Effects of insulin on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

AimIn 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of type 2 diabetes. This expert panel, after identifying the effects of glucose-lowering agents on major adverse cardiovascular events (MACEs), all-cause mortality, and hospitalization for heart failure (HHF) as critical outcomes, decided to perform a systematic review and meta-analysis on the effect of insulin with this respect.Data synthesisA MEDLINE database search was performed to identify all RCTs, up to June 1st, 2021, with duration≥52 weeks, in which insulin was compared with either placebo or active comparators. The principal endpoints were MACE and HHF (restricted for RCT reporting MACEs within their outcomes), all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified outcomes). Mantel-Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all the endpoints considered.Six RCTs (enrolling 8091 patients and 10,139 in the insulin and control group, respectively) were included in the analysis for MACEs and HF, and 18 in that for all-cause mortality (9760 and 11,694 patients in the insulin and control group, respectively). Treatment with insulin neither significantly increased nor reduced the risk of MACE, all-cause mortality, and HHF in comparison with placebo/active comparators (MH-OR: 1.09, 95% CI 0.97–1.23; 0.99, 95% CI 0.91, 1.08; and 0.90, 95% CI 0.78, 1.04, respectively).ConclusionsThis meta-analysis showed no significant effects of insulin on incident MACE, all-cause mortality, and HHF.     

Effect of insulin secretagogues on major cardiovascular events and all-cause mortality: A meta-analysis of randomized controlled trials

Background and aimIn 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of type 2 diabetes. This expert panel, after identifying the effects of glucose-lowering agents on major adverse cardiovascular events (MACEs) and all-cause mortality as critical outcomes, decided to perform a systematic review and meta-analysis on the effect of insulin secretagogues (sulfonylureas and glinides) with this respect.Methods and resultsA MEDLINE database search was performed to identify all RCTs, up to January 1st, 2020, with duration≥52 weeks, in which insulin secretagogues (glibenclamide, gliclazide, glimepiride, glipizide, chlorpropamide, repaglinide, nateglinide) were compared with either placebo or active comparators. The principal endpoints were MACE (restricted for RCT reporting MACEs within their outcomes) and all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified outcomes). Mantel-Haenszel odds ratio (MH–OR) with 95% Confidence Interval (95% CI) was calculated for all the endpoints considered. Fourteen RCTs were included in the analysis for MACEs (919 in insulin secretagogues and 1,087 in control group). Insulin secretagogues were not significantly associated with an increased risk of MACEs in comparison with controls (MH–OR 1.08 [95% CI 0.96, 1.22], p = 0.20). When considering the 48 RCTs fulfilling criteria for inclusion in the analysis on all-cause mortality, insulin secretagogues were associated with a significantly increased risk of all-cause mortality (MH–OR 1.11 [1.00, 1.23], p = 0.04).ConclusionsThis meta-analysis suggests that insulin secretagogues are associated with an increased risk of all-cause mortality when compared with placebo or other anti-hyperglycaemic drugs.     

Effect of metformin on all-cause mortality and major adverse cardiovascular events: An updated meta-analysis of randomized controlled trials

AimsThe Italian Society of Diabetology and the Italian Association of Clinical Diabetologists are developing new guidelines for drug treatment of type 2 diabetes. The effects of anti-hyperglycaemic drugs on all-cause mortality and major adverse cardiovascular events (MACEs) were included among the critical clinical outcomes. We have therefore carried out an updated meta-analysis on the effects of metformin on these outcomes.Data synthesisA MEDLINE and EMBASE search was performed to identify all randomized controlled trials (RCTs) with duration ≥52 weeks (published up to August 2020), in which metformin was compared with either placebo/no therapy or active comparators. MACEs (restricted for RCT reporting MACEs within their study endpoints) and all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified endpoints) were considered as the primary endpoints. Mantel-Haenszel odds ratio (MH–OR) with 95% confidence interval was calculated for all endpoints considered. Metformin was associated with a nonsignificant reduction of all-cause mortality (n = 13 RCTs; MH–OR 0.80 [95% CI 0.60, 1.07]). However, this association became statistically significant after excluding RCTs comparing metformin with sulfonylureas, SGLT-2 inhibitors or GLP-1 analogues (MH–OR 0.71 [0.51, 0.99]). Metformin was associated with a lower risk of MACEs compared with comparator treatments (n = 2 RCTs; MH–OR 0.52 [0.37, 0.73]), p < 0.001. Similar results were obtained in a post-hoc analysis including all RCTs fulfilling criteria for inclusion in the analysis (MH–OR: 0.57 [0.42, 0.76]).ConclusionsThis updated meta-analysis suggests that metfomin is significantly associated with lower risk of MACEs and tendentially lower all-cause mortality compared to placebo or other anti-hyperglycaemic drugs.     

