Increased prevalence of cardiovascular risk factors in children and adolescents with type 1 diabetes and hypertension: The SWEET international database.

AIMS: To investigate the prevalence of modifiable cardiovascular risk factors (CVRFs), including dyslipidaemia, obesity and high glycated haemoglobin (HbA1c) concentration, in patients with type 1 diabetes (T1D), and to evaluate their association with blood pressure (BP) categories. METHODS: We analysed 21 634 children and adolescents with T1D from the SWEET international database with office BP values assessed at a three or more visits within a year from 2010 to 2021. Participants were classified into a normotensive group, a group with elevated BP (90 to 94th percentile) or a hypertensive group (≥95th percentile), based on the median BP for the visits within the last treatment year. The prevalences of dyslipidaemia [cholesterol ≥ 5.18 mmol/L (200 mg/dL)  and/or HDL cholesterol ≤ 1.036 mmol/L (40 mg/dL)  and/or LDL cholesterol ≥ 2.59 mmol/L (100 mg/dL)], obesity (body mass index ≥2 standard deviation score) and elevated HbA1c [≥ 75 mmol/mol (9%)] were evaluated in patients within each BP group. RESULTS: Patients with hypertension/elevated BP had less favourable lipid profiles, and a higher prevalence of obesity and HbA1c ≥ 75 mmol/mol than normotensive patients. A total of 38.4% of hypertensive patients and 36.0% of those with elevated BP had one CVRF, 15.1% and 10.1%, respectively, had two CVRFs, and 2.3% and 0.8%, respectively, had three CVRFs. Patients with hypertension/elevated BP had a higher prevalence of one or more CVRFs versus normotensive patients (P < 0.001). Obesity was the CVRF most strongly related to hypertension. Girls had a higher prevalence of one or more CVRFs than boys. Similar results were found in patients aged ≥13 years with hypertension compared to those aged <13 years. CONCLUSIONS: The prevalence of modifiable CVRFs is higher in children and adolescents with T1D who have elevated BP/hypertension than in those with normotension, suggesting that they are more vulnerable to future morbidity and mortality requiring early detection and intervention.

One "misunderstood" health issue: demonstrating and communicating the safety of influenza a vaccination in pregnancy: a systematic review and meta-analysis.

BACKGROUND: The American College of Obstetricians and Gynecologists (ACOG) makes certain recommendations including the annual influenza vaccination of pregnant and pre-pregnant women during influenza (flu) season with an inactivated influenza vaccine as soon as it becomes available. The Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices in association with ACOG state that the vaccine is safe to be given any trimester during pregnancy. However, due to a lack of communication, the public is unaware of the effects of influenza A vaccination in pregnancy. Since this is a vital public health concern, we aimed to communicate with evidence, the safety of influenza A vaccination in pregnancy in order to improve the rate of influenza A vaccines in pregnant women. METHODS: This health communication issue was based on the impact of influenza vaccine on fetal outcomes. Therefore, a search was carried out through medical-based online databases including: Cochrane Central, EMBASE, Web of Science, MEDLINE, http://www.ClinicalTrials.gov , and Google scholar for relevant English-based publications. Adverse fetal outcomes were considered as the endpoints of this analysis. The most specific RevMan 5.3 (latest version) software was used to carry out this analysis. Risk ratios (RR) with 95% confidence intervals (CI) were involved in data and results representation and interpretation. RESULTS: A total number of 679, 992 pregnant women participated in this analysis. Based on this current analysis, premature/preterm birth (< 37 weeks) was significantly reduced in pregnant women who were vaccinated for influenza A (RR: 0.80, 95% CI: 0.69-0.92; P = 0.002) as compared to those women who were not vaccinated. Similarly, influenza A vaccination decreased the risk for very preterm birth (< 32 weeks) (RR: 0.70, 95% CI: 0.58-0.84; P = 0.0001). The risks for infants with low birth weight (RR: 0.71, 95% CI: 0.49-1.04; P = 0.08), very low birth weight (RR: 0.69, 95% CI: 0.23-2.11; P = 0.52) and infants small for gestational age (RR: 0.93, 95% CI: 0.83-1.05; P = 0.26) were not increased with the vaccine. Influenza A vaccination was not associated with increased risks of stillbirth (RR: 0.63, 95% CI: 0.38-1.03; P = 0.07), birth defects (RR: 0.67, 95% CI: 0.26-1.72; P = 0.41), admission to neonatal intensive care unit or Apgar score < 7 in 5 min. CONCLUSION: Influenza vaccine is completely safe in pregnancy. It significantly lowers premature birth and is not associated with any serious adverse neonatal outcome. Hence, this important piece of information should be communicated and conveyed to all pregnant women, for a safer and healthier pregnancy. At last, this public health issue should further be addressed to the population through media and other communication means in order to improve the rate of influenza A vaccines in pregnant women for a healthier and more productive population.

Tobacco smoking and semen quality in infertile males: a systematic review and meta-analysis.

