiovascular events/survival. The study performed a nonrandomized analysis of survival/cardiovascular events and control of six risk factors (no smoking, non-high-density lipoprotein cholesterol <130 mg/dl, triglycerides <150 mg/dl, blood pressure [systolic <130 mmHg; diastolic <80 mmHg], glycosylated hemoglobin <7%) in BARI 2D.
In 2265 patients (mean age 62 years, 29% women) followed up for 5 years, the mean number of risk factors in control improved from 3.5 at baseline to 4.2 at 5 years (P < 0.0001). The number of risk factors in control during the trial was strongly related to death (P = 0.0010) and the composite of death, myocardial infarction, and stroke (P = 0.0035) in fully adjusted models. Participants with 0-2 risk factors in control during follow-up had a 2-fold higher risk of death (hazard ratio [HR]: 2.0; P = 0.0031) and a 1.7-fold higher risk of the composite endpoint (HR: 1.7; P = 0.0043), compared with those with six risk factors in control.
Simultaneous control of multiple risk factors through protocol-guided intensive medical therapy is feasible and decreases cardiovascular morbidity and mortality in patients with coronary disease and type 2 DM.
| Long-term Outcomes in Patients with Diabetes Mellitus Related to Prolonging Clopidogrel More Than 12 Months After Coronary Stenting|| |
Thukkani AK, Agrawal K, Prince L, Smoot KJ, Dufour AB, Cho K, et al. Long-term outcomes in patients with diabetes mellitus related to prolonging clopidogrel more than 12 months after coronary stenting. J Am Coll Cardiol 2015;66:1091-101.
Previous studies showed that discontinuing dual antiplatelet therapy (DAPT) in the first 12 months after percutaneous coronary artery intervention (PCI) increased the risk of myocardial infarction (MI), stent thrombosis, and death and led to the current recommendations of DAPT for a year. More recently, the DAPT study showed that in patients who are free of ischemic and major bleeding events in the 1 st year after PCI, prolonging DAPT a further 18 months reduced recurrent ischemic events. However, concerns of increased bleeding have elicited support for limiting prolonged treatment to high-risk patients. The aim of this study was to determine the effect of prolonging clopidogrel therapy >12 months versus <12 months after PCI on very late outcomes in patients with diabetes mellitus (DM).
Using the Veterans Health Administration database, 28,849 patients undergoing PCI between 2002 and 2006 were categorized into three groups: (1) 16,332 without DM; (2) 9905 with DM treated with oral medications or diet; and (3) 2612 with DM treated with insulin. Clinical outcomes, stratified by stent type, <4 years after PCI were determined from the Veterans Health Administration and Medicare Databases and risk was assessed by multivariable and propensity score analyses using a landmark analysis starting 1 year after the index PCI. The primary endpoint of the study was the risk of all-cause death or MI. In patients with DM treated with insulin who received drug-eluting stents (DES), prolonged clopidogrel treatment was associated with a decreased risk of death (hazard ratio [HR]: 0.59; 95% confidence interval [CI]: 0.42-0.82) and death or MI (HR: 0.67; 95% CI: 0.49-0.92). Similarly, in patients with noninsulin-treated DM receiving DES, prolonged clopidogrel treatment was associated with less death (HR: 0.61; 95% CI: 0.48-0.77) and death or MI (HR: 0.61; 95% CI: 0.5-0.75). Prolonged clopidogrel treatment was not associated with a lower risk in patients without DM or in any group receiving bare-metal stents.
Extending the duration of clopidogrel treatment >12 months may decrease very late death or MI only in patients with DM receiving first-generation DES. Future studies should address this question in patients receiving second-generation DES.
| Single-staged Compared with Multi-staged PCI in Multivessel NSTEMI Patients|| |
The SMILE trial
Sardella G, Lucisano L, Garbo R, Pennacchi M, Cavallo E, Stio RE, et al. Single-staged compared with multi-staged PCI in multivessel NSTEMI patients: The SMILE trial. J Am Coll Cardiol 2016;67:264-72.
Percutaneous coronary intervention (PCI) is the treatment of choice in patients with acute coronary syndromes (ACS). The role of complete coronary revascularization by PCI in patients with non-ST-segment elevation myocardial infarction (NSTEMI) is not clear. Histopathological, intravascular ultrasound, and optical coherence tomography analysis suggest that secondary plaque ruptures in patients with ACS are frequent (about 25%). Therefore, as observed in clinical observational studies, routine PCI of nonculprit arteries in NSTEMI may be of benefit. The aim of this study was to compare long-term outcomes in terms of major adverse cardiovascular and cerebrovascular events of two different complete coronary revascularization strategies in patients with NSTEMI and multivessel coronary artery disease: 1-stage PCI (1S-PCI) during the index procedure versus multistage PCI (MS-PCI) complete coronary revascularization during the index hospitalization.
