Journal Wrap | Recommended Articles from Diabetes Care, the European Heart Journal and the Journal of the American Heart Association

The hottest research from various peer-reviewed journals – handpicked weekly by the Editorial Board led by Kim Eagle, MD, MACC.

Metformin Lowers Risk of CV Events in Prediabetes

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Patients with prediabetes may be at a high risk for cardiovascular events, but therapy with metformin may lower this risk by reducing coronary endothelial dysfunction, according to a study published in Diabetes Care.

Celestino Sardu, MD, MSc, PhD, et al., enrolled 258 propensity score-matched (PSM) patients with stable angina undergoing coronary angiography in the study. Data from 86 PSM patients with normoglycemia (NG), 86 PSM patients with prediabetes (pre-DM), and 86 PSM patients with prediabetes treated with metformin (pre-DM metformin) were analyzed. During coronary angiography, nonobstructive coronary stenosis (NOCS) was categorized by luminal stenosis <40 percent and fractional flow reserve >0.80.

In addition, they assessed the endothelial function, measuring coronary artery diameter of the left anterior descending coronary (LAD) at baseline and after the infusion of acetylcholine, using an intracoronary Doppler guide wire. Major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction and heart failure, was evaluated at 24 months of follow-up. Overall survival and event-free survival were assessed by Kaplan-Meier survival curves and compared by the log-rank test.


At baseline, NG patients had a lower percentage of LAD endothelial dysfunction compared with pre-DM patients (p<0.05). The pre-DM patients had a higher percentage of endothelial LAD dysfunction, as compared with the pre-DM metformin patients (p<0.05). At 24 months, MACE was higher in pre-DM vs. NG (p<0.05). In pre-DM metformin patients, MACE was lower compared with pre-DM patients (p<0.05).

The researchers state their data suggest that in pre-DM, the hyperglycemia and the insulin resistance might lead to endothelial dysfunction in the absence of severe coronary stenosis by alterations in vasomotor tone and by the overproduction of inflammatory molecules and reactive oxygen species.

These inflammatory molecules may lead to a subclinical endothelial function in the context of NOCS in patients with prediabetes, which might increase the risk for the initiation and progression of coronary atherosclerosis in patients with prediabetes in the absence of severe coronary stenosis.

"Although American Diabetes Association guidelines suggest that patients with prediabetes be treated with metformin to reduce the risk of developing diabetes, to date metformin use is <1 percent among adults with prediabetes and only slightly more common among those with additional risk factors for diabetes," the authors write. "In this context, our data may help to reduce the important gap in the prevention and treatment of coronary disease induced by dysglycemia and insulin resistance."

Sardu C, Paolisso P, Sacra C, et al. Diabetes Care 2019;42:1946-1955.


In-Stent Restenosis: Moderate Advantage For Repeat DES vs. PCB Angioplasty

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In patients with coronary in-stent restenosis (ISR), repeat stenting with a drug-eluting stent (DES) is moderately more effective than angioplasty with a paclitaxel-coated balloon (PCB) at reducing the need for target lesion revascularization (TLR) at three years, according to research published in the European Heart Journal.

Daniele Giacoppo, MD, et al., conducted the DAEDALUS study, a comprehensive, investigator-initiated, collaborative, individual patient data meta-analysis comparing angioplasty with PCB alone vs. repeat stenting with DES alone for the treatment of coronary ISR.

A total of 10 randomized clinical trials were included with 1,976 patients enrolled (1,033 assigned to PCB and 943 to DES). A two-stage meta-analysis with individual trial risk estimate extractions by Cox proportional hazards regression and subsequent pooling by fixed- and random-effects models was conducted as a sensitivity analysis for each outcome.


At the three-year follow-up, a total of 243 primary efficacy outcome events (TLR defined as any revascularization) occurred, with 144 occurring in the PCB group and 99 in the DES group, which corresponds to cumulative incidences of 16 percent (IQR 13.5-18.4 percent) and 12 percent (IQR 9.7-14.3 percent), respectively (p=0.020). Patients in the PCB group experienced a 32 percent relative risk increase in TLR compared with patients in the DES group.

The incidence of the primary safety composite endpoint of all-cause death, myocardial infarction or target lesion thrombosis was similar between groups, as were the rates of a composite endpoint including both efficacy and safety components. The rates of individual endpoints, including all-cause mortality, were not significantly different between groups.

"Current European guidelines on myocardial revascularization recommend the use of either PCB or DES for the treatment of coronary ISR (class of recommendation I, level of evidence A)," the authors write. "The results of the DAEDALUS study support the use of both types of device in a mixed population of patients with coronary ISR. The moderate advantage in efficacy of repeat stenting with DES should be weighted against the potential advantages of avoiding additional layers of stent and the absence of significant differences in terms of safety."

