|Year : 2016 | Volume
| Issue : 2 | Page : 79-81
Alok Kumar Singh
Department of Cardiology, Heritage Hospital, Varanasi, Uttar Pradesh, India
|Date of Web Publication||6-Jun-2016|
Alok Kumar Singh
Department of Cardiology, Heritage Hospital, Varanasi, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Singh AK. Journal watch. Heart India 2016;4:79-81
The AFTER EIGHT trial: Invasive versus conservative strategy in patients aged 80 years or older 
Older patients of unstable angina (USA) and non-ST-segment elevation myocardial infarction (NSTEMI) are at a higher risk compared with younger patients and are less likely to receive invasive therapies in compared to younger patients. These subgroups of patients are mostly underrepresented in large landmark randomized revascularization trials. Therefore, the available data are not enough to recommend revascularization in this age group. The AFTER EIGHT trial compared an early invasive strategy with a conservative strategy in patients aged 80 years or older. This study enrolled 457 patients of 80 years or older of USA and NSTEMI; the patients were randomized to an invasive strategy (n = 229) or to a conservative strategy (n = 228). The study was an open-label trial. Clinically, unstable patients with continuing chest pain or other ischemic symptoms or signs, cardiogenic shock, continuing bleeding problems, or life expectancy <12 months were excluded from the study. The primary endpoint was a composite of MI, need for urgent revascularization, stroke, and all-cause death. The patients randomized to a conservative strategy received optimum medical treatment in their local hospitals. Patients randomized to an invasive strategy were transported to Oslo University Hospital. Patients undergoing percutaneous coronary intervention were returned to their local hospitals after 6-18 h, whereas patients undergoing only coronary angiography were returned to local hospitals after 4-6 h. Over a median follow-up of 1.53 years, the primary outcome occurred in 40.6% of the invasive group and 61.4% of the conservative group (hazard ratio [HR]: 0.53, 95% confidence interval [CI], 0.41-0.69, P = 0.0001). HRs for the four components of the primary endpoint were 0.52 (0.35-0.76; P = 0.0010) for MI, 0.19 (0.07-0.52; P = 0.0010) for the need for urgent revascularization, 0.60 (0.25-1.46; P = 0.2650) for stroke, and 0.89 (0.62-1.28; P = 0.5340) for all-cause death. Four (1.7%) major and 23 (10.0%) minor bleeding complications occurred in the invasive group, whereas 4 (1.8%) major and 16 (7.0%) minor bleeding complications occurred in the conservative group. Overall conclusion of the study was an invasive strategy was superior to a conservative strategy in clinically stable patients aged 80 years or older with NSTEMI or USA. However, superiority of the invasive strategy was decreased with increasing age. In AFTER-EIGHT study, there were only 34 patients older than 90 years, so benefit of an invasive strategy is still uncertain for patients older than 90 years.
The SEPTAL CRT trial: Right ventricular (RV) septal versus apical pacing in CRT 
Nonresponse to cardiac resynchronization therapy remains a significant problem in up to 30% of patients. It is not clear, whether the RV lead position improves the response to CRT. The multicenter, randomized SEPTAL CRT trial investigated the effects of the RV lead positions on the parameters left ventricle (LV) reverse remodeling. This study enrolled 263 patients with a mean age of 63.4 ± 9.5 years. The patients were randomized RV septal (n = 131) versus RV apical (n = 132) pacing. LV end-systolic volume reduction at 6 months was −25.3 ± 39.4 mL in the septal group versus −29.3 ± 44.5 mL in the apical group (P = 0.79). RV septal pacing is noninferior to RV apical pacing. The percentage of "echo-responders" was also similar between the two groups. Procedural or device-related complications were not different between the groups. Hence, overall conclusion of the study was nonresponder rate of CRT cannot be changed by changing the RV lead position.
