Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD.
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ABSTRACT:
SUBMITTER: Hermida RC
PROVIDER: S-EPMC3279936 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Blood pressure (BP) follows a circadian variation, increasing during active hours, showing a small postprandial valley and a deeper decrease during sleep. Nighttime reduction of 10-20% relative to daytime BP is defined as a dipper pattern, and a reduction of less than 10%, as a non-dipper pattern. Despite this BP variability, hypertension's diagnostic criteria and therapeutic objectives are usually based on BP average values. Indeed, studies have shown that chrono-pharmacological optimization significantly reduces long-term cardiovascular risk if a BP dipper pattern is maintained. Changes in the effect of antihypertensive medications can be explained by circadian variations in their pharmacokinetics (PK) and pharmacodynamics (PD). Nevertheless, BP circadian variation has been scarcely included in PK-PD models of antihypertensive medications to date. In this work, we developed PK-PD models that include circadian rhythm to find the optimal dosing time (Ta) of first-line antihypertensive medications for dipper and non-dipper patterns. The parameters of the PK-PD models were estimated using global optimization, and models were selected according to the lowest corrected Akaike information criterion value. Simultaneously, sensitivity and identifiability analysis were performed to determine the relevance of the parameters and establish those that can be estimated. Subsequently, Ta parameters were optimized to maximize the effect on BP average, BP peaks, and sleep-time dip. As a result, all selected models included at least one circadian PK component, and circadian parameters had the highest sensitivity. Furthermore, Ta with which BP>130/80 mmHg and a dip of 10-20% are achieved were proposed when possible. We show that the optimal Ta depends on the therapeutic objective, the medication, and the BP profile. Therefore, our results suggest making chrono-pharmacological recommendations in a personalized way.
| S-EPMC9704759 | biostudies-literature
Project description:Introduction: There is conflicting evidence for the association between antihypertensive medications and colorectal cancer risk, possibly reflecting methodological limitations of previously conducted studies. Here, we aimed to clarify associations between commonly prescribed antihypertensive medication classes and colorectal cancer risk in a large, retrospective, cohort study. Methods: Using linked administrative data between 1996 and 2017 from British Columbia, we identified a cohort of 1,693,297 men and women who were 50 years of age or older, initially cancer-free and nonusers of antihypertensive medications. Medication use was parameterized as ever use, cumulative duration, and cumulative dose. Cox proportional hazard models were used to estimate hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) for associations of time-varying medication use [angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and diuretics] with colorectal cancer risk. Results: There were 28,460 incident cases of colorectal cancer identified over the follow-up period (mean = 12.9 years). When medication use was assessed as ever/never, diuretics were associated with increased risk of colorectal cancer (HR 1.08, 95% CI 1.04-1.12). However, no similar association was observed with cumulative duration or cumulative dose of diuretics. No significant associations between the other four classes of medications and colorectal cancer risk were observed. Conclusion: No compelling evidence of associations between antihypertensive medications and colorectal cancer were observed.
| S-EPMC10662292 | biostudies-literature
Project description:Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0×10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ? 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD.
| S-EPMC4627813 | biostudies-literature
Project description:Non-adherence to antihypertensive medications is a major cause of uncontrolled hypertension, leading to cardiovascular morbidity and mortality. Ensuring consistent medication possession is crucial in addressing non-adherence. Community-based medication delivery is a strategy that may improve medication possession, adherence, and blood pressure (BP) reduction. Our program in Kenya piloted a community medication delivery program, coupled with blood pressure monitoring and adherence evaluation. Between September 2019 and March 2020, patients who received hypertension care from our chronic disease management program also received community-based delivery of antihypertensive medications. We calculated number of days during which each patient had possession of medications and analyzed the relationship between successful medication delivery and self-reported medication adherence and BP. A total of 128 patient records (80.5% female) were reviewed. At baseline, mean systolic blood pressure (SBP) was 155.7 mmHg and mean self-reported adherence score was 2.7. Sixty-eight (53.1%) patients received at least 1 successful medication delivery. Our pharmacy dispensing records demonstrated that medication possession was greater among patients receiving medication deliveries. Change in self-reported medication adherence from baseline worsened in patients who did not receive any medication delivery (+0.5), but improved in patients receiving 1 delivery (-0.3) and 2 or more deliveries (-0.8). There was an SBP reduction of 1.9, 6.1, and 15.5 mmHg among patients who did not receive any deliveries, those who received 1 delivery, and those who received 2 or more medication deliveries, respectively. Adjusted mixed-effect model estimates revealed that mean SBP reduction and self-reported medication adherence were improved among individuals who successfully received medication deliveries, compared to those who did not. A community medication delivery program in western Kenya was shown to be implementable and enhanced medication possession, reduced SBP, and significantly improved self-reported adherence. This is a promising strategy to improve health outcomes for patients with uncontrolled hypertension that warrants further investigation.