Giacoppo D, Alfonso F, Xu B, et al. Eur Heart J 2019;Sep 11:[Epub ahead of print].


PINNACLE: Smoking Cessation Assistance Lacking at Cardiology Practices

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Only one in three smokers treated at U.S. cardiology practices linked to the NCDR PINNACLE Registry receive smoking cessation assistance from the practice despite the documented benefits of cessation. The lack of progress in helping patients stop smoking and the need for improved actions were detailed in a study published in the Journal of the American Heart Association.

Mayank Sardana, MBBS, et al., measured the rates of smoking cessation assistance by examining data from 328,749 smokers treated at 348 cardiology practices enrolled in the PINNACLE registry, the largest outpatient quality improvement registry in cardiology.

The smokers were treated between January 1, 2013, and March 31, 2016. A high prevalence of cardiovascular factors was present in the smokers, including hypertension in 61 percent, dyslipidemia in 54 percent and diabetes in 20 percent – and nearly one-third had coronary artery disease.


Smoking cessation assistance was documented in 34 percent of patient encounters. Because assessing rates of cessation assistance could be skewed by only measuring recent clinical encounters, the rates of smoking cessation assistance during any clinical encounter during the study period also were measured.

Researchers found that cessation assistance was recorded in 34 percent of cardiology-related encounters vs. 33 percent of any clinical encounters. Of the 112,884 encounters in which assistance was documented, cessation pharmacotherapy was prescribed in only 10 percent.

Evaluation of the large variation in providing smoking cessation revealed several factors associated with a lower odds of receiving assistance: older age, diabetes, atrial fibrillation, and practice location in the South Census region and rural or suburban areas.

The authors write that their findings call for immediate action from providers and public health organizations to improve the adherence to providing smoking cessation assistance at outpatient cardiology practices.

"Our findings suggest the presence of a large deficit and largely idiosyncratic provider-level variation in the provision of smoking cessation assistance," researchers concluded. They added, "Our findings form the basis for further investigation into other contributors to smoking cessation assistance, such as economic, social, environmental and organizational factors that could enhance the rates of smoking cessation assistance and reduce variation in care."

Sardana M, Tang Y, Magnani JW, et al. J Am Heart Assoc 2019;8: e011412.


Contemporary Use of Hybrid Revascularization Characterized Using NCDR Data

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Hybrid revascularization, combining PCI and CABG, for the treatment of multivessel coronary artery disease (CAD), is used infrequently. While the risk-adjusted in-hospital mortality rate was not different between hybrid revascularization and multivessel PCI, the analysis found patients who had hybrid revascularization were less likely to receive P2Y12 inhibitors at discharge. The findings were published in the Journal of the American Heart Association.

Angela Lowenstern, MD, et al., used NCDR data from 2009 to 2017 to review the treatment of 775,000 patients with multivessel CAD. Of those patients, 1,126 (0.2 percent) had hybrid revascularization and 256,865 (33 percent) had multivessel PCI. Patients undergoing hybrid revascularization were younger and more likely had significant left main disease or proximal left anterior descending disease.


Of the patients treated with hybrid revascularization, two-thirds (68.7 percent) had a CABG procedure after PCI – but only 79.4 percent were prescribed a P2Y12 inhibitor at discharge. There was also a lower rate of discharge P2Y12 use with hybrid revascularization vs. multivessel PCI (83.1 percent vs. 98.0 percent; p<0.001).

Unadjusted in-hospital mortality rates were higher with hybrid revascularization than multivessel PCI (1.5 percent vs. 0.9 percent), which was not significant after multivariable adjustment.

Risk-adjusted mortality did not differ in relation to the order of revascularization in those who had hybrid revascularization.

Researchers observed limited use of hybrid coronary revascularization in contemporary clinical practice. Of the 711 hospitals performing nonemergency PCIs, only 358 performed at least one hybrid revascularization during the study period. Approximately one-third of hybrid revascularizations were performed as CABG followed by PCI and two-thirds had CABG performed following PCI.

"Further work is necessary to fully clarify the comparative effectiveness of hybrid coronary revascularization versus multivessel PCI and the patient populations where hybrid coronary revascularization is most beneficial, and to optimize the postprocedural medical management and outcomes of these patients," researchers concluded.

Lowenstern A, Wu J, Bradley ST, et al. Am Heart J 2019;215:67-77.


Keywords: ACC Publications, Cardiology Magazine, Diabetes Mellitus, Metformin, Angioplasty, Smoke, Smoke Inhalation Injury, Smoking Cessation, Smoke-Free Policy, Myocardial Revascularization, Cerebral Revascularization, National Cardiovascular Data Registries

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