A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with or without statins for cardiovascular outcomes

2018 ◽  
Vol 25 (8) ◽  
pp. 844-853 ◽  
Author(s):  
Safi U Khan ◽  
Swapna Talluri ◽  
Haris Riaz ◽  
Hammad Rahman ◽  
Fahad Nasir ◽  
...  

Background The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design Bayesian network meta-analysis was conducted to compare treatment groups. Methods Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception – September 2017). Results In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55–0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62–0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49–0.79; GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major adverse cardiovascular event reduction in secondary prevention trials (SUCRA, 95%). Statins had the highest probability of having lowest rates of all-cause mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83–0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77–0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as the second best treatment (SUCRA, 78%) followed by ezetimibe + statin (SUCRA, 50%). Conclusion PCSK9 inhibitors were ranked as the most effective treatment for reducing major adverse cardiovascular events, myocardial infarction and stroke, without having major safety concerns. Statins were ranked as the most effective therapy for reducing mortality.

BMJ ◽  
2020 ◽  
pp. m3342 ◽  
Author(s):  
Kristian B Filion ◽  
Lisa M Lix ◽  
Oriana HY Yu ◽  
Sophie Dell’Aniello ◽  
Antonios Douros ◽  
...  

Abstract Objective To compare the risk of cardiovascular events between sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors among people with type 2 diabetes in a real world context of clinical practice. Design Multi-database retrospective cohort study using a prevalent new user design with subsequent meta-analysis. Setting Canadian Network for Observational Drug Effect Studies (CNODES), with administrative healthcare databases from seven Canadian provinces and the United Kingdom, 2013-18. Population 209 867 new users of a SGLT2 inhibitor matched to 209 867 users of a DPP-4 inhibitor on time conditional propensity score and followed for a mean of 0.9 years. Main outcome measures The primary outcome was major adverse cardiovascular events (MACE, a composite of myocardial infarction, ischaemic stroke, or cardiovascular death). Secondary outcomes were the individual components of MACE, heart failure, and all cause mortality. Cox proportional hazards models were used to estimate site specific adjusted hazards ratios and 95% confidence intervals, comparing use of SGLT2 inhibitors with use of DPP-4 inhibitors in an as treated approach. Site specific results were pooled using random effects meta-analysis. Results Compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with decreased risks of MACE (incidence rate per 1000 person years: 11.4 v 16.5; hazard ratio 0.76, 95% confidence interval 0.69 to 0.84), myocardial infarction (5.1 v 6.4; 0.82, 0.70 to 0.96), cardiovascular death (3.9 v 7.7; 0.60, 0.54 to 0.67), heart failure (3.1 v 7.7; 0.43, 0.37 to 0.51), and all cause mortality (8.7 v 17.3; 0.60, 0.54 to 0.67). SGLT2 inhibitors had more modest benefits for ischaemic stroke (2.6 v 3.5; 0.85, 0.72 to 1.01). Similar benefits for MACE were observed with canagliflozin (0.79, 0.66 to 0.94), dapagliflozin (0.73, 0.63 to 0.85), and empagliflozin (0.77, 0.68 to 0.87). Conclusions In this large observational study conducted in a real world clinical practice context, the short term use of SGLT2 inhibitors was associated with a decreased risk of cardiovascular events compared with the use of DPP-4 inhibitors. Trial registration ClinicalTrials.gov NCT03939624 .


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 174-174
Author(s):  
Nina C Raju ◽  
Magda Sobieraj-Teague ◽  
John W Eikelboom

Abstract Abstract 174 Primary prevention with aspirin reduces the risk of non-fatal cardiovascular events but has not been demonstrated to reduce mortality. We performed an updated meta-analysis of randomised controlled trials of aspirin in primary prevention to obtain best estimates of the benefits and harm of aspirin compared with no aspirin with a focus on mortality. Eligible articles were identified by computerized search of MEDLINE, EMBASE, Cochrane library and CINAHL databases, review of bibliographies of relevant publications and a related article search using PubMed. The outcomes of interest included all cause mortality, cardiovascular mortality, the composite of myocardial infarction, stroke or death, and bleeding. 2 reviewers independently extracted study information and data. Data were pooled from individual trials using the DerSimonian-Laird random-effects model and results are presented as relative risk (RR) and 95% confidence intervals (CI). 8 studies comprising a total of 96,726 subjects were included. Aspirin reduced all-cause mortality (RR 0.94; 95%CI 0.88–1.00), the composite of myocardial infarction, stroke or cardiovascular death (RR 0.87; 95%CI 0.82–0.93), and myocardial infarction (RR 0.8; 95%CI 0.66–0.98) but did not significantly reduce cardiovascular mortality (RR 0.94; 95%CI 0.82–1.08) or stroke (RR 0.93; 95%CI 0.81–1.07). Aspirin increased the risk of major bleeding (RR; 1.69 95%CI 1.38–2.08), gastrointestinal bleeding (RR 1.38; 95%CI 1.16–1.65) and hemorrhagic stroke (RR 1.36; 95%CI 1.01–1.84). There was no interaction between subjects with or without diabetes for the outcomes of all cause mortality, cardiovascular mortality, the composite of myocardial infarction, stroke or death. Aspirin therapy in subjects with no prior history of cardiovascular disease reduces the risk of cardiovascular events, myocardial infarction and overall mortality. These benefits are achieved at the expense of increased bleeding. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Author(s):  
Mei-Chuan Lee ◽  
Yi-Ming Hua ◽  
Chun-Ting Yang ◽  
Wei-Ting Chang ◽  
Fang-Hsiu Kuo ◽  
...  

