scholarly journals Statins to mitigate cardiotoxicity in cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis

Author(s):  
Mary Obasi ◽  
Arielle Abovich ◽  
Jacqueline B. Vo ◽  
Yawen Gao ◽  
Stefania I. Papatheodorou ◽  
...  

Abstract Purpose Cardiotoxicity affects 5–16% of cancer patients who receive anthracyclines and/or trastuzumab. Limited research has examined interventions to mitigate cardiotoxicity. We examined the role of statins in mitigating cardiotoxicity by performing a systematic review and meta-analysis of published studies. Methods A literature search was conducted using PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central. A random-effect model was used to assess summary relative risks (RR), weighted mean differences (WMD), and corresponding 95% confidence intervals. Testing for heterogeneity between the studies was performed using Cochran’s Q test and the I2 test. Results Two randomized controlled trials (RCTs) with a total of 117 patients and four observational cohort studies with a total of 813 patients contributed to the analysis. Pooled results indicate significant mitigation of cardiotoxicity after anthracycline and/or trastuzumab exposure among statin users in cohort studies [RR = 0.46, 95% CI (0.27–0.78), p = 0.004, $${ }I^{2}$$ I 2  = 0.0%] and a non-significant decrease in cardiotoxicity risk among statin users in RCTs [RR = 0.49, 95% CI (0.17–1.45), p = 0.20, $$I^{2}$$ I 2  = 5.6%]. Those who used statins were also significantly more likely to maintain left ventricular ejection fraction compared to baseline after anthracycline and/or trastuzumab therapy in both cohort studies [weighted mean difference (WMD) = 6.14%, 95% CI (2.75–9.52), p < 0.001, $$I^{2}$$ I 2  = 74.7%] and RCTs [WMD = 6.25%, 95% CI (0.82–11.68, p = 0.024, $$I^{2}$$ I 2  = 80.9%]. We were unable to explore publication bias due to the small number of studies. Conclusion This meta-analysis suggests that there is an association between statin use and decreased risk of cardiotoxicity after anthracycline and/or trastuzumab exposure. Larger well-conducted RCTs are needed to determine whether statins decrease risk of cardiotoxicity from anthracyclines and/or trastuzumab. Trial Registration Number and Date of Registration PROSPERO: CRD42020140352 on 7/6/2020.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23081-e23081
Author(s):  
Sae Jang ◽  
Kathryn Jean Ruddy ◽  
Charles L. Loprinzi ◽  
Saro Armenian ◽  
Daniel John Lenihan ◽  
...  

e23081 Background: Anthracycline-induced cardiotoxicity (AIC) is a well-known phenomenon, but the true incidence is poorly defined, and definitions of AIC in the literature are variable. We performed a systematic review and meta-analysis to elucidate AIC definitions and the incidence of clinical heart failure (HF) and subclinical AIC reported in adult breast cancer and lymphoma patients after anthracycline (AC) therapy. Methods: 3,428 abstract and titles were identified via PubMed search. Inclusion criteria for full text review included minimum of 100 adult patients receiving ACs; median/mean follow up of at least 12 months; and specified evaluation of left ventricular ejection fraction. Outcomes were divided into clinical HF and subclinical AIC. Meta-analysis was performed with MedCalc software with random effects model. Results: 366 full text articles were reviewed. 24 studies, including a total of 11,065 patients, reported clinical HF findings; 21 studies, including a total of 8,098 patients, reported subclinical AIC findings. Meta-analysis showed an overall incidence of clinical HF of 3.1% (range 0 to 29%, CI 1.9 to 4.6%, I2= 93.9%); an incidence of 2.0% (CI 0.9 to 3.6%, I2 = 91.6%) in breast cancer patients receiving AC; and 4.8% in lymphoma patients receiving AC (CI 2.1 to 8.6%, I2 = 93.6%). Subclinical AIC was seen in 13.8% overall patients (range 2 to 45%, CI 10.4 to 17.7%, I2= 95.3%); 10.3% of breast cancer patients (CI 7.0 to 14.3%, I2= 95.0%); and 19.8% of lymphoma patients (CI 12.3 to 28.6%, I2= 94.4%). Incidence of HF correlated with increasing age (r = 0.51, p = 0.06) and cumulative dose (r = 0.51 , p = 0.19). There was notable heterogeneity of AIC definitions between studies (Table). Conclusions: Cardiotoxicity is not uncommon among patients who receive AC, particularly at doses given for the treatment of lymphoma. However, there was considerable heterogeneity in HF incidences. More uniform criteria and precise estimates are needed to inform clinical practice and trials. [Table: see text]


2021 ◽  
Vol 11 (18) ◽  
pp. 8336
Author(s):  
Pedro Antunes ◽  
Dulce Esteves ◽  
Célia Nunes ◽  
Anabela Amarelo ◽  
José Fonseca-Moutinho ◽  
...  