BACKGROUND: Nowadays, the total number of couples visiting an infertility clinic is on the rise. Tobacco smoking is considered one of the major factors leading to male infertility. In this study, we aimed to systematically investigate the impact of tobacco smoking on semen quality in infertile male participants. METHODS: Online databases (Cochrane Central database of Randomized Controlled Trials and the databases of MEDLINE and EMBASE respectively) were searched for relevant English publications that satisfied the inclusion and exclusion criteria of this analysis. The clinical endpoints which were assessed included semen parameters (oligozoospermia, asthenozoospermia, teratozoospermia, and azoospermia), morphological defects of spermatozoa and the hormones involved in reproduction. RevMan 5.3 software was used to analyze the data whereby mean difference (MD) and risk ratios (RR) with 95% confidence intervals (CI) were generated to represent the results. RESULTS: Sixteen studies with a total number of 10,823 infertile male participants (5257 smokers and 5566 non-smokers) were included. Results of this analysis showed oligozoospermia to be significantly higher in smokers (RR: 1.29, 95% CI: 1.05-1.59; P = 0.02). Morphological defect of spermatozoa (MD: 2.44, 95% CI: 0.99-3.89; P = 0.001) was also significantly higher in smokers whereby significant head (MD: 1.76, 95% CI: 0.32-3.20; P = 0.02), neck (MD: 1.97, 95% CI: 0.75-3.18; P = 0.002) and tail (MD: 1.29, 95% CI: 0.35-2.22; P = 0.007) defects were observed. However, smoking did not affected the pH (MD: 0.04, 95% CI: [- 0.03-0.11]; P = 0.30) and motility (RR: 1.42, 95% CI: 0.97-2.09; P = 0.07) of spermatozoa. Additionally, tobacco smoking did not cause any dis-balance in hormones which were involved in reproduction. CONCLUSIONS: In conclusion, with reference to the clinical endpoints which were studied in this analysis, tobacco smoking was associated with a lower sperm count and an increase in the number of morphological defects of spermatozoa. However, the pH and motility of spermatozoa as well as the production of hormones which were involved in reproduction were not affected in this population of infertile males.

Post percutaneous coronary interventional adverse cardiovascular outcomes and bleeding events observed with prasugrel versus clopidogrel: direct comparison through a meta-analysis.

BACKGROUND: Due to limitations associated with clopidogrel following percutaneous coronary intervention (PCI), other newer oral anti-platelet agents are being studied. We aimed to systematically carry out a direct comparison of outcomes observed with prasugrel versus clopidogrel following PCI. METHODS: Common online searched databases (The Cochrane library, EMBASE, MEDLINE and Google scholar) were used to retrieve relevant publications. Primary endpoints were the adverse cardiovascular outcomes. Secondary outcomes were the bleeding events. This analysis was carried out by RevMan 5.3, whereby odds ratios (OR) and 95% confidence intervals (CI) were considered as the statistical parameters. RESULTS: Eight studies with a total number of 18,122 participants were included in this direct analysis. Prasugrel was associated with significantly lower adverse cardiovascular outcomes in comparison to clopidogrel following PCI. All-cause mortality, myocardial infarction, stroke, stent thrombosis and major adverse cardiac events were all significantly lower with prasugrel (OR: 0.47, 95% CI: 0.35-0.63; P = 0.0001), (OR: 0.68, 95% CI: 0.57-0.80; P = 0.00001), (OR: 0.60, 95% CI: 0.38-0.96; P = 0.03), (OR: 0.46, 95% CI: 0.30-0.72; P = 0.0006) and (OR: 0.61, 95% CI: 0.53-0.70; P = 0.00001) respectively. When the bleeding outcomes were analyzed, Thrombolysis in Myocardial Infarction (TIMI) defined major and minor bleeding were not significantly different (OR: 0.91, 95% CI: 0.66-1.27; P = 0.59) and (OR: 1.16, 95% CI: 0.85-1.59; P = 0.35) respectively. However, the combined 'all bleeding events' was significantly higher with prasugrel (OR: 1.32, 95% CI: 1.03-1.70; P = 0.03), but when patients with STEMI and those undergoing elective PCI were separately analyzed, no significant difference in overall bleeding was observed. CONCLUSION: Adverse cardiovascular outcomes were significantly lower with the use of prasugrel in comparison to clopidogrel following PCI. In addition, TIMI defined major and minor bleeding were not significantly different showing prasugrel to be well-tolerated following PCI especially in patients with acute coronary syndrome.

Arterial/venous thrombosis, fetal loss and stillbirth in pregnant women with systemic lupus erythematosus versus primary and secondary antiphospholipid syndrome: a systematic review and meta-analysis.

BACKGROUND: We aimed to systematically compare arterial/venous thrombosis, fetal loss and stillbirth in pregnant women with systemic lupus erythematosus (SLE), primary anti-phospholipid syndrome (PAPS) and secondary anti-phospholipid syndrome (SAPS). METHODS: Online databases were carefully searched for relevant publications comparing SLE with PAPS and/or SAPS in pregnancy. Studies were included if: they compared SLE with APS [SLE versus PAPS or SLE versus SAPS or SLE versus PAPS and SAPS respectively] in pregnant women; and they reported specific adverse outcomes as their clinical endpoints including arterial/venous thrombosis, fetal loss and stillbirth. Risk ratios (RR) with 95% confidence intervals (CIs) were used as statistical parameters and the analysis was carried out by the RevMan 5.3 software. RESULTS: A total number of 941 pregnant women were included: 556 were candidates of SLE; 200 were candidates of PAPS; and 185 were candidates of SAPS. APS was associated with a significantly higher risk of fetal loss (RR: 4.49, 95% CI: 2.09-9.64; P = 0.0001). In addition, stillbirth and arterial/venous thrombosis were also significantly increased with APS (RR: 6.65, 95% CI: 2.14-20.60; P = 0.001) and (RR: 3.95, 95% CI: 1.28-12.16; P = 0.02) respectively. When patients with PAPS were compared with patients who suffered from SLE alone, fetal loss and arterial/venous thrombosis were still significantly higher with the former. When SAPS were compared with SLE (without anti-phospholipid antibodies), arterial/venous thrombosis, stillbirth and fetal loss were still significantly higher with SAPS. However, no significant difference was observed in arterial/venous thrombosis and fetal loss between PAPS and SAPS. CONCLUSIONS: PAPS and SAPS were associated with significantly higher arterial/venous thrombosis, fetal loss and stillbirth in comparison to SLE. However, no significant difference was observed when PAPS was compared to SAPS.