All-cause mortality and cardiovascular events in patients with type 2 diabetes treated with alpha-glucosidase inhibitors: A meta-analysis of randomized controlled trials

AimAlpha-glucosidase inhibitors are approved drugs for treating type 2 diabetes (T2DM); however, their effects on mortality and cardiovascular safety are unclear. This meta-analysis was aimed at evaluating the effects of alpha-glucosidase inhibitors on all-cause mortality and major cardiovascular events (MACE).Data synthesisA Medline, Embase, Cochrane database searching for alpha-glucosidase inhibitors was performed up to July 1st, 2021. All randomized controlled trials (RCT) with a duration ≥52 weeks and comparing the effects of alpha-glucosidase inhibitors with placebo or active drugs were collected. Further inclusion criteria were: RCT reporting MACE within their primary outcome, or as pre-defined secondary outcome; and RCT enrolling at least 100 patients with T2DM. Mantel-Haenszel odds ratio (MH–OR) with 95% confidence intervals were calculated for the aforementioned outcomes. A total of eight RCTs, enrolling 1124 and 908 patients on alpha-glucosidase inhibitors and comparators, respectively, were identified. No trials reported information on MACE. Treatment with alpha-glucosidase inhibitors was not associated with a significant increase of all-cause mortality compared with other therapies or no therapy/placebo (MH–OR 0.76 [0.28; 2.05]).ConclusionsThe evidence of beneficial or detrimental effects of alpha-glucosidase inhibitors on all-cause mortality and cardiovascular events is not sufficient to draw any conclusions.     

Improvement of glycemic control in type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials

AimDifferent guidelines provide similar, but not identical, therapeutic targets for HbA1c in type 2 diabetes. These targets can also depend from the different pharmacological strategies adopted for intensifying glycemic control.Data synthesisThis meta-analysis includes randomized trials adopting any pharmacological regimen for intensifying glycemic control in T2DM (versus standard of care/placebo), with a trial duration ≥2 years and a between-group HbA1c difference≥0.5%. The primary outcome was to assess the effects of the improvement of glycemic control on major cardiovascular events (MACE), ocular and renal complications, and severe hypoglycemia. Mantel-Haenszel odds ratios (MH–OR) with 95% Confidence Intervals were calculated for all the outcomes considered.We included 13 trials fulfilling the inclusion criteria. The improvement of glycemic control was associated with a lower risk of MACE (MH–OR:0.89 [95%CI 0.85–0.94]) and renal adverse events (MH–OR 0.73 [0.65–0.82]), but not all-cause mortality (MH–OR 0.95 [0.88–1.01]) and ocular adverse complications (MH–OR 0.94 [0.72–1.22]). For glucose-lowering drugs inducing hypoglycemia, a protective effect on the risk of microvascular complications, but not of MACE and all-cause mortality, was observed only for HbA1c ≤ 48 mmol/mol, but with higher risk of severe hypoglycaemia (MH–OR 2.72 [1.79–4.13]). Drugs not inducing hypoglycaemia were associated with a reduction of MACE, renal adverse events, and all-cause mortality, for HbA1c< 7% (no data for lower targets).ConclusionsThe present meta-analysis show that the improvement of glycemic control with drugs not inducing hypoglycemia is associated with a reduction in the risk of long-term chronic vascular and renal complications, and all-cause mortality.     