| S-EPMC9462824 | biostudies-literature
Project description:Few studies have examined the associations of hypertension and antihypertensive medications with ovarian cancer. In particular, beta-blockers, one of the most commonly prescribed medications to treat hypertension, may reduce ovarian cancer risk by inhibiting beta-adrenergic signaling. We prospectively followed 90,384 women in the Nurses' Health Study (NHS) between 1988-2012 and 113,121 NHSII participants between 1989-2011. Hypertension and use of antihypertensive medications were self-reported biennially. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We documented 948 ovarian cancer cases during follow-up. Similar results were observed in the two cohorts. While hypertension was not associated with ovarian cancer risk (Pooled HR = 1.01; 95% CI = 0.88, 1.16), current use of any antihypertensive medication was associated with slightly increased risk compared to never users (Pooled HR = 1.18; 95% CI: 1.02, 1.37). This increased risk was primarily due to use of thiazide diuretics (Pooled HR = 1.37; 95% CI: 1.13, 1.68). No associations were observed for beta-blockers or angiotensin-converting-enzyme inhibitors. Calcium channel blockers (CCBs) were associated with suggestively reduced risk (NHS HR = 0.73; 95% CI: 0.53, 1.01), after adjusting for all antihypertensive medications. Associations were similar among hypertensive women and stronger for longer use of thiazide diuretics and CCBs. In conclusion, our results provided no evidence that beta-blockers were associated with reduced ovarian cancer risk. In contrast, we observed an increased risk for use of thiazide diuretics that should be confirmed in other studies.
| S-EPMC5105887 | biostudies-literature
Project description:Cardiovascular disease (CVD) remains a leading cause of death in patients with type 2 diabetes (T2D). In addition to glycemic control, a major focus of diabetes treatment involves cardiovascular (CV) risk reduction. In 2008, the US Food and Drug Administration (FDA) instituted a new requirement that new drugs developed and studied for the treatment of T2D must undergo CV safety testing. Since the advent of this new policy, canagliflozin, empagliflozin, liraglutide and semaglutide have demonstrated superior CV event reduction - via a composite of reduction in CV death, nonfatal myocardial infarction (MI), and nonfatal stroke - compared with placebo in patients with T2D and existing CVD, or at high risk of CVD. Multiple studies are underway to evaluate the CV outcomes of other antihyperglycemic agents. In a time when there are numerous drugs in the T2D armamentarium, positive CV outcomes data influence drug selection and aids practitioners in making more individualised therapeutic recommendations for their patients.
| S-EPMC5813471 | biostudies-literature
Project description:Inconsistent findings have been obtained for previous studies evaluating the association between antihypertensive medication (AHM) adherence and the risk of stroke. This dose-response meta-analysis was designed to investigate the association between AHM adherence and stroke risk. MEDLINE and Embase databases were systematically searched to identify relevant studies. The quantification of adherence to AHM was calculated as the percentage of the sum of days with AHM actually taken divided by the total number of days in a specific period. Summary relative risks (RR) and 95% CIs were estimated using a random-effects model. Stratified and dose-response analyses were also performed. A total of 18 studies with 1 356 188 participants were included. The summary RR of stroke for the highest compared with the lowest AHM adherence level was 0.73 (95% CI, 0.67-0.79). Stratified by stroke subtype, a higher AHM adherence was associated with lower risks of ischemic stroke (RR, 0.74; 95% CI, 0.69-0.79) and hemorrhagic stroke (RR, 0.55; 95% CI, 0.42-0.72). Moreover, both fatal (RR, 0.51; 95% CI, 0.36-0.73) and nonfatal stroke (RR, 0.52; 95% CI, 0.28-0.94) were lower in participants with higher AHM adherence. The results of a dose-response analysis indicated that a 20% increment in AHM adherence level was associated with a 9% lower risk of stroke (RR, 0.91; 95% CI, 0.86-0.96). Higher AHM adherence is dose-dependently associated with a lower risk of stroke in patients with hypertension.