Impact of systemic lupus erythematosus on maternal and fetal outcomes following pregnancy: A meta-analysis of studies published between years 2001-2016.

BACKGROUND: Previous research has already shown systemic lupus erythematosus (SLE) to have severe consequences on pregnancy outcomes. However, insufficient number of participants, which were mainly limited to one particular region, limited outcomes analyzed and lack of evidence based analysis to support systematic reviews of the literature were the limitations observed. Therefore, by improving these limitations, we aimed to systematically show the impact of SLE on maternal and fetal outcomes following pregnancy. METHODS: The Cochrane Database of Randomized Controlled Trials, EMBASE and Medline databases were carefully searched for appropriately relevant English language studies comparing maternal and/or fetal outcomes (endpoints) in pregnant women with and without SLE. With the presence of discontinuous data, risk ratios (RR) and 95% confidence intervals (CI) were calculated and the final analysis was carried out by RevMan 5.3 software. RESULTS: Eleven studies with a total number of 529,778 participants were included. This current analysis showed cesarean operation to be significantly higher in patients with SLE (RR: 1.85, 95% CI: 1.63-2.10; P = 0.00001). Pre-eclampsia and hypertension also significantly affected women with SLE, (RR: 1.91, 95% CI: 1.44-2.53; P = 0.00001) and (RR: 1.99, 95% CI: 1.54-2.56; P = 0.00001) respectively. In addition, spontaneous abortion, thromboembolic disease, and post-partum infection were also significantly higher in the SLE subgroup (RR: 1.51, 95% CI: 1.26-1.82; P = 0.0001), (RR: 11.29, 95% CI: 6.05-21.07; P = 0.00001) and (RR: 4.35, 95% CI: 2.69-7.03; P = 0.00001) respectively. Live birth significantly favored infants who were born from mothers without SLE (RR: 1.38, 95% CI: 1.14-1.67; P = 0.001). Significantly higher premature birth and infants classified as 'small for gestational age' were associated with SLE, (RR: 3.05, 95% CI: 2.56-3.63; P = 0.00001) and (RR: 1.69, 95% CI: 1.53-1.88; P = 0.00001) respectively. In addition, SLE was significantly associated with increased number of infants that required neonatal intensive care unit and infants with congenital defects (RR: 2.76, 95% CI: 2.27-3.35; P = 0.00001) and (RR: 2.63, 95% CI: 1.93-3.58; P = 0.00001) respectively. CONCLUSIONS: This meta-analysis has shown SLE to indeed have a high impact on maternal and fetal outcomes following pregnancy. Therefore, special treatments and care should be allocated to those women in order to manage adverse outcomes that might follow, and to improve successful normal delivery, term infants and to reduce congenital abnormalities in infants who were born from mothers with SLE.

Choosing between Enoxaparin and Fondaparinux for the management of patients with acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND: Enoxaparin and Fondaparinux are potential anticoagulants which are used peri-operatively in the management of patients with Acute Coronary Syndrome (ACS). We aimed to compare the adverse clinical outcomes which are associated with the use of these anticoagulants in patients who were treated for ACS. METHODS: Online databases (PubMed/Medline, EMBASE, Cochrane library) were searched for studies which compared differences in clinical outcomes observed with the use of enoxaparin and fondaparinux in patients who were treated peri-operatively for ACS. Statistical analysis was carried out by Revman 5.3 software with odds ratio (OR) and 95% confidence intervals (CI) as the analytical parameters. RESULTS: Seven studies with a total number of 9618 patients (mainly composed of non-ST elevated myocardial infarction/NSTEMI) were included. This analysis showed mortality to be similarly observed between enoxaparin and fondaparinux with OR: 1.05, 95% CI: 0.67-1.63; P = 0.84. Myocardial infarction (MI) and stroke were also not significantly different throughout different follow up periods. However, minor, major and total bleeding were significantly lower with fondaparinux (OR: 0.40, 95% CI: 0.27-0.58; P = 0.00001), (OR: 0.46, 95% CI: 0.32-0.66; P = 0.0001) and (OR: 0.47, 95% CI: 0.37-0.60; P = 0.00001) respectively during the 10-day follow up period. Even during a follow up period of 30 days or a midterm follow up, major and minor bleeding still significantly favored fondaparinux in comparison to enoxaparin. CONCLUSION: In patients who were treated for ACS, fondaparinux might be a better choice when compared to enoxaparin in terms of short to midterm bleeding events. This result was mainly applicable to patients with NSTEMI. However, due to a limited number of patients analyzed, further larger randomized trials should be able to confirm this hypothesis.