The angiographic and clinical outcomes after coronary stenting in patients with metabolic syndrome

BackgroundMetabolic syndrome (MetS) is regarded as a risk factor for coronary artery disease (CAD). But the influence of MetS on morbidity and mortality after stent implantation in CAD patients remains unknown.MethodsThis article presents a meta-analysis of available data on the association between the MetS and the risk of angiographic and clinical outcomes following stent implantation.ResultsMetS was associated with a significant increased risk of post-stent all-cause mortality (odd ratio (OR), 2.17, 95% CI, 1.56–3.01), in-lesion restenosis (OR, 1.35, 95% CI, 1.00–1.84) and major adverse cardiac events (MACE) (OR 1.35, 95% CI 1.13–1.61) in CAD patients. Even with drug-eluting stent (DES) implantation, significant increased risk in all-cause mortality (OR, 2.25, 95% CI, 1.61–3.15) and MACE (OR 1.42, 95% CI 1.14–1.76) were remain in patients with MetS. However, the OR of cardiovascular (CV) mortality (1.25, 95% CI 0.71–2.22), MI (1.27, 95% CI 0.87–1.85) and TLR (OR 1.21, 95% CI 0.96–1.53) was not statistically different between the patients with and without metabolic syndrome.ConclusionsMetabolic syndrome is an important risk factor in patients with CAD following stent implantation. Although DES implantation decreased the incidence of angiographic events, further progress in adequate treatment of MetS is still required to improve the clinical outcome.     

Impact of Diabetes Mellitus on Outcomes of Percutaneous Coronary Intervention in Chronic Total Occlusions: A Systematic Review and Meta-Analysis

BackgroundPatients with diabetes mellitus (DM) have a high prevalence of coronary chronic total occlusions (CTOs). We conducted a systematic review and meta-analysis to characterize outcomes after CTO percutaneous coronary intervention (PCI) in patients without or with DM.MethodsPubMed, EMBASE, Cochrane, and Google Scholar were queried for studies comparing non-DM vs. DM patients undergoing attempted CTO PCI. The primary outcome was all-cause mortality at longest follow-up (at least 6 months). Secondary outcomes were major adverse cardiovascular events (MACE) which is a composite endpoint including myocardial infarction, cardiac or all-cause mortality and any revascularization in patients after CTO PCI, target vessel revascularization (TVR), myocardial infarction (MI), Japanese chronic total occlusion (J-CTO) score and prevalence of multivessel (MV) CTO disease. We used a random effects model to calculate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsSixteen studies, including 2 randomized control trials and 14 observational studies, met inclusion criteria. At longest follow-up, all-cause mortality (OR 0.54 [95% CI 0.37–0.80], p < 0.0001) and MACE (OR 0.82 [95% CI 0.72–0.93], p < 0.00001) were significantly lower in non-DM CTO patients. MV CTO disease was less prevalent in patients without DM (OR 0.80 [95% CI 0.69–0.93], p = 0.004). However, there were no differences in MI, TVR and J-CTO score.ConclusionsNon-diabetics undergoing CTO PCI have lower all-cause mortality and MACE than diabetics. Future research may determine if DM control improves diabetics' CTO PCI outcomes.     

Effects of SGLT2 inhibitors on cardiovascular and renal outcomes in type 2 diabetes: A meta-analysis with trial sequential analysis

Background:It is unclear whether there are false positive or negative results in the effects of sodium-glucose transporter 2 (SGLT2) inhibitors on various cardiovascular and renal outcomes in patients with type 2 diabetes. We aimed to explore this issue by a meta-analysis with trial sequential analysis.Methods:We included randomized trials evaluating the effects of SGLT2 inhibitors on cardiorenal endpoints in type 2 diabetic patients. Eight endpoints evaluated in the study were fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, major adverse cardiovascular events (MACE), cardiovascular death or hospitalization for heart failure (CVD or HHF), all-cause death (ACD), cardiovascular death (CVD), hospitalization for heart failure (HHF), and kidney function progression (KFP). Meta-analysis and trial sequential analysis was conducted for each endpoint.Results:Seven randomized trials of SGLT2 inhibitors were included for pooled analysis. Compared with placebo, SGLT2 inhibitors significantly reduced the risk of MACE (HR 0.89, 95% confidence interval [CI] 0.84–0.94), MI (HR 0.91, 95% CI 0.84–0.99), CVD (HR 0.86, 95% CI 0.79–0.93), CVD or HHF (HR 0.77, 95% CI 0.73–0.82), HHF (HR 0.67, 95% CI 0.62–0.74), KFP (HR 0.63, 95% CI 0.56–0.70), and ACD (HR 0.88, 95% CI 0.83–0.94), whereas SGLT2 inhibitors did not have significant effects on stroke (HR 0.98, 95% CI 0.88–1.09). Trial sequential analyses for MI and stroke showed that cumulative Z curve did not cross trial sequential monitoring boundary and required information size, whereas those for the other 6 endpoints showed that cumulative Z curve crossed trial sequential monitoring boundary and/or required information size.Conclusions:Compared with placebo, SGLT2 inhibitors conclusively reduce the risk of MACE, CVD or HHF, ACD, CVD, HHF, and KFP in patients with type 2 diabetes, whereas the effects of SGLT2 inhibitors on MI and stroke are not conclusive and need to be further assessed in future studies with the adequate sample size to reject or accept the effect size.     

