Use Of Cardioprotective Therapies Research Articles

Cardiovascular Disease in Patients With Breast Cancer Treated in the Modern Era

With improving cancer survivorship, cardiovascular disease (CVD) has become a leading cause of death in breast cancer (BC) survivors. At present, there is no prospectively validated, contemporary risk assessment tool specific to this patient cohort. Accordingly, we sought to investigate long-term cardiovascular outcomes in early-stage BC patients utilising a well characterised database at a quaternary referral centre. With the assembly of this cohort, we have derived a BC cardiovascular risk index titled the 'CRIB (Cardiovascular Risk Index in Breast Cancer)' to estimate the risk of a major adverse cardiovascular event (MACE) in women undergoing treatment for BC. A retrospective cohort study was conducted examining all female patients aged ≥18 years of age who underwent treatment for early-stage BC at a cancer centre in Melbourne, Australia, between 2009 and 2019. The primary aim of this study was to assess causes and predictors of MACE. A total of 1,173 women with early-stage BC were included. During a median follow-up of 4.4 (1.8-6.7) years, 80 (6.8%) women experienced a MACE. These women were more likely to be older, with a high burden of cardiovascular risk factors and were more likely to have a history of established coronary artery disease (CAD) (p≤0.001 for all). A CRIB ≥3 (2 points: renal impairment, 1 point: age ≥65 years, body mass index [BMI]>27, diabetes, hypertension, history of smoking) demonstrated moderate discrimination (c-statistic 0.75) with appropriate calibration. A CRIB ≥3, which represented 23.9% of our cohort, was associated with a high risk of MACE (odds ratio [OR] 17.85, 95% confidence interval [CI] 6.36-50.05; p<0.001). A total of 138 (11.8%) women died during the study period. Mortality was significantly higher in patients who experienced a MACE (HR 2.72, 95%CI 1.75-4.23; p<0.001). Cardiovascular risk stratification at the time of BC diagnosis using the novel CRIB may help guide surveillance and the use of cardioprotective therapies as well as identify those who require long-term cardiac follow-up.

Cardiac toxicity of chemotherapy for breast cancer: do angiotensin-converting enzyme inhibitors and beta blockers protect?

Cardiotoxicity is a relatively frequent and potentially serious side effect of anticancer treatments, particularly anthracyclines and trastuzumab, widely used in the treatment of breast cancer. The increase in cancer survivors has generated a growing interest in the prevention of cardiotoxicity. Although early studies suggested an overall benefit on cardiac function with the use of ACE inhibitors (ACEIs) and beta blockers (BBs), more recent randomized trials have demonstrated little or no effect of pharmacological interventions. Even the various meta-analyses conducted in this area have provided weak results in favour of cardioprotective therapies for which the benefit would not always justify the risk of developing side effects. Given the incompleteness of the evidence, there is no clear consensus on which patients should initiate cardioprotective therapy. As recommended in the new guidelines of the European Society of Cardiology, risk stratification before treatment is crucial to identify high-risk patients who would benefit most from the use of cardioprotective therapy. Randomized trials are currently underway to evaluate other therapeutic strategies such as sacubitril/valsartan, and the possibility of using gliflozins in the future cannot be excluded. However, rigorous control and treatment of risk factors remain the primary focus in the management of these patients.

Gender differences in cardiovascular risk, treatment, and outcomes: a post hoc analysis from the REWIND trial