Bleeding events associated with a low dose (110 mg) versus a high dose (150 mg) of dabigatran in patients treated for atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: The newer oral anticoagulant dabigatran is considered to be more beneficial in patients with non-valvular Atrial Fibrillation (AF) when compared to warfarin. However, because bleeding events which are associated with a low dose (110 mg) versus a high dose (150 mg) of dabigatran have seldom been compared, we aimed to systematically solve this important issue through this meta-analysis. METHODS: English publications comparing 110 mg with 150 mg dabigatran in patients who were treated for AF were electronically searched through medical databases. Bleeding outcomes were the major clinical endpoints to be assessed. Odds Ratios (OR) and 95% Confidence Intervals (CIs) for each subgroup were calculated and the main analysis was carried out by the latest version of the RevMan 5.3 software. RESULTS: Twenty-nine thousand two hundred and sixty-four (29,264) patients were included in this meta-analysis. Fifteen thousand eight hundred and forty-eight (15,848) patients were treated with 110 mg dabigatran whereas 13,416 patients were treated with 150 mg dabigatran. 110 mg dabigatran was associated with a significantly lower rate of minor bleeding (OR: 1.19, 95% CI: 1.10-1.27; P < 0.00001). A similar rate of fatal and major bleeding was observed with both dosages (OR: 1.12, 95% CI: 0.69-1.82; P = 0.65) and (OR: 1.09, 95% CI: 0.86-1.37; P = 0.49) respectively. However, ischemic stroke insignificantly favored a higher dose of dabigatran, (OR: 0.77, 95% CI: 0.51-1.16; P = 0.21). In addition, this analysis showed mortality to significantly favor 150 mg of dabigatran (OR: 0.41, 95% CI: 0.34-0.50; P < 0.00001). CONCLUSION: No significant differences in major and fatal bleedings were observed with 110 mg versus 150 mg dabigatran. However, 110 mg dabigatran was associated with a significantly lower risk of minor bleeding. These results should further be confirmed in future trials.

Are women with type 2 diabetes mellitus more susceptible to cardiovascular complications following coronary angioplasty?: a meta-analysis.

BACKGROUND: Scientific reports have shown Type 2 Diabetes Mellitus (T2DM) to be independently associated with adverse outcomes following Percutaneous Coronary Intervention (PCI). However, gender difference has also often been a controversial issue following PCI. Till date, very few meta-analyses have systematically compared the adverse cardiovascular outcomes in male versus female patients with T2DM following PCI. Therefore, we aimed to carry out this analysis in order to find out an answer to this interesting question. METHODS: Electronic databases were searched for English language publications reporting adverse cardiovascular outcomes in male versus female patients with diabetes mellitus respectively following coronary angioplasty. The RevMan 5.3 software was used to analyze selected adverse cardiovascular events whereby Odds Ratios (OR) and 95% Confidence Intervals (CI) were the statistical parameters. RESULTS: A total number of 19,304 patients with T2DM (12,986 male patients versus 6318 female patients) were included in this analysis. At baseline, female patients were older (68.7 versus 62.9 years), with a higher percentage of hypertension (75.6% versus 66.5%) and dyslipidemia (53.3% versus 50.0%) whereas majority of the male patients were smokers (46.3% versus 14.9%). Results of this analysis showed short and long-term mortality to be significantly higher in female patients with T2DM (OR: 1.71, 95% CI: 1.46-2.00; P = 0.00001), and (OR: 1.20, 95% CI: 1.07-1.35; P = 0.002) respectively. In addition, women were also more at risk for short and long-term major adverse cardiac events (MACEs) with OR: 1.49, 95% CI: 1.07-2.07; P = 0.02 and OR: 1.15, 95% CI: 1.04-1.28; P = 0.009 respectively. Subgroup analysis showed this significant result to have mainly been observed in patients with acute myocardial infarction compared to those with stable coronary artery disease. CONCLUSIONS: Following PCI, women with T2DM were indeed more susceptible to short and long-term cardiovascular complications compared to male patients with the same chronic disease. Even though this result was more applicable to patients with acute myocardial infarction, the fact that women were older with higher co-morbidities at baseline compared to men, should also not be ignored.

Comparing Stent Thrombosis associated with Zotarolimus Eluting Stents versus Everolimus Eluting Stents at 1 year follow up: a systematic review and meta-analysis of 6 randomized controlled trials.

BACKGROUND: Two thousand fifteen has been a winning year for Drug Eluting Stents (DES). Increase in the number of patients with cardiovascular diseases treated by Percutaneous Coronary Intervention (PCI) has resulted to a high demand for second generation DES. This current analysis aimed to compare the different types of Stent Thrombosis (ST) associated with Zotarolimus Eluting Stents (ZES) versus Everolimus Eluting Stents (EES) at 1 year follow up. METHODS: Electronic databases were searched for studies comparing ZES with EES. Different types of ST reported at 1 year follow up were considered as the primary endpoints in this analysis. Odds Ratios (OR) with 95% Confidence Intervals (CIs) were used as the statistical parameters and the pooled analyses were carried out by the RevMan 5 · 3 software. RESULTS: A total number of 10,512 patients were included in this analysis. No significant difference in any definite ST, acute definite ST, subacute definite ST, and late definite ST were observed between ZES and EES, at 1 year follow up with OR: 1.70, 95% CI: 0.92 - 3.16; P = 0.09, OR: 3.44, 95% CI: 0.82 - 14.43; P = 0.09, OR: 1.13, 95% CI: 0.43 - 2.95; P = 0.80 and OR: 2.39, 95% CI: 0.83 - 6.85; P = 0.11 respectively. Moreover, any definite or probable ST and definite/probable/possible ST were also not significantly different with OR: 1.39, 95% CI: 0.89 - 2.17; P = 0.15 and OR: 1.19, 95% CI: 0.84 - 1.70; P = 0.33 respectively. In addition, any probable ST, acute probable ST, late probable ST and possible ST were also not significantly different at 1 year follow up with OR: 1.11, 95% CI: 0.60 - 2.05; P = 0.75, OR: 0.53, 95% CI: 0.12 - 2.40; P = 0.41, OR: 1.67, 95% CI: 0.35 - 7.86; P = 0.52 and OR: 1.08, 95% CI: 0.64 - 1.82; P = 0.78 respectively. CONCLUSION: At 1 year follow up, ZES were not associated with significantly lower or higher definite and probable ST compared to EES. In addition, no significant difference was observed in acute, subacute and late definite or probable ST. However, further trials are recommended to assess the effects of these second-generation DES during the long-term.

Does infection with human immunodeficiency virus have any impact on the cardiovascular outcomes following percutaneous coronary intervention?: a systematic review and meta-analysis.

