Journal of Clinical and Preventive Cardiology

: 2016  |  Volume : 5  |  Issue : 4  |  Page : 149--152

Key messages from the European Society of Cardiology 2016 annual meeting

Manish Bansal 
 Department of Cardiology, Medanta The Medicity, Gurgaon, Haryana, India

Correspondence Address:
Manish Bansal
DNB Cardiology, FACC, FASE 3rd Floor OPD, Medanta - The Medicity, Gurgaon - 122 001, Haryana

How to cite this article:
Bansal M. Key messages from the European Society of Cardiology 2016 annual meeting.J Clin Prev Cardiol 2016;5:149-152

How to cite this URL:
Bansal M. Key messages from the European Society of Cardiology 2016 annual meeting. J Clin Prev Cardiol [serial online] 2016 [cited 2020 Dec 2 ];5:149-152
Available from:

Full Text

 Danish Study to Assess the Efficacy of Implantable Cardioverter defibrillators in Patients with Nonischemic Systolic Heart Failure on Mortality (DANISH)

Køber L, Thune JJ, Nielsen JC, Haarbo J, Videbðk L, Korup E, et al. Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med 2016;375:1221-30.

Trial summary

Background: While the role of implantable cardioverter defibrillators (ICDs) in reducing mortality in patients with ischemic left ventricular (LV) systolic dysfunction is well established, the same in patients with nonischemic LV systolic dysfunction is less clear. The improvements in pharmacological treatment of heart failure over the years and the use of cardiac resynchronization therapy (CRT) have further increased this uncertainty.

Methods: A total of 1116 patients with symptomatic systolic heart failure (LV ejection fraction ≤35%) not caused by coronary artery disease were randomized to ICD group (n = 556) or to controlled group (n = 560). In both groups, depending on the QRS duration on electrocardiogram, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death.

Results: The patients were followed up for a median duration of 67.6 months. Over this period, 120 patients (21.6%) in the ICD group and 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval [CI], 0.68-1.12; P = 0.28) died due to any cause [Figure 1]. However, in the subgroup of patients who were younger than 68 years of age, the rate of death from any cause was significantly lower in the ICD group than in the control group (hazard ratio, 0.64; 95% CI, 0.45-0.90; P = 0.01). Overall, sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31-0.82; P = 0.005).{Figure 1}

Conclusions: This trial demonstrated that in patients with nonischemic systolic heart failure, prophylactic ICD implantation does not significantly reduce all-cause mortality.


Currently, prophylactic implantation of ICDs is a Class I recommendation in patients with systolic heart failure, regardless of the underlying etiology (i.e., ischemic versus nonischemic). However, while the evidence supporting this recommendation is quite strong for patients with ischemic heart disease, the same is not true for those with nonischemic heart failure. The latter are at relatively lower risk of sudden death and therefore are less likely to benefit from ICD.

In the present trial, which included only the patients with nonischemic systolic heart failure, ICDs did not reduce all-cause mortality. However, ICDs did reduce sudden cardiac death significantly, which is the primary purpose for using ICDs. However, the sudden cardiac deaths accounted for only one-thirds of all cardiovascular deaths. In addition, nearly one-fourth of all deaths were due to noncardiovascular causes. These findings indicate that the lack of benefit of ICDs on all-cause mortality in this study was mainly because of overall low risk of sudden cardiac death in the population studied. This low risk could be attributed to the high use of guideline-directed medical therapy (angiotensin converting enzyme inhibitors or angiotensin-receptor blockers and beta-blockers in almost all patients and a mineralocorticoid receptor antagonist in nearly 60% of patients) as well as implantation of CRT in a large proportion (58%) of the patients. CRT is known to result in greater benefit in nonischemic LV systolic dysfunction as compared to ischemic LV systolic dysfunction. Therefore, the presence of CRT in the vast majority of the patients in this study would have minimized any potential benefit from ICD. It is, however, noteworthy that in younger patients who are at a lower risk of dying because of comorbidities, ICDs resulted in a significant reduction in all-cause mortality as well. Thus, the findings of this study suggest that younger patients with nonischemic systolic heart failure should continue to receive prophylactic ICD implantation, whereas in older patients, a less aggressive approach can be followed.

 Sleep Apnea Cardiovascular Endpoints (SAVE)

McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med 2016;375:919-31.

Trial summary

Background: Although obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular events, it is unclear whether its treatment with continuous positive airway pressure (CPAP) reduces cardiovascular risk.

Methods: This study randomly assigned 2717 patients (age between 45 and 75 years) with moderate-to-severe OSA and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Mean follow-up duration was 3.7 years.