Objectives. To assess whether the use of cardioprotective therapies for type 2 diabetes varies by gender and whether the risk of cardiovascular events is higher in women versus men in the REWIND trial, including an international type 2 diabetes patient population with a wide range of baseline risk. Design. Gender differences in baseline characteristics, cardioprotective therapy, and the achieved clinical targets at baseline and two years were analyzed. Hazards for cardiovascular outcomes (fatal/nonfatal stroke, fatal/nonfatal myocardial infarction, cardiovascular death, all-cause mortality, and heart failure hospitalization), in women versus men were analyzed using two Cox proportional hazard models, adjusted for randomized treatment and key baseline characteristics respectively. Time-to-event analyses were performed in subgroups with or without history of cardiovascular disease using Cox proportional hazards models that included gender, subgroup, randomized treatment, and gender-by-subgroup interactions. Results. Of 9901 participants, 46.3% were women. Significantly fewer women than men had a cardiovascular disease history. Although most women met treatment targets for blood pressure (96.7%) and lipids (72.8%), fewer women than men met the target for cardioprotective therapies at baseline and after two years, particularly those with prior cardiovascular disease, who used less renin-angiotensin-aldosterone system inhibitors, statins, and aspirin than men. Despite these differences, women had lower hazards than men for all outcomes except stroke. No significant gender and cardiovascular disease history interactions were identified for cardiovascular outcomes. Conclusions. In REWIND, most women met clinically relevant treatment targets, but in lower proportions than men. Women had a lower risk for all cardiovascular outcomes except stroke. Clinical trials.gov registration number: NCT01394952

Temporal trends in medical cardioprotective treatment in patients with abdominal aortic aneurysms: A population-based national cohort study

Background and Aims : Patients with abdominal aortic aneurysmal (AAA) disease suffer high morbidity and mortality, driven mainly by cardiovascular comorbidity, and not the aneurysmatic disease itself. Initiation of cardioprotective therapy with statin and antiplatelets is recommended at AAA diagnosis. However, the implementation of recommendations over time is not well described. We aimed to provide up-to-date insights on temporal trends in the use of cardioprotective therapy in patients diagnosed with AAA.

Кардіоваскулярна токсичність у хворих на рак грудної залози: діагностика, лікування, профілактика

За останні десятиліття виживання хворих на рак грудної залози (РГЗ) значно поліпшилося завдяки прогресу медикаментозного лікування та вдосконаленню радіаційних технологій. Класична хіміотерапія, яка базується переважно на антрациклінах, а також таргетна терапія та імунотерапія підвищили шанси на виживання в пацієнтів із РГЗ. Однак як відомі хіміотерапевтичні засоби, так і деякі нові молекули можуть викликати серцево-судинні побічні ефекти, які потенційно погіршують прогноз. Механізми серцево-судинних ускладнень дуже варіюють залежно від виду сполук, і можуть супроводжуватися тимчасовою дисфункцією кардіоміоцитів або індукувати незворотне пошкодження міокарда. Хворі на РГЗ є потенційно пацієнтами високого ризику кардіотоксичності, оскільки вони отримують комбіноване протипухлинне лікування, тому потребують ретельного кардіомоніторингу, особливо пацієнти з наявними серцево-судинними захворюваннями чи численними факторами ризику. З практичної точки зору це можливо внаслідок тісної співпраці кардіологів і онкологів. Стратифікація ризику серцево-судинних ускладнень до початку протипухлинного лікування, індивідуалізований підбір терапії, моніторинг функції серця для раннього виявлення ускладнень, а також вчасне застосування кардіопротекторної терапії, з метою як профілактики, так і лікування ускладнень, сприятимуть поліпшенню виживання та якості життя у хворих на РГЗ.

Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy

BackgroundIn patients at risk of cancer therapy-related cardiac dysfunction (CTRCD), initiation of cardioprotective therapy (CPT) is constrained by the low sensitivity of ejection fraction (EF) for minor changes in left ventricular (LV) function. Global longitudinal strain (GLS) is a robust and sensitive marker of LV dysfunction, but existing observational data have been insufficient to support a routine GLS-guided strategy for CPT. ObjectivesThis study sought to identify whether GLS-guided CPT prevents reduction in LVEF and development of CTRCD in high-risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care. MethodsIn this international, multicenter, prospective, randomized controlled trial, 331 anthracycline-treated patients with another heart failure risk factor were randomly allocated to CPT initiation guided by either ≥12% relative reduction in GLS (n = 166) or >10% absolute reduction of LVEF (n = 165). Patients were followed for EF and development of CTRCD (symptomatic EF reduction of >5% or >10% asymptomatic to <55%) over 1 year. ResultsOf 331 randomized patients, 2 died, and 22 withdrew consent or were lost to follow-up. Among 307 patients (age: 54 ± 12 years; 94% women; baseline LVEF: 59 ± 6%; GLS: –20.6 ± 2.4%) with a median (interquartile range) follow-up of 1.02 years (0.98 to 1.07 years), most (n = 278) had breast cancer. Heart failure risk factors were prevalent: 29% had hypertension, and 13% had diabetes mellitus. At the 1-year follow-up, although the primary outcome of change in LVEF was not significantly different between the 2 arms, there was significantly greater use of CPT, and fewer patients met CTRCD criteria in the GLS-guided than the EF-guided arm (5.8% vs. 13.7%; p = 0.02), and the 1-year EF was 57 ± 6% versus 55 ± 7% (p = 0.05). Patients who received CPT in the EF-guided arm had a larger reduction in LVEF at follow-up than in the GLS-guided arm (9.1 ± 10.9% vs. 2.9 ± 7.4%; p = 0.03). ConclusionsAlthough the change in LVEF was not different between the 2 arms as a whole, when patients who received CPT were compared, those in the GLS-guided arm had a significantly lower reduction in LVEF at 1 year follow-up. Furthermore, GLS-guided CPT significantly reduced a meaningful fall of LVEF to the abnormal range. The results support the use of GLS in surveillance for CTRCD. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628)

Implementing simple algorithms to improve glucose and lipid management in people with diabetes and acute coronary syndrome.

Diabetes mellitus is associated with increased risk of adverse outcomes following acute coronary syndrome. Translating evidence-based recommendations into practice is necessary to improve outcomes. We evaluated whether implementing algorithms to guide inpatient care improved glycaemic control, and increased use of sodium-glucose co-transporter 2 (SGLT2) inhibitors and lipid-lowering medication in a tertiary cardiac unit. A 3-month audit (phase 1) was conducted to evaluate hyperglycaemia and dyslipidaemia management, and medication prescriptions. Consecutive people with diabetes admitted for acute coronary syndrome were prospectively identified. Target blood glucose level was defined as 5-10mmol/l. A multidisciplinary committee designed and implemented decision-support algorithms plus education. A 3-month post-implementation audit (phase 2) was conducted. There were 104 people in phase 1 and 101 in phase 2, with similar characteristics [HbA1c 64±20mmol/mol vs. 61±21mmol/mol (8.0±1.8% vs. 7.8±1.9%]. Post implementation, the incidence of blood glucose levels >10mmol/l was lower [phase 1: 46.4% vs. phase 2: 31.8%, rate ratio(RR)=0.77, 95% confidence intervals (CI) 0.60-0.98; P=0.031], without a difference in blood glucose levels <5mmol/l (phase 1: 4.9% vs. phase 2: 4.5%, RR=1.20, 95% CI 0.70-2.08; P=0.506). SGLT2 inhibitor prescriptions increased significantly (baseline to discharge: 12.5% to 15.4% vs. 7.9% to 24.8%; P=0.007) but high-intensity statin prescriptions did not (baseline to discharge: 35.6% to 72.1% vs. 40.6% to 85.1%; P=0.074). Prescription rates of non-statin lipid-lowering medications were not significantly increased. Implementing decision-support algorithms was associated with improved inpatient glycaemic control and increased use of cardioprotective therapies at discharge in people with diabetes and acute coronary syndrome.

Progressive left ventricular dysfunction and myocardial fibrosis in Duchenne and Becker muscular dystrophy: a longitudinal cardiovascular magnetic resonance study.

