Prophylactic use of carvedilol to prevent ventricular dysfunction in patients with cancer treated with doxorubicin

Abuosa, Ahmed; Elshiekh, Ayman Hassan; Qureshi, Kahekashan; Abrar, Mohammed Burhan; Kholeif, Mona A.; Kinsara, Abdulhalim Jamal; Andejani, Abdulwahab; Ahmed, Adel H.; Cleland, John G.F.

doi:10.1016/j.ihj.2018.06.011

Cited by 41 publications

(27 citation statements)

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“…The analysis included 10 studies [13][14][15][16][17][18][19][20]25,26 with 385 patients in the beta-blocker group and 384 control patients. The mean LVEF difference between the beta-blocker group and the control group was 2.57%, 95% CI (0.63-4.51), P = 0.009.…”

Section: Resultsmentioning

confidence: 99%

“…The most frequent tumour disease was breast cancer followed by haematological malignancies. Eight eligible trials assessing beta-blockers (carvedilol, nebivolol, bisoprolol, and metoprolol), [13][14][15][16][17][18][19][20] four studies assessing ACE inhibitors/ARBs (enalapril, telmisartan, candesartan, and perindopril), [21][22][23][24] and two studies assessing beta-blockers and ACE inhibitors/ARBs in parallel arms 25,26 were identified ( Table 1). The sample sizes in groups were rather low, ranging from n = 18 to n = 103.…”

Section: Resultsmentioning

confidence: 99%

“…The mean LVEF difference between the beta-blocker group and the control group was 2.57%, 95% CI (0.63-4.51), P = 0.009. The analysis included 10 studies [13][14][15][16][17][18][19][20]25,26 with 385 patients in the beta-blocker group and 384 control patients. The heterogeneity was considerable between the selected studies, as shown by an I 2 value of 86%, with P < 0.001 ( Figure 1).…”

Section: Resultsmentioning

confidence: 99%

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Heart failure from cancer therapy: can we prevent it?

et al. 2019

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Aims Conventional cytotoxic chemotherapy is still among the most effective treatment options for many types of cancer. However, cardiotoxicity, notably the decrease in left ventricular function under these regimens, can impair prognosis. Thus, prevention and treatment of cardiotoxicity are crucial. The present meta‐analysis aims to assess the efficacy of beta‐blockers or angiotensin‐converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) for prevention of cardiotoxicity. Methods and results We systematically searched Pubmed, Cochrane, EMBASE, and Web of Science databases for randomized controlled trials published until February 2019. The analysis included randomized studies that reported on left ventricular ejection fraction (LVEF) after 6 months of chemotherapy in cancer patients who received beta‐blockers or ACE inhibitors/ARBs for prevention of cardiotoxicity compared with controls. Studies on combination cardioprotective therapies were excluded from the analysis. The primary endpoint was prevention of a decrease in LVEF as defined by the individual study and as assessed by either transthoracic echocardiography or magnetic resonance imaging. We here show that patients under anthracycline‐based chemotherapy have a moderate yet significant benefit in LVEF from beta‐blockers or ACEs/ARBs. The beta‐blocker analysis included 769 cancer patients, and the ACE inhibitors/ARBs analysis included a total of 581 cancer patients. The mean LVEF difference between the beta‐blocker group and the control group was 2.57% (95% confidence interval 0.63–4.51, P = 0.009). The mean difference for ACE inhibitors/ARBs was 4.71% (95% confidence interval 0.38–9.03, P = 0.03). However, the beneficial effects throughout the studies were variable as documented by significant heterogeneity between the studies. Conclusions Systematic evidence is needed to solidly found recommendations for cardioprotective prevention during chemotherapy. Likewise, trials on other neurohumoral drugs (spironolactone) and lipid‐lowering approaches are required to improve protection for cardio‐oncology patients.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Heart failure from cancer therapy: can we prevent it?

et al. 2019

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“…As the cardiotoxic mechanism of anthracyclines involves inducing oxidative stress and mitochondrial dysfunction, protective agents that are able to lower the production of ROS or lower the workload of the heart during anthracycline treatment may be beneficial to reduce anthracycline-induced cardiotoxicity. Factors that may reduce oxidative stress in the heart, such as statins and natural antioxidants, and compounds that reduce the workload of the heart, such as angiotensin-converting-enzyme (ACE) inhibitors and beta-blockers, have been combined with anthracyclines in clinical trials, with mixed success (66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77). As far as known, these compounds have never been tested in hPSC-cardiomyocytes for assessment of their direct cardioprotective potential, even though reducing oxidative stress in particular can be readily modeled in vitro.…”

Section: Protective Agents To Alleviate Cardiotoxicitymentioning

confidence: 99%

Human Pluripotent Stem Cell-Derived Cardiomyocytes for Assessment of Anticancer Drug-Induced Cardiotoxicity

Schwach

Slaats

Passier

2020

Front. Cardiovasc. Med.

