Effect of Sex Difference on Discordance Between Instantaneous Wave-Free Ratio and Fractional Flow Reserve.

BACKGROUND: Physiology-guided percutaneous coronary intervention (PCI) has demonstrated to improve clinical outcomes. Previous trials showed the agreement between iFR and FFR is approximately 80%, however the details of discordance pattern remain to be elucidated. METHODS: We retrospectively reviewed 1024 consecutive intermediate stenotic lesions for which functional evaluation using both iFR and FFR were performed between January 2015 and June 2016. The lesions were classified into 4 groups according to iFR and FFR concordance [(iFR+/FFR+) and (iFR-/FFR-)] or discordance [(iFR+/FFR-) and (iFR-/FFR+)]. RESULTS: Our study evaluated 451 lesions, 264 lesions (58.5%) from men and 187 lesions (41.5%) from women. iFR was similar between women and men, however FFR was significantly higher in women than men. The rate of discordance between iFR and FFR was 21.3% (iFR+/FFR- 12.4% and iFR-/FFR+ 8.9%) in overall cohort. The prevalence of overall concordance and discordance were similar between men and women, however iFR+/FFR- discordance was significantly higher in women (17.1% vs. 9.1%) whereas iFR-/FFR+ discordance was significantly higher in men (11.3% vs. 4.8%). In multivariable analysis, female sex and older age were significantly associated with iFR+/FFR- discordance (odds ratio 1.88 and 1.48, respectively). Conversely, younger age, higher stenosis, and concomitant chronic total occlusion were independent predictors for iFR-/FFR+ discordance (odds ratio 0.67, 1.82, and 4.32, respectively). CONCLUSIONS: Despite similar prevalence of overall concordance and discordance between men and women, iFR+/FFR- discordance was higher in women and iFR-/FFR+ discordance was higher in men. Multivariable analysis showed female sex to be independent predictor of iFR+/FFR- discordance.

Newer-Generation Ultrathin Strut Drug-Eluting Stents Versus Older Second-Generation Thicker Strut Drug-Eluting Stents for Coronary Artery Disease.

BACKGROUND: Contemporary second-generation drug-eluting stents (DES) have superior efficacy and safety in comparison with early-generation stents in patients undergoing percutaneous coronary intervention, in part, related to their thinner struts. Whether newer-generation ultrathin DES further improve clinical outcomes in comparison with older second-generation thicker strut DES is unknown. METHODS: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for randomized clinical trials that compared newer-generation ultrathin strut DES (defined as strut thickness <70 µm) versus thicker strut second-generation DES and reported clinical outcomes. The primary outcome was target lesion failure (composite of cardiovascular death, target vessel myocardial infarction or ischemia-driven target lesion revascularization) evaluated at 1-year follow-up. Tests for subgroup effects based on the ultrathin strut DES type and the comparator DES type were performed by using meta-regression analysis. RESULTS: We identified 10 trials that randomly assigned 11 658 patients and evaluated 3 newer-generation ultrathin strut DES: Orsiro stent (60 µm), MiStent (64 µm), and BioMime (65 µm). In comparison with thicker strut second-generation DES, newer-generation ultrathin strut DES were associated with a 16% reduction in target lesion failure (relative risk, 0.84; 95% CI, 0.72-0.99) driven by less myocardial infarction (relative risk, 0.80; 95% CI, 0.65-0.99). Ultrathin strut DES were also associated with qualitatively lower rates of any stent thrombosis (relative risk, 0.72; 95% CI, 0.51-1.01). Tests for subgroup effects based on the ultrathin strut DES type ( P=0.58) and the comparator DES type ( P=0.98) were not significant, suggesting consistent outcomes across the 3 ultrathin strut DES and with the different DES comparators. CONCLUSIONS: In patients undergoing percutaneous coronary intervention, newer-generation ultrathin strut DES further improve 1-year clinical outcomes in comparison with contemporary thicker strut second-generation DES.

Meta-Analysis of Culprit-Only Versus Multivessel Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Coronary Disease.

