Journal Wrap

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

HOPE 4: Trained Community Health Workers, Multifaceted Intervention Reduces CV Risk in Middle-Income Countries

A comprehensive model of care designed to address community-specific barriers and primarily driven by locally-trained nonphysician health workers (NPHWs) substantially reduced cardiovascular disease risk in 30 communities in Colombia and Malaysia, according to results of the HOPE 4 trial presented at ESC Congress 2019 and published in The Lancet.

In designing the intervention with the goal of improving detection and control of high blood pressure – with a particular focus on low- and middle-income countries, which suffer the greatest disease burden – the researchers first identified barriers to treatment at the level of the patient, health care provider and health system.


The intervention strategy consisted of: community screening, detection, treatment, and control of cardiovascular disease risk factors by NPHWs (in collaboration with local physicians) guided by tablet-based simplified management algorithms, decision support, and counseling programs; provision of free locally available combination antihypertensive medications and a statin recommended by NPHWs, but supervised by local physicians; and support from a participant-nominated treatment supporter (friend or family member) to improve adherence to medications and health behaviors.

After enrollment in each community was completed, community clusters were randomized to either the intervention or usual care and followed for 12 months. Usual care included being given health literature on cardiovascular disease that was available locally and a recommendation to see their health care provider as usual.

In total, 14 (n=644) communities were assigned to the intervention and 16 communities (n=727) to usual care. Most of the participants (n=1,008; 73.5 percent) had a history of hypertension and were taking antihypertensive medications, but their blood pressure was not controlled.

Results showed a greater reduction in the primary endpoint of 10-year cardiovascular risk as measured by the Framingham Risk Score at 12 months in the intervention group vs. the control group (–11.17 percent vs. –6.40 percent), with a difference of change of –4.78 percent; p<0.0001. In the intervention group, there was a 34.2 percent relative reduction in the FRS estimate compared with baseline.

Greater absolute reductions were also seen in the intervention group compared with the control group for systolic blood pressure (11.45 mm Hg) and for LDL-C (15.85 mg/dL) (p<0.001 for both). More patients in the intervention group achieved blood pressure control, defined as <140 mm Hg systolic, than in the control group (69 percent vs. 30 percent; p<0.001). Medication adherence was higher with the intervention.

The community-based intervention was successful in urban and rural settings in two different countries and continents, with widely varying health systems and cultural backgrounds, wrote the authors, "which suggests our findings are widely applicable." They also noted the high degree of agreement in clinical decision-making between the NPHWs and physicians.

"Adoption of the HOPE 4 strategy could substantially enhance reduction in cardiovascular disease risk in those with hypertension, and in doing so help achieve the UN's General Assembly target that calls for a one-third reduction in premature cardiovascular disease mortality by 2030," said the researchers.

Schwalm JD, McCready T, Lopez-Jaramillo P, et al. Lancet 2019;Sept 2:[Epub ahead of print].


SwedeHF Registry: ICDs Underused in Primary Prevention, Mortality Reduction Across Heart Failure Subgroups

In a contemporary population of heart failure with reduced ejection fraction (HFrEF), ICDs for primary prevention were found to reduce short- and long-term mortality, but only a small fraction of eligible patients received them. The findings from the SwedeHF Registry were presented at ESC Congress 2019 and published in Circulation.

"Most randomized trials on ICD use for primary prevention of sudden cardiac death in HFrEF enrolled patients more than 20 years ago," said principal investigator Benedikt Schrage, MD. "However, characteristics and management of HFrEF have substantially changed since then and it is not known whether ICD improves outcomes on top of contemporary treatments." Whether all subgroups benefit equally from an ICD is unclear.


Of 16,702 eligible patients in SwedeHF registered between May 11, 2000 and Dec. 31, 2016, only 1,599 (9.6 percent) had an ICD. Their mean age was 73 years and most (73 percent) were men. The propensity-matched study population consisted of 1,296 patients with an ICD and 1,296 patients without an ICD.

Patients who received an ICD were younger, more likely to be men and to receive guideline-directed medical therapy for HF. They were also more likely to have a history of ischemic heart disease, lower ejection fraction and a longer duration of HF, but less likely to have other comorbidities.

