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Reproductive Biology and Endocrinology... Mar 2024Pregnancy is characterized by profound circulatory changes and compensatory adjustments in the renin-angiotensin-aldosterone system (RAAS). Differences in regulatory... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pregnancy is characterized by profound circulatory changes and compensatory adjustments in the renin-angiotensin-aldosterone system (RAAS). Differences in regulatory response may antedate or accompany vascular complicated pregnancy. We performed a systematic review and meta-analysis to delineate the trajectory of active plasma renin concentration (APRC) in healthy pregnancy and compare this to complicated pregnancy.
METHODS
We performed a systematic review and meta-analysis on APRC during normotensive and hypertensive pregnancies, using PubMed (NCBI) and Embase (Ovid) databases. We included only studies reporting measurements during pregnancy together with a nonpregnant reference group measurement. Risk of bias was assessed with QUIPS. Ratio of the mean (ROM) and 95% confidence intervals (CI) of APRC values between pregnant and nonpregnant women were estimated for predefined intervals of gestational age using a random-effects model. Meta-regression was used to analyze APRC over time.
RESULTS
In total, we included 18 studies. As compared to nonpregnant, APRC significantly increased as early as the first weeks of healthy pregnancy and stayed increased throughout the whole pregnancy (ROM 2.77; 95% CI 2.26-3.39). APRC in hypertensive complicated pregnancy was not significantly different from nonpregnancy (ROM 1.32; 95% CI 0.97-1.80).
CONCLUSION
Healthy pregnancy is accompanied by a profound rise in APRC in the first trimester that is maintained until term. In hypertensive complicated pregnancy, this increase in APRC is not observed.
Topics: Pregnancy; Female; Humans; Renin; Pregnancy Complications; Hypertension; Renin-Angiotensin System; Blood Pressure; Aldosterone
PubMed: 38454417
DOI: 10.1186/s12958-024-01200-2 -
Exploratory Research in Clinical and... Sep 2023Hypertension has affected over 1.13 billion people worldwide in 2015 and it's one of the most preventable risk-factors for morbidity and mortality. Antihypertensives... (Review)
Review
BACKGROUND
Hypertension has affected over 1.13 billion people worldwide in 2015 and it's one of the most preventable risk-factors for morbidity and mortality. Antihypertensives significantly reduce cardiovascular risks. Several studies on antihypertensives' prescribing patterns were conducted worldwide, and guidelines were developed on hypertension management. However, no systematic reviews were conducted globally to synthesize the evidence from these studies. This review aims to evaluate antihypertensives' prescription patterns, and adherence to international guidelines for hypertension management worldwide.
METHODS
Full-text antihypertensives' prescribing patterns evaluation studies were included. Reviews, commentaries, guidelines, and editorials were excluded. Various databases were searched including PubMed, Embase, and others. Studies were limited to English only and to articles published from (01/01/2010) to (20/03/2020). Crowe Critical Appraisal Tool (CCAT) was used for quality assessment.
RESULTS
The most commonly prescribed antihypertensives as monotherapy in adult patients with no comorbidities were ACEIs/ARBs (Angiotensin converting enzyme inhibitors/Angiotensin receptor blockers), followed by CCBs (Calcium channel blockers), and BBs (Beta Blockers). Most commonly prescribed dual combinations were thiazide diuretics+ACEIs/ARBs, BBs + CCBs and CCBs+ACEIs/ARBs. Among diabetic patients, the most common agents were ACEIs/ARBs. Among patients with heart diseases, CCBs were prescribed frequently. While patients with kidney diseases, CCBs and ARBs were most prescribed. Of the 40 studies included in the review, only four studies directly assessed the prescribing patterns of antihypertensives in adherence to clinical practice guidelines. And only two studies confirmed adherence to guidelines. Furthermore, the quality of the majority of studies was moderate (50%), while 25% of articles were reported as either high or low quality.
CONCLUSION
This review revealed that there are areas for improvement for prescribing practices of antihypertensives in concordance with the latest evidence and with clinical practice guidelines.
PubMed: 37635839
DOI: 10.1016/j.rcsop.2023.100315 -
Pharmaceuticals (Basel, Switzerland) Jul 2023There are significant considerations about the prevention of cardiotoxicity caused by trastuzumab therapy in patients with breast cancer, leading to discontinuation.... (Review)
Review
There are significant considerations about the prevention of cardiotoxicity caused by trastuzumab therapy in patients with breast cancer, leading to discontinuation. Recently, randomized controlled trials (RCTs) have evaluated the effects of early commitment of beta-blockers (BBs), angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) during trastuzumab chemotherapy in order to prevent the related cardiotoxicity. The present systematic review and meta-analysis of six RCTs included patients who have predominantly non-metastatic, HER2-positive, breast cancer and received trastuzumab as primary or adjuvant therapy. Those patients did not have any obvious cardiac dysfunction or any previous therapy with cardioprotective agent. We evaluated the efficacy of the aforementioned medications for primary prevention of cardiotoxicity, using random effects models. Any preventive treatment did not reduce cardiotoxicity occurrence compared to controls (Odds ratios (OR) = 0.92, 95% CI 0.54-1.56, = 0.75). Results were similar for ACEIs/ARBs and beta-blockers. Treatment with ACEIs/ARBs led to a slight, but significant, increase in LVEF in patients compared to the placebo group. Only two studies reported less likelihood of discontinuation of trastuzumab treatment. More adequately powered RCTs are needed to determine the efficacy of routine prophylactic therapy.
