Debate: PCI or CABG for multivessel disease? Viewpoint: No clear winner in an unfair fight

The Arterial Revascularization Therapy Study (ARTS) and the Stent or Surgery (SoS) trial each randomized patients with multivessel disease to either stenting or bypass surgery. The ARTS showed no difference in mortality between the two strategies, other than in diabetic patients, who fared better with surgery. The SoS trial demonstrated increased mortality in the stent arm, a difference that was not attributable to diabetes. Both trials found that the rates of repeat revascularization were lower with surgery, although the rate with stenting was much lower than had been seen in previous trials of angioplasty. Use of antiplatelet therapy such as intravenous glycoprotein IIb/IIIa inhibitors, especially with their pronounced effects in diabetics and in those with multivessel disease, could potentially equalize the playing field or perhaps even tip the balance in favor of percutaneous intervention

Mechanical Thrombectomy for Acute Ischemic Stroke A Meta-Analysis of Randomized Trials

AbstractBackgroundAcute ischemic stroke is a leading cause of serious disability and death worldwide. Individual randomized trials have shown possible benefits of mechanical thrombectomy after usual care compared with usual care alone (i.e., intravenous thrombolysis) in the management of acute ischemic stroke patients.ObjectivesThis study systematically determined if mechanical thrombectomy after usual care would be associated with better outcomes in patients with acute ischemic stroke caused by large artery occlusion.MethodsThe authors included randomized trials that compared mechanical thrombectomy after usual care versus usual care alone for acute ischemic stroke. Random effects summary risk ratios (RR) were constructed using a DerSimonian and Laird model.ResultsNine trials with 2,410 patients were available for analysis. Compared with usual care alone, mechanical thrombectomy was associated with a higher incidence of achieving good functional outcome, defined as a modified Rankin scale (mRS) of 0 to 2 (RR: 1.45; 95% confidence interval [CI]: 1.22 to 1.72; p < 0.0001) and excellent functional outcome defined as mRS 0 to 1 (RR: 1.67; 95% CI: 1.27 to 2.19; p < 0.0001) at 90 days. There was a trend toward reduced all-cause mortality with mechanical thrombectomy (RR: 0.86; 95% CI: 0.72 to 1.02; p = 0.09). The risk of symptomatic intracranial hemorrhage was similar with either treatment modality (RR 1.06: 95% CI: 0.73 to 1.55; p = 0.76).ConclusionsIn acute ischemic stroke due to large artery occlusion, mechanical thrombectomy after usual care was associated with improved functional outcomes compared with usual care alone, and was found to be relatively safe, with no excess in intracranial hemorrhage. There was a trend for reduction in all-cause mortality with mechanical thrombectomy

Paradoxical Association of Smoking With In‐Hospital Mortality Among Patients Admitted With Acute Ischemic Stroke

Background: Compared to those who never smoked, a paradoxical effect of smoking on reducing mortality in patients admitted with myocardial ischemia has been reported. We sought to determine if this effect was present in patients hospitalized with ischemic stroke. Methods and Results: Using the local Get with the Guidelines‐Stroke registry, we analyzed 4305 consecutively admitted ischemic stroke patients (March 2002–December 2011). The sample was divided into smokers versus nonsmokers. The main outcome of interest was the overall inpatient mortality. Compared to nonsmokers, tobacco smokers were younger, more frequently male and presented with fewer stroke risk factors such as hypertension, hyperlipidemia, diabetes, coronary artery disease, and atrial fibrillation. Smokers also had a lower average NIH Stroke Scale (NIHSS) and fewer received tissue plasminogen activator (tPA). Patients in both groups had similar adherence to early antithrombotics, dysphagia screening prior to oral intake, and deep vein thrombosis (DVT) prophylaxis. Smoking was associated with lower all‐cause in‐hospital mortality (6.6% versus 12.4%; unadjusted OR 0.46; CI [0.34 to 0.63]; P<0.001). In multivariable analysis, adjusted for age, gender, ethnicity, hypertension, diabetes mellitus, hyperlipidemia, CAD, atrial fibrillation, NIHSS, and tPA, smoking remained independently associated with lower mortality (adjusted OR 0.64; CI [0.42 to 0.96]; P=0.03). Conclusions: Similar to myocardial ischemia, smoking was independently associated with lower inpatient mortality in acute ischemic stroke. This effect may be due to tobacco‐induced changes in cerebrovascular vasoreactivity, or may be due in part to residual confounding. Larger, multicenter studies are needed to confirm the finding and the effect on 30‐day and 1‐year mortality