Recently, several randomized controlled trials (RCT) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) have compared a strategy of routine multivessel percutaneous coronary intervention (PCI) performed either as a single procedure or as staged procedures to culprit-only PCI. All of these trials have been underpowered for clinical end points. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for RCT comparing multivessel PCI with culprit-only PCI in patients with STEMI and MVD. The primary efficacy outcome was the composite rate of death or MI. Other efficacy outcomes included death, MI, and repeat revascularization. Safety outcomes were contrast-associated acute kidney injury, stroke, and major bleeding. Pairwise direct comparison and mixed-treatment comparison network meta-analyses were performed. Eleven trials that enrolled 3,150 patients with a total of 5,296 patient-years of follow-up were included. In direct comparison meta-analysis, single-procedure multivessel PCI was associated with a reduction in the risk of death or MI (rate ratio [RR] = 0.52; 95% confidence interval [CI] 0.37 to 0.73; p <0.001), due to less death (RR = 0.64; 95% CI 0.40 to 1.02; p = 0.06) and MI (RR = 0.42; 95% CI 0.25 to 0.69; p <0.0001) compared with culprit-only PCI. No heterogeneity (I2 = 0) was present between studies. In contrast, staged multivessel PCI did not significantly reduce death or MI compared with culprit-only PCI. Both multivessel PCI strategies reduced the risk of repeat revascularization without significant differences in safety outcomes. Results were consistent in the mixed-treatment comparison meta-analysis. In conclusion, the present meta-analysis suggests that single-procedure multivessel PCI may be the preferred strategy in patients with STEMI and MVD.

Renin angiotensin system inhibitors for patients with stable coronary artery disease without heart failure: systematic review and meta-analysis of randomized trials.

OBJECTIVE:  To critically evaluate the efficacy of renin angiotensin system inhibitors (RASi) in patients with coronary artery disease without heart failure, compared with active controls or placebo. DESIGN:  Meta-analysis of randomized trials. DATA SOURCES:  PubMed, EMBASE, and CENTRAL databases until 1 May 2016. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:  Randomized trials of RASi versus placebo or active controls in patients with stable coronary artery disease without heart failure (defined as left ventricular ejection fraction ≥40% or without clinical heart failure). Each trial had to enroll at least 100 patients with coronary artery disease without heart failure, with at least one year's follow-up. Studies were excluded if they were redacted or compared use of angiotensin converting enzyme inhibitors with angiotensin receptor blockers. Outcomes were death, cardiovascular death, myocardial infarction, angina, stroke, heart failure, revascularization, incident diabetes, and drug withdrawal due to adverse effects. RESULTS:  24 trials with 198 275 patient years of follow-up were included. RASi reduced the risk of all cause mortality (rate ratio 0.84, 95% confidence interval 0.72 to 0.98), cardiovascular mortality (0.74, 0.59 to 0.94), myocardial infarction (0.82, 0.76 to 0.88), stroke (0.79, 0.70 to 0.89), angina, heart failure, and revascularization when compared with placebo but not when compared with active controls (all cause mortality, 1.05, 0.94 to 1.17; Pinteraction=0.006; cardiovascular mortality, 1.08, 0.93 to 1.25, Pinteraction<0.001; myocardial infarction, 0.99, 0.87 to 1.12, Pinteraction=0.01; stroke, 1.10, 0.93 to 1.31; Pinteraction=0.002). Bayesian meta-regression analysis showed that the effect of RASi when compared with placebo on all cause mortality and cardiovascular mortality was dependent on the control event rate, such that RASi was only beneficial in trials with high control event rates (>14.10 deaths and >7.65 cardiovascular deaths per 1000 patient years) but not in those with low control event rates. CONCLUSIONS:  In patients with stable coronary artery disease without heart failure, RASi reduced cardiovascular events and death only when compared with placebo but not when compared with active controls. Even among placebo controlled trials in this study, the benefit of RASi was mainly seen in trials with higher control event rates but not in those with lower control event rates. Evidence does not support a preferred status of RASi over other active controls.

Optimal Systolic Blood Pressure Target After SPRINT: Insights from a Network Meta-Analysis of Randomized Trials.