PubMed: 37513895
DOI: 10.3390/ph16070983 -
Journal of Clinical Medicine Mar 2024: Sacubitril/valsartan improves heart failure (HF) outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, randomized controlled trials... (Review)
Review
The Efficacy and Safety of Sacubitril/Valsartan Compared to Valsartan in Patients with Heart Failure and Mildly Reduced and Preserved Ejection Fractions: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
: Sacubitril/valsartan improves heart failure (HF) outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, randomized controlled trials (RCTs) in patients with heart failure and mildly reduced ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) have shown inconsistent results. We conducted this meta-analysis to comprehensively evaluate the efficacy and safety of sacubitril/valsartan compared to valsartan within this specific patient population. : We searched the MEDLINE database and ClinicalTrials.gov and identified four RCTs that could be included in our analysis, with 3375 patients in the sacubitril/valsartan group and 3362 in the valsartan group. : Our study shows that, in patients with HFmrEF and HFpEF, sacubitril/valsartan was superior to valsartan in some of the key HF outcomes, such as the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS), with a small but significant mean difference of 1.13 (95% confidence interval or CI of 0.15 to 2.11, -value 0.024), an improvement in the New York Heart Association (NYHA) class (odds ratio or OR of 1.32, 95% CI 1.11 to 1.58, -value 0.002), and the composite outcome of hospitalizations for HF and cardiovascular death, with a relative risk (RR) of 0.86 (95% CI 0.75 to 0.99, -value 0.04). However, there was no additional benefit with sacubitril/valsartan compared to valsartan for the outcomes of cardiovascular death and all-cause mortality. In terms of side effects, sacubitril/valsartan was associated with a higher risk of hypotension when compared to valsartan (OR 1.67, 95% CI 1.27 to 2.19, -value < 0.0001), but did not show an increased risk of hyperkalemia or worsening renal function. : In individuals with HFmrEF or HFpEF, sacubitril/valsartan can result in improvements in the HF outcomes of the KCCQ CSS, the NYHA class, and the composite outcome of hospitalization for HF and cardiovascular death when compared to valsartan. While there was a higher risk of hypotension with sacubitril/valsartan compared to valsartan, there was no corresponding increase in the risk of hyperkalemia or worsening renal function.
PubMed: 38541798
DOI: 10.3390/jcm13061572 -
Drug Safety May 2024Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug...
BACKGROUND
Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug absorption, potentially affecting pharmacokinetics, particularly in the case of medications with a narrow therapeutic index.
PURPOSE
The purpose of this systematic review is to summarize data on drug-drug interactions between GLP1RAs and oral drugs.
DATA SOURCES
The PubMed and EMBASE databases were searched up to November, 1st 2023.
STUDY SELECTION
We selected pharmacokinetic studies of any injectable GLP1RA given with an oral medication, and product prescribing sheets reporting data without access to the original study.
DATA EXTRACTION
Two authors independently extracted the data.
DATA SYNTHESIS
Twenty-two reports and six prescribing sheets were included. Treatment with GLP1RAs resulted in unaffected or reduced C and delayed t of drugs with high solubility and permeability (warfarin, contraceptive pills, acetaminophen), drugs with high solubility and low permeability (angiotensin converting enzyme inhibitors), drugs with low solubility and high permeability (statins) and drugs with low solubility and permeability (digoxin). However, the use of GLP1RAs did not exert clinically significant changes in the AUC or differences in clinically relevant endpoints.
LIMITATIONS
The major limitations of the studies that are included in this systematic review are the enrollment of healthy subjects and insufficient data in conditions that might affect pharmacokinetics (e.g., kidney dysfunction).
CONCLUSIONS
To conclude, reduced C and delayed t of drugs co-administered with GLP1RAs are consistent with the known delayed gastric output by the latter. Nevertheless, the overall drug exposure was not considered clinically significant. Dose adjustments are probably not required for simultaneous use of GLP1RAs with oral medications. Still, results should be carefully generalized to cases of background kidney dysfunction or when using drugs with narrow therapeutic index. The study is registered in PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332339 .