BACKGROUND: A direct link between human immunodeficiency virus (HIV)-infected patients and the risk of cardiovascular diseases (CVD) has been shown in recent scientific research. However, this issue is controversial since other previous reports showed no apparent impact of HIV or its anti-retroviral drugs on the cardiovascular system. We aimed to systematically compare the postinterventional adverse cardiovascular outcomes which were observed in patients with and without HIV infection during a mean follow up period ranging from 1 year to 3 years. METHODS: Common electronic databases were searched for studies which compared postinterventional adverse cardiovascular outcomes [mortality, myocardial infarction (MI), cardiac death, target vessel revascularization (TVR), target lesion revascularization (TLR), stroke and major adverse cardiac events (MACEs)] in patients with and without HIV infection. Statistical analysis was carried out by the RevMan 5.3 software whereby Odds Ratios (OR) and 95% Confidence Intervals (CIs) were generated. RESULTS: Two thousand two hundred and sixty-eight (2268) patients (821 patients were HIV positive and 1147 patients were HIV negative) were analyzed. The current results showed that mortality was not significantly increased among patients who were HIV positive with OR: 1.13, 95% CI: 0.65-1.96; P = 0.66. Cardiac death was also similarly reported with OR: 1.16, 95% CI: 0.50-2.68; P = 0.74. However, even if recurrent MI, TVR, TLR, MACEs and stroke were higher in patients who were HIV positive, with OR: 1.32, 95% CI: 0.88-2.12; P = 0.18, OR: 1.36, 95% CI: 0.88-2.12; P = 0.17, OR: 1.22, 95% CI: 0.72-2.06; P = 0.46, OR: 1.29, 95% CI: 0.89-1.85; P = 0.17 and OR: 1.47, 95% CI: 0.44-4.89; P = 0.53 respectively, these results were not statistically significant. CONCLUSION: Patients who were infected with HIV had similar mortality post coronary intervention compared to patients who were not infected by the virus, during a mean follow-up period of 1-3 years. In addition, no significant increase in MI, TVR, TLR, MACEs and stroke were observed during this follow up period. Therefore, it might be concluded that no apparent impact of HIV on the cardiovascular outcomes was observed post coronary intervention.

Is the concomitant use of clopidogrel and Proton Pump Inhibitors still associated with increased adverse cardiovascular outcomes following coronary angioplasty?: a systematic review and meta-analysis of recently published studies (2012 - 2016).

BACKGROUND: Controversies were previously observed with the concomitant use of clopidogrel and Proton Pump Inhibitors (PPIs), especially omeprazole, following coronary angioplasty. Even though several studies showed no interaction between clopidogrel and PPIs, questions have been raised about the decrease in antiplatelet effects of clopidogrel with PPIs. A previously published meta-analysis showed concomitant use of clopidogrel and PPIs to be associated with higher adverse cardiovascular outcomes. However, data which were used were extracted from studies published before the year 2012. Whether these controversies still exist in this new era is not clear. Therefore, we aim to show if the concomitant use of clopidogrel and PPIs is still associated with higher adverse outcomes following Percutaneous Coronary Intervention (PCI) using data obtained from recently published studies (2012 to 2016). METHODS: Electronic databases were searched for recent publications (2012-2016) comparing (clopidogrel plus PPIs) versus clopidogrel alone following PCI. Adverse cardiovascular outcomes were considered as the clinical endpoints. Odds Ratios (OR) with 95% Confidence Intervals (CI) were used as the statistical parameters and the pooled analyses were performed with RevMan 5.3 software. RESULTS: Eleven studies with a total number of 84,729 patients (29,235 patients from the PPIs group versus 55,494 patients from the non-PPIs group) were included. Results of this analysis showed that short term mortality and Target Vessel Revascularization (TVR) significantly favored the non-PPIs group with OR: 1.55; 95% CI: 1.43-1.68, P < 0.00001 and OR: 1.26; 95% CI: 1.06-1.49, P = 0.009 respectively. Long-term Major Adverse Cardiac Events (MACEs), Myocardial Infarction (MI), Stent Thrombosis (ST) and TVR significantly favored patients who did not use PPIs with OR: 1.37; 95% CI: 1.23-1.53, P < 0.00001, OR: 1.41; 95% CI: 1.26-1.57, P < 0.00001 and OR: 1.38; 95% CI: 1.13-1.70, P = 0.002 and OR: 1.28; 95% CI: 1.01-1.61, P = 0.04 respectively. However, the result for long term mortality was not statistically significant. CONCLUSION: The combined use of clopidogrel with PPIs is still associated with significantly higher adverse cardiovascular events such as MACEs, ST and MI following PCI supporting results of the previously published meta-analysis. However, long-term mortality is not statistically significant warranting further analysis with randomized patients.

Major adverse cardiac events and mortality in chronic obstructive pulmonary disease following percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: We aimed to systematically compare Major Adverse Cardiac Events (MACEs) and mortality following Percutaneous Coronary Intervention (PCI) in patients with and without Chronic Obstructive Pulmonary Diseases (COPD) through a meta-analysis. METHODS: Electronic databases (Cochrane library, EMBASE and Medline/PubMed) were searched for English publications comparing in-hospital and long-term MACEs and mortality following PCI in patients with a past medical history of COPD. Statistical analysis was carried out by Revman 5.3 whereby Odds Ratio (OR) and 95% Confidence Intervals (CI) were considered the relevant parameters. RESULTS: A total number of 72,969 patients were included (7518 patients with COPD and 65,451 patients without COPD). Results of this analysis showed that in-hospital MACEs were significantly higher in the COPD group with OR: 1.40, 95% CI: 1.19-1.65; P = 0.0001, I2 = 0%. Long-term MACEs were still significantly higher in the COPD group with OR: 1.58, 95% CI: 1.38-1.81; P = 0.00001, I2 = 29%. Similarly, in-hospital and long-term mortality were significantly higher in patients with COPD, with OR: 2.25, 95% CI: 1.78-2.85; P = 0.00001, I2 = 0% and OR: 2.22, 95% CI: 1.33-3.71; P = 0.002, I2 = 97% respectively. However, the result for the long-term death was highly heterogeneous. CONCLUSION: Since in-hospital and long-term MACEs and mortality were significantly higher following PCI in patients with versus without COPD, COPD should be considered a risk factor for the development of adverse clinical outcomes following PCI. However, the result for the long-term mortality was highly heterogeneous warranting further analysis.

