Dataset Information

Systematic review and meta-analysis: SGLT2 inhibitors, blood pressure and cardiovascular outcomes.

ABSTRACT:

Objective

Clinical trials suggest that SGLT2 inhibitors reduce the risk of cardiovascular mortality in patients with type 2 diabetes, however the mechanism is unclear. Our objective was to test the hypothesis that blood pressure reduction is one potential mechanism underlying the observed improvements in cardiovascular outcomes with SGLT2 inhibitors.

Methods

We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (inception-June 2019) for randomized controlled trials that reported the effect of SGLT2 inhibitors compared with placebo on cardiovascular outcomes in adults with type 2 diabetes. Two reviewers independently extracted data and assessed study quality. Random effects meta-analyses, stratified meta-analyses and meta-regressions were conducted to evaluate the association between blood pressure reduction in SGLT2 inhibitor treated patients and cardiovascular outcomes.

Results

Of 11,232 articles identified, 40 articles (n?=?54,279 participants) were included. The relative risk of cardiovascular mortality was reduced by 18% with the use of SGLT2 inhibitors compared with placebo (RR 0.82; 95%CI 0.74, 0.91, I²?=?0.0%). Meta-regression analysis revealed no detectable difference in cardiovascular mortality (RR 0.93; 95%CI 0.88, 1.13, p?=?0.483), 3-point major adverse cardiovascular events (p?=?0.839) or congestive heart failure hospitalizations (p?=?0.844) with change in mean systolic blood pressure.

Conclusions

Cardiovascular events are reduced in participants with type 2 diabetes treated with SGLT2 inhibitors compared with placebo. There was no significant relationship between the risk of developing adverse cardiovascular events and blood pressure reduction with SGLT2 inhibitors. There is insufficient evidence to suggest that blood pressure reduction is a significant contributor to the cardiovascular benefits observed.

SUBMITTER: Benham JL

PROVIDER: S-EPMC7892922 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Systematic review and meta-analysis: SGLT2 inhibitors, blood pressure and cardiovascular outcomes.

Benham Jamie L JL Booth Jane E JE Sigal Ronald J RJ Daskalopoulou Stella S SS Leung Alexander A AA Rabi Doreen M DM

International journal of cardiology. Heart & vasculature 20210210

<h4>Objective</h4>Clinical trials suggest that SGLT2 inhibitors reduce the risk of cardiovascular mortality in patients with type 2 diabetes, however the mechanism is unclear. Our objective was to test the hypothesis that blood pressure reduction is one potential mechanism underlying the observed improvements in cardiovascular outcomes with SGLT2 inhibitors.<h4>Methods</h4>We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (inception-June 2019) for randomized controll ...[more]

PMID: 33659605

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Project description:Objective To systematically review studies quantifying the associations of long term (clinic), mid-term (home), and short term (ambulatory) variability in blood pressure, independent of mean blood pressure, with cardiovascular disease events and mortality.Data sources Medline, Embase, Cinahl, and Web of Science, searched to 15 February 2016 for full text articles in English.Eligibility criteria for study selection Prospective cohort studies or clinical trials in adults, except those in patients receiving haemodialysis, where the condition may directly impact blood pressure variability. Standardised hazard ratios were extracted and, if there was little risk of confounding, combined using random effects meta-analysis in main analyses. Outcomes included all cause and cardiovascular disease mortality and cardiovascular disease events. Measures of variability included standard deviation, coefficient of variation, variation independent of mean, and average real variability, but not night dipping or day-night variation.Results 41 papers representing 19 observational cohort studies and 17 clinical trial cohorts, comprising 46 separate analyses were identified. Long term variability in blood pressure was studied in 24 papers, mid-term in four, and short-term in 15 (two studied both long term and short term variability). Results from 23 analyses were excluded from main analyses owing to high risks of confounding. Increased long term variability in systolic blood pressure was associated with risk of all cause mortality (hazard ratio 1.15, 95% confidence interval 1.09 to 1.22), cardiovascular disease mortality (1.18, 1.09 to 1.28), cardiovascular disease events (1.18, 1.07 to 1.30), coronary heart disease (1.10, 1.04 to 1.16), and stroke (1.15, 1.04 to 1.27). Increased mid-term and short term variability in daytime systolic blood pressure were also associated with all cause mortality (1.15, 1.06 to 1.26 and 1.10, 1.04 to 1.16, respectively).Conclusions Long term variability in blood pressure is associated with cardiovascular and mortality outcomes, over and above the effect of mean blood pressure. Associations are similar in magnitude to those of cholesterol measures with cardiovascular disease. Limited data for mid-term and short term variability showed similar associations. Future work should focus on the clinical implications of assessment of variability in blood pressure and avoid the common confounding pitfalls observed to date.Systematic review registration PROSPERO CRD42014015695.

