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      Comparative effectiveness of ACE inhibitors and angiotensin receptor blockers in patients with prior myocardial infarction

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          Abstract

          Objective

          Although ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly prescribed for patients with coronary artery disease, whether these medications are similarly effective is still a subject of intense debate. Our objective was to compare the clinical effectiveness of ACEIs and ARBs in patients with prior myocardial infarction (MI).

          Methods

          All residents older than 65 years, alive on 1 April 2012, with a prior MI were included. Propensity weighting was used to balance potentially confounding baseline covariates between the treatment groups. The primary outcome was a composite of cardiovascular death, hospitalisation for MI or unstable angina at 3 years.

          Results

          Our cohort included 59 353 patients with MI; their mean age was 77 years and 40% were women. In the propensity-weighted cohort, the primary outcome occurred in 6.5% in the ACEI group and 5.7% in the ARB group at 1 year (HR comparing ACEI with ARB 1.14, 95% CI 1.05 to 1.23, p<0.001). At 3 years, the primary outcome occurring in 16.0% with ACEIs and 15.1% with ARBs (HR 1.07; 95% CI 1.02 to 1.12; p<0.001). A significant interaction with sex was observed, with women prescribed ACEIs having a higher hazards (HR 1.17; 95% CI 1.10 to 1.26) compared with ARBs, while no significant difference was seen among men (HR 1.00; 95% CI 0.93 to 1.06, interaction p<0.001).

          Conclusions

          Despite previous concerns regarding ARBs, we found that they had slightly lower rates of adverse clinical cardiovascular outcomes among older patients with MI compared with ACEIs. The observed difference in clinical outcomes may be related to a sex difference in effectiveness.

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          Most cited references19

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          Adjusted survival curves with inverse probability weights.

          Kaplan-Meier survival curves and the associated nonparametric log rank test statistic are methods of choice for unadjusted survival analyses, while the semiparametric Cox proportional hazards regression model is used ubiquitously as a method for covariate adjustment. The Cox model extends naturally to include covariates, but there is no generally accepted method to graphically depict adjusted survival curves. The authors describe a method and provide a simple worked example using inverse probability weights (IPW) to create adjusted survival curves. When the weights are non-parametrically estimated, this method is equivalent to direct standardization of the survival curves to the combined study population.
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            A Tutorial and Case Study in Propensity Score Analysis: An Application to Estimating the Effect of In-Hospital Smoking Cessation Counseling on Mortality

            Propensity score methods allow investigators to estimate causal treatment effects using observational or nonrandomized data. In this article we provide a practical illustration of the appropriate steps in conducting propensity score analyses. For illustrative purposes, we use a sample of current smokers who were discharged alive after being hospitalized with a diagnosis of acute myocardial infarction. The exposure of interest was receipt of smoking cessation counseling prior to hospital discharge and the outcome was mortality with 3 years of hospital discharge. We illustrate the following concepts: first, how to specify the propensity score model; second, how to match treated and untreated participants on the propensity score; third, how to compare the similarity of baseline characteristics between treated and untreated participants after stratifying on the propensity score, in a sample matched on the propensity score, or in a sample weighted by the inverse probability of treatment; fourth, how to estimate the effect of treatment on outcomes when using propensity score matching, stratification on the propensity score, inverse probability of treatment weighting using the propensity score, or covariate adjustment using the propensity score. Finally, we compare the results of the propensity score analyses with those obtained using conventional regression adjustment.
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              Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis.

              Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may have different effects on cardiovascular (CV) events in patients with diabetes mellitus (DM). To conduct a meta-analysis to separately evaluate the effects of ACEIs and ARBs on all-cause mortality, CV deaths, and major CV events in patients with DM. DATA SOURCES Data sources included MEDLINE (1966-2012), EMBASE (1988-2012), the Cochrane Central Register of Controlled Trials, conference proceedings, and article reference lists. We included randomized clinical trials reporting the effects of ACEI and ARB regimens for DM on all-cause mortality, CV deaths, and major CV events with an observation period of at least 12 months. Studies were excluded if they were crossover trials. Dichotomous outcome data from individual trials were analyzed using the risk ratio (RR) measure and its 95% CI with random-effects models. We estimated the difference between the estimates of the subgroups according to tests for interaction. We performed meta-regression analyses to identify sources of heterogeneity. Primary end points were all-cause mortality and death from CV causes. Secondary end points were the effects of ACEIs and ARBs on major CV events. Twenty-three of 35 identified trials compared ACEIs with placebo or active drugs (32,827 patients) and 13 compared ARBs with no therapy (controls) (23,867 patients). When compared with controls (placebo/active treatment), ACEIs significantly reduced the risk of all-cause mortality by 13% (RR, 0.87; 95% CI, 0.78-0.98), CV deaths by 17% (0.83; 0.70-0.99), and major CV events by 14% (0.86; 0.77-0.95), including myocardial infarction by 21% (0.79; 0.65-0.95) and heart failure by 19% (0.81; 0.71-0.93). Treatment with ARBs did not significantly affect all-cause mortality (RR, 0.94; 95% CI, 0.82-1.08), CV death rate (1.21; 0.81-1.80), and major CV events (0.94; 0.85-1.01) with the exception of heart failure (0.70; 0.59-0.82). Both ACEIs and ARBs were not associated with a decrease in the risk for stroke in patients with DM. Meta-regression analysis showed that the ACEI treatment effect on all-cause mortality and CV death did not vary significantly with the starting baseline blood pressure and proteinuria of the trial participants and the type of ACEI and DM. Angiotensin-converting enzyme inhibitors reduced all-cause mortality, CV mortality, and major CV events in patients with DM, whereas ARBs had no benefits on these outcomes. Thus, ACEIs should be considered as first-line therapy to limit excess mortality and morbidity in this population.
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                Author and article information

                Journal
                Open Heart
                Open Heart
                openhrt
                openheart
                Open Heart
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2053-3624
                4 May 2019
                2019
                : 6
                : 1
                : e001010
                Affiliations
                [1 ] Institute for Clinical Evaluative Sciences , Toronto, Ontario, Canada
                [2 ] University of Toronto , Toronto, Ontatio, Canada
                [3 ] Western University of Health Services , Pomona, California, USA
                Author notes
                [Correspondence to ] Dr Dennis Ko; dennis.ko@ 123456ices.on.ca
                Author information
                http://orcid.org/0000-0001-6840-8051
                Article
                openhrt-2019-001010
                10.1136/openhrt-2019-001010
                6546192
                31218004
                7ca4116a-6e35-429e-8e90-9f904630088e
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 10 January 2019
                : 08 March 2019
                : 01 April 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004411, Heart and Stroke Foundation of Canada;
                Award ID: G-14-0005977
                Funded by: FundRef http://dx.doi.org/10.13039/501100000024, Canadian Institutes of Health Research;
                Award ID: FDN-154333
                Categories
                Cardiac Risk Factors and Prevention
                1506
                Original research article
                Custom metadata
                unlocked

                angiotensin converting enzyme inhibitor,angiotensin receptor blocker,myocardial infarction,sex difference

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