In the SMILE (Impact of Different Treatment in Multivessel NSTEMI Patients: One Stage Versus Multistaged PCI) trial, 584 patients were randomly assigned in a 1:1 manner to 1S-PCI or MS-PCI. The primary study endpoint was the incidence of major adverse cardiovascular and cerebrovascular events, which were defined as cardiac death, death, reinfarction, rehospitalization for unstable angina, repeat coronary revascularization (target vessel revascularization), and stroke at 1 year.
The occurrence of the primary endpoint was significantly lower in the 1-stage group (1S-PCI: 13.63% vs. MS-PCI: 23.19%; hazard ratio [HR]: 0.549; P = 0.004). The 1-year rate of target vessel revascularization was significantly higher in the MS-PCI group (1S-PCI: 8.33% vs. MS-PCI: 15.20%; HR: 0.522; P = 0.01). When the analyses were limited to cardiac death (HR: 0.624; P = 0.27) and MI (HR: 0.678; P = 0.46), no significant differences were observed between groups.
In multivessel NSTEMI patients, complete 1-stage coronary revascularization is superior to MS-PCI regarding major adverse cardiovascular and cerebrovascular events.
| Effects of Ranolazine on Angina and Quality of Life After Percutaneous Coronary Intervention with Incomplete Revascularization|| |
Results from the ranolazine for incomplete vessel revascularization (RIVER-PCI) trial
Alexander KP, Weisz G, Prather K, James S, Mark DB, Anstrom KJ, et al. Effects of ranolazine on angina and quality of life after percutaneous coronary intervention with incomplete revascularization: Results from the ranolazine for incomplete vessel revascularization (RIVER-PCI) trial. Circulation 2016;133:39-47.
The large-scale, placebo-controlled randomized ranolazine in patients with incomplete revascularization after percutaneous coronary intervention (RIVER-PCI) trial was designed to evaluate the efficacy of ranolazine in addition to standard medical therapy in patients with incomplete revascularization (ICR) following PCI. The main results of RIVER-PCI published in Lancet revealed that ranolazine compared with placebo did not reduce the primary composite end point of ischemia-driven re-hospitalization or revascularization after a median follow-up of 643 days (26.2% vs. 28.3%, respectively; HR 0.95; 95% confidence interval [CI]: 0.82-1.10). Ranolazine is an inhibitor of the late sodium current, and it minimizes the adverse effect of intracellular sodium and calcium overload in the setting of myocardial ischemia, thereby reducing angina frequency and improving exercise performance in patients with chronic angina. It was hypothesized that ranolazine would be effective in reducing angina and improving the quality of life (QOL) in ICR post-PCI patients.
2604 patients with a history of chronic angina who had ICR post-PCI were randomized 1:1 to oral ranolazine versus placebo and QOL analyses included 2389 randomized subjects. Angina and QOL questionnaires were collected at baseline and months 1, 6, and 12. Ranolazine patients were more likely than placebo to discontinue study drug by 12 months (27.2% vs. 21.3%, P < 0.001). Following qualifying index PCI, the primary QOL outcome (Seattle Angina Questionnaire [SAQ] angina frequency score) improved markedly, but similarly, in the ranolazine and placebo groups, respectively, from baseline (67.3 ± 24.5 vs. 69.7 ± 24.0, P = 0.01) to month 1 (86.6 ± 18.1 vs. 85.8 ± 18.5, P = 0.27) and month 12 (88.4 ± 17.8 vs. 88.5 ± 17.8, P = 0.94). SAQ angina frequency repeated measures did not differ in adjusted analysis between groups post baseline (mean difference 1.0; 95% CI: 0.2-2.2; P = 0.11). Improvement in SAQ angina frequency was observed with ranolazine at month 6 among diabetics (mean difference 3.3; 95% CI: 0.6-6.1; P = 0.02) and those with more angina (baseline SAQ angina frequency ≤60; mean difference 3.4; 95% CI: 0.6-6.2; P = 0.02), but was not maintained at month 12.
After ICR following PCI, there was no incremental benefit in angina or QOL measures by adding ranolazine in this angiographically-identified population.