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Drug Interactions; Glucagon-Like Peptide 1; Warfarin
PubMed: 38273155
DOI: 10.1007/s40264-023-01392-3 -
Journal of Pharmacy & Pharmaceutical... 2023Hyperkalemia is a common electrolyte disorder in patients with chronic kidney disease (CKD) that increases in prevalence with the decline of glomerular fltration rate... (Review)
Review
Hyperkalemia is a common electrolyte disorder in patients with chronic kidney disease (CKD) that increases in prevalence with the decline of glomerular fltration rate (GFR). Another risk of hyperkalemia is the use of renin-angiotensin-aldosterone system inhibitors (RAASi) and/or mineralocorticoid receptor antagonists (MRAs) in managing CKD and proteinuria. The treatment of chronic hyperkalemia is challenging especially for outpatients. Treatment options for hyperkalemia include the potassium exchange resins of which two new potassium binders, Patiromer Sorbitex Calcium, and Sodium Zirconium Cyclosilicate (SZC) have demonstrated their clinical efficacy in reducing serum potassium with a positive safety profile. The old potassium exchange resin sodium polystyrene sulfonate (Kayexalate™) has some negative side effects including colonic necrosis, hypomagnesemia, and hypernatremia. In this review and literature search, we compare the available oral potassium exchange resins, highlight their advantages and disadvantages and comment on efficacy and safety parameters specifically in CKD patients.
Topics: Humans; Hyperkalemia; Mineralocorticoid Receptor Antagonists; Potassium; Renal Insufficiency, Chronic; Renin-Angiotensin System
PubMed: 38173862
DOI: 10.3389/jpps.2023.11892 -
JMIR Cardio Dec 2023Suboptimal adherence to cardiac pharmacotherapy, recommended by the guidelines after acute coronary syndrome (ACS) has been recognized and is associated with adverse... (Review)
Review
BACKGROUND
Suboptimal adherence to cardiac pharmacotherapy, recommended by the guidelines after acute coronary syndrome (ACS) has been recognized and is associated with adverse outcomes. Several randomized controlled trials (RCTs) have shown that eHealth technologies are useful in reducing cardiovascular risk factors. However, little is known about the effect of eHealth interventions on medication adherence in patients following ACS.
OBJECTIVE
The aim of this study is to examine the efficacy of the eHealth interventions on medication adherence to selected 5 cardioprotective medication classes in patients with ACS.
METHODS
A systematic literature search of PubMed, Embase, Scopus, and Web of Science was conducted between May and October 2022, with an update in October 2023 to identify RCTs that evaluated the effectiveness of eHealth technologies, including texting, smartphone apps, or web-based apps, to improve medication adherence in patients after ACS. The risk of bias was evaluated using the modified Cochrane risk-of-bias tool for RCTs. A pooled meta-analysis was performed using a fixed-effect Mantel-Haenszel model and assessed the medication adherence to the medications of statins, aspirin, P2Y12 inhibitors, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and β-blockers.
RESULTS
We identified 5 RCTs, applicable to 4100 participants (2093 intervention vs 2007 control), for inclusion in the meta-analysis. In patients who recently had an ACS, compared to the control group, the use of eHealth intervention was not associated with improved adherence to statins at different time points (risk difference [RD] -0.01, 95% CI -0.03 to 0.03 at 6 months and RD -0.02, 95% CI -0.05 to 0.02 at 12 months), P2Y12 inhibitors (RD -0.01, 95% CI -0.04 to 0.02 and RD -0.01, 95% CI -0.03 to 0.02), aspirin (RD 0.00, 95% CI -0.06 to 0.07 and RD -0.00, 95% CI -0.07 to 0.06), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (RD -0.01, 95% CI -0.04 to 0.02 and RD 0.01, 95% CI -0.04 to 0.05), and β-blockers (RD 0.00, 95% CI -0.03 to 0.03 and RD -0.01, 95% CI -0.05 to 0.03). The intervention was also not associated with improved adherence irrespective of the adherence assessment method used (self-report or objective).
CONCLUSIONS
This review identified limited evidence on the effectiveness of eHealth interventions on adherence to guideline-recommended medications after ACS. While the pooled analyses suggested a lack of effectiveness of such interventions on adherence improvement, further studies are warranted to better understand the role of different eHealth approaches in the post-ACS context.
