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Comparison of Cardiovascular Events Among Users of Different Classes of Antihypertension Medications: A Systematic Review and Network Meta-analysis.

ABSTRACT: Importance:Antihypertension medications have been associated with prevention of cardiovascular events, although less is known about the comparative effectiveness of different medication classes. Objective:To compare contemporary aggregated first-in-trial cardiovascular events among patients with hypertension and no substantial comorbidities. Data Sources:The PubMed, Embase, and Cochrane Library databases were systematically searched for articles published between January 1, 1990, and October 24, 2017. Study Selection:Randomized clinical trials that tested commonly used antihypertension medications (angiotensin-converting enzyme inhibitors, dihydropyridine calcium channel blockers, nondihydropyridine calcium channel blockers, ?-blockers, angiotensin receptor blockers, and diuretics) and that reported selected cardiovascular outcomes for at least 6 months of follow-up. Data Extraction and Synthesis:The analysis was conducted from October 2017 to December 2019. Two reviewers extracted the number of cardiovascular events at the end of treatment for all study groups. For each outcome, a frequentist network meta-analysis was used to compare risk reductions between medication classes (random-effects models weighted by the inverse variance). The dose-response association between a 10-mm Hg reduction of systolic blood pressure and a 5-mm Hg reduction of diastolic blood pressure and the risk of first-in-trial cardiovascular events was estimated. Main Outcomes and Measures:First-in-trial cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and revascularization. Results:In this systematic review and network meta-analysis, data were pooled from 46 eligible clinical trials (248?887 total participants with a mean [SD] age of 65.6 [5.8] years; 52.8% men). In the network meta-analysis, compared with placebo, angiotensin-converting enzyme inhibitors, dihydropyridine calcium channel blockers, and thiazide diuretics were reported to be similarly effective in reducing overall cardiovascular events (25%), cardiovascular death (20%), and stroke (35%); angiotensin-converting enzyme inhibitors were reported to be the most effective in reducing the risk of myocardial infarction (28%); and diuretics were reported to be the most effective in reducing revascularization (33%). In the metaregression analyses, each 10-mm Hg reduction in systolic blood pressure and 5-mm Hg reduction in diastolic blood pressure was significantly associated with a lower risk of cardiovascular death, stroke, and overall cardiovascular events. Conclusions and Relevance:In this network meta-analysis of clinical trials of patients with hypertension and no substantial comorbidities, different classes of antihypertension medications were associated with similar benefits in reducing cardiovascular events. Future studies should compare the effectiveness of combinations of antihypertension medications in reducing cardiovascular events.

SUBMITTER: Wei J

PROVIDER: S-EPMC7043193 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Comparison of Cardiovascular Events Among Users of Different Classes of Antihypertension Medications: A Systematic Review and Network Meta-analysis.

Wei Jingkai J Galaviz Karla I KI Kowalski Alysse J AJ Magee Matthew J MJ Haw J Sonya JS Narayan K M Venkat KMV Ali Mohammed K MK

JAMA network open 20200205 2

<h4>Importance</h4>Antihypertension medications have been associated with prevention of cardiovascular events, although less is known about the comparative effectiveness of different medication classes.<h4>Objective</h4>To compare contemporary aggregated first-in-trial cardiovascular events among patients with hypertension and no substantial comorbidities.<h4>Data sources</h4>The PubMed, Embase, and Cochrane Library databases were systematically searched for articles published between January 1, ...[more]

