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Sex differences in the adherence of antihypertensive drugs: a systematic review with meta-analyses.

ABSTRACT: OBJECTIVES:Poor worldwide rate of blood pressure control is largely due to poor adherence to antihypertensive (AHT) drug treatment. The question of whether sex affects adherence has long been debated but conflicting findings have been reported on this issue. Our objective was to evaluate sex differences in the adherence to AHT therapy. RESEARCH DESIGN AND METHODS:Studies were identified through a systematic search of PubMed, CINAHL, PsycINFO, Web of Science and Google Scholar (through January 2020) and manual handsearching of relevant articles. Observational studies reporting adherence to AHT drugs measured by self-report or pharmacy refill prescription-based methods among men and women were included. Summarised estimates of ORs with 95% CIs were calculated using random-effects model and meta-regression models. RESULTS:From 12?849 potentially relevant publications, 82 studies (15?517?457 men and 18?537?599 women) were included. No significant between-sex differences in adherence to AHT were observed, whether all study-specific estimates were summarised (ORs 1.04, 95%?CI 1.00 to 1.09, p=0.07), nor estimates were pooled according to the method for measuring adherence. Among patients aged 65 years or older, lower self-reported adherence was observed in women (ORs 0.84, 95%?CI 0.72 to 0.97, p=0.02), while the main result remained unchanged according to other subgroup analyses. CONCLUSIONS:Definitive evidence of sex differences in adherence to AHT therapy cannot be drawn. Our little knowledge about factors affecting adherence, in particular of sex effect among elderly, urgently requires high-quality studies investigating these issues.

SUBMITTER: Biffi A

PROVIDER: S-EPMC7348648 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Sex differences in the adherence of antihypertensive drugs: a systematic review with meta-analyses.

Biffi Annalisa A Rea Federico F Iannaccone Teresa T Filippelli Amelia A Mancia Giuseppe G Corrao Giovanni G

BMJ open 20200708 7

<h4>Objectives</h4>Poor worldwide rate of blood pressure control is largely due to poor adherence to antihypertensive (AHT) drug treatment. The question of whether sex affects adherence has long been debated but conflicting findings have been reported on this issue. Our objective was to evaluate sex differences in the adherence to AHT therapy.<h4>Research design and methods</h4>Studies were identified through a systematic search of PubMed, CINAHL, PsycINFO, Web of Science and Google Scholar (thr ...[more]

PMID: 32641331

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Project description:BackgroundHypertension drives the global burden of cardiovascular disease and its prevalence is estimated to increase by 30% by the year 2025. Nonadherence to chronic medication regimens is common; approximately 43% to 65.5% of patients who fail to adhere to prescribed regimens are hypertensive patients. Nonadherence to medications is a potential contributing factor to the occurrence of concomitant diseases.ObjectiveThis systematic review applied a meta-analytic procedure to investigate the medication nonadherence in adult hypertensive patients.MethodsOriginal research studies, conducted on adult hypertensive patients, using the 8-item Morisky medication adherence scale (MMAS-8) to assess the medication adherence between January 2009 and March 2016 were included. Comprehensive search strategies of 3 databases and MeSH keywords were used to locate eligible literature. Study characteristics, participant demographics, and medication adherence outcomes were recorded. Effect sizes for outcomes were calculated as standardized mean differences using random-effect model to estimate overall mean effects.ResultsA total of 28 studies from 15 countries were identified, in total comprising of 13,688 hypertensive patients, were reviewed. Of 25 studies included in the meta-analysis involving 12,603 subjects, a significant number (45.2%) of the hypertensive patients and one-third (31.2%) of the hypertensive patients with comorbidities were nonadherent to medications. However, a higher proportion (83.7%) of medication nonadherence was noticed in uncontrolled blood pressure (BP) patients. Although a higher percentage (54%) of nonadherence to antihypertensive medications was noticed in females (P < 0.001), the risk of nonadherence was 1.3 times higher in males, with a relative risk of 0.883. Overall, nearly two-thirds (62.5%) of the medication nonadherence was noticed in Africans and Asians (43.5%).ConclusionNonadherence to antihypertensive medications was noticed in 45% of the subjects studied and a higher proportion of uncontrolled BP (83.7%) was nonadherent to medication. Intervention models aiming to improve adherence should be emphasized.

