20
views
0
recommends
+1 Recommend
2 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Effectiveness of Ivabradine Treatment in Different Subpopulations with Stable Angina in Clinical Practice: A Pooled Analysis of Observational Studies

      research-article

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objectives: The efficacy of ivabradine has been demonstrated in different subpopulations of stable angina patients in randomized clinical trials. This study explored its effectiveness in subpopulations seen in clinical practice as they often differ from those of randomized trials. Methods: Data were pooled from three German observational studies with similar inclusion criteria (stable angina and heart rate ≥60 bpm). All patients received 2.5, 5, or 7.5 mg b.i.d. of ivabradine for 4 months, with or without concomitant beta-blocker. Antianginal effectiveness was analyzed in subpopulations defined by gender, age, heart rate, angina severity, use of concomitant beta-blocker, previous percutaneous coronary intervention procedure, and comorbidities (including previous myocardial infarction and diabetes). Results: Treatment data were available on 8,555 patients, where therapy with ivabradine was associated with a significant reduction in the frequency of angina attacks and consumption of short-acting nitrates of 87%. Effectiveness was maintained in all investigated subpopulations, with a reduction in antianginal parameters of 82-90%. Clinical status (Canadian Cardiovascular Society class) and quality of life were also improved. Ivabradine was well tolerated in all subgroups. Conclusions: Ivabradine is effective and safe in all subpopulations of angina patients seen in clinical practice, independent of age, comorbidities, and use of beta-blocker.

          Related collections

          Most cited references35

          • Record: found
          • Abstract: found
          • Article: not found

          Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review.

          Selective eligibility criteria of randomized controlled trials (RCTs) are vital to trial feasibility and internal validity. However, the exclusion of certain patient populations may lead to impaired generalizability of results. To determine the nature and extent of exclusion criteria among RCTs published in major medical journals and the contribution of exclusion criteria to the representation of certain patient populations. The MEDLINE database was searched for RCTs published between 1994 and 2006 in certain general medical journals with a high impact factor. Of 4827 articles, 283 were selected using a series technique. Trial characteristics and the details regarding exclusions were extracted independently. All exclusion criteria were graded independently and in duplicate as either strongly justified, potentially justified, or poorly justified according to previously developed and pilot-tested guidelines. Common medical conditions formed the basis for exclusion in 81.3% of trials. Patients were excluded due to age in 72.1% of all trials (60.1% in pediatric populations and 38.5% in older adults). Individuals receiving commonly prescribed medications were excluded in 54.1% of trials. Conditions related to female sex were grounds for exclusion in 39.2% of trials. Of all exclusion criteria, only 47.2% were graded as strongly justified in the context of the specific RCT. Exclusion criteria were not reported in 12.0% of trials. Multivariable analyses revealed independent associations between the total number of exclusion criteria and drug intervention trials (risk ratio, 1.35; 95% confidence interval, 1.11-1.65; P = .003) and between the total number of exclusion criteria and multicenter trials (risk ratio, 1.26; 95% confidence interval, 1.06-1.52; P = .009). Industry-sponsored trials were more likely to exclude individuals due to concomitant medication use, medical comorbidities, and age. Drug intervention trials were more likely to exclude individuals due to concomitant medication use, medical comorbidities, female sex, and socioeconomic status. Among such trials, justification for exclusions related to concomitant medication use and comorbidities were more likely to be poorly justified. The RCTs published in major medical journals do not always clearly report exclusion criteria. Women, children, the elderly, and those with common medical conditions are frequently excluded from RCTs. Trials with multiple centers and those involving drug interventions are most likely to have extensive exclusions. Such exclusions may impair the generalizability of RCT results. These findings highlight a need for careful consideration and transparent reporting and justification of exclusion criteria in clinical trials.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results