Background: we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of exercise training on cardiac function and circulating biomarkers outcomes among women with breast cancer (BC) receiving anthracycline or trastuzumab-containing therapy. Methods: PubMed, EMBASE, Cochrane Library, Web of Science and Scopus were searched. The primary outcome was change on left ventricular ejection fraction (LVEF). Secondary outcomes included diastolic function, strain imaging and circulating biomarkers. Results: Four RCTs were included, of those three were conducted during anthracycline and one during trastuzumab, involving 161 patients. All trials provided absolute change in LVEF (%) after a short to medium-term of treatment exposure (≤6 months). Pooled data revealed no differences in LVEF in the exercise group versus control [mean difference (MD): 2.07%; 95% CI: −0.17 to 4.34]. Similar results were observed by pooling data from the three RCTs conducted during anthracycline. Data from trials that implemented interventions with ≥36 exercise sessions (n = 3) showed a significant effect in preventing LVEF decline favoring the exercise (MD: 3.25%; 95% CI: 1.20 to 5.31). No significant changes were observed on secondary outcomes. Conclusions: exercise appears to have a beneficial effect in mitigating LVEF decline and this effect was significant for interventions with ≥36 exercise sessions.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Kawakami ◽  
N Nerlekar ◽  
K H Haugaa ◽  
T Edvardsen ◽  
T H Marwick

Abstract Background Recent studies have demonstrated that left ventricular mechanical dispersion (LVMD) assessed by speckle tracking might be a powerful marker in risk stratification for ventricular arrhythmias (VA). We sought to perform a systematic review and meta-analysis to i) assess the prognostic value of this parameter (previous studies were predominantly single-center), ii) define the value relative to other parameters, iii) identify the most appropriate cutoff for designating risk. Purpose To assess the association between LVMD and the incidence of VA. Methods A systemic review of studies reporting the predictive value of LVMD for VA was undertaken from a search of Medline and Embase. LVMD was defined as the standard deviation of time from Q/R on ECG to peak negative strain from each LV segment. VA events were defined as sudden cardiac death, cardiac arrest, documented ventricular tachyarrhythmia, and appropriate implantable cardioverter defibrillator therapy. Hazard ratios (HRs) were extracted from univariable and multivariable models reporting on the association of LVMD and VA and described as pooled estimates with 95% confidence intervals (CIs). In a meta-analysis, the predictive value of LVMD was compared to that of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). Results Among 3198 patients (weighted mean, 63 years, 30% female; 82% ischemic heart disease) in 12 published articles, 387 (12%) had VA events over a follow-up (17–70 months). Patients with VA events had a significantly greater mechanical dispersion compared with those without VA events (weighted mean difference, −20.3 ms; 95% CI, −27.3 to −13.2; p<0.01); 60 ms was found to be the optimal cutoff LVMD value for predicting VA events. Each 10 ms increment of LVMD was significantly and independently associated with VA events (HR, 1.19; 95% CI, 1.09 to 1.29; p<0.01). The predictive value of LVMD was superior to that of LVEF or GLS (Figure). Figure 1 Conclusion LVMD assessed by speckle tracking provides important predictive value for VA in patients with a number of cardiac diseases and appears to have superior predictive value to LVEF and GLS for risk stratification.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Carlos A Godoy Rivas ◽  
Samuel Urrutia ◽  
Eleazar Montalvan ◽  
Mario Rodriguez ◽  
Eduardo Venegas ◽  
...  

Introduction: Heart Failure (HF) is categorized according to the AHA/ACC 2013 HF Guidelines based on Left Ventricular Ejection Fraction (LVEF); HF with Reduced Ejection Fraction (HFrEF, EF≤40%), and HF with preserved EF (HFpEF, EF ≥ 50%). There is a group of “borderline” patients with EF 41%-49%, termed Heart Failure with Mid-Range Ejection Fraction (HFmrEF). Given this category is not well understood, we sought to evaluate clinical characteristics and management patterns for patients with HFmrEF. Methods: A systematic review was performed using Ovid MEDLINE, EMBASE, Cochrane CENTRAL and LILACS (1946 – 03/2018). Search terms included HF, mid-range, borderline LVEF with several ranges (40-50 or 40-45 or 45-50). Variables characterizing clinical features and medications were extracted for each HF group and adjusted odds ratios (ORs) were pooled. Results: Of 1,131 abstracts identified, 24 met inclusion criteria (total patients 480,188). Patients with HFmrEF compared to those with HFrEF were more likely to be female (OR 1.42), have hypertension [HTN] (OR 1.34) and diabetes (OR 1.11), higher SBP (OR 1.17), better NYHA-FC (FC I OR 1.73, FC II 1.33), less likely to have coronary artery disease [CAD] (OR 0.74) and more likely to be treated with ACEI, ARB, BB, Digoxin, MRA and statins (Figure 1-2). HFmrEF patients when compared to those with HFpEF were less likely to be female (OR 0.54) or have HTN (OR 0.68), and more likely to have CAD (OR 1.25), and to be treated with HF medications and statins. Conclusions: Patients with HFmrEF have higher SBP and better NYHA-FC (I and II) compared to HFrEF patients and are less likely to be female and more likely to have CAD compared to HFpEF patients. Further research is needed to help guide management in this unique but clinically important population. Figure 1A. Forest plot of adjusted ORs comparing baseline clinical characteristics of HFrEF vs HFmrEF patients Figure 1B. Forest plot of adjusted ORs comparing baseline clinical characteristics of HFmrEF vs HFpEF patients Figure 2A. Forest plot of adjusted ORs comparing medications used in HFrEF vs HFmrEF patients Figure 2B. Forest plot of adjusted ORs comparing medications used in HFmrEF vs HFpEF patients


