Atenolol 50mg / Nifedipine 20mg modified-release capsules

IntroductionOur objective was to evaluate whether antihypertensives affect fetal (FHR) or neonatal (neoHR) heart rate.Material and methodsElectronic databases and clinical trial registers were searched to August 31, 2024. Eligibility included randomized (RCTs) or observational studies evaluating antihypertensives for pregnancy hypertension. Two reviewers independently assessed studies for inclusion and extracted data. Random effects meta-analysis was used to determine risk ratios (RRs) and 95% confidence intervals (CIs). Network meta-analysis was undertaken in a sensitivity analysis.ResultsFifty-four RCTs (n = 5736 pregnancies) and 28 observational studies (n = 2 283 855) reported FHR (usually visually-interpreted) or neoHR (usually clinically-assessed). FHR: NON-SEVERE HYPERTENSION: Antihypertensives did not increase adverse FHR effects in RCTs of antihypertensives versus placebo/no therapy (RR = 1.08, 95% CI [0.62-1.89]; I2 = 43%; N = 10, n = 1567 pregnancies), antihypertensives versus methyldopa (RR = 1.40 [0.97-2.04]; I2 = 0%; N = 6, n = 515), or labetalol or pure beta-blockers versus other antihypertensives (RR = 1.70 [0.96-2.99]; I2 = 30%; N = 5, n = 501). In observational studies, adverse FHR effects were more common with: labetalol versus methyldopa, nifedipine or Chinese herbal medication (RR = 2.17 [1.15-4.08]; I2 = 47%; N = 4, n = 664), and bendroflumethiazide versus metoprolol (but not hydralazine), but 95% CIs were wide. FHR: SEVERE HYPERTENSION: Antihypertensives had no FHR effects in RCTs of antihypertensives versus either: placebo/no therapy (RR = 0.43 [0.16-1.20]; I2 = 0%; N = 3, n = 242), hydralazine (RR = 0.71 [0.29-1.72]; I2 = 13%; N = 11, n = 727), or CCBs (RR = 0.52 [0.12-2.16]; I2 = 0%, N = 9, n = 1675). In observational studies, there was no difference for labetalol versus other antihypertensives (RR = 0.34 [0.10-1.14], I2 = 87%; N = 4, n = 590), with heterogeneity due to a lower-quality labetalol versus hydralazine study. There were fewer adverse FHR effects for nifedipine versus hydralazine study (RR = 0.09 [0.01-0.68]; n = 49).NeohrSEVERE HYPERTENSION: RCTs of antihypertensives versus placebo/no therapy were not associated with adverse neoHR effects (RR = 1.26 [0.31-5.19]; I2 = 66%; N = 4, n = 406), with heterogeneity attributed to more neoHR effects with continuously monitored neoHR. Observational studies revealed no effect on neoHR of antihypertensives versus no therapy (RR = 1.06 [0.67-1.67]; I2 = 54%; N = 4, n = 37 359), but labetalol was associated with more adverse effects and metoprolol with fewer. In RCTs of antihypertensives versus other antihypertensives, there was no difference in adverse neoHR (RR = 3.0 [0.13-71.74]; N = 3, n = 162). Observational studies showed adverse neoHR effects in labetalol versus pure beta-blockers (RR = 1.99 [1.36-2.91]; I2 = 0%; N = 3, n = 16 204). No severe hypertension RCTs reported neoHR. Observational studies were limited. Network meta-analysis showed no significant relationships between antihypertensives and FHR or neoHR; 95% CIs were very wide.ConclusionsEvidence is inadequate to draw reliable conclusions about the impact of antihypertensives on FHR or neoHR. At present, adverse FHR or neoHR effects should be attributed to evolving placental dysfunction.