BACKGROUND: The optimal on-treatment blood pressure (BP) target has been a matter of debate. The recent SPRINT trial showed significant benefits of a BP target of <120 mm Hg, albeit with an increase in serious adverse effects related to low BP. METHODS: PubMed, EMBASE, and CENTRAL were searched for randomized trials comparing treating with different BP targets. Trial arms were grouped into 5 systolic BP target categories: 1) <160 mm Hg, 2) <150 mm Hg, 3) <140 mm Hg, 4) <130 mm Hg, and 5) <120 mm Hg. Efficacy outcomes of stroke, myocardial infarction, death, cardiovascular death, heart failure, and safety outcomes of serious adverse effects were evaluated using a network meta-analysis. RESULTS: Seventeen trials that enrolled 55,163 patients with 204,103 patient-years of follow-up were included. There was a significant decrease in stroke (rate ratio [RR] 0.54; 95% confidence interval [CI], 0.29-1.00) and myocardial infarction (RR 0.68; 95% CI, 0.47-1.00) with systolic BP <120 mm Hg (vs <160 mm Hg). Sensitivity analysis using achieved systolic BP showed a 72%, 97%, and 227% increase in stroke with systolic BP of <140 mm Hg, <150 mm Hg, and <160 mm, respectively, when compared with systolic BP <120 mm Hg. There was no difference in death, cardiovascular death, or heart failure when comparing any of the BP targets. However, the point estimate favored lower BP targets (<120 mm Hg, <130 mm Hg) when compared with higher BP targets (<140 mm Hg or <150 mm Hg). BP targets of <120 mm Hg and <130 mm Hg ranked #1 and #2, respectively, as the most efficacious target. There was a significant increase in serious adverse effects with systolic BP <120 mm Hg vs <150 mm Hg (RR 1.83; 95% CI, 1.05-3.20) or vs <140 mm Hg (RR 2.12; 95% CI, 1.46-3.08). BP targets of <140 mm Hg and <150 mm Hg ranked #1 and #2, respectively, as the safest target for the outcome of serious adverse effects. Cluster plots for combined efficacy and safety showed that a systolic BP target of <130 mm Hg had optimal balance between efficacy and safety. CONCLUSIONS: In patients with hypertension, a on-treatment systolic BP target of <130 mm Hg achieved optimal balance between efficacy and safety.

Complete vs Culprit-Only Percutaneous Coronary Intervention in STEMI With Multivessel Disease: A Meta-analysis and Trial Sequential Analysis of Randomized Trials.

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) and multivessel disease (MVD) most commonly are treated with culprit-only percutaneous coronary intervention (PCI). However, this has been recently challenged, suggesting benefit with complete revascularization (CR). Still, these latest findings are largely based on clinical trials powered for composite outcomes that frequently include "softer" end points. We performed a meta-analysis comparing routine culprit-only PCI vs CR in STEMI, with an emphasis on "hard" clinical end points. METHODS: MEDLINE, EMBASE, ISI Web of Science, and CENTRAL were searched from 1996-May 2015. Studies included patients with STEMI and MVD who received primary PCI. The primary end point was long-term death/myocardial infarction (MI). Data were combined using a fixed-effects model. RESULTS: Seven randomized trials (2004 patients: 1065 CR and 939 culprit-only PCI procedures) were included. Compared with culprit-only PCI, CR reduced the composite of death/MI (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.52-0.96) but not death (OR, 0.78; 95% CI, 0.53-1.15) or recurrent MI (OR, 0.85; 95% CI, 0.58-1.24) alone. If CR was performed during the index catheterization, a reduction in death/MI was observed (death/MI: OR, 0.41; 95% CI, 0.25-0.65; death: OR, 0.59; 95% CI, 0.34-1.00; recurrent MI: OR, 0.35; 95% CI, 0.18-0.69). If staged, no benefits were noted (death/MI: OR, 0.99; 95% CI, 0.67-1.45; death: OR, 0.95; 95% CI, 0.56-1.61; recurrent MI: OR, 1.02; 95% CI, 0.61-1.70). However, when trial sequential analysis was performed for the overall population, the cumulative z-curve did not cross the monitoring boundary, suggesting a lack of evidence for reducing death/MI with CR (similar for index catheterization). CONCLUSIONS: In STEMI with MVD, there is insufficient evidence to support a reduction in death/MI with CR. Our results reinforce the need for larger clinical trials powered for robust clinical end points.

