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Take a look at a selection of our recent media coverage:

No effect of systolic BP on cardiovascular outcomes in heart failure treated with empagliflozin

4th October 2021

Systolic BP has been shown not to effect the reduction in cardiovascular outcomes for heart failure patients treated with empagliflozin.

As a drug class, the sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown in a systematic review to have a moderate effect on major adverse cardiovascular events in patients with established atherosclerotic cardiovascular disease. Moreover, the same review identified how SGLT2is can also reduce hospitalisation for heart failure (HF) and progression of renal disease regardless of existing atherosclerotic cardiovascular disease. In addition to these positive effects on cardiovascular outcomes, SGLT2is have been shown to reduce 24-hour blood pressure (BP) in diabetic patients. Nevertheless, this blood pressure-lowering effect is of concern in those with HF, especially as between 15 and 20% of HF patients have low systolic BP and therefore at a higher risk of in-hospital and post-discharge mortality.

In an effort to evaluate whether the baseline systolic BP affected outcomes associated with the use of empagliflozin, an international team, led by researchers from Saarland University, Germany, enrolled patients in the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction (EMPEROR-Reduced) trial. Patients with class II, III, or IV heart failure and an ejection fraction of less than 40% were randomised in a 1:1 fashion to either empagliflozin (10mg daily) or placebo in addition to their usual therapy for heart failure. For the study, patients were grouped according to their baseline systolic BP, as <110mmHg, 110–130mmHg or > 130mmHg and the primary outcome in the EMPEROR-Reduced trial was a composite of adjudicated cardiovascular death or hospitalisation for heart failure. For the present study, the researchers focused on whether the baseline systolic BP influenced the outcomes of cardiovascular death and hospitalisations for HF in patients given empagliflozin compared to placebo.

Findings

A total of 3730 patients were randomised to either empagliflozin (1863) or placebo and all patients had a left ventricular ejection fraction of less than 30%. Over a median of 16 months, the event rate per 100 patients years (pys) of follow-up, the primary outcome increased from 16.5 among the high SBP group to 20.8 for the intermediate group, and to 26.3 per 100 among the patients with low SBP (p=0.0015). Compared with placebo, treatment with empagliflozin significantly decreased the risk of cardiovascular death among the low systolic BP (hazard ratio, HR = 0.78, 95% CI 0.61–1.00), intermediate (HR = 0.71, 95% CI 0.58–0.87) and high (HR = 0.82. 95% CI 0.62–1.09) groups. However, while there were reductions in rates of HF hospitalisation with empagliflozin compared with placebo, this was only significant for patients with intermediate (110–130mmHg) systolic BP (HR = 0.66, 95% CI 0.50–0.88).

The authors concluded that empagliflozin reduced the risk of cardiovascular death and the number of HF hospitalisations and that this effect occurred independently of the baseline systolic BP.

Citation

Bohm M et al. Empagliflozin Improves Cardiovascular and Renal Outcomes in Heart Failure Irrespective of Systolic Blood Pressure. J Am Coll Cardiol 2021.

Increased cancer risk among those with heart failure

6th July 2021

A retrospective cohort study of heart failure patients has revealed a significantly higher incidence of all types of cancer.

Patients with heart failure (HF) have both a functional impairment and a poor health-related quality of life. However, it is not always the HF which has the biggest impact on quality of life. For example, one study of over 700 HF patients, found that less than half (48%) reported that their quality of life was limited by heart failure, with nearly a fifth (18%) citing other medical problems as the dominant factor. Similarly, a Swedish study of 10,500 patients observed that depression and anxiety had the strongest associations with functional limitations and patient-rated health. In fact, Heart failure has a poor prognosis and a UK study estimated 10-years survival to be only 26.2%.

Interestingly, other data point to a potential relationship between the presence of heart failure and cancer. In 2020 it was observed that among patients with ejection fractions less than 45%, cancer accounted for 6 to 14% of all deaths and was independent of treatment. This led the authors to conclude that cancer is a major, yet overlooked cause of non-cardiovascular death in heart failure. Given this potentially overlooked cause of death, a team from the Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Dusseldorf, Germany, undertook a retrospective analysis of the incidence of cancer in patients after a diagnosis of HF. The team turned to the German Disease Analyser database, which contains information on prescriptions, diagnoses together with basic demographic and medical data in an anonymous format that comes directly from a sample of general practitioners and specialists throughout the country. For their analysis, included patients were over 18 years of age with an initial diagnosis of HF and individuals already diagnosed with cancer were excluded from the dataset. Patients with HF were propensity-matched by sex, age, yearly consultation frequency together with the presence of two co-morbidities; obesity and diabetes and followed for a period of 10 years.

Findings
A total of 100,124 patients with a mean age of 72.6 years (54% female) were matched with a non-heart failure cohort. Diabetes and obesity were present in 37.4% and 15.9% respectively in the heart failure group and patients visited their general practitioner an average of six times per year. The prevalence of cancer in HF patients was 25.7% compared with 16.2% in the control cohort (p < 0.001). This pattern was similar for both sexes, with 23.2% vs 13.8% (males) and 28.6% vs 18.8% (females). In regression analysis, heart failure was significantly associated with the incidence of cancer (hazard ratio (HR) = 1.76, 95% CI 1.71–1.81, p < 0.001), with a similar and significant effect seen in the two sexes, i.e., males (HR = 1.69) and females (HR = 1.69). When examining the relationship between cancer location and HF, the strongest association was for the lip, oral cavity and pharynx (HR = 2.10, 95% CI 1.66–2.17, p < 0.001), followed by respiratory organs (HR = 1.91) and female genital cancer (HR = 1.86).

While the authors suggested that these associations were not indicative or a direct causal relationship, they noted evidence from other work indicating how circulating levels of cardiovascular peptides such as N-terminal pro BNP are elevated in heart failure patients with cancer. They concluded by calling for future studies to clarify this relationship.

Citation
Roderburg C et al. Heart failure is associated with an increased incidence of cancer diagnosis. ESC Heart Fail 2021