            Randomized controlled trials (RCTs) are conducted under idealized and rigorously controlled conditions that may compromise their external validity. A literature review was conducted of published English language articles that reported the findings of studies assessing external validity by a comparison of the patient sample included in RCTs reporting on pharmaceutical interventions with patients from everyday clinical practice. The review focused on publications in the fields of cardiology, mental health, and oncology. A range of databases were interrogated (MEDLINE; EMBASE; Science Citation Index; Cochrane Methodology Register). Double-abstract review and data extraction were performed as per protocol specifications. Out of 5,456 de-duplicated abstracts, 52 studies met the inclusion criteria (cardiology, n = 20; mental health, n = 17; oncology, n = 15). Studies either performed an analysis of the baseline characteristics (demographic, socioeconomic, and clinical parameters) of RCT-enrolled patients compared with a real-world population, or assessed the proportion of real-world patients who would have been eligible for RCT inclusion following the application of RCT inclusion/exclusion criteria. Many of the included studies concluded that RCT samples are highly selected and have a lower risk profile than real-world populations, with the frequent exclusion of elderly patients and patients with co-morbidities. Calculation of ineligibility rates in individual studies showed that a high proportion of the general disease population was often excluded from trials. The majority of studies (n = 37 [71.2 %]) explicitly concluded that RCT samples were not broadly representative of real-world patients and that this may limit the external validity of the RCT. Authors made a number of recommendations to improve external validity. Findings from this review indicate that there is a need to improve the external validity of RCTs such that physicians treating patients in real-world settings have the appropriate evidence on which to base their clinical decisions. This goal could be achieved by trial design modification to include a more representative patient sample and by supplementing RCT evidence with data generated from observational studies. In general, a thoughtful approach to clinical evidence generation is required in which the trade-offs between internal and external validity are considered in a holistic and balanced manner. Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1023-4) contains supplementary material, which is available to authorized users.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial.

              Ivabradine specifically inhibits the I(f) current in the sinoatrial node to lower heart rate, without affecting other aspects of cardiac function. We aimed to test whether lowering the heart rate with ivabradine reduces cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular systolic dysfunction. Between December, 2004, and December, 2006, we screened 12 473 patients at 781 centres in 33 countries. We enrolled 10 917 eligible patients who had coronary artery disease and a left-ventricular ejection fraction of less than 40% in a randomised, double-blind, placebo-controlled, parallel-group trial. 5479 patients received 5 mg ivabradine, with the intention of increasing to the target dose of 7.5 mg twice a day, and 5438 received matched placebo in addition to appropriate cardiovascular medication. The primary endpoint was a composite of cardiovascular death, admission to hospital for acute myocardial infarction, and admission to hospital for new onset or worsening heart failure. We analysed patients by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00143507. Mean heart rate at baseline was 71.6 (SD 9.9) beats per minute (bpm). Median follow-up was 19 months (IQR 16-24). Ivabradine reduced heart rate by 6 bpm (SE 0.2) at 12 months, corrected for placebo. Most (87%) patients were receiving beta blockers in addition to study drugs, and no safety concerns were identified. Ivabradine did not affect the primary composite endpoint (hazard ratio 1.00, 95% CI 0.91-1.1, p=0.94). 1233 (22.5%) patients in the ivabradine group had serious adverse events, compared with 1239 (22.8%) controls (p=0.70). In a prespecified subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not affect the primary composite outcome (hazard ratio 0.91, 95% CI 0.81-1.04, p=0.17), cardiovascular death, or admission to hospital for new-onset or worsening heart failure. However, it did reduce secondary endpoints: admission to hospital for fatal and non-fatal myocardial infarction (0.64, 95% CI 0.49-0.84, p=0.001) and coronary revascularisation (0.70, 95% CI 0.52-0.93, p=0.016). Reduction in heart rate with ivabradine does not improve cardiac outcomes in all patients with stable coronary artery disease and left-ventricular systolic dysfunction, but could be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients who have heart rates of 70 bpm or greater.
                Bookmark

                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                Cardiology
                S. Karger AG (Basel, Switzerland karger@ 123456karger.com http://www.karger.com )
                0008-6312
                1421-9751
                October 2016
                23 June 2016
                : 135
                : 3
                : 141-150
                Affiliations
                aDepartment of Medicine and Heart Centre, University Hospital of the Martin Luther University of Halle-Wittenberg, Halle (Saale), bCardioCentrum, and cDepartment of Cardiology, Pneumology and Angiology, Düsseldorf University Hospital, Düsseldorf, dDepartment of Cardiology and Angiology, Johanniter Hospital, Geesthacht, eDepartment of Cardiology and Angiology, University Heart Center, Hamburg, fDepartment of Medical Affairs, Servier Deutschland GmbH, Munich, gDepartment of Geriatrics, Evangelisches Geriatriezentrum, and hChair of Geriatrics, Charité - Universitätsmedizin Berlin, Berlin, Germany
                Article
                CRD2016135003141 Cardiology 2016;135:141-150
                10.1159/000447443
                27333284
                56958ae7-189c-4fff-afe0-38275835e8b5
                © 2016 The Author(s) Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 12 February 2016
                : 06 June 2016
                Page count
                Figures: 3, Tables: 3, References: 39, Pages: 10
                Categories
                Original Research

                Medicine,General social science
                Stable angina pectoris,Subpopulation,Heart rate,Ivabradine,Pooled analysis,Clinical practice,Observational studies

                Comments

                Comment on this article