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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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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