| S-EPMC5586324 | biostudies-literature
Project description:Background The DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) trial (NCT03036150) demonstrated that dapagliflozin reduced the risk of kidney and cardiovascular events in patients with chronic kidney disease and albuminuria with and without type 2 diabetes. We aimed to determine whether baseline cardiovascular medication use modified the dapagliflozin treatment effect. Methods and Results We randomized 4304 adults with baseline estimated glomerular filtration rate 25 to 75 mL/min per 1.73 m2 and urinary albumin:creatinine ratio 200 to 5000 mg/g to dapagliflozin 10 mg or placebo once daily. The primary end point was a composite of ≥50% estimated glomerular filtration rate decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (hospitalized heart failure or cardiovascular death), and all-cause mortality. We categorized patients according to baseline cardiovascular medication use/nonuse. Patients were required by protocol to receive a stable (and maximally tolerated) dose of a renin-angiotensin-aldosterone system inhibitor. We observed consistent benefits of dapagliflozin relative to placebo, irrespective of baseline use/nonuse of renin-angiotensin-aldosterone system inhibitors (98.1%), calcium channel blockers (50.7%), β-adrenergic antagonists (39.0%), diuretics (43.7%), and antithrombotic (47.4%), and lipid-lowering (15.0%) agents. Use of these drugs in combination with dapagliflozin did not increase the number of serious adverse events. Conclusions The safety profile and efficacy of dapagliflozin on kidney and cardiovascular end points in patients with chronic kidney disease were consistent among patients treated and not treated at baseline with a range of cardiovascular medications. Registration Information clinicaltrials.gov. Identifier: NCT03036150.
| S-EPMC10227210 | biostudies-literature
Project description:ObjectiveLimited research has examined the effects of antihypertensive medication use and physical function. These studies provided mixed findings while employing a convenience sample and limiting their examination to few indices of physical function and few classes of antihypertensive medications. The purpose of this study was to examine whether several antihypertensive medication classes were associated with several measures of physical function in a national sample of U.S. middle-to-older age adults.MethodsData from the 1999-2002 and 2011-2012 NHANES were used. Antihypertensive medication use was assessed from an interviewer, and included angiotensin converting enzyme (ACE) inhibitors, peripherally-acting antiadrenergic agents and centrally-acting antiadrenergic agents. Physical function-related parameters included objectively-measured lower extremity isokinetic knee extensor strength (IKES), objectively-measured grip strength, laboratory-assessed walking performance (8 and 20 ft walk tests) and self-reported physical activity engagement.ResultsThose on ACE inhibitors had a 37% reduced odds (OR = 0.63, 95% CI: 0.48-0.83, P = .002) of engaging in moderate-to-vigorous physical activity, had reduced knee extensor strength (? = - 15.4, 95% CI: - 27.2 to - 3.4, P = .01) and took longer to complete the 20 ft (? = .42, 95% CI: 0.02-0.81, P = .04) and 8 ft walking tests (? = .22, 95% CI: 0.05-0.39, P = .01). Those on peripherally-acting antiadrenergic agents had reduced grip strength (? = - 4.8, 95% CI: - 9.1 to - 0.5, P = .02).ConclusionsAntihypertensive medication use, particularly ACE inhibitors, is associated with various measures of reduced physical function. Clinicians are encouraged to monitor the long-term mobility function of their patients on antihypertensive medications.
| S-EPMC4929186 | biostudies-literature
Project description:BackgroundTo further inform benefits and risks of medications on physical function in aging populations, we have evaluated the associations of antihypertensive (antiHTN) class and number used with skeletal muscle function, mobility, sedentary time, and symptoms in older persons.MethodsUsing baseline data from the Lifestyle Interventions and Independence in Elder (LIFE) study (N = 1567, mean age 78.9 years) and multivariable models, we evaluated cross-sectional associations of antiHTN class and number used with physical measures and symptom questionnaires. AntiHTN class included diuretics, angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB), and beta blockers (BB). Physical measures included respiratory muscle weakness (maximal inspiratory pressure), grip weakness (dynamometer), impaired lower extremity proximal muscle strength (chair stands), impaired balance (three-stage test), slow gait (400 m walk), mobility impairment (Short Physical Performance Battery), and high sedentary time (accelerometry). Symptoms included dyspnea and fatigue. Covariates included clinical characteristics and non-antiHTNs.ResultsUse of any antiHTN was highly prevalent (n = 1248 [79.6%]). In the antiHTN subgroup, each antiHTN class was well represented (ranging 36.6%-62.7%) and included use of three or more antiHTNs (32.0%). In adjusted models, the only statistically significant associations were use of BB and three or more antiHTNs with high sedentary time: odds ratios (95% confidence intervals) 1.44 (1.12, 1.85) and 1.52 (1.04, 2.23), respectively.ConclusionUse of BB and three or more antiHTNs yielded 44% and 52% increased odds of accelerometry-defined high sedentary time, respectively. Notably, high sedentary time is a risk factor for adverse health outcomes. Thus, future work should evaluate whether high sedentary time mitigates benefits or increases risks, regarding antiHTN use in aging populations.
| S-EPMC7395796 | biostudies-literature