Abstract BackgroundHeart failure (HF) has become a healthcare challenge worldwide. Recently, certain trials on sodium-glucose co-transporter-2 (SGLT2) inhibitor showed benefits for patients with HF. This study aimed to systematically review the literature and investigate the clinical efficacy of SGLT2 inhibitors in cardiovascular events among patients with and without HF. Methods We searched randomized controlled trials (RCTs) in PubMed, Cochrane databases, Embase, and ClinicalTrials.gov registry form inception to October 2020. Dichotomous variables were pooled using a random-effects model and presented with a risk ratio (RR) and 95% confidence interval (CI). Subgroup meta-analyses were carried out by high/low SGLT2/SGLT1 selectivity and individual SGLT2 inhibitor.ResultsA total of 10 RCTs comprised of 52,607 patients were eligible for the analyses. SGLT2 inhibitors reduced the risk of total cardiovascular death or hospitalization for HF (RR 0.79, [95% CI: 0.74 to 0.84]; p < 0.01, I2 = 31%). Apart from stroke, SGLT2 inhibitors contributed to a risk reduction in major adverse cardiovascular events (MACE, RR 0.93, [95% CI: 0.88 to 0.99]; p = 0.03, I2 = 0), all-cause mortality (RR 0.92, [95% CI: 0.85 to 0.99]; p = 0.03, I2 = 0), cardiovascular death (RR 0.91, [95% CI: 0.83 to 0.99]; p = 0.03, I2 = 0), hospitalization for HF (RR 0.72, [95% CI: 0.66 to 0.79]; p < 0.01, I2 = 0), and myocardial infarction (RR 0.89, [95% CI: 0.80 to 0.99]; p = 0.03, I2 = 0). For HF patients, SGLT2 inhibitors had more clinical benefits in terms of all-cause mortality and cardiovascular death, while advantages were observed in MACE and myocardial infarction for non-HF patients. Furthermore, SGLT2 inhibitors with low SGLT2/SGLT1 selectivity have better efficacy for hospitalization of HF, compared with high-selectivity inhibitors (RR 0.51 [95% CI: 0.35-0.75] versus 0.73 [95% CI: 0.66-0.81] for HF patients). ConclusionsSGLT2 inhibitors significantly mitigate hospitalization for HF. Between HF and non-HF populations, this regimen reduce mortality for HF patients and improve MACE and myocardial infarction for non-HF patients. The SGLT2 inhibitor, mixed with the effect of SGLT1 inhibitors, may lead to a lower risk of hospitalization for HF.


2021 ◽  
Vol 8 ◽  
Author(s):  
Zhuo-Ming Huang ◽  
Wen-Rong Chen ◽  
Qi-Wen Su ◽  
Zhuo-Wen Huang

Background: The metabolic syndrome (MS) is significantly associated with the risk of incident heart failure (HF). However, there are still great controversies about the impact of MS on the prognosis in patients with established HF. This meta-analysis aimed to ascertain the effect of MS on the prognosis in patients with HF.Methods: We searched multiple electronic databases, including PubMed, Opengrey, EMBASE, and Cochran Library, for potential studies up to February 15, 2021. Observational studies that reported the impact of MS on the prognosis in patients with established HF were included for meta-analysis.Results: Ten studies comprising 18,590 patients with HF were included for meta-analysis. The median follow-up duration of the included studies was 2.4 years. Compared with HF patients without MS, the risk of all-cause mortality and cardiovascular mortality was not increased in HF with MS (HR = 1.04, 95% CI = 0.88–1.23 for all-cause mortality; HR = 1.66, 95% CI = 0.56–4.88 for cardiovascular mortality, respectively). However, there was a significant increase in composited cardiovascular events in the HF patients with MS compared with those without MS (HR = 1.73, 95% CI = 1.23–2.45).Conclusions: In patients with established HF, the presence of MS did not show an association on the risk of all-cause mortality or cardiovascular mortality, while it may increase the risk of composite cardiovascular events.