The SPRINT trial: Intensive versus standard blood pressure control 
Randomized controlled trials in patients with hypertension demonstrated the benefit of treatment to achieve a systolic blood pressure (SBP) of <150 mm Hg, but there is limited randomized data about lower blood-pressure targets. SPRINT compared the effects of antihypertensive treatment with an SBP target of <120 mm Hg (intensive treatment) versus <140 mm Hg (standard treatment) in 9361 hypertensive adults ≥50 years of age who had an average SBP of 130-180 mm Hg. SPRINT was designed to recruit study participants with an average cardiovascular (CVD) risk of ≈2% per year. The SPRINT (SBP Intervention Trial) study evaluated the benefit of lowering SBP to <120 mm Hg. The trial was sponsored by the NHLBI in the USA. The patients were randomized to intensive therapy targeting an SBP <120 mm Hg, or standard therapy targeting an SBP <140 mm Hg. Patients with diabetes mellitus, prior stroke, or advanced chronic kidney disease were excluded from the study. All major classes of antihypertensive agents were allowed. Investigators could also prescribe other antihypertensive medications at their discretion. The primary outcome of the study was the composite of MI, other acute coronary syndromes, stroke, heart failure, or CVD death. Mean SBP at 1 year was 121.4 mm Hg in the intensive control group versus 136.2 mm Hg in the standard group. In a median follow-up of 3.26 years, the primary endpoint events occurred less in the intensive control group (1.65% vs. 2.19% per year, HR: 0.75, 95% CI, 0.64-0.89, P < 0.001); therefore, the study was terminated prematurely. All-cause mortality rate was also lower in the intensive control group (HR: 0.73, 95% CI, 0.60-0.90, P = 0.003). Separation in mortality between the groups became apparent at approximately 2 years. The rate of serious adverse events was 38.3% in the intensive-treatment group and 37.1% in the standard treatment group (P = 0.25). Serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury/failure were more frequent in the intensive treatment group than in the standard treatment, whereas the rate of injurious falls or bradycardia was similar in the two groups. Overall conclusion of the study was targeting an SBP of <120 mm Hg in patients at high risk for CVD events but without diabetes was more beneficial compared with an SBP target of <140 mm Hg. One important thing to understand, control of SBP to <120 mm Hg was achieved in less than half the participants. Therefore, achieving a systolic blood pressure goal of <120 mm Hg in routine daily practice, especially in elderly hypertensives would be more demanding.
The TUXEDO-India trial: Paclitaxel-eluting versus everolimus-eluting stents in diabetes 
Everolimus-eluting stents have been shown to be superior to paclitaxel-eluting stents with respect to both angiographic and clinical end points in most patients, but the results in the population with diabetes have not been so consistent. In subgroup analyses of randomized trials in diabetic patients, efficacy and safety of paclitaxel-eluting stents were similar to those of limus-eluting stents. However, previous randomized trials were not sufficiently powered to evaluate the clinical outcomes in patients with diabetes. The TUXEDO-India trial compared paclitaxel-eluting stents with everolimus-eluting stents in patients with diabetes. This study included 1830 patients with stable coronary artery disease or acute coronary syndrome and randomly assigned to receive either a paclitaxel-eluting stent (Taxus element) (n = 914) or an everolimus-eluting stent (Xience Prime) (n = 916). The primary endpoint of the study was the composite of cardiac death, target vessel MI, or ischemia-driven target vessel revascularization at 1 year. The rate of the primary endpoint was 5.6% in the paclitaxel-eluting stent group versus 2.9% in the everolimus-eluting stent group. Paclitaxel-eluting stents did not only meet the criterion for noninferiority to everolimus-eluting stents (relative risk 1.89, 95% CI, 1.20-2.99, P = 0.38 for noninferiority) but also everolimus-eluting stents were superior to paclitaxel-eluting stents (P = 0.005). The rates of spontaneous MI, stent thrombosis, target vessel revascularization, and target-lesion revascularization were also higher in the paclitaxel-eluting stent group compared with the everolimus-eluting stent group. Overall conclusion of the study was everolimus-eluting stent were superior to paclitaxel-eluting Taxus Element stent in diabetic patients.