Results showed over a median follow-up of 2.69 years, there were 985 deaths (37.7 percent) in the matched cohort. For the endpoint of all-cause mortality, the risk of death was 12.7 percent and 16.9 percent in the ICD and non-ICD recipients, for an absolute risk reduction at one year of 4.2 percent (hazard ratio [HR], 0.73; p<0.01). At five years, the absolute risk reduction was 2.1 percent (HR, 0.88; p=0.04).

At one year, there were 737 cardiovascular deaths (28.2 percent). The one-year risk for cardiovascular mortality was 10.1 percent and 13.9 percent in the ICD ad non-ICD recipients, respectively, for an absolute risk reduction of 3.8 percent (p<0.01). At five years, this risk was 36.6 percent and 39.5 percent (HR, 0.88).

The short-term and long-term mortality benefit was consistent across subgroups, including patients with or without ischemic heart disease, men and women, patients younger and older than 75 years, those enrolled earlier vs. later in SwedeHF and thus receiving less or more contemporary treatment, and for patients with or without CRT.

"Our findings support the current recommendations and call for better implementation of ICD use in clinical practice," concluded Schrage.

In an accompanying editorial, Sana M. Al-Khatib, MD, MHS, and Fred M. Kusumoto, MD, FACC, comment that "the small number of patients who received an ICD may have magnified the apparent benefit of ICD due to unidentified covariates associated with risk of SCD; however, the authors used rigorous statistical methods including propensity score matching, and the results of the negative control analysis lend credibility to their findings."

While noting that the subgroups were too small for sufficient statistical power for robust comparisons, among other caveats, Al-Khatib and Kusumoto concluded the study "adds to the mounting evidence that ICDs are associated with improved survival in contemporary patients with HFrEF and highlights the need for strategies to improve their utilization."

Schrage B, Uijl A, Benson L, et al. Circulation 2019;Sept 3:[Epub ahead of print].


CLARIFY Findings Shed Light on Contemporary Profile of Patients With CCS

Results from the CLARIFY study presented during ESC Congress 2019 provide helpful information for characterizing the spectrum of patients with chronic coronary syndrome (CCS) – information that could help inform future management of this patient population, as well as future studies, researchers said.

The study, which was also published in the European Heart Journal, looked at 32,703 patients with CCS from 45 middle- to high-income countries enrolled in the prospective observational CLARIFY registry between November 2009 and June 2010. The primary outcome was cardiovascular death or nonfatal myocardial infarction (MI) over five years.

Overall findings showed the primary outcome occurred in 8.0 percent of patients. Using a Cox proportional hazards model, Emmanuel Sorbets, MD, PhD, et al., identified several main independent predictors of the primary outcome, including prior hospitalization for heart failure, current smoking, atrial fibrillation, living in Central/South America, prior MI, prior stroke, diabetes, current angina and peripheral artery disease.


Additionally, researchers noted that prescription rates of evidence-based secondary prevention therapies were high. They also highlighted substantial variations in clinical profiles across geographical regions. For example, patients in the Middle East had the lowest rates of current heart failure symptoms and lower extremity artery disease, along with the highest body mass index and highest prevalence of diabetes.

In contrast, patients from Asia had the lowest prevalence of prior MI, the highest rate of prior PCI, the highest rate of stroke, and the smallest body mass index and use of statins. Central and South America had the lowest rate of current smokers, prior stroke or angina, but the highest rate of hypertension.

Among the study limitations, CLARIFY reflects only middle- or high-income countries, making it impossible to extrapolate findings to large and important regions such as Africa and Asia where access to more advanced medical care is limited. Yet, Sorbets and colleagues say their findings are important given the substantial changes in the profile of CCS over the last decades.

Sorbets E, Fox KM, Elbez Y, et al. Eur Heart J 2019;Sept 3:[Epub ahead of print].


Does Lifelong Genetic Exposure to Lower LDL-C, Lower SBP Reduce Cardiovasular Risk?

A study of nearly 450,000 participants from the UK suggests lifelong genetic exposure to lower levels of LDL-C coupled with lower systolic blood pressure (SBP) is associated with lower cardiovascular risk. The findings were presented as part of ESC Congress 2019 and published in the Journal of the American Medical Association.

Brian A. Ference, MD, MPhil, MSc, FACC, and Deepak L. Bhatt, MD, MPH, FACC, et al., used genetic LDL-C and SBP scores to divide participants into three groups: lifetime exposure to lower LDL-C, lower SBP, or both. Participants ranged from 40 to 80 years of age, with a median age of 65.2 years, and more than half (54.1 percent) were women. Differences in plasma LDL-C, SBP and cardiovascular event rates were then compared between the groups to estimate associations with lifetime cardiovascular disease risks.