Aspirin in the primary prevention of cardiovascular disease on diabetic patients: Systematic review and meta-analysis

AimsThe publication of new trials brought additional data to the controversial topic of aspirin use in diabetic patients for primary prevention. Therefore, we aimed to systematically review all randomized controlled trials evaluating the clinical impact of aspirin in this setting.MethodsWe searched for randomized controlled trials (RCTs) evaluating the impact of aspirin in patients with diabetes in primary prevention, in MEDLINE, EMBASE, CENTRAL (November/2018). The primary outcomes were all-cause mortality and the composite outcome of major adverse cardiovascular events (MACE). A meta-analysis was performed deriving risk ratios (RR) and 95% confidence intervals (CI).ResultsAll-cause mortality was not significantly reduced with RR 0.96 (95% CI 0.90–1.03; 7RCT; 27,595 patients). Regarding MACE, there was an 8% risk reduction (RR 0.92, 95% CI 0.84-0.999; I² = 0%; 8RCT; 29,814 patients). The risks of major bleeding (RR 1.30, 95% CI 1.10–1.53; 2RCTs, 18,019 patients), and major GI bleeding (RR 1.39, 95% CI 1.08–1.80; 2RCTs, 18,019 patients) were significantly increased.The risks of cardiovascular mortality, myocardial infarction, stroke and amputation were not significantly different from control arm.ConclusionsAspirin use among diabetic patients in primary prevention appears was associated with increased risk of major bleeding, a modest decrease of MACE and lack of mortality benefit.     

Radial vs. Femoral Access for Percutaneous Coronary Artery Intervention in Patients With ST-Elevation Myocardial Infarction

BackgroundWe aimed to compare the safety and efficacy of transradial vs transfemoral access for coronary angiography and intervention in patients presenting with ST-segment elevation myocardial infarction (STEMI) without cardiogenic shock.MethodsPubMed, Embase and Cochrane Central were searched for randomized controlled trials (RCTs) comparing outcomes of STEMI patients who underwent transradial angiography (TRA) compared to transfemoral angiography (TFA). Our outcomes of interest were major adverse cardiac events (MACE), all-cause mortality, severe bleeding, access site bleeding, myocardial infarction, stroke, and major vascular complications. Summary statistics are reported as odds ratios (OR) with 95% confidence intervals (CI).ResultsIn a pooled analysis of 17 RCTs with 12,118 randomized patients, the use of transradial compared to transfemoral approach in STEMI patients without cardiogenic shock was associated with a significant reduction in MACE [OR 0.85 (95% CI 0.73–0.99; p = 0.04; NNT = 111; I² = 0%)] and all-cause mortality [OR 0.71 (95% CI 0.57–0.88; p < 0.01; NNT = 111; I² = 0%)]. Severe bleeding [OR 0.57 (95% CI 0.44–0.74; p < 0.01; NNT = 77; I² = 0%)], access-site bleeding [OR 0.39 (95% CI 0.26–0.59; p < 0.01; NNT = 67; I² = 24%)], and major vascular complications [OR of 0.31 (95% CI 0.17–0.55; p < 0.01; NNT = 125; I² = 0%)] were lower in TRA compared to TFA. There was no difference in stroke (0.6% vs 0.5%) or recurrent myocardial infarction (2.01% vs 2.02%) between the two approaches.ConclusionsFor coronary intervention in STEMI patients without cardiogenic shock, there is a clear mortality benefit with the TRA over TFA. Further studies are needed to see if this mortality benefit persists over the long-term.     