Outcomes with bioabsorbable vascular scaffolds versus everolimus eluting stents: Insights from randomized trials.

BACKGROUND: Bioresorbable vascular scaffolds (BVS) have been shown to be non-inferior to second generation drug eluting stents in recent clinical trials. However, the trials were not powered for individual endpoints and there is concern for increased device thrombosis with BVS. METHODS: We performed a systematic search for randomized clinical trials of BVS versus EES. Efficacy outcomes were target lesion revascularization (TLR) and target vessel revascularization (TVR). Safety outcomes were death, myocardial infarction (MI), and device thrombosis. Meta-regression analyses were performed to evaluate the association of device thrombosis with clinical characteristics (percent patients with acute coronary syndrome) and device deployment characteristics (percent with post stent balloon dilation). RESULTS: We identified six RCTs that enrolled 3738 patients. When compared with EES, BVS was associated with similar risk of TLR (RR=1.06; 95% CI 0.73-1.54), TVR (RR=1.00; 95% CI 0.74-1.35), death (RR=1.11; 95% CI 0.53-2.33) and cardiovascular death (RR=1.39; 95% CI 0.43-4.43) but numerically higher MI (RR=1.35; 95% CI 0.98-1.86) and definite or probable device thrombosis (RR=2.11; 95% CI 0.99-4.47). In a sensitivity analysis using the Peto odds ratio method, the risk of definite or probable device thrombosis was significantly increased (OR=2.08; 95% CI 1.06-4.08; P=0.03), although this did not reach statistical significance in four other models. The risk of definite or probable device thrombosis with BVS was reduced in trials where more post stent balloon dilation was used and in patients without acute coronary syndrome. Moreover, trial sequential analysis showed that the cumulative z-curve crossed the conventional boundary and not the trial sequential boundary, indicating lack of robust data to support increased definite or probable device thrombosis with BVS. CONCLUSIONS: In patients with noncomplex obstructive coronary disease, BVS are comparable to EES for most efficacy and safety outcomes except for a numerical increase in device thrombosis and MI. The risk of the latter outcomes was mitigated in trials where more post stent balloon dilation was used and in patients without acute coronary syndrome. Moreover, with only 3738 patients, the trials are underpowered to detect a difference in rare events such as device thrombosis.

Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and meta-analysis of randomized trials.

OBJECTIVE: To evaluate the outcomes with use of renin angiotensin system (RAS) blockers compared with other antihypertensive agents in people with diabetes. DESIGN: Meta-analysis. DATA SOURCES AND STUDY SELECTION: PubMed, Embase, and the Cochrane central register of controlled trials databases for randomized trials of RAS blockers versus other antihypertensive agents in people with diabetes mellitus. Outcomes were death, cardiovascular death, myocardial infarction, angina, stroke, heart failure, revascularization, and end stage renal disease. RESULTS: The search yielded 19 randomized controlled trials that enrolled 25,414 participants with diabetes for a total of 95,910 patient years of follow-up. When compared with other antihypertensive agents, RAS blockers were associated with a similar risk of death (relative risk 0.99, 95% confidence interval 0.93 to 1.05), cardiovascular death (1.02, 0.83 to 1.24), myocardial infarction (0.87, 0.64 to 1.18), angina pectoris (0.80, 0.58 to 1.11), stroke (1.04, 0.92 to 1.17), heart failure (0.90, 0.76 to 1.07), and revascularization (0.97, 0.77 to 1.22). There was also no difference in the hard renal outcome of end stage renal disease (0.99, 0.78 to 1.28) (power of 94% to show a 23% reduction in end stage renal disease). CONCLUSIONS: In people with diabetes, RAS blockers are not superior to other antihypertensive drug classes such as thiazides, calcium channel blockers, and ß blockers at reducing the risk of hard cardiovascular and renal endpoints. These findings support the recommendations of the guidelines of the European Society of Cardiology/European Society of Hypertension and eighth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure to also use other antihypertensive agents in people with diabetes but without kidney disease.

Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Patients Without Heart Failure? Insights From 254,301 Patients From Randomized Trials.

OBJECTIVES: To compare the efficacy and safety of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in patients without heart failure. PATIENTS AND METHODS: Meta-analysis of randomized trials identified using PubMed, Embase, and Cochrane Central Register of Controlled Trials searches from January 1, 1980, through April 13, 2015, of ACEis and ARBs compared with placebo or active controls and corroborated with head-to-head trials of ARBs vs ACEis. Outcomes were all-cause mortality, cardiovascular death, myocardial infarction (MI), angina, stroke, heart failure, revascularization, and new-onset diabetes. RESULTS: Our search yielded 106 randomized trials that enrolled 254,301 patients. Compared with placebo, ACEis but not ARBs reduced the outcomes of all-cause mortality (ACEis vs placebo: relative risk [RR], 0.89; 95% CI, 0.80-1.00; ARBs vs placebo: RR, 1.01; 95% CI, 0.96-1.06; Pinteraction=.04), cardiovascular death (RR, 0.83; 95% CI, 0.70-0.99 and RR, 1.02; 95% CI, 0.92-1.14; Pinteraction=.05), and MI (RR, 0.83; 95% CI, 0.78-0.90 and RR, 0.93; 95% CI, 0.85-1.03; Pinteraction=.06). The meta-regression analysis revealed that the difference between ACEis and ARBs compared with placebo was due to a higher placebo event rate in the ACEis trials (most of these trials were conducted a decade earlier than the ARB trials) for the outcome of all-cause mortality (P=.001), cardiovascular death (P<.001), and MI (P=.02). Sensitivity analyses restricted to trials published after 2000 revealed similar outcomes with ACEis vs placebo and ARBs vs placebo (Pinteraction>.05). Head-to-head comparison trials of ARBs vs ACEis exhibited no difference in outcomes except for a lower risk of drug withdrawal due to adverse effects with ARBs (RR, 0.72; 95% CI, 0.65-0.81). CONCLUSION: In patients without heart failure, evidence from placebo-controlled trials (restricted to trials after 2000), active controlled trials, and head-to-head randomized trials all suggest ARBs to be as efficacious and safe as ACEis, with the added advantage of better tolerability.

Complete versus culprit-only revascularization for ST-segment-elevation myocardial infarction and multivessel disease: a meta-analysis and trial sequential analysis of randomized trials.

BACKGROUND: The 2013 American College of Cardiology Foundation/American Heart Association guidelines for patients with ST-segment-elevation myocardial infarction gives a class III indication for nonculprit artery percutaneous coronary intervention at the time of primary percutaneous coronary intervention, driven by data from observational studies. However, more recent trials suggest otherwise. METHODS AND RESULTS: We conducted PUBMED, EMBASE, and CENTRAL searches for randomized trials comparing complete versus culprit-only revascularization in patients with ST-segment-elevation myocardial infarction. Efficacy outcomes were major adverse cardiovascular events, as well as death, cardiovascular death, myocardial infarction, and repeat revascularization. Safety outcomes were contrast-induced nephropathy, contrast volume used, and procedure time. Five trials with 1165 patients fulfilled the inclusion criteria. Complete revascularization (68% during index percutaneous coronary intervention) was associated with significant reduction in major adverse cardiovascular events (rate ratio =0.48; 95% confidence interval =0.37-0.61), death (rate ratio =0.60; 95% confidence interval =0.38-0.97), cardiovascular death (rate ratio =0.38, 95% confidence interval =0.20-0.73), and repeat revascularization (rate ratio =0.42; 95% confidence interval =0.31-0.57) when compared with culprit-only revascularization. However, trial sequential analyses (similar to interim analysis of a randomized trial) powered for a 25% relative reduction showed firm evidence (cumulative z-curve crossed the monitoring boundary) only for major adverse cardiovascular events driven by a decrease in repeat revascularization with no firm evidence for reduction in death and myocardial infarction. Moreover, there was a significant increase in contrast volume use (mean difference 85.12 [70.41-83.00] ml) and procedure time (mean difference 16.42 [13.22-19.63] mins) with complete revascularization without increase in contrast-induced nephropathy. CONCLUSIONS: In patients with ST-segment-elevation myocardial infarction, immediate or staged complete revascularization results in significant reduction in major adverse cardiovascular events driven largely by reduction in repeat revascularization with no firm evidence for the reduction in death or myocardial infarction when compared with culprit-only revascularization.

