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The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key Takeaway

  • Prophylactic therapy with beta blockers or with dexrazoxane may protect against cardiac dysfunction caused by chemotherapy regimens containing anthracyclines (ANT) or trastuzumab (TZB).

Why This Matters

  • ANT and TZB are both effective in the treatment of breast cancer but can be cardiotoxic, in that continuous use can lead to reduced cardiac function.

  • Some drugs currently available for treatment of heart failure with reduced ejection fraction and others with antioxidative effects may potentially be given for prevention of cardiotoxic effects related to ANT and TZB chemotherapy.

Study Design

  • A meta-analysis was conducted using English-language reports identified from the PubMed, Embase, and Cochrane Library databases using the keywords anthracyclines, trastuzumab, desogen and apri cardiotoxicity, and prevention.

  • Selected studies had to meet the following criteria: randomized trial, enrollment of adult patients with cancer, an intervention group given prophylactic therapeutics for cardiac dysfunction related to cancer therapy, and cardiac functional assessments conducted prior to chemotherapy and at follow-up.

  • Subgroup analyses that explored different chemotherapy combinations containing ANT and TZB were considered.

Key Results

  • A meta-analysis was performed with the 24 identified reports that met all the study-selection criteria. They encompassed a total of 3159 patients, of whom 94% were women. Mean ages in the studies ranged from 36 to 61 years.

  • The malignancy most often treated in the studies was breast cancer, followed by lymphoma and lung cancer.

  • Chemotherapy consisted of ANT without TZB in 17 studies; ANT plus TZB in two studies; ANT with or without TZB in three studies; and TZB with or without ANT in two studies.

  • Randomized therapy consisted of an ACE inhibitor in five studies, an angiotensin receptor blocker in four studies, a beta blocker in 11 studies, spironolactone in one study, and dexrazoxane in three studies. Salidroside, prenylamine, N-acetylcysteine, and rosuvastatin were each used in one trial.

  • All studies used echocardiography to evaluate cardiac function, except for one study that used cardiac magnetic resonance imaging and multiple-gated acquisition scans. Ten studies also assessed cardiac damage by measurement of inflammatory markers, cardiac enzymes, and natriuretic peptides.

  • Follow-up periods in the studies ranged from 1 week to 10 years but were usually 3 months to 1 year.

  • Some beta blockers, but not others, showed some action in preventing cardiac dysfunction associated with ANT and TZB, as measured variously by biomarkers, left-ventricular ejection fraction (LVEF), and echocardiographic measures of diastolic function.

  • Beneficial effects from beta blockers, especially nebivolol, were more consistently seen in studies of patients receiving ANT.

  • Dexrazoxane appeared to protect against reduced LVEF primarily in patients receiving ANT.

Limitations

  • Assignment to treatment groups was not rigorously randomized in all studies, and patients were not always blind to randomized therapy.

  • Follow-up durations across the 24 studies were inconsistent.

Disclosures

  • No funding for the study was reported, and the authors have disclosed no relevant financial relationships.

This is a summary of a preprint research study, “Preventive Strategies for Anthracyclines and Trastuzumab Induced Cardiotoxicity: A Systematic Review and Meta-Analysis,” written by Cátia Oliveira, from Hospital de Braga, and Rui Campos, from University of Minho, published on ResearchSquare.com and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com.

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