Research Article | Volume 20 Issue 1 (Jan-Dec, 2015) | Pages 1 - 6
News from the 2017 American Heart Association Congress
1
Author affiliationг: Comprehensive Heart Failure Center, University Clinic Würzburg, Am Schwarzenberg 15, Haus A15, 97078 Würzburg, Germany Addreгг for correгpondence: Christoph Maack, Comprehensive Heart Failure Center, University Clinic Würzburg, Am Schwarzenberg 15, Haus A15, 97078 Würzburg, Germany
Under a Creative Commons license
Open Access
Received
Jan. 1, 2017
Revised
Jan. 1, 2017
Accepted
July 8, 2017
Published
Dec. 31, 2017
Abstract

he 2017 American Heart Association (AHA) Scientific Sessions took place in Anaheim, CA, USA from November 11 to 15, 2017. A special highlight was the presentation of the new guidelines for the prevention, detection, evaluation, and management of high blood pressure in adults as a collaborative guideline of the AHA together with the American College of Cardiology (ACC) and several other organizations.1 Furthermore, in the aftermath of the presentations and publications of the CANTOS trial results2,3 during the Annual Congress of the European Society of Cardiology (ESC) in Barcelona in September, some relevant additional analyses from this innovative anti-inflammatory treatment were presented. In addition, a large trial examining the effect of bicarbonate and acetylcysteine on renal outcomes after angiography (PRESERVE trial) was presented.5 Finally, additional highlights from the field of heart failure and post–myocardial infarction will be summarized here.

NEW GUIDELINES FOR HYPERTENSION

For the treatment of high blood pressure, the 2013 ESC guidelines define grade 1 hypertension as a blood pressure of 140-159/90-99 mm Hg (systolic/diastolic), grade 2 as 160-179/100-109 mm Hg, and grade 3 as any blood pressure ≥180/110 mm Hg. A blood pressure of 130-139 mm Hg is categorized as “high normal.” In the meantime, the SPRINT trial7 showed that intensive blood pressure treatment, targeting a systolic blood pressure <120 mm Hg, reduced the primary composite end point of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes, but also all-cause mortality compared with standard treatment with a usual blood pressure target of 140 mm Hg. However, a post hoc analysis of the ONTARGET and TRANSCEND trials8 revealed that a J-shaped relation between blood pressure lowering and outcome existed, with an optimal risk reduction at an achieved blood pressure of ≈130 mm Hg, but a re-increase in risk at values <120 mm Hg.

 

In the newest guidelines, the four major points include: (i) a strong emphasis on the accuracy of blood pressure measurements using out-of-office blood pressure measurements to confirm the diagnosis and for drug titration; (ii) a new approach to the decision-making process for a treatment that incorporates the underlying cardiovascular risk; (iii) lower targets for blood pressure during the management of hypertension; and (iv) strategies to improve blood pressure control with an emphasis on lifestyle approaches (treatment cornerstone). Accordingly, the new AHA/ ACC guidelines on hypertension redefined the thresholds for high blood pressure as follows:

 

Normal blood pressure: <120 mm Hg systolic and <80 mm Hg diastolic
Elevated blood pressure: 120-129 mm Hg systolic and <80 mm Hg diastolic
Stage 1 hypertension: 130-139 mm Hg systolic or 80-89 mm Hg diastolic
Stage 2 hypertension: ≥140 mm Hg systolic or ≥90 mm Hg diastolic

 

With this new definition, the prevalence of hypertension in the US population increased from 32% to 46% overnight, according to the presenter and lead author of the new AHA/ACC guidelines, Professor Whelton. However, the treatment consequences were also adapted. By lowering the definition of hypertension, the guidelines recommend an earlier intervention to prevent further blood pressure increases and the complications of hypertension. For patients who have stage 1 hypertension, but otherwise have a low cardiovascular risk (ie, no clinical cardiovascular disease and a 10-year atherosclerotic cardiovascular disease risk <10%), the guidelines recommend nonpharmacological approaches, mostly lifestyle changes, and a repeat blood pressure evaluation within 3 to 6 months. For patients who have stage 1 hypertension and an estimated 10-year atherosclerotic cardiovascular disease risk ≥10%, they recommend that the patients be managed initially with a combination of nonpharmacological and antihypertensive drug therapy, and have a repeat blood pressure evaluation in 1 month (in addition to lifestyle changes). The cardiovascular risk can be assessed with the atherosclerotic cardiovascular disease risk calculator, which is available online (http://tools. acc.org/ASCVD-Risk-Estimator-Plus/) or as a smartphone application. The risk is considered "elevated" when the value is ≥10% (for heart disease or stroke) and/or if the patient has manifest clinical cardiovascular disease, chronic kidney disease, or diabetes mellitus. When a patient has an elevated risk and stage 1 hypertension, the guidelines recommend treatment with at least one antihypertensive drug. If a patient has stage 2 hypertension, treatment with two or more antihypertensive drugs plus lifestyle changes are recommended. 