This study examined the progression of left ventricular dysfunction and myocardial fibrosis in patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) to evaluate the effects of angiotensin-converting enzyme inhibitor (ACEI). Ninety-eight cardiovascular magnetic resonance (CMR) studies in 34 consecutive patients with DMD (n = 21) or BMD (n = 13) were retrospectively reviewed. Left ventricular ejection fraction (LVEF) and the extent of myocardial late gadolinium enhancement (LGE) were semiautomatically quantified. During the study period, five patients had already been treated with ACEI at the first CMR; five were started on ACEI at LVEF ≥ 55% and 10at LVEF < 55%. All patients had hyperenhanced myocardium on LGE images at the first CMR (median extent, 3.3%; interquartile range 0.1-14.3%). A mixed-effects model for longitudinal data of each patient, adjusted for age, type of muscular dystrophy, steroid use, and ACEI use showed that higher age (β=- 1.1%/year; 95% confidence interval [CI], - 1.8% to - 0.4%; p = 0.005) and no use of ACEI (β=- 3.1%; 95% CI, - 5.4% to - 0.8%; p = 0.009) were significantly associated with a lower LVEF. When ACEI use was stratified by time of initiation (LVEF ≥ 55% vs. < 55%), only ACEI initiation at LVEF < 55% had a beneficial effect on LVEF at each imaging examination (β = 3.7%; 95% CI, 0.9-6.4%; p = 0.010). ACEI use or the time of initiation of ACEI did not significantly affect age-related increase in LGE. ACEI attenuated the age-related decline in LVEF only in patients with DMD or BMD and reduced LVEF, suggesting that further investigation on prophylactic use of cardioprotective therapy in these patients is warranted.

Priorities in the Cardiovascular Care of Breast Cancer Survivors.

Breast cancer is the most common malignancy in women with more than 3 million breast cancer survivors in the United States alone. Survivors of breast cancer suffer from an increased burden of cardiovascular risk factors and disease. The focus of this review is to describe the epidemiology of cardiovascular disease in breast cancer survivors, including the cardiovascular concerns observed with common cancer therapies. Strategies to improve upon the early detection and treatment of cardiovascular disease, including clinical prediction algorithms, biomarkers, and imaging measures are also reviewed, and the use of cardioprotective therapies to mitigate risk are summarized. Finally, the need for evidence-based research to inform and improve upon the multidisciplinary care of this growing population is highlighted.

PP.28.06] ISK PROFILE OF PATIENTS WITH TYPE 2 DIABETES AND ARTERIAL HYPERTENSION IN BULGARIAN GENERAL POPULATION

Objective: The aim of the study was to analyse the risk profile of patients with type 2 diabetes (T2D) and primary hypertension (AH) in a cohort of patients treated in Bulgarian General Practitioners’ practices. Design and method: A retrospective study of patients’ recordings in Bulgarian GPs’ practices was conducted in 2016. We were analysed the data from electronic health records of 142827 persons aged >18 years, and found 15933 patients with T2D and 45393 patients with high blood pressure or treated for AH. The patients with T2D and AH were selected and we were analysed the risk profile of 5926 consecutive patients aged >40 years (blood pressure, heart rate, lipid parameters, blood glucose levels and HbA1c, kidney function), known comorbidities, control of the blood pressure and of the lipid parameters, the use of cardioprotective therapy. The study was initiated and conducted by the National Association of General Practitioners in Bulgaria (NAGPB). Results: The prevalence of AH in the population >18 years of age was 31.8%. The prevalence of T2D was 7.0%. The mean blood pressure among 5926 patients aged >40 years was 137.7/86 mmHg and the heart rate - 74.5 beats/minute. The mean fasting blood glucose was 7.42 mmol/L, the mean HbA1c - 7.54%, the mean total cholesterol - 5.4 mmol/L, the mean triglycerides - 2.06 mmol/L, the mean LDL-cholesterol - 3.2 mmol/L (calculated according to Friedewald formula), the mean HDL-cholesterol - 1.34 mmol/L. The mean eGFR in men was 93.27 mL/min/1.73m2, and in women - 73.06 mL/min/1.73m2. 63.59% of the patient had blood pressure <140/85 mmHg. The blood pressure of the patients with HbA1c <7% was 133.6 /85.3 mmHg with heart rate 73.8 beats/minute, and in those with HbA1c >7% the mean blood pressure was 145.6 /84.3 mmHg and heart rate - 75.7 beats/minute. Conclusions: The blood pressure and glycemic control among the patients with T2D and hypertension is good, but further activities for improvement of the lipid risk in high and very high risk population are mandatory. The bad glycemic control is associated with worse blood pressure control.