The CURRENT Aortic Stenosis (AS) (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe AS)-Early aortic valve replacement (AVR) strategy in patients with asymptomatic severe AS 
Current American Heart Association/American College of Cardiology and European Society of Cardiology guidelines recommend in most cases, a strategy of deferring AVR until symptoms emerge among asymptomatic patients with severe AS. The CURRENT AS study is a large multicenter registry enrolling 3815 consecutive patients with severe AS over the period of 8 years between 2003 and 2011. The registry included patients with severe AS; peak aortic jet velocity >4.0 m/s, or mean aortic pressure gradient >40 mm Hg, or aortic valve area <1.0 cm 2 . Of 3815 patients included in the registry, 2005 were symptomatic and 1808 were asymptomatic (two patients had unknown symptomatic status). Asymptomatic patients were subdivided into two groups: The initial AVR group (n = 291) and the conservative group (n = 1517). The selection of initial AVR was determined by physicians and baseline characteristics of the groups were different from each other. Thus, a propensity score-matched cohort of 582 patients (291 patients from each group) was developed. The primary endpoint was all-cause death and hospitalization due to heart failure. Baseline characteristics of the initial AVR and conservative groups were largely comparable, but the initial AVR group was slightly younger (71.6 years vs. 73.1 years, P = 0.047) had greater AS severity (mean gradient, 54 ± 20 vs. 45 ± 20 mm Hg) and slightly lower STS score (2.0 vs. 2.4, P = 0.007). The 30-day mortality rate following AVR was 1.4%. Among 291 asymptomatic patients in the initial AVR group, 184 patients had 1 or more formal indications for AVR: Very severe AS (vmax ≥5.0 m/s or mean gradient ≥60 mm Hg) in 118 patients, ejection fraction <50% in 19 patients, other cardiac surgery in 24 patients, rapid hemodynamic progression in 32 patients, and infective endocarditis in one patient. During the follow-up, AVR was performed in 41% of the conservative group. The 5-year incidence of all-cause death was 15.4% in the initial AVR group and 26.4% in the conservative group (P = 0009), and the 5-year incidence of heart failure hospitalization was 3.8% versus 19.9%, respectively (P < 0.001). The incidences of CVD death and aortic valve-related death were also significantly lower in the initial AVR group compared with the conservative group. The incidence of sudden death trended lower in the initial AVR group (3.6% vs. 5.8%, P = 0.06). In the entire cohort, sudden death occurred in 7.6% (1.5%/year) of the conservative group versus 3.6% (0.7%/year) of the initial AVR group. Among 82 patients experiencing sudden death in the conservative group, 57 patients died abruptly without preceding symptoms. Because of retrospective in nature, this study has serious limitations. These limitations should be taken into account while evaluating the study findings but at the same time studies supporting the watchful waiting approach for patients with asymptomatic severe AS is not higher quality study in comparison to this study. We need randomized trials comparing an initial AVR strategy with watchful waiting for AVR until the emergence of symptoms in asymptomatic patients with severe AS.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Tegn N, Abdelnoor M, Aaberge L, Endresen K, Smith P, Aakhus S, et al.
Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): An open-label randomised controlled trial. Lancet 2016;387:1057-65.
Leclercq C, Sadoul N, Mont L, Defaye P, Osca J, Mouton E, et al.
Comparison of right ventricular septal pacing and right ventricular apical pacing in patients receiving cardiac resynchronization therapy defibrillators: The SEPTAL CRT Study. Eur Heart J 2016;37:473-83.
SPRINT Research Group, Wright JT Jr., Williamson JD, Whelton PK, Snyder JK, Sink KM, et al.
A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015;373:2103-16.
Kaul U, Bangalore S, Seth A, Arambam P, Abhaychand RK, Patel TM, et al.
Paclitaxel-eluting versus everolimus-eluting coronary stents in diabetes. N Engl J Med 2015;373:1709-19.
Taniguchi T, Morimoto T, Shiomi H, Ando K, Kanamori N, Murata K, et al.
Initial surgical versus conservative strategies in patients with asymptomatic severe aortic stenosis. J Am Coll Cardiol 2015;66:2827-38.