PMID: 32083689

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Project description:BackgroundRecent trials suggested that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduced cardiovascular events. Comparative effectiveness of these new antidiabetic drug classes remains unclear. We therefore performed a network meta-analysis to compare the effect on cardiovascular outcomes among GLP-1 RAs, SGLT-2 and dipeptidyl peptidase-4 (DPP-4) inhibitors.MethodsMEDLINE, EMBASE, Cochrane database, ClinicalTrials.gov, and congress proceedings from recent cardiology conferences were searched up to April 20, 2019. Cardiovascular outcome trials and renal outcome trials reporting cardiovascular outcomes on GLP-1 RAs, SGLT-2 and DPP-4 inhibitors in patients with type 2 diabetes mellitus were included. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes were nonfatal myocardial infarction, nonfatal stroke, cardiovascular mortality, all-cause mortality, hospitalisation for heart failure (HF), and renal composite outcome. ORs and 95% CI were calculated using random-effects models.ResultsFourteen trials enrolling 121,047 patients were included. SGLT-2 inhibitors reduced cardiovascular deaths and all-cause deaths compared to placebo (OR 0.82, 95% CI 0.73-0.93 and OR 0.84, 95% CI 0.77-0.92) and DPP-4 inhibitors (OR 0.83, 95% CI 0.70-0.99 and OR 0.83, 95% CI 0.73-0.94), respectively. SGLT-2 inhibitors and GLP-1 RAs significantly reduced MACE (OR 0.88, 95% CI 0.82-0.95 and OR 0.87, 95% CI 0.82-0.93), hospitalisation for HF (OR 0.68, 95% CI 0.61-0.77 and OR 0.87, 95% CI 0.82-0.93), and renal composite outcome (OR 0.59, 95% CI 0.52-0.67 and OR 0.86, 95% CI 0.78-0.94) compared to placebo, but SGLT-2 inhibitors reduced hospitalisation for HF (OR 0.79, 95% CI 0.69-0.90) and renal composite outcome (OR 0.69, 95% CI 0.59-0.80) more than GLP-1 RAs. Only GLP-1 RAs reduced nonfatal stroke (OR 0.88, 95% CI 0.77-0.99). DPP-4 inhibitors did not lower the risk of these outcomes when compared to placebo and were associated with higher risks of MACE, hospitalisation for HF, and renal composite outcome when compared to the other two drug classes.ConclusionsSGLT-2 inhibitors show clear superiority in reducing cardiovascular and all-cause deaths, hospitalisation for HF, and renal events among new antidiabetic drug classes. GLP-1 RAs also have cardiovascular and renal protective effects. DPP-4 inhibitors have no beneficial cardiovascular effects and are therefore inferior to the other two drug classes. SGLT-2 inhibitors should now be the preferred treatment for type 2 diabetes mellitus.

Project description:Importance:There are few studies comparing the optimal level of treated blood pressure (BP) between high- and low-risk patients. Objective:To examine whether optimally treated BP is different according to risk status. Design, Setting, and Participants:Population-based cohort study using data from the National Health Information Database in Korea from 2002 to 2015 and 2006 to 2017. A total of 1?402?975 adults aged 40 to 79 years who had no known cardiorenal disease were included. Exposures:Systolic BP treated with antihypertensive medication. Main Outcomes and Measures:The yearly rates of critical cardiorenal events and all-cause death were estimated according to the levels of treated systolic BP and the presence of 5 risk factors (hypertension, diabetes, hyperlipidemia, proteinuria, and smoking). Results:During the study periods, 225?103 of 487?412 participants (54.0% male; median [interquartile range] age, 50 [44-59] years) in the primary cohort and 360?503 of 915?563 participants (50.1% male; median [interquartile range] age, 52 [46-60] years) in the secondary cohort received antihypertensive treatment. In total, 28?411 of 51?292 cardiorenal incidents and 33?102 of 72?500 deaths were noted in ever-treated participants. The absolute increase in cardiorenal and mortality risk associated with inadequately treated BP was greater in participants with multiple risk factors than in those with 1 or 0 risk factors. The hazard ratios for critical cardiorenal events increased as the treated systolic BP increased to more than 130 to 140 mm Hg. The hazard ratio for all-cause mortality for patients with 3 or more risk factors and treated systolic BP within the range of 110 to 119 mm Hg was 1.21 (95% CI, 1.07-1.37); 130 to 139 mm Hg, 1.04 (95% CI, 0.98-1.11); 140 to 149 mm Hg, 1.12 (95% CI, 1.05-1.20); 150 to 159 mm Hg, 1.21 (95% CI, 1.11-1.32); and 160 mm Hg or greater, 1.46 (95% CI, 1.32-1.62) compared with high-risk patients with BP of 120 to 129 mm Hg. For participants with 1 or 0 risk factors and treated systolic BP within the range of 110 to 119 mm Hg, the hazard ratio was 1.14 (95% CI, 1.07-1.22); 130 to 139 mm Hg, 0.97 (95% CI, 0.93-1.02); 140 to 149 mm Hg, 1.00 (95% CI, 0.91-1.09); 150 to 159 mm Hg, 1.06 (95% CI, 0.99-1.14); and 160 mm Hg or greater, 1.26 (95% CI, 1.15-1.37). However, when categorized using cardiovascular risk calculators, there was no consistent trend in mortality thresholds of BP across the risk score categories. Conclusions and Relevance:These results suggest that intensive BP control is appropriate for reducing all-cause mortality in addition to cardiorenal risk in higher- rather than lower-risk patients. However, caution may be required when determining BP targets using current risk calculators.