Cancer Therapy-Related Cardiac Dysfunction: Unresolved Issues

An increasing awareness of chemotherapy and radiotherapy as preventable causes of cardiac failure among large numbers of patients surviving cancer has contributed to the development of cardio-oncology as a subspecialty. Perhaps the most important driver has been that the aging of the population undergoing cancer therapy has provided an increasing number of patients at risk for the development of heart failure. Cardio-oncology has many unresolved questions. In this article the 6 most important unresolved issues requiring additional research are discussed: (1) the frequency of overt heart failure as a manifestation of cardiotoxicity; (2) the optimal diagnostic approach to cardiotoxicity in the context of large numbers of patients requiring repeated testing; (3) the need for better risk prediction; (4) alternatives to the use of ejection fraction as the cornerstone of evaluation; (5) definition of the best strategy for protection; and (6) the need for evidence-based algorithms to guide late follow-up. When this evidence base is mature, we will have a better understanding of the magnitude of the problem of cardiotoxicity, who best to screen (and how), who justifies the use of cardioprotective therapy, and how all at-risk patients should be followed over the decades following cancer therapy.

Cardiovascular risk profile of patients included in stent trials; a pooled analysis of individual patient data from randomised clinical trials: insights from 33 prospective stent trials in Europe

Few data document trends in cardiovascular (CV) risk-factors in patients with or without previous symptomatic CV disease. We assessed the prevalence and trends in (non) modifiable CV risk-factors, and the use of cardioprotective therapies in patients enrolled in coronary stent trials. This analysis included prospective data on 10,253 mainly European adults who were enrolled in 32 coronary stent studies between 1995 and 2006. Data was collected at the time of enrolment using a standardised patient clinical record form, and was analysed by considering three consecutive time periods: 1995-1997 (I), 1998-2002 (II) and 2003-2006 (III) rendering approximately equal numbers per period. Overall the proportion of active smokers remained constant (Period I to III: 28%, 27%, 21%, p=0.45), however the proportion increased in females below 50 years (about 2%/ year, R.RR: 1.20, P: 0.05 period III versus I). Prevalent diabetes increased (16%, 17%, 25%; p=0.029). The prevalence of a body-mass index (BMI) ≥25 kg/m² was high, but no trend was observed (69%, 68%, 70%; p=0.24). The proportion of patients with elevated blood pressure (i.e., ≥140/90 mmHg, in diabetes ≥130/80 mmHg) remained unchanged (55%, 50.%, 53%; p=0.22), despite an increase in the number of patients taking anti-hypertensive agents (84%, 89%, 90%; p=0.30). Conversely, the proportion of patients with elevated total cholesterol (i.e., ≥4.5 mmol/L) decreased (80%, 66%, 52%; p=0.002), which was consistent with the increase in patients taking lipid lowering drugs (32%, 62%, 69%; p=0.083). The portion of patients reaching therapeutic targets for blood lipids improved, but no improvement was seen in blood pressure control (p=0.29). There is an unmet clinical need in primary and secondary CV prevention in Europe. Patients requiring PCI are an important target population in whom lifestyle changes and aggressive secondary preventative measures should be aimed. Ultimately PCI should open the door towards optimising secondary prevention.