Intravenous iron in patients with heart failure and iron deficiency: an updated meta-analysis

Aims

For patients with heart failure (HF) and iron deficiency (ID), randomized trials suggest that intravenous (IV) iron reduces hospitalizations for heart failure (HHF), but uncertainty exists about the effects in subgroups and the impact on mortality. We conducted a meta-analysis of randomized trials investigating the effect of IV iron on clinical outcomes in patients with HF.

Methods and results

We identified randomized trials published between 1 January 2000 and 5 November 2022 investigating the effect of IV iron versus standard care/placebo in patients with HF and ID in any clinical setting, regardless of HF phenotype. Trials of oral iron or not in English were not included. The main outcomes of interest were a composite of HHF and cardiovascular death (CVD), on HHF alone and on cardiovascular and all-cause mortality. Ten trials were identified with 3373 participants, of whom 1759 were assigned to IV iron. IV iron reduced the composite of recurrent HHF and CVD (rate ratio 0.75, 95% confidence interval [CI] 0.61–0.93; p < 0.01) and first HHF or CVD (odds ratio [OR] 0.72, 95% CI 0.53–0.99; p = 0.04). Effects on cardiovascular (OR 0.86, 95% CI 0.70–1.05; p = 0.14) and all-cause mortality (OR 0.93, 95% CI 0.78–1.12; p = 0.47) were inconclusive. Results were similar in analyses confined to the first year of follow-up, which was less disrupted by the COVID-19 pandemic. Subgroup analyses found little evidence of heterogeneity for the effect on the primary endpoint, although patients with transferrin saturation <20% (OR 0.67, 95% CI 0.49–0.92) may have benefited more than those with values ≥20% (OR 0.99, 95% CI 0.74–1.30) (heterogeneity p = 0.07).

Conclusion

In patients with HF and ID, this meta-analysis suggests that IV iron reduces the risk of HHF but whether this is associated with a reduction in cardiovascular or all-cause mortality remains inconclusive.     

Meta-Analysis of Provisional Versus Systematic Double-Stenting Strategy for Left Main Bifurcation Lesions

ObjectiveWe sought to compare the clinical outcomes with provisional versus double-stenting strategy for left main (LM) bifurcation percutaneous coronary intervention (PCI).BackgroundDespite two recent randomized controlled trials (RCTs) and several observational reports, the optimal LM bifurcation PCI technique remains controversial.MethodsPubMed, Cochrane Central Register of Controlled-Trials (CENTRAL), Clinicaltrials.gov, International Clinical Trial Registry Platform were leveraged for studies comparing PCI bifurcation techniques for LM coronary lesions using second-generation drug eluting stents (DES). The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes of interest were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), target vessel or lesion revascularization, and stent thrombosis.ResultsTwo RCTs and 10 observational studies with 7105 patients were included. Median follow-up duration was 42 months (IQR: 25.7). Double stenting was associated with a trend towards higher incidence of MACE (odds ratio [OR] 1.20; 95 % confidence interval [CI] 0.94 to 1.53) compared with provisional stenting. This was mainly driven by higher rates of target lesion revascularization (TLR) (OR 1.50; 95 % CI 1.07 to 2.11). There were no statistically significant differences in the incidence of all-cause mortality, cardiovascular mortality, MI, or stent thrombosis. On subgroup analysis according to the study type, provisional stenting was associated with lower MACE and TLR in observational studies, but not in RCTs.ConclusionFor LM bifurcation PCI using second-generation DES, a provisional stenting strategy was associated with a trend towards lower incidence of MACE driven by statistically significant lower rates of TLR, compared with systematic double stenting. These differences were primarily driven by observational studies. Further RCTs are warranted to confirm these findings.     