 

Salt sensitivity may be a marker for increased cardiovascular disease and all-cause mortality risk independently of blood pressure. The new guidelines specified that certain groups with various demographic, physiological, and genetic characteristics tend to be particularly sensitive to the effects of dietary sodium on blood pressure. Salt sensitivity is especially common in blacks, older adults, and those with a higher level of blood pressure or comorbidities, such as chronic kidney disease, diabetes mellitus, or the metabolic syndrome. Therefore, the new guidelines highlight that the current techniques for recognizing salt sensitivity are impractical in routine clinical practice, so salt sensitivity is best considered as a group characteristic. 

 

Reinforcing the importance of lifestyle changes for the prevention and treatment of hypertension, a trial that investigated effects of nutritional sodium reduction and the application of the so-called DASH diet (Dietary Approaches to Stop Hypertension) was presented., The DASH diet is rich in fruits, vegetables, and low-fat dairy products, and it was shown to reduce saturated fat and cholesterol. Both the DASH diet and lowering sodium led to meaningful reductions in blood pressure in 412 patients who are naive of medical treatment, with the largest effects observed in patients with a baseline blood pressure between 150 and 160 mm Hg. In these patients, the combination of DASH and a low sodium diet reduced systolic blood pressure by up to 20 mm Hg. These results highlight the importance of lifestyle changes, particularly choosing the right diet for the prevention and treatment of hypertension. 

ANTI-INFLAMMATORY TREATMENT WITH CANAKINUMAB: WHICH PATIENTS BENEFIT THE MOST?

It is well established that inflammation plays an important pathophysiological role in atherosclerosis in general, in coronary artery disease, in particular. At the 2017 ESC congress, the results of the CANTOS trial were presented and published. In CANTOS, anti-inflammatory treatment of patients with a previous myocardial infarction with canakinumab, an antibody targeting interleukin 18, reduced the levels of the inflammatory marker CRP, the incidence of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), and interestingly, also the incidence of lung cancer and lung cancer mortality., Two major downsides of this innovative treatment regimen are that it is very expensive and that the overall risk reduction achieved (15%) was moderate. At the AHA con- gress, Ridker presented a further analysis of CANTOS, which revealed that, in those patients who responded to the first single dose of canakinumab with a reduction in CRP to &lt;2 mg/L, the drug reduced cardiovascular mortality and all-cause mortality by 31%.4 Furthermore, the risk to develop or die from lung cancer was reduced by 71% in those patients with a CRP &lt;2 mg/L. In contrast, in those patients in whom the CRP values remained at 2 mg/L or above, no significant risk reduction in all-cause, cardiovascular, or lung cancer mortality was achieved.4 These results may help to stratify treatment to those with the highest benefit by a simple clinical read-out (ie, reduction in CRP after an initial dose).

PREVENTION OF ANGIOGRAPHY-INDUCED ACUTE KIDNEY INJURY

The application of contrast media in the context of cardiac catheterization or other forms of angiography imposes a risk of acute kidney injury. It has been asserted that urinary alkalization and/or scavenging reactive oxygen species may mitigate renal tubular epithelial cell injury induced by contrast media. However, several smaller clinical trials that tested the use of acetylcysteine or sodium bi-carbonate had inconsistent results. Therefore, the PRESERVE trial assessed the impact of sodium bicarbonate and acetylcysteine vs standard treatment (including sodium chloride infusion) on renal function (ie, need for dialysis, persistent increase in serum creatinine level of more than 50% at 90 days) and death after angiography in a much larger population. However, in 4 993 patients randomized to acetylcysteine vs placebo or sodium bicarbonate vs sodium chloride in a 2 x 2 fashion, none of these treatments improved the occurrence of this composite end point vs standard treatment. Therefore, it is recommended to treat patients with sodium chloride only and avoid the application of acetylcysteine or sodium bicarbonate as a prophylaxis for acute kidney injury before angiography. 

LEFT VENTRICULAR SYSTOLIC DYSFUNCTION AS AN IMPORTANT PREDICTOR OF OUTCOME IN CARDIOGENIC SHOCK

A common cause for acute heart failure, particularly cardiogenic shock, is myocardial infarction. At the AHA congress, the data from the FAST-MI program were presented. Here, the outcomes of 4 156 patients with myocardial infarction were assessed and related to LVEF at baseline. 10 Three percent of patients with myocardial infarction had cardiogenic shock. An early percutaneous coronary intervention was performed more often in patients with systolic dysfunction (ie, LVEF ≤40%) than without. Cardiogenic shock was associated with an impaired 3-year outcome in patients with an LVEF ≤40% or >40%. However, an LVEF ≤40% carried a more than 2-fold elevated risk of 3-year outcomes in patients with cardiogenic shock and acute myocardial infarction.