2020 ◽  
Vol 48 (6) ◽  
pp. 030006052092634 ◽  
Author(s):  
Chuannan Zhai ◽  
Kai Hou ◽  
Rui Li ◽  
YueCheng Hu ◽  
JingXia Zhang ◽  
...  

Objective Statins have been shown to be beneficial for the prevention of cardiovascular events. In elderly individuals, the efficacy of statins remains controversial and the comparative effect of statins has not been assessed. Methods MEDLINE, Embase, and the Cochrane Central database were searched for randomized controlled trials that assessed statins in older patients. Results Seventeen trials were analyzed. When used for secondary prevention, statins were associated with reduced risk of cardiovascular events, all-cause mortality, cardiovascular mortality, revascularization, and stroke. When used for primary prevention, statins reduced the risk of myocardial infarction and revascularization, but did not significantly affect other outcomes. A modest difference between pharmaceutical statin products was found, and high-quality evidence indicated that intensive atorvastatin had the greatest benefits for secondary prevention. Conclusions In secondary prevention, evidence strongly suggests that statins are associated with a reduction in the risk of all-cause mortality, cardiovascular events, cardiovascular mortality, and revascularization. However, differences in the effects of various statins do not appear to have significant effects on therapy in secondary prevention for the elderly.


BMC Medicine ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Georg Gelbenegger ◽  
Marek Postula ◽  
Ladislav Pecen ◽  
Sigrun Halvorsen ◽  
Maciej Lesiak ◽  
...  

Abstract Background The role of aspirin in primary prevention of cardiovascular disease (CVD) remains unclear. We aimed to investigate the benefit-risk ratio of aspirin for primary prevention of CVD with a particular focus on subgroups. Methods Randomized controlled trials comparing the effects of aspirin for primary prevention of CVD versus control and including at least 1000 patients were eligible for this meta-analysis. The primary efficacy outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, major adverse cardiovascular events (MACE), myocardial infarction, ischemic stroke, and net clinical benefit. The primary safety outcome was major bleeding. Subgroup analyses involving sex, concomitant statin treatment, diabetes, and smoking were performed. Results Thirteen randomized controlled trials comprising 164,225 patients were included. The risk of all-cause and cardiovascular mortality was similar for aspirin and control groups (RR 0.98; 95% CI, 0.93–1.02; RR 0.99; 95% CI, 0.90–1.08; respectively). Aspirin reduced the relative risk (RRR) of major adverse cardiovascular events (MACE) by 9% (RR 0.91; 95% CI, 0.86–0.95), myocardial infarction by 14% (RR 0.86; 95% CI, 0.77–0.95), and ischemic stroke by 10% (RR 0.90; 95% CI, 0.82–0.99), but was associated with a 46% relative risk increase of major bleeding events (RR 1.46; 95% CI, 1.30–1.64) compared with controls. Aspirin use did not translate into a net clinical benefit adjusted for event-associated mortality risk (mean 0.034%; 95% CI, − 0.18 to 0.25%). There was an interaction for aspirin effect in three patient subgroups: (i) in patients under statin treatment, aspirin was associated with a 12% RRR of MACE (RR 0.88; 95% CI, 0.80–0.96), and this effect was lacking in the no-statin group; (ii) in non-smokers, aspirin was associated with a 10% RRR of MACE (RR 0.90; 95% CI, 0.82–0.99), and this effect was not present in smokers; and (iii) in males, aspirin use resulted in a 11% RRR of MACE (RR 0.89; 95% CI, 0.83–0.95), with a non-significant effect in females. Conclusions Aspirin use does not reduce all-cause or cardiovascular mortality and results in an insufficient benefit-risk ratio for CVD primary prevention. Non-smokers, patients treated with statins, and males had the greatest risk reduction of MACE across subgroups. Systematic review registration PROSPERO CRD42019118474.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L.M Lobo ◽  
G Masson ◽  
G Molinero ◽  
G Masson ◽  
A Lavalle Cobo ◽  
...  

Abstract Background Colchicine is a microtubule inhibitor with anti-inflammatory proprieties. As the body and quality of evidence regarding the efficacy of colchicine for cardiovascular prevention is controversial, the aims of this study was to evaluate the effect of colchicine therapy on vascular events. Methods A meta-analysis was performed of randomized controlled clinical trials of colchicine on high cardiovascular risk populations, reporting data from stroke, myocardial infarction, cardiovascular mortality and all-cause mortality, after searching the PubMed/MEDLINE, Embase and Cochrane Controlled Trials databases. A random-effects meta-analysis model was then applied. Results Nine eligible trials of colchicine therapy, involving a total of 6630 patients, were considered eligible for analysis (3359 subjects were allocated to receive colchicine while 3271 subjects were allocated to the respective control arms). The stroke incidence was lower in the colchicine group compared with placebo arm (OR, 0.33; 95% CI, 0.15–0.70; six studies evaluated). We did not find a significant reduction in the incidence of myocardial infarction, cardiovascular mortality or all-cause mortality. Conclusion Our data suggest that in a population with high cardiovascular risk, the use of colchicine results in significantly reduction on stroke risk. Colchicine is an accessible drug that could be successfully utilized for the prevention of atherosclerotic cerebrovascular disease. The tolerability and benefits should be confirmed in ongoing clinical trials. Forest Plot Primary endpoint Funding Acknowledgement Type of funding source: None