Project description:Randomized trials of anti-hypertensive treatment demonstrating reduced risk of cardiovascular events in older adults included participants with less comorbidity than clinical populations. Whether these results generalize to all older adults, most of whom have multiple chronic conditions, is uncertain.To determine the association between anti-hypertensive medications and CV events and mortality in a nationally representative population of older adults.Competing risk analysis with propensity score adjustment and matching in the Medicare Current Beneficiary Survey cohort over three-year follow-up through 2010.4,961 community-living participants with hypertension.Anti-hypertensive medication intensity, based on standardized daily dose for each anti-hypertensive medication class participants used.Cardiovascular events (myocardial infarction, unstable angina, cardiac revascularization, stroke, and hospitalizations for heart failure) and mortality.Of 4,961 participants, 14.1% received no anti-hypertensives; 54.6% received moderate, and 31.3% received high, anti-hypertensive intensity. During follow-up, 1,247 participants (25.1%) experienced cardiovascular events; 837 participants (16.9%) died. Of deaths, 430 (51.4%) occurred in participants who experienced cardiovascular events during follow-up. In the propensity score adjusted cohort, after adjusting for propensity score and other covariates, neither moderate (adjusted hazard ratio, 1.08 [95% CI, 0.89-1.32]) nor high (1.16 [0.94-1.43]) anti-hypertensive intensity was associated with experiencing cardiovascular events. The hazard ratio for death among all participants was 0.79 [0.65-0.97] in the moderate, and 0.72 [0.58-0.91] in the high intensity groups compared with those receiving no anti-hypertensives. Among participants who experienced cardiovascular events, the hazard ratio for death was 0.65 [0.48-0.87] and 0.58 [0.42-0.80] in the moderate and high intensity groups, respectively. Results were similar in the propensity score-matched subcohort.In this nationally representative cohort of older adults, anti-hypertensive treatment was associated with reduced mortality but not cardiovascular events. Whether RCT results generalize to older adults with multiple chronic conditions remains uncertain.

Project description:More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety.To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults.Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers).Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias.During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years.Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.

Project description:Background and objectivesSome evidence suggests that bisphosphonates may reduce atherosclerosis, while concerns have been raised about atrial fibrillation. We conducted a meta-analysis to determine the effects of bisphosphonates on total adverse cardiovascular (CV) events, atrial fibrillation, myocardial infarction (MI), stroke, and CV death in adults with or at risk for low bone mass.MethodsA systematic search of MEDLINE and EMBASE through July 2014 identified 58 randomized controlled trials with longer than 6 months in duration that reported CV events. Absolute risks and the Mantel-Haenszel fixed-effects odds ratios (ORs) and 95% confidence intervals (CIs) of total CV events, atrial fibrillation, MI, stroke, and CV death were estimated. Subgroup analyses by follow-up duration, population characteristics, bisphosphonate types, and route were performed.ResultsAbsolute risks over 25-36 months in bisphosphonate-treated versus control patients were 6.5% versus 6.2% for total CV events; 1.4% versus 1.5% for atrial fibrillation; 1.0% versus 1.2% for MI; 1.6% versus 1.9% for stroke; and 1.5% versus 1.4% for CV death. Bisphosphonate treatment up to 36 months did not have any significant effects on total CV events (14 trials; ORs [95% CI]: 0.98 [0.84-1.14]; I2 = 0.0%), atrial fibrillation (41 trials; 1.08 [0.92-1.25]; I2 = 0.0%), MI (10 trials; 0.96 [0.69-1.34]; I2 = 0.0%), stroke (10 trials; 0.99 [0.82-1.19]; I2 = 5.8%), and CV death (14 trials; 0.88 [0.72-1.07]; I2 = 0.0%) with little between-study heterogeneity. The risk of atrial fibrillation appears to be modestly elevated for zoledronic acid (6 trials; 1.24 [0.96-1.61]; I2 = 0.0%), not for oral bisphosphonates (26 trials; 1.02 [0.83-1.24]; I2 = 0.0%). The CV effects did not vary by subgroups or study quality.ConclusionsBisphosphonates do not have beneficial or harmful effects on atherosclerotic CV events, but zoledronic acid may modestly increase the risk of atrial fibrillation. Given the large reduction in fractures with bisphosphonates, changes in osteoporosis treatment decision due to CV risk are not justified.

Dataset Information

Comparison of Cardiovascular Events Among Users of Different Classes of Antihypertension Medications: A Systematic Review and Network Meta-analysis.

Publications

Comparison of Cardiovascular Events Among Users of Different Classes of Antihypertension Medications: A Systematic Review and Network Meta-analysis.

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