Comparison of coronary artery bypass graft surgery and percutaneous coronary intervention in patients with diabetes.

OPINION STATEMENT: The optimal revascularization strategy in patients with diabetes is controversial. The Bypass Angioplasty Revascularization Investigation (BARI) trial, done more than a decade ago, suggested a mortality benefit of coronary artery bypass graft surgery (CABG) when compared with percutaneous coronary intervention (PCI) (with plain old balloon angioplasty) in the subgroup of patients with diabetes. In addition, several observational studies and meta-analyses similarly suggest a benefit of CABG over PCI in patients with diabetes. However, most of these studies compared CABG with PCI using balloon angioplasty, bare metal stents, or first-generation drug-eluting stents. In this review, we critically examine the data for optimal revascularization strategy in patients with diabetes and ask the question whether the currently available data from randomized trials that used outdated stents are applicable to current day practice.

Anticoagulant therapy during primary percutaneous coronary intervention for acute myocardial infarction: a meta-analysis of randomized trials in the era of stents and P2Y12 inhibitors.

OBJECTIVES: To investigate the relative benefits of unfractionated heparin, low molecular weight heparin(LMWH), fondaparinux, and bivalirudin as treatment options for patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). DESIGN: Mixed treatment comparison and direct comparison meta-analysis of randomized trials in the era of stents and P2Y12 inhibitors. DATA SOURCES AND STUDY SELECTION: A search of Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) for randomized trials comparing unfractionated heparin plus glycoprotein IIb/IIIa inhibitor(GpIIb/IIIa inhibitor), unfractionated heparin, bivalirudin, fondaparinux, or LMWH plus GpIIb/IIIa inhibitor for patients undergoing primary PCI. OUTCOMES: The primary efficacy outcome was short term (in hospital or within 30 days) major adverse cardiovascular event; the primary safety outcome was short term major bleeding. RESULTS: We identified 22 randomized trials that enrolled 22,434 patients. In the mixed treatment comparison models, when compared with unfractionated heparin plus GpIIb/IIIa inhibitor, unfractionated heparin was associated with a higher risk of major adverse cardiovascular events (relative risk 1.49 (95% confidence interval 1.21 to 1.84), as were bivalirudin (relative risk 1.34 (1.01 to 1.78)) and fondaparinux (1.78 (1.01 to 3.14)). LMWH plus GpIIb/IIIa inhibitor showed highest treatment efficacy, followed (in order) by unfractionated heparin plus GpIIb/IIIa inhibitor, bivalirudin, unfractionated heparin, and fondaparinux. Bivalirudin was associated with lower major bleeding risk compared with unfractionated heparin plus GpIIb/IIIa inhibitor (relative risk 0.47 (0.30 to 0.74)) or unfractionated heparin (0.58 (0.37 to 0.90)). Bivalirudin, followed by unfractionated heparin, LMWH plus GpIIb/IIIa inhibitor, unfractionated heparin plus GpIIb/IIIa inhibitor, and fondaparinux were the hierarchy for treatment safety. Results were similar in direct comparison meta-analyses: bivalirudin was associated with a 39%, 44%, and 65% higher risk of myocardial infarction, urgent revascularization, and stent thrombosis respectively when compared with unfractionated heparin with or without GpIIb/IIIa inhibitor. However, bivalirudin was associated with a 48% lower risk of major bleeding compared with unfractionated heparin plus GpIIb/IIIa inhibitor and 32% lower compared with unfractionated heparin alone. CONCLUSIONS: In patients undergoing primary PCI, unfractionated heparin plus GpIIb/IIIa inhibitor and LMWH plus GpIIb/IIIa inhibitor were most efficacious, with the lowest rate of major adverse cardiovascular events, whereas bivalirudin was safest, with the lowest bleeding. These relationships should be considered in selecting anticoagulant therapies in patients undergoing primary PCI.

