Review Suggests Individualized, Integrated Treatment For Blood Glucose Regulation

Blood glucose regulation is an important aspect of cardiovascular disease prevention and should be addressed on an individual basis tailored to the needs of the patient, according to a review paper published in the Journal of the American College of Cardiology (JACC). The article is part of an eight-part cardiovascular health promotion series in JACC.

Peter E.H. Schwarz, MD, MBA, et al., reviewed recent evidence on medical and lifestyle interventions targeting blood sugar regulation. Forty-four studies were included in the analysis. They looked to 1) outline likely pathophysiological mechanisms by which blood glucose regulation affects cardiovascular disease risk and evidence of pharmacological interventions targeting these pathways; 2) identify evidence-based individual-level interventions for supporting effective behavior change to regulate blood sugar and thereby reduce cardiovascular disease risk; 3) identify evidence-based population-level interventions for supporting effective behavior change to regulate blood sugar and thereby reduce cardiovascular disease risk; and 4) translate key findings into applicable recommendations highlighting competencies for training for health promotion and for standardizing health promotion care paths.

The review found that intensive glucose lowering can reduce microvascular and macrovascular morbidities and cardiovascular mortality, even though doing so was once thought to have no benefit on cardiovascular outcomes. However, the authors add that the baseline blood pressure of patients with type 2 diabetes must be considered before beginning therapy, as it can counteract the beneficial impact on cardiovascular outcomes. Lifestyle interventions such as diet and exercise can also be effective and have fewer side effects. The authors add that more research is needed to establish both the clinical and cost effectiveness of lifestyle interventions.

The authors also found evidence supporting a shift from treatment by doctors to community health workers and other community-based health practitioners such as nurses and pharmacists, writing this could be of most benefit in rural areas and other settings where resources and services are lacking. Additionally, they observed potential for community-based multidisciplinary teams to increase effectiveness in both individual- and community-level interventions.

According to the authors, their findings support the potential for integrating prevention services.

"Combining the results derived from the single sections [of the review] suggests integrating future services and policy efforts to develop standardized care pathways covering diabetes prevention, diabetes management and cardiovascular disease prevention," they write.

Schwarz PEH, Timpel P, Harst L, et al. J Am Coll Cardiol 2018;72:1829-44.

AFib Patients With Cancer History Less Likely to See Cardiologist, Take Anticoagulants

Atrial fibrillation (AFib) patients with a history of cancer may be less likely to see a cardiologist or fill anticoagulant prescriptions compared with AFib patients who never had cancer, according to a study published in the Journal of the American College of Cardiology.

Wesley T. O'Neal, MD, MPH, et al., examined the relationship between early cardiology involvement after an AFib diagnosis in patients with a history of cancer and how that affected outcomes. Of more than 380,000 AFib patients in the MarketScan database, 17 percent had a history of cancer. Prostate and breast cancers were the most common types, and patients with a history of cancer were also older and more likely to have other cardiovascular conditions.

Results showed that patients with a history of cancer were less likely to see a cardiologist after AFib diagnosis and less likely to fill prescriptions for oral anticoagulants. Differences were similar when looking at active cancers vs. remote history of cancer. The researchers confirmed that a beneficial association existed between early cardiology involvement at the time of AFib diagnosis among patients with a history of cancer. After 1.1 years of follow-up, cancer patients who saw a cardiologist were more likely to fill their prescriptions, had a reduced risk of stroke and did not have an increased risk of bleeding. These patients were more likely to be hospitalized, which may be due to more aggressive treatments.

According to a related editorial comment, the number of cancer survivors in the U.S. is expected to increase from over 15 million to over 20 million by 2026, which will lead to an increased focus on addressing their long-term medical and psychosocial needs.

O'Neal WT, Claxton JS, Sandesara PB, et al. J Am Coll Cardiol 2018;72:1913-22.

Women Treated For Cancer at Risk For HF During, After Pregnancy

Young women previously treated for cancer with chemotherapy or radiation therapy with a prior history of cardiotoxicity may be more likely to develop clinical congestive heart failure (CHF) during and after pregnancy, according to a study published in the Journal of the American College of Cardiology.

Paaladinesh Thavendiranathan, MD, SM, et al., followed 78 cancer survivors from a high-risk pregnancy clinic who had 94 pregnancies over a 10-year period. All the women had received cancer therapy as children, adolescents or young adults. Of the total women, 55 had received anthracycline-based chemotherapy, and 23 received non-anthracycline chemotherapy or radiation therapy only.

Of survivors exposed to anthracyclines, 13 women had a prior history of cardiotoxicity, and 12 of these women had been treated with anthracycline-based chemotherapy. During pregnancy or soon after delivery, CHF occurred in 31 percent of women with a history of cardiotoxicity, with no reports of acute coronary syndrome or arrhythmia. There was no difference in the age at cancer diagnosis, age at pregnancy, cancer type or exposure to anthracyclines between the women diagnosed with CHF and without. There were no maternal deaths.

"For women without a history of cardiotoxicity, their risk of developing CHF during pregnancy is very low," Thavendiranathan says. "However, for women who have been exposed to cardiotoxic treatments and have had prior cardiotoxicity, there's approximately a one in three chance of developing CHF with pregnancy. These women should receive close cardiac surveillance during pregnancy."

Liu S, Aghel N, Belford L, et al. J Am Coll Cardiol 2018;72:2087-89.