Project description:BackgroundGuidelines recommend intensive blood pressure (BP) lowering in patients at high risk. While placebo-controlled trials have demonstrated 22% reductions in coronary heart disease (CHD) and stroke associated with a 10-mmHg difference in systolic BP, it is unclear if more intensive BP lowering strategies are associated with greater reductions in risk of CHD and stroke. We did a systematic review to assess the effects of intensive BP lowering on vascular, eye, and renal outcomes.Methods and findingsWe systematically searched Medline, Embase, and the Cochrane Library for trials published between 1950 and July 2011. We included trials that randomly assigned individuals to different target BP levels. We identified 15 trials including a total of 37,348 participants. On average there was a 7.5/4.5-mmHg BP difference. Intensive BP lowering achieved relative risk (RR) reductions of 11% for major cardiovascular events (95% CI 1%-21%), 13% for myocardial infarction (0%-25%), 24% for stroke (8%-37%), and 11% for end stage kidney disease (3%-18%). Intensive BP lowering regimens also produced a 10% reduction in the risk of albuminuria (4%-16%), and a trend towards benefit for retinopathy (19%, 0%-34%, p = 0.051) in patients with diabetes. There was no clear effect on cardiovascular or noncardiovascular death. Intensive BP lowering was well tolerated; with serious adverse events uncommon and not significantly increased, except for hypotension (RR 4.16, 95% CI 2.25 to 7.70), which occurred infrequently (0.4% per 100 person-years).ConclusionsIntensive BP lowering regimens provided greater vascular protection than standard regimens that was proportional to the achieved difference in systolic BP, but did not have any clear impact on the risk of death or serious adverse events. Further trials are required to more clearly define the risks and benefits of BP targets below those currently recommended, given the benefits suggested by the currently available data.

Project description:ImportanceHigh blood pressure (BP) is the most important risk factor for death and cardiovascular disease (CVD) worldwide. The optimal cutoff for treatment of high BP is debated.ObjectiveTo assess the association between BP lowering treatment and death and CVD at different BP levels.Data sourcesPrevious systematic reviews were identified from PubMed, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effect. Reference lists of these reviews were searched for randomized clinical trials. Randomized clinical trials published after November 1, 2015, were also searched for in PubMed and the Cochrane Central Register for Controlled Trials during February 2017.Study selectionRandomized clinical trials with at least 1000 patient-years of follow-up, comparing BP-lowering drugs vs placebo or different BP goals were included.Data extraction and synthesisData were extracted from original publications. Risk of bias was assessed using the Cochrane Collaborations assessment tool. Relative risks (RRs) were pooled in random-effects meta-analyses with Knapp-Hartung modification. Results are reported according to PRISMA guidelines.Main outcomes and measuresPrespecified outcomes of interest were all-cause mortality, cardiovascular mortality, major cardiovascular events, coronary heart disease (CHD), stroke, heart failure, and end-stage renal disease.ResultsSeventy-four unique trials, representing 306 273 unique participants (39.9% women and 60.1% men; mean age, 63.6 years) and 1.2 million person-years, were included in the meta-analyses. In primary prevention, the association of BP-lowering treatment with major cardiovascular events was dependent on baseline systolic BP (SBP). In trials with baseline SBP 160 mm Hg or above, treatment was associated with reduced risk for death (RR, 0.93; 95% CI, 0.87-1.00) and a substantial reduction of major cardiovascular events (RR, 0.78; 95% CI, 0.70-0.87). If baseline SBP ranged from 140 to 159 mm Hg, the association of treatment with mortality was similar (RR, 0.87; 95% CI, 0.75-1.00), but the association with major cardiovascular events was less pronounced (RR, 0.88; 95% CI, 0.80-0.96). In trials with baseline SBP below 140 mm Hg, treatment was not associated with mortality (RR, 0.98; 95% CI, 0.90-1.06) and major cardiovascular events (RR, 0.97; 95% CI, 0.90-1.04). In trials including people with previous CHD and mean baseline SBP of 138 mm Hg, treatment was associated with reduced risk for major cardiovascular events (RR, 0.90; 95% CI, 0.84-0.97), but was not associated with survival (RR, 0.98; 95% CI, 0.89-1.07).Conclusions and relevancePrimary preventive BP lowering is associated with reduced risk for death and CVD if baseline SBP is 140 mm Hg or higher. At lower BP levels, treatment is not associated with any benefit in primary prevention but might offer additional protection in patients with CHD.