LEFT VENTRICULAR SYSTOLIC DYSFUNCTION AS AN IMPORTANT PREDICTOR OF OUTCOME IN CARDIOGENIC SHOCK

A common cause for acute heart failure, particularly cardiogenic shock, is myocardial infarction. At the AHA congress, the data from the FAST-MI program were presented. Here, the outcomes of 4 156 patients with myocardial infarction were assessed and related to LVEF at baseline. 10 Three percent of patients with myocardial infarction had cardiogenic shock. An early percutaneous coronary intervention was performed more often in patients with systolic dysfunction (ie, LVEF ≤40%) than without. Cardiogenic shock was associated with an impaired 3-year outcome in patients with an LVEF ≤40% or >40%. However, an LVEF ≤40% carried a more than 2-fold elevated risk of 3-year outcomes in patients with cardiogenic shock and acute myocardial infarction.

OTHER HEART FAILURE TRIALS

One major focus of clinical heart failure trial results presented at the AHA congress was on the cardiovascular effects of SGLT2 inhibitors. The treatment of patients with diabetes has been a therapeutic dilemma for many years, since several glucose-lowering treatments increased or did not lower cardiovascular end points, particularly heart failure end points. A change in paradigm was achieved with the EMPA-REG OUTCOME trial, in which the treatment of patients with diabetes who were at a high cardiovascular risk with the SGLT2 inhibitor empagliflozin was associated with a substantial reduction in cardiovascular, heart failure, and total mortality. Since EMPA-REG, many more studies have tried to elucidate the mechanism of action that accounts for this result, and whether this has been a class effect or a result specific for empagliflozin. 

 

Meanwhile, data from the CANVAS program were published, revealing that the SGLT2 inhibitor canagliflozin also reduced the combined primary end point of cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke.12 However, an unexpected increase in the rate of amputations occurred, especially the toes and metatarsals. 12 To assess whether empagliflozin could also pose a risk to those patients at a particularly high risk for amputations, ie, those with peripheral ar- tery disease, a post hoc analysis of the EMPA-REG OUTCOME trial was conducted. However, in the 623 (of a total of 7022) patients with peripheral artery disease in EMPA REG OUTCOME, empagliflozin reduced the risk of total mortality by 38%, with no increase in amputations (HR, 0.84). Therefore, it is still unclear why canagliflozin, but not empagliflozin, increased the rate of amputations

 

Meanwhile, data from the CANVAS program were published, revealing that the SGLT2 inhibitor canagliflozin also reduced the combined primary end point of cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke.12 However, an unexpected increase in the rate of amputations occurred, especially the toes and metatarsals. 12 To assess whether empagliflozin could also pose a risk to those patients at particularly high risk for amputations, ie, those with peripheral artery disease, a post hoc analysis of the EMPA-REG OUTCOME trial was conducted. However, in the 623 (of a total of 7022) patients with peripheral artery disease in EMPA REG OUTCOME, empagliflozin reduced the risk of total mortality by 38%, with no increase in amputations (HR, 0.84). Therefore, it is still unclear why canagliflozin, but not empagliflozin, increased the rate of amputations.

 

In the CVD-REAL Nordic Registry, real life data of the SGLT2 inhibitor dapagliflozin vs dipeptidyl peptidase-4 inhibitors were assessed in a population of 40 908 patients with a 1:3 propensity score matching between 2012 and 2015. In this analysis, dapagliflozin was associated with a 21% lower rate of MACE (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular mortality), a 38% lower rate of heart failure hospitalizations, and a 41% lower rate of all-cause mortality. These data reinforce the idea that SGLT2 inhibitors may have benefits on heart failure outcomes as a class effect. Further prospective trials will have to confirm these observations.

 

According to the current ESC guidelines for the treatment of heart failure, treatment with ivabradine should be initiated in addition to B-blockers in patients with sinus rhythm and a heart rate ≥70/min. At the AHA congress, Yuri Lopatin presented the results from the Optimize Heart Failure programs from 414 patients hospitalized for heart failure. The main results from this nonrandomized. trial were that patients who were discharged on ivabradine and a B-blocker had a more efficient lowering of their heart rate, a further improvement in LVEF, and a reduction in death and rehospitalization. Therefore, these observational data suggest that adding ivabradine to the treatment in patients who are in the hospital due to decompensation is safe and presumably helpful to improve cardiac function and avoid rehospitalization.

Recommended Articles
How do gender differences affect cardiovascular risk factors
Research Article
The First Results from the OPTIMIZE Heart Failure Care Program
Published: 31/12/2017
Perfusion cardiovascular magnetic resonance : will it replace SPECT?
Research Article
Update on the ESC Eurobservational Research Programme Registries
Published: 31/12/2017
Chat on WhatsApp
Copyright © Dialogues in Cardiovascular Medicine untill unless otherwise stated