Bleeding outcomes associated with rivaroxaban and dabigatran in patients treated for atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Warfarin is commonly used as a secondary prevention of stroke in patients with atrial fibrillation (AF). However, limitations have been observed even with the use of this medication. Recently, several newer direct oral anticoagulants (DOACs) have been approved for use by the food and drug administrations. Unfortunately, these newer drugs have seldom been compared directly with each other. Therefore, this study aimed to compare the bleeding events associated with rivaroxaban and dabigatran in patients treated for non-valvular AF. METHODS: EMBASE, Medline (National Library of Medicine) and the Cochrane Central Registry of Controlled Trials were searched for studies comparing rivaroxaban with dabigatran using the terms 'rivaroxaban, dabigatran and atrial fibrillation'. Primary endpoints were: any bleeding outcomes, intracranial bleeding and gastro-intestinal (GI) bleeding. Secondary outcomes included stroke/systemic embolism (SE)/transient ischemic attack (TIA), venous thromboembolism and mortality. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated. The pooled analyses were carried out with RevMan 5.3 software. All the authors had full access to the data and approved the manuscript as written. RESULTS: A total number of 4895 patients were included. This analysis showed that rivaroxaban was not associated with a significantly higher bleeding event when compared to dabigatran (OR: 1.28, 95% CI: 0.95-1.72; P = 0.11). GI bleeding was similarly manifested between these two DOACs (OR: 0.98, 95% CI: 0.43-2.25; P = 0.97). Even if intracranial bleeding was higher with the use of rivaroxaban, (OR: 2.18, 95% CI: 0.51-9.25; P = 0.29), the result was not statistically significant. Moreover, stroke/SE/TIA and venous thromboembolism were also not significantly different (OR: 0.81, 95% CI: 0.53-1.23; P = 0.32) and (OR: 2.06, 95% CI: 0.73-5.82; P = 0.17) respectively. However, even if mortality favored dabigatran (OR: 1.42, 95% CI: 0.99-2.06; P = 0.06), this result only approached statistical significance. CONCLUSION: Head to head comparison showed that rivaroxaban was not associated with significantly higher bleeding events compared to dabigatran. Intracranial bleeding, GI bleeding, stroke/SE/TIA, venous thromboembolism and mortality were also not significantly different between these two DOACs. However, due to the limited number of patients analyzed, and which were mainly obtained from observational studies, this hypothesis might only be confirmed in future randomized trials. Furthermore, the CHADS2-VASC and HAS-BLED score which might play an important role in predicting bleeding risks should also not be ignored.

Coronary artery bypass surgery compared with percutaneous coronary interventions in patients with insulin-treated type 2 diabetes mellitus: a systematic review and meta-analysis of 6 randomized controlled trials.

BACKGROUND: Data regarding the long-term clinical outcomes in patients with insulin-treated type 2 diabetes mellitus (ITDM) revascularized by either coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI) are still controversial. We sought to compare the long-term (≥1 year) adverse clinical outcomes in patients with ITDM who underwent revascularization by either CABG or PCI. METHODS: Randomized Controlled Trials (RCTs) comparing the long-term clinical outcomes in patients with ITDM and non-ITDM revascularized by either CABG or PCI were searched from electronic databases. Data for patients with ITDM were carefully retrieved. Odd Ratio (OR) with 95 % confidence interval (CI) was used to express the pooled effect on discontinuous variables and the pooled analyses were performed with RevMan 5.3. RESULTS: Six RCTs involving 10 studies, with a total of 1297 patients with ITDM were analyzed (639 patients from the CABG group and 658 patients from the PCI group). CABG was associated with a significantly lower mortality rate compared to PCI with OR: 0.59, 95 % CI 0.42-0.85; P = 0.004. Major adverse cardiovascular and cerebrovascular events as well as repeated revascularization were also significantly lower in the CABG group with OR: 0.51, 95 % CI 0.27-0.99; P = 0.03 and OR 0.34, 95 % CI 0.24-0.49; P < 0.00001 respectively. However, compared to PCI, the rate of stroke was higher in the CABG group with OR: 1.41, 95 % CI 0.64-3.09; P = 0.40, but this result was not statistically significant. CONCLUSION: CABG was associated with significantly lower long-term adverse clinical outcomes compared to PCI in patients with ITDM. However, due to an insignificantly higher rate of stroke in the CABG group, further researches with a larger number of randomized patients are required to completely solve this issue.

Should a prolonged duration of dual anti-platelet therapy be recommended to patients with diabetes mellitus following percutaneous coronary intervention? A systematic review and meta-analysis of 15 studies.