Project description:ObjectiveTo investigate the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with diabetes with cardiovascular disease (CVD) or at high cardiovascular risk.DesignSystematic review and meta-analysis of randomized controlled trials (RCTs).Data sourcesPubmed, Embase, the Cochrane Library, and ClinicalTrial.gov from their inception to August 28, 2021.Review methodsRandomized control trials (RCTs) assess the effects of SGLT2i in patients with diabetes with cardiovascular disease or at high cardiovascular risk. Primary outcomes included the composite outcome of cardiovascular death (CV death) and hospitalization for heart failure (HHF), HHF, and renal composite outcomes. Secondary outcomes included major adverse cardiovascular events (MACE), CV death, all-cause mortality, and change from the baseline in HbA1c. Additionally, we assessed the effects of treatment in prespecified subgroups on the combined risk of primary and secondary outcomes. These subgroups were based on history of heart failure (HF), estimated glomerular filtration rate (eGFR) levels, and history of hypertension (HTN). A meta-analysis was carried out by using fixed effect models to calculate hazard ratio (HR) or mean difference (MD) between the SGLT2i administrated groups and the control groups.ResultsFour major studies (n = 42,568) were included. Primary outcomes showed that SGLT2i was associated with significantly lower risk of CV death/HHF (HR, 0.90; 95% confidence interval, 0.84 to 0.98; P for heterogeneity = 0.01), HHF (HR, 0.84; 95% CI, 0.73 to 0.98; p = 0.02), and renal composite outcomes (HR, 0.83; 95%CI, 0.74 to 0.92; p = 0.0007) in patients with diabetes with CVD or at high CV risk. Secondary outcome showed that the use of SGLT2i was associated with significant reduction of the HbA1c level (MD, -0.30; 95% CI, -0.36 to -0.23; p < 0.00001). In subgroup analyses, SGLT2i significantly reduced the risk of renal composite outcomes in patients without history of HF (HR, 0.75; 95% CI, 0.62 to 0.91; p = 0.003 < 0.025). No statistically significant differences were observed in other secondary outcomes and subgroup analyses.ConclusionsThe SGLT2i showed benefits on CV death/HHF, HHF, renal composite outcomes, and HbA1c reduction in patients with diabetes with CVD or at high CV risk. The benefits of improving renal composite outcomes were observed only in patients with diabetes without HF history.Systematic review registrationPROSPERO CRD42021227400.

Dataset Information

Systematic review and meta-analysis: SGLT2 inhibitors, blood pressure and cardiovascular outcomes.

Objective

Methods

Results

Conclusions

Publications

Systematic review and meta-analysis: SGLT2 inhibitors, blood pressure and cardiovascular outcomes.

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