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High-dose versus low-dose angiotensin converting enzyme inhibitors in heart failure: systematic review and meta-analysis.

ABSTRACT: OBJECTIVE:To systematically review evidence comparing the effect of low-dose versus high-dose ACE inhibitors (ACEIs) on all-cause and cardiovascular mortality and hospitalisation, functional capacity and side effects in patients with heart failure (HF). METHODS:We searched PubMed, Embase, Cochrane CENTRAL and LILACS up to January 2019. We included randomised controlled trials (RCTs) comparing low-dose versus high-dose ACEIs in adults with HF with reduced left ventricular ejection fraction (HFrEF). Study selection and data extraction were performed by two independent reviewers. Risk of bias was assessed with RoB 2.0, and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). We conducted random effects meta-analysis and trial sequential analysis. RESULTS:We included eight RCTs (5829 patients with HF). In comparison with low-dose ACEIs, high-dose ACEIs showed a non-significant effect on all-cause mortality (8 RCTs, n=5828, relative risk (RR) 0.95, 95% CI 0.88 to 1.02; moderate quality of evidence), cardiovascular mortality (6 RCTs, n=4048, RR 0.93, 95%?CI 0.85 to 1.01; moderate quality of evidence), all-cause hospitalisation (5 RCTs, n=5394, RR 0.95, 95%?CI 0.82 to 1.10; moderate quality of evidence) and cardiovascular hospitalisation (4 RCTs, n=5242, RR 0.98, 95%?CI 0.83 to 1.17; low quality of evidence). High-dose ACEI increased functional capacity (4 studies, n=555, standardised mean difference 0.38, 95%?CI 0.20 to 0.55; low quality of evidence) and the risk of hypotension (4 RCTs, n=3783, RR 1.64, 95%?CI 1.30 to 2.05; moderate quality of evidence). High-dose ACEI had no effect on dizziness (3 RCTs, n=4994, RR 1.37, 95%?CI 0.97 to 1.93; low quality of evidence), but decreased the risk of cough (4 RCTs, n=5146, RR 0.85, 95%?CI 0.73 to 0.98; moderate quality of evidence). CONCLUSIONS:The magnitude of benefit of using high dose versus low to intermediate doses of ACEIs might be less than traditionally suggested in clinical guidelines. These findings might help clinicians address the complex task of HF management in a more rational and timely fashion, saving efforts to implement strategies with the greatest net clinical benefit.

SUBMITTER: Migliavaca CB

PROVIDER: S-EPMC7443275 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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High-dose versus low-dose angiotensin converting enzyme inhibitors in heart failure: systematic review and meta-analysis.

Migliavaca Celina Borges CB Stein Cinara C Colpani Verônica V Eibel Bruna B Bgeginski Roberta R Simões Marcus Vinicius MV Rohde Luiz Eduardo LE Falavigna Maicon M

Open heart 20200801 2

<h4>Objective</h4>To systematically review evidence comparing the effect of low-dose versus high-dose ACE inhibitors (ACEIs) on all-cause and cardiovascular mortality and hospitalisation, functional capacity and side effects in patients with heart failure (HF).<h4>Methods</h4>We searched PubMed, Embase, Cochrane CENTRAL and LILACS up to January 2019. We included randomised controlled trials (RCTs) comparing low-dose versus high-dose ACEIs in adults with HF with reduced left ventricular ejection ...[more]

PMID: 32820054

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Project description:BackgroundExisting clinical trial data do not address whether all angiotensin-converting-enzyme (ACE) inhibitors are similarly beneficial in improving survival and reducing the rate of readmission among patients with congestive heart failure. We sought to answer this question using administrative databases from Canada's 3 most populous provinces.MethodsUsing linked hospital discharge and prescription claims databases in Quebec, Ontario and British Columbia, we identified all patients 65 years or older who were admitted to hospital because of congestive heart failure between Jan. 1, 1998, and Mar. 31, 2002, and who had not been admitted for the same reason in the 3 years preceding the study period. We analyzed the association between the type of ACE inhibitor prescribed within 30 days after discharge and subsequent mortality using Cox proportional hazards models. We then adjusted for demographic, clinical, physician and hospital-related variables, with additional time-dependent variables representing current drug use and dosage. We chose ramipril as the reference category for comparison with the other ACE inhibitors because it has increasingly been prescribed to patients with congestive heart failure.ResultsA total of 43 316 patients with congestive heart failure filled prescriptions for ACE inhibitors within 30 days after discharge from hospital. Demographic, clinical and prescription-related characteristics were similar among users of each type of ACE inhibitor. In the time-dependent model, the mortality associated with 5 ACE inhibitors was similar to that with ramipril: adjusted hazard ratios (and 95% confidence intervals [CIs]) were 0.95 (0.89-1.02) for lisinopril, 0.92 (0.85-1.00) for fosinopril, 0.99 (0.88-1.11) for quinapril, 0.90 (0.77-1.06) for perindopril and 1.00 (0.80-1.24) for cilazapril. However, use of enalapril or captopril was associated with higher mortality compared with ramipril: adjusted hazard ratios (and 95% CIs) were 1.10 (1.04-1.16) for enalapril and 1.13 (1.01-1.26) for captopril.InterpretationWhen prescribing ACE inhibitors to patients, physicians should consider a possible 10%-15% increase in mortality with captopril and enalapril compared with ramipril among patients with congestive heart failure.