Efficacy of cilostazol on platelet reactivity and cardiovascular outcomes in patients undergoing percutaneous coronary intervention: insights from a meta-analysis of randomised trials.

BACKGROUND: Cilostazol overcomes high on-treatment platelet reactivity (HTPR) and reduces adverse cardiovascular (CV) outcomes after percutaneous coronary intervention (PCI). However, the role for triple antiplatelet therapy (TAPT) with cilostazol in addition to aspirin and clopidogrel after PCI is not well defined. METHODS: We conducted a MEDLINE/EMBASE/CENTRAL search for randomised trials, until May 2014, evaluating TAPT compared with dual antiplatelet therapy (DAPT) of aspirin and clopidogrel alone in patients undergoing PCI and reporting platelet reactivity and/or CV outcomes. The primary platelet reactivity outcome was differences in platelet reactivity unit (PRU) with secondary outcomes of %platelet inhibition and rate of HTPR. The primary CV outcome was major adverse cardiovascular events (MACE), with secondary outcomes of death, cardiovascular death, myocardial infarction, stent thrombosis (ST), target lesion revascularisation (TLR) and target vessel revascularisation (TVR) as well as safety outcomes of bleeding and drug discontinuations. RESULTS: In 17 trials that evaluated platelet reactivity outcomes, the mean PRU value was 47.73 units lower with TAPT versus DAPT (95% CI -61.41 to -34.04, p<0.0001; mean PRU 182.90 vs 232.65). TAPT also increased platelet inhibition by 12.71% (95% CI 10.76 to 14.67, p<0.0001), and led to a 60% reduction in the risk of HTPR (relative risk=0.40; 95% CI 0.30 to 0.53) compared with DAPT. Moreover, among the 34 trials that evaluated CV outcomes, TAPT reduced the risk of MACE (incident rate ratio (IRR)=0.68; 95% CI 0.60 to 0.78), TLR (IRR=0.57; 95% CI 0.44 to 0.73), TVR (IRR=0.69; 95% CI 0.59 to 0.81) and ST (IRR=0.63; 95% CI 0.40 to 0.98) with no difference for other outcomes including bleeding, even in trials using drug-eluting stents. Drug discontinuation due to adverse effects was, however, higher with TAPT vs DAPT (IRR=1.59; 95% CI 1.32 to 1.91). CONCLUSIONS: In patients undergoing PCI, addition of cilostazol to DAPT results in decreased platelet reactivity and a significant reduction in CV outcomes including ST, even in the drug-eluting stent era.

Outcomes with coronary artery bypass graft surgery versus percutaneous coronary intervention for patients with diabetes mellitus: can newer generation drug-eluting stents bridge the gap?

