Does Patient-Applied Testosterone Replacement Therapy Pose Risk for Blood Pressure Elevation? Circadian Medicine Perspectives.

We reviewed medication package inserts, US Food and Drug Administration (FDA) reports, and journal publications concerning the 10 nonbiosimilar patient-applied (PA) testosterone (T) replacement therapies (TRTs) for intraday serum T patterning and blood pressure (BP) effects. Blood T concentration is circadian rhythmic in young adult eugonadal males, being highest around awakening and lowest before bedtime. T level and 24 h variation are blunted in primary and secondary hypogonadism.

Ingestion-time differences in the pharmacodynamics of dual-combination hypertension therapies: Systematic review and meta-analysis of published human trials.

The pharmacodynamics of hypertension medications can be significantly affected by circadian rhythms in the biological mechanisms of the 24 h blood pressure (BP) pattern. Hypertension guidelines fail to recommend the time of day when patients, including those who require treatment with multiple medications, are to ingest BP-lowering therapy. We conducted a systematic review of published prospective trials that investigated hypertension medications for ingestion-time differences in BP-lowering, safety, patient adherence, and markers of target organ pathology.

Elevated asleep blood pressure and non-dipper 24h patterning best predict risk for heart failure that can be averted by bedtime hypertension chronotherapy: A review of the published literature.

Several prospective studies consistently report elevated asleep blood pressure (BP) and blunted sleep-time relative systolic BP (SBP) decline (non-dipping) are jointly the most significant prognostic markers of cardiovascular disease (CVD) risk, including heart failure (HF); therefore, they, rather than office BP measurements (OBPM) and ambulatory awake and 24 h BP means, seemingly are the most worthy therapeutic targets for prevention. Published studies of the 24 h BP pattern in HF are sparse in number and of limited sample size. They report high prevalence of the abnormal non-dipper/riser 24 h SBP patterning.

Extent of asleep blood pressure reduction by hypertension medications is ingestion-time dependent: Systematic review and meta-analysis of published human trials.

Combined evidence of published prospective outcome trials and meta-analyses substantiate elevated asleep blood pressure (BP) and blunted sleep-time relative BP decline (non-dipping), regardless of wake-time office BP and awake or 24 h BP means, are jointly the most highly significant independent prognostic markers of cardiovascular disease (CVD) risk and worthy therapeutic targets for prevention. Nonetheless, current guidelines continue to recommend the diagnosis of hypertension, when based on ambulatory BP monitoring (ABPM), rely, solely, on either the 24 h or "daytime" BP means. They also fail to recommend the time to treat patients.

Ingestion-time differences in the pharmacodynamics of hypertension medications: Systematic review of human chronopharmacology trials.

Pharmacokinetics of hypertension medications is significantly affected by circadian rhythms that influence absorption, distribution, metabolism and elimination. Furthermore, their pharmacodynamics is affected by ingestion-time differences in kinetics and circadian rhythms comprising the biological mechanism of the 24 h blood pressure (BP) pattern. However, hypertension guidelines do not recommend the time to treat patients with medications.

Guidelines for the design and conduct of human clinical trials on ingestion-time differences - chronopharmacology and chronotherapy - of hypertension medications.

Current hypertension guidelines fail to provide a recommendation on when-to-treat, thus disregarding relevant circadian rhythms that regulate blood pressure (BP) level and 24 h patterning and medication pharmacokinetics and pharmacodynamics. The ideal purpose of ingestion-time (chronopharmacology, i.e.

Ingestion-time - relative to circadian rhythms - differences in the pharmacokinetics and pharmacodynamics of hypertension medications.

Introduction: Hypertension guidelines do not recommend the time to administer blood pressure (BP)-lowering medications, despite multiple prospective clinical trials reporting both improved normalization of BP 24 h patterning and reduced cardiovascular disease (CVD) events when ingested at bedtime rather than upon awakening.

Areas Covered: We review: (i) circadian rhythm-dependent influences on the pharmacokinetics (PK) and pharmacodynamics (PD) of hypertension medications; (ii) reports of ingestion-time differences in PK and PD of such therapies; and (iii) (chrono)prevention of CVD morbidity and mortality achieved by the simple and low-cost bedtime hypertension chronotherapy strategy, i.e.

Does Timing of Antihypertensive Medication Dosing Matter?

Purpose Of Review: Current hypertension guidelines do not provide recommendation on when-to-treat. Herein, we review the current evidence on ingestion-time differences of hypertension medications in blood pressure (BP)-lowering effects and prevention of cardiovascular disease (CVD) events.

Recent Findings: The vast (81.

Chronotherapy for reduction of cardiovascular risk.

Numerous prospective studies establish that elevated asleep blood pressure (BP) constitutes a significant cardiovascular disease (CVD) risk factor, irrespective of daytime office BP measurements or awake and 24h BP measurements. Moreover, except for a small number of studies with flawed methodology, multiple clinical trials of high consistency document significantly better BP-lowering efficacy of hypertension medication and their combinations when ingested at bedtime compared to upon awakening as is customary. Additionally, recent trials conclude bedtime hypertension chronotherapy markedly reduces CVD risk not only in the general population, but also in more vulnerable patients of advanced age, with kidney disease, diabetes, or resistant hypertension.