Prasugrel vs Ticagrelor for DAPT in Patients with ACS Undergoing PCI: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

IntroductionDual antiplatelet therapy (DAPT) with a P2Y12 inhibitor added to aspirin is considered the standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous intervention (PCI). Prasugrel and ticagrelor are commonly used P2Y12 inhibitors, and a few head-to-head randomized control trials (RCTs) have been performed. We performed a systematic review and meta-analysis of these RCTs to compare the efficacy and adverse effects between these two agents when used in patients with ACS undergoing PCI.MethodsWe searched PubMed/MEDLINE and Cochrane library for RCTs comparing prasugrel to ticagrelor in ACS. The primary endpoint was major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stent thrombosis, major bleeding, and all bleeding event. Estimates were calculated as random effects risk ratios (RRs) with 95% confidence intervals (CI).ResultsSix trials with 6807 patients were included. There were no significant difference of MACE (RR 0.93; 95% CI [0.72–1.20]; p = 0.59; I² = 26%), all-cause mortality (RR 0.92; 95% CI [0.73–1.17]; p = 0.51; I² = 0%), cardiovascular mortality (RR 0.99; 95% CI [0.75–1.31]; p = 0.96; I² = 0%), MI (RR 0.87; 95% CI [0.60–1.27]; p = 0.48; I² = 27%), stent thrombosis (RR 0.64; 95% CI [0.39–1.04]; p = 0.07; I² = 0%), major bleeding (RR 0.94; 95% CI [0.70–1.26]; p = 0.68; I² = 6%), and all bleeding event (RR 0.92; 95% CI [0.77–1.09]; p = 0.32; I² = 0%) for prasugrel compared with ticagrelor.ConclusionThere are no significant difference of MACE, all-cause mortality, cardiovascular mortality, MI, stent thrombosis, and bleeding between prasugrel and ticagrelor when added to aspirin among patients with ACS undergoing PCI.     

Drug-Eluting Stents Versus Bare-Metal Stents in Large Coronary Artery Revascularization: Systematic Review and Meta-Analysis

ObjectivesWe aim to determine if drug eluting stents (DES) are better than bare-metal stents (BMS) in large coronary artery (diameter ≥ 3 mm) percutaneous coronary intervention (PCI).BackgroundDES have become the standard of care for PCI in coronary artery disease (CAD). However, the superiority of DES over BMS in large vessel CAD is not clear and previous studies have shown conflicting results.MethodsRandomized controlled trials (RCTs) comparing outcomes of PCI with BMS and DES for large vessel CAD were identified from the year 2000 to August 2019. The outcomes were studied individually and included all-cause mortality, myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis. Aggregated odds ratio and 95% CI were calculated using a random-effects model.ResultsEight RCTs were included (4 with data for first-generation DES, 3 with data for second-generation DES, and 1 with data for both first- and second-generation DES). Compared to BMS, second generation DES had a significantly lower rate of all-cause mortality (2.4% vs. 3.9%, OR 0.74, 95% CI 0.56–0.98, P 0.04), TLR (3.5% vs. 8.6% OR 0.38 95% CI 0.28–0.53, P < 0.001), and MI (2.1% vs. 2.9% OR 0.73 95% CI 0.53–1.0, P 0.05). The difference in all-cause mortality was not seen with first-generation DES.ConclusionNewer DES are associated with a lower mortality, TLR, and MI and thus should be preferred over BMS for large coronary artery PCI.     

Outcomes With Drug-Coated Balloons vs. Drug-Eluting Stents in Small-Vessel Coronary Artery Disease

BackgroundThe use of drug-coated balloons (DCBs) in small-vessel coronary artery disease (SVD) remains controversial.MethodsWe performed a meta-analysis of all randomized controlled trials (RCTs) reporting the outcomes of DCB vs. DES in de-novo SVD. We included a total of 5 RCTs (1459 patients), with (DCB n = 734 and DES n = 725).ResultsOver a median follow-up duration of 6 months, DCB was associated with smaller late lumen loss (LLL) compared with DES (mean difference −0.12 mm) (95% confidence intervals (CI) [−0.21, −0.03 mm], p = 0.01). Over a median follow-up of 12 months, both modalities had similar risk of major adverse cardiovascular events (MACE) (8.7% vs. 10.2%; odds ratio (OR): 0.94, 95% CI [0.49–1.79], p = 084), all-cause mortality (1.17% vs. 2.38%; OR: 0.53, 95% CI [0.16–1.75], p = 0.30), target lesion revascularization (TLR) (7.9% vs. 3.9%; OR: 1.26, 95% CI [0.51–3.14], p = 0.62), and target vessel revascularization (TVR) (8.2% vs. 7.8%; OR: 1.06, 95% CI [0.40–2.82], p = 0.91). DCBs were associated with lower risk of myocardial infarction (MI) compared with DES (1.55% vs. 3.31%; OR: 0.48, 95% CI [0.23–1.00], p = 0.05, I2 = 0%).ConclusionPCI of SVD with DCBs is associated with smaller LLL, lower risk of MI, and similar risk of MACE, death, TLR, and TVR compared with DES over one year. DCB appears as an attractive alternative to DES in patients with de-novo SVD, but long-term clinical data are still needed.     