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BackgroundHypertension (HTN) is a global public health issue, with high prevalence and a significant impact on cardiovascular morbidity and mortality. Cardioselective beta-blockers, such as atenolol, are widely used in the treatment of HTN, although their indication as first-line therapy remains controversial.ObjectiveTo evaluate the efficacy and safety of atenolol in the treatment of primary HTN, compared with other first-line classes of antihypertensive drugs.MethodsA systematic review was conducted based on a research question structured using the PICO format. Randomized clinical trials comparing atenolol with other antihypertensive agents were included. Searches were performed in three international databases. Methodological quality was assessed using the RoB 2 tool, and the certainty of evidence was rated using the GRADE system. The primary composite outcome was the occurrence of major cardiovascular events. Secondary outcomes included all-cause mortality, acute myocardial infarction, and stroke, each analyzed separately.ResultsSeven clinical trials met the inclusion criteria. Compared with amlodipine and losartan, atenolol was associated with a slightly higher incidence of cardiovascular events, with low and moderate certainty of evidence, respectively. The combination of hydrochlorothiazide and amiloride demonstrated a greater reduction in cardiovascular events compared to atenolol, although with very low certainty of evidence. Blood pressure (BP) reduction was similar across the compared treatments.ConclusionsDespite the limitations of available evidence, atenolol showed comparable efficacy in BP reduction, with small differences in cardiovascular outcomes favoring other antihypertensive classes. Its use may be considered among the options for combination therapy in the treatment of primary HTN in adults. Other beta-blockers were not evaluated in this systematic review.

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Hypertensive disorders of pregnancy, particularly preeclampsia, are a leading cause of maternal and perinatal morbidity. While antihypertensive therapy is recommended, clinical uncertainty persists regarding the optimal agent to maximize maternal safety while minimizing adverse neonatal outcomes such as neonatal intensive care unit (NICU) admission. This review aimed to evaluate the comparative effectiveness and safety of pharmacological antihypertensive agents versus standard care or placebo in the management of hypertensive disorders of pregnancy through a network meta-analysis (NMA). A systematic review and frequentist random-effects NMA of randomized controlled trials (RCTs) was conducted. Major databases were searched for RCTs comparing antihypertensive agents (labetalol, nifedipine, methyldopa, hydralazine, prazosin) and controls. The primary neonatal outcome evaluated in this network was NICU admission. Risk of bias was assessed using the Cochrane RoB 2 tool, and the certainty of evidence was evaluated using the GRADE framework. Twenty-five RCTs were included in the qualitative and quantitative synthesis. The network geometry was anchored by labetalol and nifedipine. In the NMA, no individual antihypertensive agent demonstrated a statistically significant reduction in the risk of NICU admission compared to labetalol. However, probabilistic ranking (P-scores) identified methyldopa (P-score = 0.859) and hydralazine (0.791) as the most favourable interventions for minimizing NICU admissions. Nifedipine showed a slightly elevated, though non-significant, risk profile compared to labetalol (RR 1.09, 95% CI 0.80-1.49). The placebo and standard care ranked lowest. The overall certainty of evidence ranged from moderate to very low due to imprecision and indirectness. Active pharmacological management of hypertension in pregnancy is superior to placebo or standard care. While labetalol and nifedipine remain mainstays for acute blood pressure control, methyldopa and hydralazine probabilistically rank higher for minimizing NICU admissions. These findings support individualized antihypertensive selection based on clinical acuity and maternal-fetal hemodynamics.