Project description:OBJECTIVE:To assess the effect of antihypertensive treatment on mortality and cardiovascular morbidity in people with diabetes mellitus, at different blood pressure levels. DESIGN:Systematic review and meta-analyses of randomised controlled trials. DATA SOURCES:CENTRAL, Medline, Embase, and BIOSIS were searched using highly sensitive search strategies. When data required according to the protocol were missing but trials were potentially eligible, we contacted researchers, pharmaceutical companies, and authorities. ELIGIBILITY CRITERIA:Randomised controlled trials including 100 or more people with diabetes mellitus, treated for 12 months or more, comparing any antihypertensive agent against placebo, two agents against one, or different blood pressure targets. RESULTS:49 trials, including 73,738 participants, were included in the meta-analyses. Most of the participants had type 2 diabetes. If baseline systolic blood pressure was greater than 150 mm Hg, antihypertensive treatment reduced the risk of all cause mortality (relative risk 0.89, 95% confidence interval 0.80 to 0.99), cardiovascular mortality (0.75, 0.57 to 0.99), myocardial infarction (0.74, 0.63 to 0.87), stroke (0.77, 0.65 to 0.91), and end stage renal disease (0.82, 0.71 to 0.94). If baseline systolic blood pressure was 140-150 mm Hg, additional treatment reduced the risk of all cause mortality (0.87, 0.78 to 0.98), myocardial infarction (0.84, 0.76 to 0.93), and heart failure (0.80, 0.66 to 0.97). If baseline systolic blood pressure was less than 140 mm Hg, however, further treatment increased the risk of cardiovascular mortality (1.15, 1.00 to 1.32), with a tendency towards an increased risk of all cause mortality (1.05, 0.95 to 1.16). Metaregression analyses showed a worse treatment effect with lower baseline systolic blood pressures for cardiovascular mortality (1.15, 1.03 to 1.29 for each 10 mm Hg lower systolic blood pressure) and myocardial infarction (1.12, 1.03 to 1.22 for each 10 mm Hg lower systolic blood pressure). Patterns were similar for attained systolic blood pressure. CONCLUSIONS:Antihypertensive treatment reduces the risk of mortality and cardiovascular morbidity in people with diabetes mellitus and a systolic blood pressure more than 140 mm Hg. If systolic blood pressure is less than 140 mm Hg, however, further treatment is associated with an increased risk of cardiovascular death, with no observed benefit.

Project description:IntroductionHypertension is a leading cause of mortality worldwide and its prevalence is expected to rise over the next decade. Sex differences exist in the epidemiology and pathophysiology of hypertension. It is well established that antihypertensive treatment can significantly reduce the risk for stroke and other cardiovascular disease events. However, it remains unclear whether this effect is dependent on sex. In this protocol, we outlined a systematic review and meta-analysis to evaluate the effects of antihypertensive therapy in (1) reducing blood pressure and (2) preventing cardiovascular morbidity and mortality outcomes for each sex separately.Methods and analysisThe following electronic databases will be searched: Medline, Embase, The Cochrane Library, PubMed, Cumulative Index of Nursing and Allied Health Literature Plus, Web of Science, grey literature (Google Scholar) and several trial registries. Search strategies will be designed to identify human adult (≥18) randomised (and non-randomised) controlled trials, prospective and retrospective cohort studies, and case-control studies concerning 'sex-specific differences associated with the efficacy of antihypertensive treatment'. A preliminary search strategy was developed for Medline (1946-16 September 2019). Two investigators will independently review each article included in the final analysis. Primary outcomes investigated are cardiovascular morbidity and mortality and systolic and diastolic blood pressure. Pooled analyses will be conducted using the random-effects model. Publication bias will be assessed by visual inspection of funnel plots and by Begg's and Egger's statistical tests. Between-studies heterogeneity will be measured using the I2 test (p<0.10). Sources of heterogeneity will be explored by sensitivity, subgroup and metaregression analyses.Ethics and disseminationThis is the first meta-analysis that will comprehensively compare the efficacy of antihypertensive treatment regimens between men and women. Findings will be shared through scientific conferences and societies, social media and consumer advocacy groups. Results will be used to inform the current guidelines for management of hypertension in men and women by demonstrating the importance of implementing sex-specific recommendations. Ethical considerations are not applicable for this protocol.