Author(s):  
Amr Abdin ◽  
Suleman Aktaa ◽  
Davor Vukadinović ◽  
Elena Arbelo ◽  
Harran Burri ◽  
...  

Abstract Background Right ventricular pacing (RVP) may cause electrical and mechanical desynchrony leading to impaired left ventricular ejection fraction (LVEF). We investigated the outcomes of RVP with His bundle pacing (HBP) and left bundle branch pacing (LBBP) for patients requiring a de novo permanent pacemaker (PPM) for bradyarrhythmia. Methods and results Systematic review of randomized clinical trials and observational studies comparing HBP or LBP with RVP for de novo PPM implantation between 01 January 2013 and 17 November 2020 was performed. Random and fixed effects meta-analyses of the effect of pacing technology on outcomes were performed. Study outcomes included all-cause mortality, heart failure hospitalization (HFH), LVEF, QRS duration, lead revision, atrial fibrillation, procedure parameters, and pacing metrics. Overall, 9 studies were included (6 observational, 3 randomised). HBP compared with RVP was associated with decreased HFH (risk ratio [RR] 0.68, 95% confidence interval [CI] 0.49–0.94), preservation of LVEF (mean difference [MD] 0.81, 95% CI − 1.23 to 2.85 vs. − 5.72, 95% CI − 7.64 to -3.79), increased procedure duration (MD 15.17 min, 95% CI 11.30–19.04), and increased lead revisions (RR 5.83, 95% CI 2.17–15.70, p = 0.0005). LBBP compared with RVP was associated with shorter paced QRS durations (MD 5.6 ms, 95% CI − 6.4 to 17.6) vs. (51.0 ms, 95% CI 39.2–62.9) and increased procedure duration (MD 37.78 min, 95% CI 20.04–55.51). Conclusion Of the limited studies published, this meta-analysis found that HBP and LBBP were superior to RVP in maintaining physiological ventricular activation as an initial pacing strategy.


Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2028 ◽  
Author(s):  
Corinne Frere ◽  
Benjamin Crichi ◽  
Barbara Bournet ◽  
Cindy Canivet ◽  
Nassim Ait Abdallah ◽  
...  

Patients with pancreatic cancer (PC) carry the highest risk of venous thromboembolism (VTE) amongst all cancer patients. Appropriate use of primary thromboprophylaxis might significantly and safely reduce its burden. We performed a systematic review of published studies and meeting abstracts using MEDLINE and EMBASE through July 2020 to evaluate the efficacy and safety of primary thromboprophylaxis in ambulatory PC patients receiving chemotherapy. The Mantel–Haenszel random effect model was used to estimate the pooled event-based risk ratio (RR) and the pooled absolute risk difference (RD) with a 95% confidence interval (CI). Five randomized controlled studies with 1003 PC patients were included in this meta-analysis. Compared to placebo, thromboprophylaxis significantly decreased the risk of VTE (pooled RR 0.31, 95% CI 0.19–0.51, p < 0.00001, I2 = 8%; absolute RD −0.08, 95% CI −0.12–−0.05, p < 0.00001, I2 = 0%), with an estimated number needed to treat of 11.9 patients to prevent one VTE event. Similar reductions of VTE were observed in studies with parenteral (RR 0.30, 95% CI 0.17–0.53) versus oral anticoagulants (RR 0.37, 95% CI 0.14–0.99) and in studies using prophylactic doses of anticoagulants (RR 0.34, 95% CI 0.17–0.70) versus supra-prophylactic doses of anticoagulants (RR 0.27, 95% CI 0.08–0.90). The pooled RR for major bleeding was 1.08 (95% CI 0.47–2.52, p = 0.85, I2 = 0%) and the absolute RD was 0.00 (95% CI −0.02–0.03, p = 0.85, I2 = 0%). Evidence supports a net clinical benefit of thromboprophylaxis in ambulatory PC patients receiving chemotherapy. Adequately powered randomized phase III studies assessing the most effective anticoagulant and the optimal dose, schedule and duration of thromboprophylaxis to be used are warranted.


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