BACKGROUND: This study aimed to compare the adverse clinical outcomes associated with a short and a prolonged duration of Dual Anti-Platelet Therapy (DAPT) in patients with Diabetes Mellitus (DM) after undergoing Percutaneous Coronary Intervention (PCI). METHODS: Medline/PubMed, EMBASE and the Cochrane library were searched for studies comparing the short and prolonged DAPT use in patients with DM. Adverse outcomes were considered as the clinical endpoints in this analysis. Odds Ratios (OR) with 95 % Confidence Intervals (CI) were used to express the pooled effect on discontinuous variables and the pooled analyses were performed with RevMan 5.3. RESULTS: Fifteen studies with a total number of 25,742 patients with DM were included in this current analysis which showed no significant differences in primary endpoints, net clinical outcomes, myocardial infarction and stroke with OR: 1.03, 95 % CI: 0.65-1.64; P = 0.90, OR: 0.96, 95 % CI: 0.69-1.34; P = 0.81, OR: 0.85, 95 % CI: 0.70-1.04; P = 0.12 and OR: 0.94, 95 % CI: 0.65-1.36; P = 0.75 respectively. Revascularization was also similar between these 2 groups of patients with DM. However, even if mortality favored prolonged DAPT use, with OR: 0.87, 95 % CI: 0.76-1.00; P = 0.05, the result only approached significance. Also, stent thrombosis insignificantly favored a prolonged DAPT duration with OR: 0.56, 95 % CI: 0.27-1.17; P = 0.12. Thrombolysis In Myocardial Infarction (TIMI) defined major and minor bleeding were not significantly different in these diabetic patients with OR: 0.91, 95 % CI: 0.60-1.37; P = 0.65 and OR: 1.08, 95 % CI: 0.62-1.91; P = 0.78 respectively. However, bleeding defined by the Bleeding Academic Research Consortium (BARC) classification was significantly higher with a prolonged DAPT use in these diabetic patients with OR: 1.92, 95 % CI: 1.58-2.34; P < 0.00001. CONCLUSION: Following PCI, a prolonged DAPT use was associated with similar adverse clinical outcomes but with a significantly increased BARC defined bleeding compared to a short term DAPT use in these patients with DM. However, even if mortality and stent thrombosis favored a prolonged DAPT use, these outcomes only either reached statistical significance or were insignificant respectively, showing that a clear decision about recommending a prolonged duration of DAPT to patients with DM might not be possible at this moment, warranting further research in this particular subgroup.

Comparing the adverse clinical outcomes associated with fraction flow reserve-guided versus angiography-guided percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Recently published randomized controlled trials have shown different results compared to the Fraction Flow Reserve Versus Angiography for Multi-vessel Evaluation (FAME) study. Therefore, this current analysis aimed to compare the adverse clinical outcomes associated with Fraction Flow Reserve (FFR)-guided versus standard angiography-guided Percutaneous Coronary Intervention (PCI) using a large number of randomized patients. METHODS: PubMed/Medline, EMBASE and the Cochrane library were searched for studies comparing FFR-guided with angiography-guided PCI. Mortality, Myocardial Infarction (MI), repeated revascularization and Major Adverse Cardiac Events (MACEs) at any follow up period following PCI were considered as the clinical endpoints in this analysis. Odds Ratios (OR) with 95% Confidence Intervals (CIs) were calculated and the analyses were carried out by the RevMan 5.3 software. Ethical approval was not necessary for this type of study. RESULTS: A total number of 2138 patients (1080 patients with FFR-guided versus 1058 patients with angiography-guided PCI) were included. Results of this analysis showed mortality not to be significantly different between FFR-guided and angiography-guided PCI with OR: 0.70, 95% CI: 0.39 - 1.25; P = 0.22, I2 = 0%. Total repeated revascularization and Target Lesion Revascularization were also similarly manifested with OR: 0.82, 95% CI: 0.60 - 1.13; P = 0.22, I2 = 0% and OR: 0.88, 95% CI: 0.43 - 1.80; P = 0.73, I2 = 0% respectively. In addition, MACEs were also not significantly lower in the FFR-guided PCI group with OR: 0.82, 95% CI: 0.64 - 1.06; P = 0.13, I2 = 0%. However, FFR-guided PCI was associated with a significantly lower rate of re-infarction with OR: 0.67, 95% CI: 0.47 - 0.96; P = 0.03, I2 = 0%. CONCLUSION: FFR-guided PCI was not associated with significantly higher adverse clinical outcomes when compared to angiography-guided PCI. A significantly lower rate of re-infarction associated with FFR-guided PCI could show an important benefit. However, due to the limited number of patients analyzed, this hypothesis should further be confirmed in future trials.

Adverse clinical outcomes associated with a low dose and a high dose of aspirin following percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Guidelines from the American Heart Association/American College of Cardiology recommend a higher dosage of aspirin daily following Percutaneous Coronary Intervention (PCI), whereas guidelines from the European Society of Cardiology recommend a lower dosage. This study aimed to compare the adverse clinical outcomes associated with a low dose and a high dose of aspirin following PCI. METHODS: Electronic databases were searched for studies comparing a low dose with a high dose aspirin following PCI. Adverse clinical outcomes were considered as the endpoints in this study. We calculated Odds Ratios (OR) with 95 % Confidence Intervals (CIs) for categorical variables. The pooled analyses were performed with RevMan 5.3 software. RESULTS: A total number of 25,083 patients were included. Results from this analysis showed that the combination of Cardiovascular (CV) death/Myocardial Infarction (MI) or stroke was not significantly different between a low and high dose of aspirin with OR: 1.08, 95 % CI: 0.98-1.18; P = 0.11. Mortality and MI were also not significantly different between these two treatment regimens following PCI with OR: 0.95, 95 % CI: 0.74-1.23; P = 0.71 and OR: 1.17, 95 % CI: 0.97-1.41; P = 0.09 respectively. However, a high dose of aspirin was associated with a significantly higher rate of Major Adverse Cardiac Events (MACEs) with OR: 1.20, 95 % CI: 1.02-1.41; P = 0.03. Thrombolysis In Myocardial Infarction (TIMI) defined minor bleeding was also significantly higher with a high dose aspirin with OR: 1.22, 95 % CI: 1.02-1.47; P = 0.03. When Stent thrombosis (ST) was compared, no significant difference was found with OR: 1.28, 95 % CI: 0.59-2.58; P = 0.53. Even if TIMI defined major bleeding favored a low dose of aspirin, with OR: 1.42, 95 % CI: 0.95-2.13; P = 0.09, or even if major bleeding was insignificantly higher with a high dose aspirin, with OR: 1.78, 95 % CI: 1.01-3.13; P = 0.05; I(2) = 94 %, higher levels of heterogeneity observed in these subgroups could not be considered significant to any extent. CONCLUSION: According to the results of this analysis, a high dose of aspirin following PCI was not associated with any significantly higher rate of CV death/MI/stroke, mortality or MI. However, MACEs significantly favored a low dose of aspirin. In addition, TIMI defined minor bleeding was significantly higher with a high dose of aspirin whereas the results for the major bleeding outcomes were not statistically significant. However, due to limited data availability and since the subgroups analyzing major bleeding were highly heterogeneous, further studies are recommended to completely solve this issue.