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Cardiotoxicity is a major cause of high attrition rates among newly developed drugs. Moreover, anti-cancer treatment-induced cardiotoxicity is one of the leading reasons of mortality in cancer survivors. Cardiotoxicity screening in vitro may improve predictivity of cardiotoxicity by novel drugs, using human pluripotent stem cell (hPSC)-derived-cardiomyocytes. Anthracyclines, including Doxorubicin, are widely used and highly effective chemotherapeutic agents for the treatment of different forms of malignancies. Unfortunately, anthracyclines cause many cardiac complications early or late after therapy. Anthracyclines exhibit their potent anti-cancer effect primarily via induction of DNA damage during the DNA replication phase in proliferative cells. In contrast, studies in animals and hPSC-cardiomyocytes have revealed that cardiotoxic effects particularly arise from (1) the generation of oxidative stress inducing mitochondrial dysfunction, (2) disruption of calcium homeostasis, and (3) changes in transcriptome and proteome, triggering apoptotic cell death. To increase the therapeutic index of chemotherapeutic Doxorubicin therapy several protective strategies have been developed or are under development, such as (1) reducing toxicity through modification of Doxorubicin (analogs), (2) targeted delivery of anthracyclines specifically to the tumor tissue or (3) cardioprotective agents that can be used in combination with Doxorubicin. Despite continuous progress in the field of cardio-oncology, cardiotoxicity is still one of the major complications of anti-cancer therapy. In this review, we focus on current hPSC-cardiomyocyte models for assessing anthracycline-induced cardiotoxicity and strategies for cardioprotection. In addition, we discuss latest developments toward personalized advanced pre-clinical models that are more closely recapitulating the human heart, which are necessary to support in vitro screening platforms with higher predictivity. These advanced models have the potential to reduce the time from bench-to-bedside of novel antineoplastic drugs with reduced cardiotoxicity.

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“…Carvedilol (CRV) ( Figure 1 ) is a non-selective blocker of α and β adrenergic receptors, and has been extensively used for the treatment of hypertension and congestive heart failure. CRV oral bioavailability ranges from 20% to 35% owing to its low water solubility and increased fast metabolism [ 1 , 2 , 3 ]. To circumvent its unsatisfactory biopharmaceutical properties, CRV has been incorporated in different types of drug delivery systems, e.g., nanoemulsions [ 4 ], solid-state cyclodextrin complexes [ 5 ], solid dispersions [ 6 ], transdermal vehicles [ 7 ], and supramolecular hydrogels [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Electroanalysis Applied to Compatibility and Stability Assays of Drugs: Carvedilol Study Case

et al. 2020

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Carvedilol (CRV) is a non-selective blocker of α and β adrenergic receptors, which has been extensively used for the treatment of hypertension and congestive heart failure. Owing to its poor biopharmaceutical properties, CRV has been incorporated into different types of drug delivery systems and this necessitates the importance of investigating their compatibility and stability. In this sense, we have investigated the applicability of several electroanalytical tools to assess CRV compatibility with lipid excipients. Voltammetric and electrochemical impedance spectroscopy techniques were used to evaluate the redox behavior of CRV and lipid excipients. Results showed that Plurol® isostearic, liquid excipient, and stearic acid presented the greatest anode peak potential variation, and these were considered suitable excipients for CRV formulation. CRV showed the highest stability at room temperature and at 50 °C when mixed with stearic acid (7% w/w). The results also provided evidence that electrochemical methods might be feasible to complement standard stability/compatibility studies related to redox reactions.

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Prophylactic use of carvedilol to prevent ventricular dysfunction in patients with cancer treated with doxorubicin

Cited by 41 publications

References 13 publications

Heart failure from cancer therapy: can we prevent it?

Heart failure from cancer therapy: can we prevent it?

Human Pluripotent Stem Cell-Derived Cardiomyocytes for Assessment of Anticancer Drug-Induced Cardiotoxicity

Electroanalysis Applied to Compatibility and Stability Assays of Drugs: Carvedilol Study Case

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