Relationships between components of blood pressure and cardiovascular events in patients with stable coronary artery disease and hypertension

Observational studies have shown a J-shaped relationship between diastolic blood pressure (BP) and cardiovascular events in hypertensive patients with coronary artery disease. We investigated whether the increased risk associated with low diastolic BP reflects elevated pulse pressure (PP). In 22 672 hypertensive patients with coronary artery disease from the CLARIFY registry (Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease), followed for a median of 5.0 years, BP was measured annually and averaged. The relationships between PP and diastolic BP, alone or combined, and the primary composite outcome (cardiovascular death or myocardial infarction) were analyzed using multivariable Cox proportional hazards models. Adjusted hazard ratios for the primary outcome were 1.62 (95% confidence interval [CI], 1.40–1.87), 1.00 (ref), 1.07 (95% CI, 0.94–1.21), 1.54 (95% CI, 1.32–1.79), and 2.34 (95% CI, 1.95–2.81) for PP&lt;45, 45 to 54 (reference), 55 to 64, 65 to 74, and ≥75 mm Hg, respectively, and 1.50 (95% CI, 1.31–1.72), 1.00 (reference), and 1.58 (95% CI, 1.42–1.77) for diastolic BPs of &lt;70, 70 to 79 (ref), and ≥80 mm Hg, respectively. In a cross-classification analysis between diastolic BP and PP, the relationship between diastolic BP and the primary outcome remained J-shaped when the analysis was restricted to patients with the lowest-risk PP (45–64 mm Hg), with adjusted hazard ratios of 1.53 (95% CI, 1.27–1.83), 1.00 (ref), and 1.54 (95% CI, 1.34–1.75) in the &lt;70, 70 to 79 (reference), and ≥80 mm Hg subgroups, respectively. The J-shaped relationship between diastolic BP and cardiovascular events in hypertensive patients with coronary artery disease persists in patients within the lowest-risk PP range and is therefore unlikely to be solely the consequence of an increased PP reflecting advanced vascular disease

Effect of Sotagliflozin on Total Hospitalizations in Patients With Type 2 Diabetes and Worsening Heart Failure A Randomized Trial

Background: In the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure) trial, sotagliflozin, a sodium-glucose cotransporter-1 and sodium-glucose cotransporter-2 inhibitor, reduced total occurrences of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure relative to placebo by 33%. Objective: To determine whether sotagliflozin increased the prespecified efficacy outcome of days alive and out of the hospital (DAOH) in the SOLOIST-WHF trial. Design: Randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT03521934) Setting: 306 sites in 32 countries. Participants: 1222 patients with type 2 diabetes and reduced or preserved ejection fraction who were recently hospitalized for worsening heart failure. Intervention: 200 mg of sotagliflozin once daily (with a possible dose increase to 400 mg) or matching placebo. Measurements: The primary analysis included hospitalizations for any reason on the basis of investigator-reported incidence and duration of admissions after randomization. Days alive and out of the hospital and its converse (days dead and days in the hospital) were analyzed using prespecified Poisson regression models. Results: Although similar proportions of patients in the sotagliflozin and placebo groups were hospitalized at least once (38.5% vs. 41.4%), fewer patients in the sotagliflozin group were hospitalized more than once (16.3% vs. 22.1%). There were 64 and 76 deaths in the sotagliflozin and placebo groups, respectively. The DAOH rate in the sotagliflozin group was 3% higher than in the placebo group (rate ratio [RR], 1.03 [95% CI, 1.00 to 1.06]; P = 0.027). This difference was primarily driven by a reduction in the rate of days dead (RR, 0.71 [CI, 0.52 to 0.99]; P = 0.041) rather than by a reduction in the rate of days hospitalized for any cause. For every 100 days of follow-up, patients in the sotagliflozin group were alive and out of the hospital for 3% or 2.9 more days than those in the placebo group (91.8 vs. 88.9 days); this difference reflected a 2.6-day difference in days dead (6.3 vs. 8.9 days) and a 0.3-day difference in days in the hospital (1.9 vs. 2.2 days). Limitation: Other than heart failure, the primary reason for each hospitalization was unspecified. Conclusion: Sotagliflozin increased DAOH, a metric that may provide an additional patient-centered outcome to capture the totality of disease burden. Future studies are needed to quantify the consequences of increasing DAOH in terms of health economics and patient quality of life.Peer reviewe

Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers.

BACKGROUND: Ticagrelor is an oral P2Y12 inhibitor that is used with aspirin to reduce the risk of ischemic events among patients with acute coronary syndromes or previous myocardial infarction. Spontaneous major bleeding and bleeding associated with urgent invasive procedures are concerns with ticagrelor, as with other antiplatelet drugs. The antiplatelet effects of ticagrelor cannot be reversed with platelet transfusion. A rapid-acting reversal agent would be useful. METHODS: In this randomized, double-blind, placebo-controlled, phase 1 trial, we evaluated intravenous PB2452, a monoclonal antibody fragment that binds ticagrelor with high affinity, as a ticagrelor reversal agent. We assessed platelet function in healthy volunteers before and after 48 hours of ticagrelor pretreatment and again after the administration of PB2452 or placebo. Platelet function was assessed with the use of light transmission aggregometry, a point-of-care P2Y12 platelet-reactivity test, and a vasodilator-stimulated phosphoprotein assay. RESULTS: Of the 64 volunteers who underwent randomization, 48 were assigned to receive PB2452 and 16 to receive placebo. After 48 hours of ticagrelor pretreatment, platelet aggregation was suppressed by approximately 80%. PB2452 administered as an initial intravenous bolus followed by a prolonged infusion (8, 12, or 16 hours) was associated with a significantly greater increase in platelet function than placebo, as measured by multiple assays. Ticagrelor reversal occurred within 5 minutes after the initiation of PB2452 and was sustained for more than 20 hours (P\u3c0.001 after Bonferroni adjustment across all time points for all assays). There was no evidence of a rebound in platelet activity after drug cessation. Adverse events related to the trial drug were limited mainly to issues involving the infusion site. CONCLUSIONS: In healthy volunteers, the administration of PB2452, a specific reversal agent for ticagrelor, provided immediate and sustained reversal of the antiplatelet effects of ticagrelor, as measured by multiple assays. (Funded by PhaseBio Pharmaceuticals; ClinicalTrials.gov number, NCT03492385.)

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

Women and Diabetes: Preventing Heart Disease in a New Era of Therapies

Despite major advances in cardiovascular research over the past decade, women with type 2 diabetes have a high risk of cardiovascular events. Several factors contribute to the poor prognosis for women, including higher levels of frailty and comorbidities, but their cardiovascular risk is underestimated and there is suboptimal implementation and uptitration of new evidence-based therapies, leading to high morbidity and mortality. Recent studies highlight the need for better management of diabetes in women that can be pursued and achieved in light of recent results from randomised controlled trials demonstrating evidence of the benefits of new therapeutic strategies in improving cardiovascular outcomes and quality of life of women covering the entire cardiovascular continuum. This review critically discusses the multiple benefits for women of new pharmacological treatments, such as glucagon-like peptide-1 receptor agonists, sodium–glucose cotransporter type 2 inhibitors (SGLT2i), proprotein convertase subtilisin/kexin type 9 inhibitors, inclisiran, icosapent ethyl and bempedoic acid in preventing cardiovascular events, and treatments, such as angiotensin receptor neprilysin inhibitors, SGLT2i, vericiguat and omecamtiv mecarbil, for preventing heart failure