Overall results showed participants with LDL-C genetic scores higher than the median had lower LDL-C levels (by 14.7 mg/dL) and an odds ratio (OR) of 0.73 for major coronary events. Similarly, participants with SBP genetic scores higher than the median had lower SBP (by 2.9 mm Hg) and an OR of 0.82 for major coronary events.

Participants in the group with both genetic scores higher than the median had LDL-C that was lower by 13.9 mg/dL, SBP that was lower by 3.1 mm Hg and an OR of 0.61 for major coronary events. Additional analysis showed exposure to increasing genetic risk scores and lower LDL-C levels and SBP was associated with dose-dependent lower risks of major coronary events.

While the findings are positive, the researchers caution that they "cannot be assumed to represent the magnitude of benefit achievable from treatment of these risk factors."

Ference BA, Bhatt DL, Catapano AL, et al. JAMA 2019;Sept 2:[Epub ahead of print].


POPular Genetics: Genotype-Guided P2Y12 Inhibitor Therapy vs. Standard Care in PCI Patients

Early CYP2C19 genetic testing to guide the selection of oral P2Y12 inhibitor therapy in patients undergoing PCI was noninferior to standard treatment with ticagrelor or prasugrel at 12 months in terms of thrombotic events, based on findings from the POPular Genetics trial presented during ESC Congress 2019 and published in the New England Journal of Medicine. Daniel M.F. Claassens, MD, and colleagues also noted that the CYP2C19 genotype-guided approach resulted in a lower incidence of bleeding.


The study randomized 2,488 patients undergoing primary PCI with stent implantation to either a genotype-guided approach (n=1,242) or standard treatment (n=1,246) for 12 months. The two primary outcomes were net adverse clinical events (i.e, death from any cause, myocardial infarction, definite stent thrombosis, stroke or major bleeding) at 12 months and major or minor bleeding at 12 months. Patients carrying the CYP2C19*2 or CYP2C19*3 loss-of-function alleles in the genotype-guided group received ticagrelor or prasugrel, and noncarriers received clopidogrel.

In overall results, the primary combined outcome occurred in 63 patients (5.1 percent) in the genotype-guided group compared with 73 patients (5.9 percent) in the standard-treatment group. In the genotype-guided group, the primary bleeding outcome occurred in 122 patients (9.8 percent) compared with 156 patients (12.5 percent) in the standard-treatment group. Researchers noted there was no difference in major bleeding between both groups (2.3 percent in both); however, the between-group difference in the primary bleeding outcome was largely driven by a lower incidence of minor bleeding in the genotype-guided group.

Claassens, et al., highlighted "lower-than-anticipated incidence of the primary combined outcome, and the fact that genetic variation is not the only factor contributing to high platelet reactivity" among the trial's limitations. The also cautioned that a "strategy based solely on the CYP2C19 genotype may not be the most useful strategy for some patients" given there are additional polymorphisms of the CYP2C19 gene for which data are conflicting.

Claassens D MF, Vos G JA, Bergmeijer TO, et al. N Engl J Med 2019;Sept 3:[Epub ahead of print].


Keywords: ACC Publications, Cardiology Magazine, Adenosine, Algorithms, American Medical Association, Angina Pectoris, Antihypertensive Agents, Atrial Fibrillation, Blood Platelets, Blood Pressure, Body Mass Index, Cardiovascular Diseases, Arteries, Alleles, Cohort Studies, Community Health Workers, Comorbidity, Control Groups, Coronary Artery Disease, Death, Sudden, Cardiac, Developed Countries, Counseling, Follow-Up Studies, Diabetes Mellitus, Genetic Variation, Genotype, Genetic Testing, Goals, Heart Failure, Hospitalization, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Incidence, Lower Extremity, Medication Adherence, Myocardial Infarction, Numbers Needed To Treat, Odds Ratio, Percutaneous Coronary Intervention, Peripheral Arterial Disease, Primary Prevention, Prevalence, Proportional Hazards Models, Prospective Studies, Research Personnel, Registries, Secondary Prevention, Risk Factors, Propensity Score, Smoking, Stroke, Stroke Volume, Stents, Tablets, Thrombosis, Ticlopidine, United Nations

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