Results: The patients randomized to CPAP group used the therapy for a mean duration of 3.3 h per night. CPAP resulted in significant reduction in mean apnea - hypopnea index (from 29.0 events/h at baseline to 3.7 events/h during follow-up), snoring, and daytime sleepiness whereas health-related quality of life and mood improved. However, there was no significant difference between the two groups in the incidence of primary end point (229 participants [17.0%] in the CPAP group and 207 participants [15.4%] in the usual care group; hazard ratio with CPAP, 1.10; 95% CI, 0.91-1.32; P = 0.34) [Figure 2]. No significant effect was noted on any individual or other composite cardiovascular end point also.{Figure 2}

Conclusions: In patients with moderate-to-severe OSA and established cardiovascular disease, CPAP therapy did not result in the reduction of cardiovascular events.


OSA is known to be associated with several cardiovascular risk factors such as hypertension, diabetes, endothelial dysfunction, as well as with incident cardiovascular disease (myocardial infarction, heart failure, arrhythmias, and stroke). Previous small-scale studies had indicated that the treatment of OSA with CPAP could possibly reduce the risk of adverse vascular events. However, the present large-scale, randomized study failed to show any significant benefit of CPAP on cardiovascular end points. There could be several explanations for this discrepancy. It is possible that 3.3 h per night use of CPAP in this study was inadequate to bring about reduction in the risk of cardiovascular events. Alternately, it is also possible that OSA might just be a cardiovascular risk marker, rather than risk contributor and therefore its correction with CPAP failed to show any cardiovascular benefit. Regardless of the underlying reason, it is clear that the use of CPAP for the sole purpose of reducing cardiovascular risk is not justified at this point. However, CPAP significantly improved sleep-related parameters and overall quality of life in the study patients and therefore, it should continue to be used for this purpose.

 Norwegian Coronary Stent Trial (NORSTENT)

Bønaa KH, Mannsverk J, Wiseth R, Aaberge L, Myreng Y, Nygård O, et al. Drug-eluting or bare-metal stents for coronary artery disease. N Engl J Med 2016;375:1242-52.

Trial summary

Background: As compared to bare-metal stents (BMSs), drug-eluting stents (DESs) are known to be associated with a reduced risk of in-stent restenosis. However, the impact of DES on incidence of myocardial infarction and cardiovascular mortality is not known.

Methods: A total of 9013 patients undergoing percutaneous coronary intervention (PCI) for stable or unstable coronary artery disease were randomly assigned to undergo implantation of either contemporary DES or BMS. The primary outcome was a composite of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up.

Results: In the group receiving DES, 96% of the patients received either everolimus- or zotarolimus-eluting stents (i.e., contemporary DES). At 6 years, the rates of the primary outcome were 16.6% in the DES group and 17.1% in the BMS group (hazard ratio, 0.98; 95% CI, 0.88-1.09; P = 0.66) [Figure 3]. The incidences of repeat revascularization and definite stent thrombosis were 16.5% and 0.8% in the group receiving DES and 19.8% and 1.2% respectively (P < 0.001 and 0.0498) in the group receiving BMS. Quality-of-life measures did not differ significantly between the two groups.

Conclusions: In patients undergoing PCI, DES implantation, in comparison to BMS, did not result in reduction in all-cause mortality or nonfatal spontaneous myocardial infarction although the rates of repeat revascularization were significantly reduced.{Figure 3}


The development of DES has been an important advancement in the field of PCI. DESs are known to result in reduced risk of in-stent restenosis, which has been a major problem with the BMS. Although not so far proven, it was assumed that this lower risk of restenosis with DES could also translate into reduction in angina frequency, risk of myocardial infarction, and possibly, even cardiovascular death. This large-scale randomized study ends this uncertainty by showing that the use of DES is not associated with any of these benefits. However, this trial once again reconfirmed superiority of DES in reducing the need for repeat revascularizations. These findings reinstill confidence in using BMS for patients in whom DES is not feasible for some reason (e.g., cost, bleeding risk, and need for noncardiac surgery), particularly if the anticipated restenosis risk is low (e.g., large vessel diameter).

 Coronary Computed Tomographic Angiography for Selective Cardiac Catheterization (CONSERVE) Study

Chang HJ, Szymonifka J, Gebow D, Bathina R, Doh J, Andreini D, et al. CONSERVE: Direct Catheterization Versus Selective Catheterization Guided by Coronary Computed Tomography in Patients with Stable Suspected Coronary Artery Disease. European Society of Cardiology Congress 2016. Rome, Italy; 29 August, 2016. [Abstract 4148].

Trial summary

Background: Nearly two-thirds of the patients undergoing invasive coronary angiography have no actionable coronary artery disease. The use of coronary computed tomography angiography as the first-line test may help identify patients who would actually benefit from invasive coronary angiography.