Adverse cardiovascular outcomes between insulin-treated and non-insulin treated diabetic patients after percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (DM) patients have worse adverse cardiovascular outcomes after Percutaneous Coronary Intervention (PCI). However, the adverse cardiovascular outcomes between insulin-treated and non-insulin treated DM patients have been a subject of debate. We sought to compare the short-term (<1 year) and long-term (≥1 year) cardiovascular outcomes between insulin-treated and non-insulin treated DM patients after PCI. METHODS: Medline and Embase databases were searched for studies by typing 'diabetes and percutaneous coronary intervention/PCI' or 'insulin-treated and non-insulin treated diabetes mellitus and PCI'. Endpoints included adverse cardiovascular outcomes reported in these DM patients during the corresponding follow-up periods. Odd Ratio (OR) with 95% confidence interval (CI) was used to express the pooled effect on discontinuous variables and the pooled analyses were performed with RevMan 5.3. RESULTS: 21 studies have been included in this meta-analysis consisting of a total of 21,759 diabetic patients (6250 insulin-treated and 15,509 non-insulin treated DM patients). Short term mortality, myocardial infarction, target lesion revascularization, major adverse cardiac effects and, stent thrombosis were significantly higher in insulin-treated diabetic patients (OR 1.69, 95% CI 1.40-2.04, p < 0.00001), (OR 1.40, 95% CI 1.16-1.70, p = 0.0005), (OR 1.37, 95% CI 1.06-1.76, p = 0.02), (OR 1.46, 95% CI 1.22-1.76, p < 0.0001) and (OR 1.66, 95% CI 1.16-2.38, p = 0.005) respectively. Long-term cardiovascular outcomes were also significantly higher in insulin-treated DM patients. CONCLUSION: Insulin treatment in these DM patients was associated with a significantly higher short and long-term adverse cardiovascular outcomes after PCI compared to those DM patients not treated by insulin therapy.

Comparing the effectiveness and safety between triple antiplatelet therapy and dual antiplatelet therapy in type 2 diabetes mellitus patients after coronary stents implantation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Since antiplatelet therapy in type 2 diabetes mellitus (T2DM) patients is very important after intracoronary stenting, and because the most commonly used therapies have been the dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel and the triple antiplatelet therapy (TAPT) consisting of aspirin, clopidogrel and cilostazol, we aim to compare the effectiveness and safety between triple antiplatelet therapy and dual antiplatelet therapy in T2DM patients. METHODS: Systematic literature search was done from the databases of PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI) and WanFang. Randomized controlled trials (RCTs) comparing the effectiveness and safety between triple therapy and dual therapy in T2DM patients after coronary stents placement were included. Endpoints included major adverse cardiac effects (MACEs), target lesion revascularization (TLR), target vessel revascularization (TVR), death, stent thrombosis, bleeding and adverse drug reactions during a 9-12 months period, as well as platelet activities. RESULTS: Four studies including 1005 patients reporting the adverse clinical outcomes and six studies including 519 patients reporting the platelet activities, with a total of 1524 patients have been analyzed in this meta-analysis. The pooling analysis shows that TAPT has significantly decreased the occurrence of MACEs (RR: 0.55; 95 % CI: 0.36-0.86, P = 0.009), TLR (RR 0.41; 95 % CI: 0.21-0.80, P = 0.008), TVR (RR 0.55; 95 % CI: 0.34-0.88, P = 0.01) and the overall incidence of Death/ Myocardial Infarction (MI)/TVR (RR 0.54; 95 % CI: 0.31-0.94, P = 0.03) during this 9 to 12 months follow up period after stents implantation. Stent thrombosis was almost similar in both groups. Bleeding seemed to favor DAPT but the result was not statistically significant. Platelet aggregation, platelet reactivity index (PRI) and platelet reactivity unit (PRU) were also reduced with Weight Mean Difference (WMD) of (-13.80; 95 % CI: -17.03 to -10.56, P < 0.00001), (-22.87; 95 % CI: -23.66 to -22.07, P < 0.00001) and (-44.17; 95 % CI: -58.56 to -29.77, P < 0.00001) respectively. CONCLUSION: Since MACEs have been significantly decreased in the triple group, TAPT appears to be more effective than DAPT in T2DM patients after intracoronary stenting. No significant difference in stent thrombosis and bleeding risks between these 2 groups shows TAPT to be almost as safe as DAPT in these diabetic patients.