BACKGROUND: Coronary artery bypass graft surgery (CABG) compared with percutaneous coronary intervention (PCI) reduces mortality in patients with diabetes mellitus. However, prior trials compared CABG with balloon angioplasty or older generation stents, and it is not known if the gap between CABG and PCI can be reduced by newer generation drug-eluting stents. METHODS AND RESULTS: PUBMED/EMBASE/CENTRAL search for randomized trials comparing mode of revascularization in patients with diabetes mellitus. Primary outcome was all-cause mortality. Secondary outcomes were myocardial infarction, repeat revascularization, and stroke. Mixed treatment comparison analyses were performed using a random-effects Poisson regression model. Sixty-eight randomized trials that enrolled 24 015 diabetic patients with a total of 71 595 patient-years of follow-up satisfied our inclusion criteria. When compared with CABG (reference rate ratio [RR]=1.0), PCI with paclitaxel-eluting stent (RR=1.57 [1.15-2.19]) or sirolimus-eluting stent (RR=1.43 [1.06-1.97]) was associated with an increase in mortality. However, PCI with cobalt-chromium everolimus-eluting stent (RR=1.11 [0.67-1.84]) was not associated with a statistically significant increase in mortality. When compared with CABG, there was excess repeat revascularization with PCI, which progressively declined from plain old balloon angioplasty (341% increase) to bare metal stent (218% increase) to paclitaxel-eluting stent (81% increase) and to sirolimus-eluting stent (47% increase). However, for PCI with cobalt-chromium everolimus-eluting stent (RR=1.31 [0.74-2.29]), the excess repeat revascularization was not statistically significant although the point estimate favored CABG. CABG was associated with numerically higher stroke. CONCLUSIONS: In patients with diabetes mellitus, evidence from indirect comparison shows similar mortality between CABG and PCI using cobalt-chromium everolimus-eluting stent. CABG was associated with numerically excess stroke and PCI with cobalt-chromium everolimus-eluting stent with numerically increased repeat revascularization. This hypothesis needs to be tested in future trials.

Clinical outcomes with ß-blockers for myocardial infarction: a meta-analysis of randomized trials.

BACKGROUND: Debate exists about the efficacy of ß-blockers in myocardial infarction and their required duration of usage in contemporary practice. METHODS: We conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials evaluating ß-blockers in myocardial infarction enrolling at least 100 patients. The primary outcome was all-cause mortality. Analysis was performed stratifying trials into reperfusion-era (> 50% undergoing reperfusion or receiving aspirin/statin) or pre-reperfusion-era trials. RESULTS: Sixty trials with 102,003 patients satisfied the inclusion criteria. In the acute myocardial infarction trials, a significant interaction (Pinteraction = .02) was noted such that ß-blockers reduced mortality in the pre-reperfusion (incident rate ratio [IRR] 0.86; 95% confidence interval [CI], 0.79-0.94) but not in the reperfusion era (IRR 0.98; 95% CI, 0.92-1.05). In the pre-reperfusion era, ß-blockers reduced cardiovascular mortality (IRR 0.87; 95% CI, 0.78-0.98), myocardial infarction (IRR 0.78; 95% CI, 0.62-0.97), and angina (IRR 0.88; 95% CI, 0.82-0.95), with no difference for other outcomes. In the reperfusion era, ß-blockers reduced myocardial infarction (IRR 0.72; 95% CI, 0.62-0.83) (number needed to treat to benefit [NNTB] = 209) and angina (IRR 0.80; 95% CI, 0.65-0.98) (NNTB = 26) at the expense of increase in heart failure (IRR 1.10; 95% CI, 1.05-1.16) (number needed to treat to harm [NNTH] = 79), cardiogenic shock (IRR 1.29; 95% CI, 1.18-1.41) (NNTH = 90), and drug discontinuation (IRR 1.64; 95% CI, 1.55-1.73), with no benefit for other outcomes. Benefits for recurrent myocardial infarction and angina in the reperfusion era appeared to be short term (30 days). CONCLUSIONS: In contemporary practice of treatment of myocardial infarction, ß-blockers have no mortality benefit but reduce recurrent myocardial infarction and angina (short-term) at the expense of increase in heart failure, cardiogenic shock, and drug discontinuation. The guideline authors should reconsider the strength of recommendations for ß-blockers post myocardial infarction.

Choosing the right coronary stent in the modern era.

Research and development in the field of coronary stent design is a fast-evolving and fascinating journey. A device that was once introduced to salvage acute closure associated with balloon angioplasty is now the standard of care for many patients with coronary artery disease. Newer generation stents are the product of remarkable progress in technology and innovation, driven by the need to make the stents easier to deliver and to improve their safety and efficacy. As such, the design of these stents has become quite sophisticated and complex. The number of available stents has increased giving patients and physicians more choices on one hand, but also created confusion in selecting the optimal stent for a given patient. Although a 'one size fits all' approach may not be reasonable, several randomized trials have attested to the efficacy and safety of newer generation durable polymer drug eluting stents. This article discusses the evidence base to support various stent choices in contemporary practice.