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BACKGROUND: Hypertensive Disorders of Pregnancy (HDPs), encompassing gestational hypertension, pre-eclampsia, and eclampsia, affect approximately 18 million pregnancies globally. While international guidelines specify management for these disorders, their implementation in low-and middle-income countries (LMICs) is unassessed. Therefore, this systematic review aims to assess the prescribing patterns for HDPs to gauge suitable recommendations for practitioners in LMICs. METHODS: A systematic review was conducted using PubMed, CINAHL, Scopus and Google Scholar using relevant terms for HDPs, prescribing patterns and LMICs. Observational studies published between January 2000 and November 2023 reporting management of HDPs in LMICs were included. The quality of the articles was screened using the National Heart Lung and Blood Institute (NHLBI) quality assessment tool. RESULTS: A total of 54 studies comprising 14,598 HDP cases from 17 LMICs were included. Of these studies, 18 reported prescriptions for gestational hypertension, in which, calcium channel blockers were reported to be prescribed in all, while the frequency of other prescribed medications included labetalol (89.0%) and methyldopa (66.7%). 41 studies reported medications for pre-eclampsia which included magnesium sulfate—MgSO4 (68.3%), nifedipine (61.0%), methyldopa (48.8%) and labetalol (43.9%) prescriptions. A majority of the 28 studies reporting on eclampsia mentioned the use of MgSO4, while 33% prescribed diazepam, and phenytoin was prescribed in 15% of the studies. CONCLUSION: Majority of LMICs tend to prescribe the established first line medications for HDPs. Slight differences are seen in combinations, likely due to use of different guidelines and medication availability. Standardization of institutional guidelines and strategies to increase adherence to guidelines across LMICs are crucial for improved outcomes and safer prescribing patterns among physicians. Several studies report an absence of institutional guidelines, while practices differ from international guidelines, necessitating the need for standardization of prescribing patterns across resource-limited settings.

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Introduction/objectivesRaynaud's phenomenon is a common vasospastic disorder associated with reduced health-related quality of life and, occasionally, ischaemic tissue damage depending on aetiology. The effect of beta-1-adrenoceptor blockers (e.g. bisoprolol, atenolol) on Raynaud's phenomenon remains unclear. We aimed to assess the association between genetically mimicked beta-1-adrenoceptor blockade and the risk of Raynaud's phenomenon.MethodsWe used two protein-coding single nucleotide polymorphisms in the ADRB1 gene, rs1801252 (A > G; Ser49Gly) and rs1801253 (G > C; Arg389Gly), to derive an unweighted allele count as the instrumental variable, using individual-level UK Biobank data. Raynaud's phenomenon was defined using International Classification of Diseases or Read codes. We used the ratio method and analysis was performed separately using systolic and diastolic blood pressure as the biomarker. To examine the validity of this approach and the Raynaud's phenomenon case definition, we also tested the known association between phosphodiesterase-5 inhibition and Raynaud's phenomenon risk.ResultsAnalysis included 4743 individuals with Raynaud's phenomenon (mean age 58 years, 68% female) and 403,762 controls. There was no evidence of an effect of genetically mimicked beta-1-adrenoreceptor blockade on the risk of Raynaud's phenomenon, using systolic blood pressure (odds ratio = 0.93 per mmHg reduction; 95% confidence interval = [0.83, 1.04]; p = 0.19) or diastolic blood pressure (odds ratio = 0.91 per mmHg reduction; 95% confidence interval = [0.78, 1.05]; p = 0.19). The positive control exposure phosphodiesterase-5 inhibition was associated with reduced Raynaud's phenomenon risk.ConclusionsWe found no genetic evidence to support a causal association between beta-1-adrenoceptor blockade and Raynaud's phenomenon risk in either direction. Randomised controlled trials are required to confirm the safety of beta-1-adrenoceptor blockers in people with Raynaud's phenomenon.

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Hypertension disorders of pregnancy affect almost 10% of pregnancies. Most hypertensive disorders associated with pregnancy, including chronic hypertension and gestational hypertension, often persist into the postpartum period. Thus, many breastfeeding mothers require ongoing antihypertensive treatment with antihypertensive medications while nursing. This highlights the importance of understanding the efficacy, safety, and potential adverse effects of antihypertensive therapy in breastfeeding mothers. Unfortunately, research in this area is limited, and references in clinical guidelines remain sparse. Our review aims to provide a comprehensive summary of the current knowledge on antihypertensive medications during breastfeeding, drawing from available research and evidence-based guidelines. This article discusses all groups of antihypertensive drugs, presenting societies' recommendations and available clinical data. Based on the available literature, calcium channel blockers (extended-release nifedipine as the first choice) and beta-blockers (labetalol, metoprolol) appear to be the drugs of choice. Our review highlights the need for further research to evaluate the long-term safety of antihypertensive medications during breastfeeding, improve clinical guidelines, and ensure optimal treatment for nursing mothers.

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