Methods: This study randomized 1503 stable patients with an American College of Cardiology/American Heart Association Class II indication for nonemergent coronary angiography to either direct or computed tomography coronary angiography (CTCA)-guided selective invasive coronary angiography. The decision to proceed with invasive coronary angiography in patients undergoing CTCA was at the discretion of the referring physician. Primary end point was a composite of death, nonfatal myocardial infarction, unstable angina, stroke, revascularization, and cardiovascular hospitalization.

Results: After a median follow-up of 12.3 months, the rates of primary end point were identical (4.6%) in both the groups (P = 0.99). However, the CTCA-guided strategy reduced rates of invasive coronary angiography by 78% (22% vs. 100%), revascularization by 41% (10% vs. 17%), and cardiovascular costs by 50% (mean per patient $3338 vs. $6740; P < 0.001).

Conclusions: In patients requiring guideline-indicated nonemergent coronary angiography, selective invasive coronary angiography informed by CTCA was associated with identical clinical outcomes while reducing the need for invasive coronary angiography by nearly 80%.


This trial showed that the use of a noninvasive test such as CTCA as the first-line investigation could significantly reduce the need for invasive coronary angiography in a sizeable proportion of patients, without adversely affecting clinical outcomes. However, this trial had certain limitations. The patients included in the study were low risk and therefore it cannot be determined whether using the same strategy in high-risk patients would be desirable. In addition, given the very low risk of major adverse cardiovascular events in the studied population, one would question whether any testing was needed at all. Finally, the study also did not provide information about how many patients met appropriate use criteria for CTCA and how other noninvasive testing strategies would compare.

 A Naturally Randomized Trial Comparing the Effect of Long-term Exposure to Low-density Lipoprotein Cholesterol, Lower Systolic Blood Pressure, or Both on the Risk of Cardiovascular Disease

Ference BA, Ference TB, Brook RD, Catapano AL, Ruff CT, Neff DR, et al. A Naturally Randomized Trial Comparing the Effect of long-term Exposure to LDL-C, lower SBP, or Both on the Risk of Cardiovascular Disease. European Society of Cardiology Congress 2016. Rome, Italy; 29 August, 2016. [Abstract 3163].

Trial summary

Background: Although both an elevated low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP) are individually associated with increased cardiovascular risk, the causal effect of combined exposure to both these risk factors is not well known.

Methods: Genetic and cardiovascular risk-factor data were collected from 102,773 individuals who had participated in one of the 14 prospective cohort or case-control studies. Genetic scores for each patient were calculated based on genetic polymorphisms known to be associated with LDL-C or SBP, and the number of alleles associated with raised LDL-C or SBP levels. On that basis, the patients were divided into four groups:

A reference groupA group with an LDL-C genetic score below the median, resulting in lower LDL-C levelsA group with an SBP score below the median, resulting in naturally lower blood pressureA group with both LDL-C and SBP below the median, resulting in both lower LDL-C and lower SBP.

The primary outcome was a composite of the first occurrence of major vascular events, including coronary death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization.

Results: After a follow-up of 32 years, a total of 14,368 cardiovascular events occurred. Lower LDL-C and lower SBP had independent, multiplicative, and cumulative effects on the risk of cardiovascular disease. The combined exposure to 1 mmol/L (18 mg/dL) lower LDL-C and 10 mm Hg lower SBP was associated with an 86.1% lower risk of cardiovascular disease (odds ratio, 0.139; 95% CI, 0.114-0.170; P < 0.00001) and a consistent 80%-90% reduction across all of the end points considered including an 84% reduction in coronary artery disease mortality that translated into a "smaller but still significant" reduction in all-cause mortality. The effect was similar in men and women, smokers and nonsmokers, people with and without diabetes, and importantly, in people with LDL-C above and below 3.5 mmol/L and those with SBP above and below 120 mm Hg.

Conclusions: LDL-C and SBP have independent, multiplicative, and cumulative causal effects on the risk of cardiovascular events. Because their effects are multiplicative and cumulative over time, long-term exposure to a combination of modestly lower LDL-C and SBP has the potential to dramatically reduce the lifetime risk of cardiovascular disease.


The recently published Heart Outcomes Prevention Evaluation-3 trial showed that combination therapy with lipid-lowering agents and antihypertensive agents did not reduce cardiovascular events overuse of lipid-lowering agents alone. This led to an uncertainty regarding the cumulative impact of blood pressure and LDL-C on the risk of cardiovascular disease. However, using a Mendelian randomization study design, the investigators of the present study demonstrated that long-term exposure to the combination of 1 mmol/L lower LDL-C and 10 mm Hg lower SBP was associated with an almost 90% lower risk of major vascular events. Importantly, this benefit was seen even in individuals with apparently normal LDL-C and SBP levels. These findings underscore the value of aggressive lifestyle management beginning in early adulthood to ensure long-term exposure to a combination of lower LDL-C and lower SBP levels. Such an approach has a potential to dramatically reduce the lifetime risk of cardiovascular disease.