Project description:Biochemical drug screening by liquid chromatography-tandem mass spectrometry in plasma is an accurate method for the quantification of plasma concentrations of antihypertensive medications in patients with hypertension. Trough concentrations could possibly be used as drug-specific cutoff values in the biochemical assessment of (non-)adherence. We performed a literature review and meta-analysis of pharmacokinetic studies to determine plasma trough concentrations of amlodipine, hydrochlorothiazide, and valsartan. PubMed was searched for pharmacokinetic studies up to September 2020. Eligible studies reported steady-state mean trough concentration and their variance. Pooled trough concentrations were estimated using a three-level random effects meta-analytic model. Moderator analyses were performed to explore sources of heterogeneity. One thousand three hundred eighteen potentially relevant articles were identified of which 45 were eligible for inclusion. The pooled mean trough concentration was 9.2 ng/mL (95% CI, 7.5-10.8) for amlodipine, 41.0 ng/mL (95% CI, 17.4-64.7) for hydrochlorothiazide, and 352.9 ng/mL (95% CI, 243.5-462.3) for valsartan. Substantial heterogeneity was present for all 3 pooled estimates. Moderator analyses identified dosage as a significant moderator for the pooled trough concentration of amlodipine (β1=0.9; P<0.05), mean age, and mean body weight for the mean trough concentration of hydrochlorothiazide (β1=2.2, P<0.05, respectively, β1=-4.0, P<0.05) and no significant moderators for valsartan. Plasma trough concentrations of amlodipine, hydrochlorothiazide, and valsartan, measured with liquid chromatography-tandem mass spectrometry, are highly heterogeneous over the different studies. Use of the pooled trough concentration as a cutoff in the biochemical assessment of adherence can result in inaccurate diagnosis of (non-)adherence, which may seriously harm the patient-physician relationship, and is therefore not recommended.

Project description:Background and purposeWomen have worse outcomes than men after stroke. Differences in presentation may lead to misdiagnosis and, in part, explain these disparities. We investigated whether there are sex differences in clinical presentation of acute stroke or transient ischemic attack.MethodsWe conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Inclusion criteria were (1) cohort, cross-sectional, case-control, or randomized controlled trial design; (2) admission for (suspicion of) ischemic or hemorrhagic stroke or transient ischemic attack; and (3) comparisons possible between sexes in ≥1 nonfocal or focal acute stroke symptom(s). A random-effects model was used for our analyses. We performed sensitivity and subanalyses to help explain heterogeneity and used the Newcastle-Ottawa Scale to assess bias.ResultsWe included 60 studies (n=582 844; 50% women). In women, headache (pooled odds ratio [OR], 1.24 [95% CI, 1.11-1.39]; I2=75.2%; 30 studies) occurred more frequently than in men with any type of stroke, as well as changes in consciousness/mental status (OR, 1.38 [95% CI, 1.19-1.61]; I2=95.0%; 17 studies) and coma/stupor (OR, 1.39 [95% CI, 1.25-1.55]; I2=27.0%; 13 studies). Aspecific or other neurological symptoms (nonrotatory dizziness and non-neurological symptoms) occurred less frequently in women (OR, 0.96 [95% CI, 0.94-0.97]; I2=0.1%; 5 studies). Overall, the presence of focal symptoms was not associated with sex (pooled OR, 1.03) although dysarthria (OR, 1.14 [95% CI, 1.04-1.24]; I2=48.6%; 11 studies) and vertigo (OR, 1.23 [95% CI, 1.13-1.34]; I2=44.0%; 8 studies) occurred more frequently, whereas symptoms of paresis/hemiparesis (OR, 0.73 [95% CI, 0.54-0.97]; I2=72.6%; 7 studies) and focal visual disturbances (OR, 0.83 [95% CI, 0.70-0.99]; I2=62.8%; 16 studies) occurred less frequently in women compared with men with any type of stroke. Most studies contained possible sources of bias.ConclusionsThere may be substantive differences in nonfocal and focal stroke symptoms between men and women presenting with acute stroke or transient ischemic attack, but sufficiently high-quality studies are lacking. More studies are needed to address this because sex differences in presentation may lead to misdiagnosis and undertreatment.

Dataset Information

Sex differences in the adherence of antihypertensive drugs: a systematic review with meta-analyses.

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Sex differences in the adherence of antihypertensive drugs: a systematic review with meta-analyses.

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