Project description:BackgroundVariation in the carboxylesterase 1 gene (CES1) may contribute to the efficacy of ACEIs. Accordingly, we examined the impact of CES1 variants on plasma angiotensin II (ATII)/angiotensin I (ATI) ratio in patients with congestive heart failure (CHF) that underwent ACEI dose titrations. Five of these variants have previously been associated with drug response or increased CES1 expression, i.e., CES1 copy number variation, the variant of the duplicated CES1 gene with high transcriptional activity, rs71647871, rs2244613, and rs3815583. Additionally, nine variants, representatives of CES1Var, and three other CES1 variants were examined.MethodsPatients with CHF, and clinical indication for ACEIs were categorized according to their CES1 genotype. Differences in mean plasma ATII/ATI ratios between genotype groups after ACEI dose titration, expressed as the least square mean (LSM) with 95% confidence intervals (CIs), were assessed by analysis of variance.ResultsA total of 200 patients were recruited and 127 patients (63.5%) completed the study. The mean duration of the CHF drug dose titration was 6.2 (SD 3.6) months. After ACEI dose titration, there was no difference in mean plasma ATII/ATI ratios between subjects with the investigated CES1 variants, and only one previously unexplored variation (rs2302722) qualified for further assessment. In the fully adjusted analysis of effects of rs2302722 on plasma ATII/ATI ratios, the difference in mean ATII/ATI ratio between the GG genotype and the minor allele carriers (GT and TT) was not significant, with a relative difference in LSMs of 0.67 (95% CI 0.43-1.07; P = 0.10). Results of analyses that only included enalapril-treated patients remained non-significant after Bonferroni correction for multiple parallel comparisons (difference in LSM 0.60 [95% CI 0.37-0.98], P = 0.045).ConclusionThese findings indicate that the included single variants of CES1 do not significantly influence plasma ATII/ATI ratios in CHF patients treated with ACEIs and are unlikely to be primary determinants of ACEI efficacy.

Project description:IntroductionThis meta-analysis aimed to summarize the available evidence to compare angiotensin-converting enzyme (ACE) inhibitors with angiotensin II receptor blockers (ARBs) on improving insulin sensitivity in hypertensive patients.MethodsRandomized controlled trials (RCTs) comparing ACE inhibitors versus ARBs published with outcomes on homeostasis model assessment of IR (HOMA-IR), glucose infusion rate (GIR), the quantitative insulin sensitivity check index (QUICKI), insulin sensitivity index (ISI) composite, fasting plasma glucose (FPG), fasting plasma insulin (FPI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were searched through 5 databases. Data were searched from their inception to July 5, 2020. Stata 14.0 was used to perform the meta-analysis.ResultsEleven RCTs (n = 1015) were included in this meta-analysis. Pooled analysis of studies showed no significant difference in HOMA-IR between ARBs and ACE inhibitors (WMD = -0.09, 95% CI: -0.69 to 0.50, P = 0.755); however, subgroup analysis of therapeutic duration showed a significant difference in HOMA-IR between ARBs and ACE inhibitors among the long-term intervention subgroup (>12 weeks) (WMD = 0.41, 95% CI: 0.06 to 0.76, P = 0.022) and hypertensive patients with diabetes mellitus subgroup (WMD = 0.55, 95% CI: 0.49 to 0.61, P < 0.001); results showed no significant difference between ARBs and ACE inhibitors on QUICKI score (WMD = -0.00, 95% CI: -0.03 to 0.03, P = 0.953) in hypertensive patients; however, the efficacy of ACE inhibitors on improving GIR and ISI composite was significantly better than that of ARBs (WMD = -1.09, 95% CI: -1.34 to -0.85, P < 0.001; WMD = -0.80, 95% CI: -1.24 to -0.36, P < 0.001, respectively). Furthermore, no significant differences were noted on FPG (WMD = 0.72, 95% CI: -1.39 to 2.83, P = 0.505), FPI (WMD = -0.48, 95% CI: -1.60 to 0.64, P = 0.398), SBP (WMD = -0.65, 95% CI: -1.76 to 0.46, P = 0.254), and DBP (WMD = -0.30, 95% CI: -1.70 to 1.10, P = 0.675) between ARBs and ACE inhibitors.ConclusionResults from this meta-analysis showed that ACE inhibitors resulted in more effective improvement of HOMA-IR compared with ARBs among the long-term intervention and hypertensive patients with DM subgroup; furthermore, the efficacy of ACE inhibitors on improving GIR and ISI composite was significantly better than that of ARBs in hypertensive patients. However, ARBs had no significant difference in QUICKI score, FPG, FPI, SBP, and DBP compared with ACE inhibitors. Larger and better-designed studies are needed to further verify this conclusion.

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High-dose versus low-dose angiotensin converting enzyme inhibitors in heart failure: systematic review and meta-analysis.

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High-dose versus low-dose angiotensin converting enzyme inhibitors in heart failure: systematic review and meta-analysis.

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