Comparison of glucagons like peptide-1 receptor agonists and dipeptidyl peptide-4 inhibitors regarding cardiovascular safety and mortality in type 2 diabetes mellitus: A network meta-analysis

AimThe effects of dipeptidyl peptide-4 inhibitors (DPP-4is) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) on type 2 diabetes mellitus (T2DM) on cardiovascular events and all-cause mortality were compared.MethodsThe literature on DPP-4is and SGLT-2is treatment of T2DM was searched through Pubmed, Embase, and the web of science databases with the search deadline May 15, 2020. Network meta-analysis (NMA) was used to compare the effects of two types of inhibitors on cardiovascular events (major adverse cardiovascular events (MACE), nonfatal myocardial infarction (MI), nonfatal stroke, and cardiovascular (CV) death) and all-cause mortality in T2DM patients.ResultsA total of 15 articles were screened, including 125,796 patients. Compared with DPP-4is, SGLT-2is can significantly reduce MACE [OR: 0.86 95% CI (0.78, 0.92)], CV death [OR: 0.85 95% CI (0.71, 1.01)], nonfatal MI [OR: 0.84 95%CI (0.74, 0.95)] and all-cause mortality [OR: 0.78 95% CI (0.69, 0.89)]. For nonfatal stroke, DPP-4is and SGLT-2is have no statistically significant difference [OR: 0.99 95% CI (0.91, 1.07)].ConclusionThese data indicate that SGLT-2is is more beneficial to MACE and all-cause mortality in T2DM patients than DPP-4is.     

Comparison of Rotational with Orbital Atherectomy During Percutaneous Coronary Intervention for Coronary Artery Calcification: A Systematic Review and Meta-Analysis

BackgroundPercutaneous coronary intervention (PCI) outcomes for patients with significant calcification have been consistently inferior compared to patients without significant calcification. Procedural success and long-term outcomes after PCI have been worse in patients with severe coronary calcium.ObjectiveA Bayesian meta-analysis of outcomes comparing rotational atherectomy (RA) with orbital atherectomy (OA) was performed.MethodsPubMed, Embase, and Cochrane Library databases were searched through 30th November 2018 and identified 4 observational studies.ResultsThe primary end-point, Major Adverse Cardiac Event (MACE) composing of death, MI and stroke at 1 year was more likely with RA (OR = 1.61; 95% CI: 1.11–2.33; p = 0.01) as compared to OA. The driver of the difference in MACE between the two groups was a statistically significant difference in mortality favoring OA (OR = 4.65; 95% CI: 1.36–15.87; p = 0.01). Peri-procedural MI, the other component of the primary end-point was 1.3 times more likely in the RA arm (OR = 1.35; 95% CI 0.95–1.92; p-0.09) and was not statistically different between the groups. The odds of a vascular complication were not different in the two groups (OR = 1.26; 95% CI: 0.73–2.17; p = 0.41).In an adjusted Bayesian analysis, mortality (OR = 3.69; 95% CI: 0.30–38.51), MACE (OR = 1.68; 95% CI: 0.55–5.49), MI (OR = 1.42; 95% CI: 0.50–4.29) and dissections/perforations (OR = 0.38; 95% CI: 0.10–1.38) were not different in RA and OA groups.ConclusionOur study is the first published Bayesian meta-analysis comparing MACE and peri-procedural outcomes in RA compared to OA. These findings lay the foundation for a randomized comparison between the two competing technologies.     