2019 ◽  
Vol 48 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Jingjing Jin ◽  
Xiaoyang Guo ◽  
Qiyao Yu

Background: The effects of beta-blockers are uncertain in dialysis patients. Except antihypertension, β-blockers may play a unique cardiovascular protective role in the population. This meta-analysis aimed to explore the effects of β-blockers therapy in adult patients treated with dialysis. Methods: We searched MEDLINE, EMBASE, and the Cochrane library from inception to May 2018 for randomized controlled trials (RCTs) and observational studies about the role of β-blockers on all-cause mortality, cardiovascular mortality, cardiovascular events, or hospitalizations in dialysis population. Results: Three RCTs and 9 observational studies met the predefined inclusion criteria. The RCTs showed significant association between β-blockers and reduced all-cause mortality (n = 363; risk ratio [RR] 0.73; 95% CI 0.54–0.97), cardiovascular mortality (n = 314; RR 0.44; 95% CI 0.29–0.68), cardiovascular events (n = 363; RR 0.52; 95% CI 0.31–0.88), or hospitalizations (n = 314; RR 0.61; 95% CI 0.48–0.78) in dialysis patients. The observational studies showed significant difference in all-cause mortality (n = 35,233; hazard ratio [HR] 0.86; 95% CI 0.80–0.92) between β-blockers and no β-blockers therapy in patients with dialysis, while the studies showed no difference in cardiovascular mortality (n = 19,413; HR 0.79; 95% CI 0.57–1.11), or cardiovascular events (n = 87,060; HR 0.79; 95% CI 0.50–1.26). Conclusions: β-blockers seem to be associated with reduced mortality in patients on dialysis. Both the statistical heterogeneity in observational studies and the small number of participants and studies in RCTs limit the strength of these findings. Video Journal Club “Cappuccino with Claudio Ronco” at  https://www.karger.com/Journal/ArticleNews/496083?sponsor=52


2018 ◽  
Vol 26 (5) ◽  
pp. 533-543 ◽  
Author(s):  
Haris Riaz ◽  
Safi U Khan ◽  
Hammad Rahman ◽  
Nishant P Shah ◽  
Edo Kaluski ◽  
...  

Background The effects of increasing high-density lipoprotein cholesterol on cardiovascular outcomes remain uncertain. Design We conducted a meta-analysis to investigate the effects of high-density lipoprotein cholesterol modifiers (niacin, fibrates and cholesteryl ester transfer protein inhibitors) on cardiovascular outcomes. Methods Thirty-one randomized controlled trials (154,601 patients) with a follow-up of 6 months or more and a sample size of 100 or more patients were selected using MEDLINE, EMBASE and CENTRAL database (inception January 2018). Results High-density lipoprotein cholesterol modifiers had no statistically significant effect on cardiovascular mortality in terms of relative risk (RR) (RR 0.94, 95% confidence interval (CI) 0.89–1.00, P = 0.05, I2 = 13%) or absolute risk (risk difference −0.0001, 95% CI −0.0014, 0.0011, P = 0.84, I2 = 28%). High-density lipoprotein cholesterol modifiers reduced the RR of myocardial infarction (RR 0.87, 95% CI 0.82–0.93, P < 0.001, I2 = 37%). This significant effect was derived by the use of fibrates (RR 0.80, 95% CI 0.73–0.87, P < 0.001, I2 = 22%) and meta-regression analysis showed that this benefit was consistent with an absolute reduction in low-density lipoprotein cholesterol. High-density lipoprotein cholesterol modifiers had no effect on stroke (RR 1.00, 95% CI 0.93–1.09, P = 0.94, I2 = 25%) or all-cause mortality (RR 1.02, 95% CI 0.97–1.08, P = 0.48, I2 = 49%). Meta-regression analyses failed to demonstrate a significant association of pharmacologically increased high-density lipoprotein cholesterol with key endpoints. In studies with background statin therapy, high-density lipoprotein cholesterol modifiers had no statistically significant impact on cardiovascular mortality, myocardial infarction, stroke or all-cause mortality ( P > 0.05). Conclusion The use of high-density lipoprotein cholesterol modifying treatments had no significant effect on cardiovascular mortality, stroke or all-cause mortality. The beneficial effect on myocardial infarction was lost when drugs were used with statin therapy.


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