SGLT-2 Inhibitors More Effective to Reduce HF Risk in T2DM Patients

Sodium glucose co-transporter (SGLT)-2 inhibitors are more effective than either glucagon-like peptide (GLP)-1 agonists or dipeptidyl peptidase (DPP)-4 inhibitors for reducing the risk of hospitalization for heart failure (HF) in type 2 diabetes (T2D), according to a study published in JACC: Heart Failure.

The study authors conducted a systematic review and network meta-analysis of randomized placebo-controlled trials, found in Embase, PubMed, Cochrane Library and clinicaltrials.gov between Dec. 1, 2008 and Nov. 24, 2017. Eligible studies were conducted in adults with T2D, compared add-on therapy of any current antidiabetic medication to placebo, and reported the incidence of HF or hospitalization for HF as a primary or secondary outcome. Excluded were studies that were observational or retrospective, completed before Food and Drug Administration guidance or did not report HF as an outcome.

Nine trials fulfilled the inclusion criteria, providing data on 87,162 participants. The classes of antidiabetic medication were: GLP-1 agonists (four studies evaluating lixisenatide, liraglutide, semaglutide and once-weekly exenatide, respectively, in 33,457 participants); DPP-4 inhibitors (three studies evaluating alogliptin, saxagliptin and sitagliptin, respectively, in 36,543 participants); and SGLT-2 inhibitors (two studies evaluating empagliflozin and canagliflozin, respectively, in 17,162 participants). A network meta-analysis was performed with the Bayesian approach using Markov chain Monte Carlo simulation method to compare the effects of glucose-lowering drugs on risk of HF hospitalization and estimate the probability that each treatment is the most effective.

The study populations had a mean age ranging from 60.3 to 65.5 years, a male preponderance (60.7 to 71.6 percent) and mean duration of T2D ranging from 7.2 to 13.9 years. Reflecting contemporary management of cardiovascular risk factors, the majority of participants were receiving statins (71.5 to 92.7 percent), aspirin (63.3 to 97.5 percent) and angiotensin-converting enzyme inhibitors (33.7 to 85 percent).

The results of the network meta-analysis revealed that SGLT-2 inhibitors yielded the greatest risk reduction for HF hospitalization compared with placebo (relative risk [RR], 0.56; 95 percent credibility interval [CrI], 0.43-0.72). Moreover, SGLT-2 inhibitors were associated with significant risk reduction in pairwise comparisons with both GLP-1 agonists (RR, 0.59; 95 percent CrI, 0.43-0.79) and DPP-4 inhibitors (RR, 0.50; 95 percent CrI, 0.36-0.70). Ranking of the classes revealed a 99.6 percent probability of SGLT-2 inhibitors being the optimal treatment for reducing HF hospitalization, followed by GLP-1 agonists (0.27 percent) and DPP-4 inhibitors (0.1 percent).

"This network meta-analysis shows that, for reducing the risk of HF, current evidence favors the choice of SGLT-2 inhibitors over either GLP-1 agonists or DPP-4 inhibitors," the authors conclude. "Moreover, their divergent respective effects in this regard yield a clear hierarchy among these classes from this perspective. Thus, an evidence base has now emerged that practitioners might consider when reviewing HF risks in the patient-centered management of T2D in clinical practice."

Kramer CK, Ye C, Campbell S, Retnakaran R. JACC Heart Fail 2018;6:823-30.

Catheter Ablation Effective For VA in Ebstein's Anomaly

Catheter ablation is an effective approach to treat ventricular arrhythmia (VA) in patients with Ebstein's anomaly (EA), according to recent research in JACC: Clinical Electrophysiology.

Jeremy P. Moore, MD, MS, et al., performed an international, retrospective study of patients with EA and VA undergoing electrophysiology testing with the intention of treating VA by catheter ablation at 11 congenital heart disease centers. A total of 24 patients (median age 17 [interquartile range, 11 to 37] years; age range one to 68 years; 42 percent men) were included.

Thirty ventricular tachycardia (VT) morphologies and three premature ventricular contraction (PVC) foci were studied. Of the combined 33 VAs, 28 were unique and 25 were completely characterized. Activation mapping (79 percent) was the most common VA mapping method (p=0.037) and irrigated radiofrequency energy was used in 50 percent of cases. Acute success was achieved in 22 (92 percent) patients.

Over a median follow-up of 3.4 years, there was one clinical recurrence in a 68-year-old patient with complete atrioventricular block following tricuspid valve (TV) replacement and who had undergone preprocedural ICD placement. The episode was terminated with a successful ICD shock. There were no deaths or cardiac transplantation at follow-up. The single patient with a failed ablation because of accelerated ventricular rhythm did not demonstrate recurrence during the follow-up period.

The authors state there are several important findings: 1) the location of VA in patients with EA is primarily determined by whether a prior TV operation had been performed; 2) for patients with no history of TV operation, the origins of VA were predominantly within the atrialized right ventricle; 3) for patients who had undergone surgical intervention, focal VA was related to sites of surgical resection or diseased Purkinje tissue, with macro–re-entrant VA most commonly related to surgical scars.

Additionally, these findings may facilitate the management of patients with EA and VA by allowing greater anticipation of VA substrates in pre- and postoperative subgroups and clarify the role of catheter-based intervention. While EA is rare, these patients are prone to sudden cardiac death. The findings may also have implications for the etiology of sudden cardiac death in this under-represented population.

Moore JP, Shannon KM, Gallotti RG, et al. JACC Clin Electrophysiol 2018;4:1300-7.