PubMed: 38113072
DOI: 10.2196/52697 -
EJHaem Nov 2023Hyperkalemia, an elevated blood potassium concentration exceeding 5.0 mEq/L, is associated with adverse outcomes and is frequently observed in hospitalized patients.... (Review)
Review
Hyperkalemia, an elevated blood potassium concentration exceeding 5.0 mEq/L, is associated with adverse outcomes and is frequently observed in hospitalized patients. Drug-induced hyperkalemia accounts for a significant proportion of cases, with heparin, commonly used for venous thrombosis prevention, suspected to contribute, though less recognized than other heparin-related side effects. Both unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been implicated in inducing hyperkalemia, primarily through the suppression of aldosterone levels and modulation of angiotensin II receptors. This systematic review examines the relationship between heparin, particularly LMWH, and hyperkalemia. Thirteen studies involving 1407 patients were analyzed. Findings indicated a lack of highquality evidence, with no significant increase in potassium levels associated with LMWH use. LMWH did not exhibit a dose-response relationship with hyperkalemia incidence. Additionally, mechanisms underlying the hypothetical LMWHinduced hyperkalemia remained inconclusive. While this suggests that LMWH is unlikely to be a primary cause of hyperkalemia, caution is warranted, especially in patients with elevated baseline potassium levels.
PubMed: 38024642
DOI: 10.1002/jha2.801 -
Minerva Cardiology and Angiology Dec 2023Marfan Syndrome (MFS) is a rare and complex genetic disorder associated with increased aortic growth and aortic disease. The effectiveness of cardiovascular medical...
INTRODUCTION
Marfan Syndrome (MFS) is a rare and complex genetic disorder associated with increased aortic growth and aortic disease. The effectiveness of cardiovascular medical therapies aiming to slow down aortic growth has been tested in several trials, particularly beta-blockers and angiotensin receptor blockers, however showing conflicting results.
EVIDENCE ACQUISITION
We conducted a systematic review on PubMed (Medline), Cochrane library, Google Scholar, and Biomed Central databases between January and February 2022. We selected relevant articles focusing on patients with MFS treated with beta-blockers, angiotensin receptors blockers, or both, and reporting data on the effect of the drugs on 1) slowing down aortic dilatation; 2) the reduction of aortic complication (aortic dissection, mortality, aortic surgery); and with a 3) follow-up length of at least two years. A total of 16 studies were selected.
EVIDENCE SYNTHESIS
Beta-blockers remain the mainstay of therapy as they have proven to slow aortic enlargement. Angiotensin receptor blockers are a useful alternative and with proven benefit as an add-on therapy to limit aortic growth. Neither beta-blockers, nor angiotensin receptor blockers have shown meaningful results on clinical aortic endpoints.
CONCLUSIONS
The current evidence of pharmacological treatment for MFS patients is conflicting due to the lack of large, randomized clinical trials with adequate follow-up studies and homogeneous age grouping. Beta-blockers and angiotensin receptor blockers are the only available treatments to reduce aortic growth. A recently published patient-level meta-analysis confirmed that angiotensin receptor blockers and beta-blockers have a similar effect on reducing the rate of increase of the aortic root Z score, used singularly or as add-on therapy. Considering the current evidence on new features related with MFS (such as mitral annular disjunction - MAD) bearing a potential additional increased arrhythmic risk, it is of paramount importance to establish the role of beta-blockers and angiotensin receptor blockers in clinical endpoints of this population as well.
Topics: Humans; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Aorta; Aortic Diseases; Cardiovascular Diseases; Marfan Syndrome
PubMed: 36939732
DOI: 10.23736/S2724-5683.23.06184-7 -
The American Journal of the Medical... Apr 2024Influenza infection is rarely associated with cardiac conduction disorder. Cardiac arrhythmias due to such an infection have a full spectrum with ventricular arrythmias...
BACKGROUND
Influenza infection is rarely associated with cardiac conduction disorder. Cardiac arrhythmias due to such an infection have a full spectrum with ventricular arrythmias being the most common.
METHODS
In our systematic review from PubMed, OVID Medline and EMBASE we have identified 23 articles describing arrythmias associated with different influenza infection. Most of them were case reports where ventricular arrhythmias were the most common.
RESULTS
Complete heart block after influenza infection is usually temporary and a permanent pacemaker is rarely needed. There are reports of Influenza associated with arrhythmias in adults, neonates, and even fetuses in pregnant woman. Different mechanisms were described in literatures by which influenza causes arrhythmias such as interleukin 6 & tumor necrosis factor-alpha mediated inflammatory response, sympathetic overactivation, focal myocarditis and cleavage of angiotensin converting enzyme 2 protein which is cardioprotective.
CONCLUSIONS
ACE 2 binder influenza viruses have more prone to be associated with cardiac conduction disorder. Oseltamivir for influenza infection is also associated with bradycardia and can shorten or lengthen QT segment. Influenza vaccination has found to be protective from cardiac arrhythmia.
Topics: Adult; Infant, Newborn; Pregnancy; Female; Humans; Influenza, Human; Arrhythmias, Cardiac; Bradycardia; Oseltamivir; Myocarditis
PubMed: 38185405
DOI: 10.1016/j.amjms.2024.01.004