Association of N-terminal pro-brain natriuretic peptide level with adverse outcomes in patients with acute myocardial infarction: A meta-analysis

BackgroundStudies evaluating the association of blood level of N-terminal pro-brain natriuretic peptide (NT-proBNP) with adverse prognosis have yielded conflicting results in patients with acute myocardial infarction (AMI). This meta-analysis sought to evaluate the prognostic value of blood level of NT-proBNP in patients with AMI.MethodsTwo authors independently searched articles in PubMed and Embase databases up to June 13, 2021. Studies evaluating the association of baseline NT-proBNP level with all-cause mortality or major adverse cardiovascular events (MACEs, including death, new or worsening heart failure, recurrent myocardial infarction, revascularization, stroke, etc.) among AMI patients were selected. Multivariable-adjusted risk ratio (RR) with 95% confidence interval (CI) was pooled by the highest vs. lowest category of NT-proBNP level.ResultsA total of 19 studies enrolling 12,158 AMI patients were identified. When compared highest with the lowest category of NT-proBNP level, the pooled RR was 5.28 (95% CI 2.87–9.73) for in-hospital/30-day death, 2.62 (95% CI 2.04–3.37) for follow-up all-cause mortality, and 2.50 (95% CI 1.91–3.28) for follow-up MACEs, respectively. Subgroup analysis further confirmed the value of NT-proBNP in predicting all-cause mortality and MACEs.ConclusionsElevated NT-proBNP level is independently associated with an increased risk of all-cause mortality and MACEs. Determination of blood NT-proBNP level can improve risk stratification of AMI patients.     

Association between uric acid levels and cardio-renal outcomes and death in patients with type 2 diabetes: A subanalysis of EMPA-REG OUTCOME

In the EMPA-REG OUTCOME trial, we explored the association between pre-randomization uric acid level tertile (<309.30 μmol/L; 309.30 to <387.21 μmol/L; ≥387.21 μmol/L) and cardiovascular (CV) death, hospitalization for heart failure (HHF), HHF or CV death, all-cause mortality, three-point major adverse CV events (MACE), and incident or worsening nephropathy. Patients with type 2 diabetes and CV disease received empagliflozin or placebo. The median baseline plasma uric acid level was 344.98 μmol/L, and patients’ baseline characteristics were mainly balanced across tertiles. Baseline uric acid levels were associated with cardio-renal outcomes: in the placebo group, for the highest versus lowest tertile, the multivariable hazard ratios for three-point MACE, HHF or CV death, and incident or worsening nephropathy were 1.22 (95% confidence interval [CI] 0.89–1.67; P = 0.2088), 1.51 (95% CI 1.02–2.23; P = 0.0396) and 1.77 (95% CI 1.33–2.34; P < 0.0001), respectively. When tested as a continuous variable, baseline uric acid was associated with all outcomes in the placebo group. Empagliflozin improved all cardio-renal outcomes across tertiles, with all interaction P values >0.05. Further investigation of these relationships is required.     

Efficacy and Safety of Low-Dose Prasugrel Versus Clopidogrel in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: a Systematic Review and Meta-analysis

Purpose

To assess the efficacy and safety of low-dose prasugrel compared to clopidogrel based on the occurrence of major adverse cardiac events (MACEs) and major bleeding in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI).

Methods

The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were systematically searched up to May 2020 to identify relevant randomized controlled trials (RCTs) and observational studies. A meta-analysis was conducted using a random effects model to estimate relative risks (RRs) with 95% confidence intervals (CIs). The primary efficacy and safety endpoints were MACE and major bleeding, respectively.

Results

Three RCTs (n?=?2884) and five observational studies (n?=?30,117) were included. A meta-analysis of RCTs revealed no significant differences in terms of MACE (RR 0.92, 95% CI 0.74 to 1.16) or major bleeding (RR 0.97, 95% CI 0.57 to 1.65) between low-dose prasugrel and clopidogrel. A meta-analysis of observational studies revealed no significant difference in terms of MACE (RR 1.13, 95% CI 0.82 to 1.55) between the two groups, but low-dose prasugrel was associated with a significantly increased risk of major bleeding (RR 1.33, 95% CI 1.02 to 1.72).

Conclusions

We found that low-dose prasugrel was not associated with changes in MACE or major bleeding compared with clopidogrel in RCTs. However, analysis of data from observational studies revealed that low-dose prasugrel was associated with an increased risk of major bleeding compared with clopidogrel.