Rahman Shah

Statins and Mortality Among Elderly Patients Hospitalized With Heart Failure

Background— Small studies suggest that statins may improve mortality in patients with heart failure (HF). Whether these results are generalizable to a broader group of patients with HF remains unclear. Our objective was to evaluate the association between statin use and survival among a national sample of elderly patients hospitalized with HF. Methods and Results— A nationwide sample of 61 939 eligible Medicare beneficiaries ≥65 years of age who were hospitalized with a primary discharge diagnosis of HF between April 1998 and March 1999 or July 2000 and June 2001 was evaluated. The analysis was restricted to patients with no contraindications to statins (n=54 960). Of these patients, only 16.7% received statins on discharge. Older patients were less likely to receive a statin at discharge. Patients with hyperlipidemia and those cared for by a cardiologist or cared for in a teaching hospital were more likely to receive a statin at discharge. In a Cox proportional hazards model that took into account demographic, clinical characteristics, treatments, physician specialty, and hospital characteristics, discharge statin therapy was associated with significant improvements in 1- and 3-year mortality (hazard ratio, 0.80; 95% CI, 0.76 to 0.84; and hazard ratio, 0.82; 95% CI, 0.79 to 0.85, respectively). Regardless of total cholesterol level or coronary artery disease status, statin therapy was associated with significant differences in mortality. Conclusions— Our data demonstrate that statin therapy is associated with better long-term mortality in older patients with HF. This study suggests a potential role for statins as an adjunct to current HF therapy. Randomized clinical trials are required to determine the role of these agents in improving outcomes in the large and growing group of patients with HF.

Protease-activated receptors in cardiovascular health and diseases

The platelet, once thought to be solely involved in clot formation, is now known to be a key mediator in various other processes such as inflammation, thrombosis, and atherosclerosis. Therefore, antiplatelet agents have become paramount in the prevention and management of various cardiovascular diseases. However, the currently most widely used antiplatelet drugs, aspirin and clopidogrel, have been shown to reduce the risk of serious vascular events only by approximately one quarter. Similarly, oral glycoprotein IIb/IIIa antagonists have been associated with excess mortality, thus restricting the use of parental glycoprotein IIb/IIIa antagonists to the treatment of acute clinical conditions. Thus, for the prevention of cardiovascular diseases, there is still a clinical need for antiplatelet drugs with higher antithrombotic efficacy but with safety profiles that allow for a preventive long-term administration. Thrombin signaling through the protease-activated receptors (PARs) has been shown to influence a wide range of physiologic and pathologic responses in cardiovascular systems. Thus, interference with PARs appears to be a promising strategy to develop new antiplatelet agents with higher efficacy. This review focuses on the cardiovascular actions of PARs that play a role in normal cardiovascular physiology and that are likely to contribute to cardiovascular diseases.

An updated comprehensive meta-analysis of bivalirudin vs heparin use in primary percutaneous coronary intervention

BACKGROUND Despite several randomized controlled trials and meta-analyses, the ideal anticoagulant for patients undergoing primary percutaneous coronary intervention (PCI) remains controversial. We performed an updated meta-analysis including recently reported randomized clinical trials that compare bivalirudin and heparin with or without provisional administration of a glycoprotein IIb/IIIa inhibitor (GPI) for primary PCI. METHODS AND RESULTS Scientific databases and Web sites were searched for randomized clinical trials. Data from 6 trials involving 14,095 patients were included. The pooled risk ratios (RRs) were calculated using random-effects models. Moderator analyses examined the impact of routine use of GPI, radial access, and P2Y12 inhibitors on safety outcomes. At 30 days, patients receiving bivalirudin had rates of major adverse cardiac events similar to those receiving heparin with or without provisional GPI (RR 1.02, 95% CI 0.87-1.19, P = .800), myocardial infarction (RR 1.41, 95% CI 0.94-2.11, P = .089), target vessel revascularization (RR 1.37, 95% CI 0.91-2.04, P = .122), and net adverse clinical events (RR 0.81, 95% CI 0.64-1.01, P = .069). However, bivalirudin use decreased the risk of all-cause mortality (RR 0.81, 95% CI 0.67-0.99, P = .041) and cardiac mortality (RR 0.68, 95% CI 0.51-0.91, P = .009) at 30 days, There were higher rates of acute stent thrombosis (RR 3.31, 95% CI 1.79-6.10, P < .001) in patients receiving bivalirudin. Bivalirudin use also decreased the risk of major bleeding at 30 days by 37% (RR 0.63, 95% CI 0.44-0.90, P = .012), but bleeding risk varied depending on routine GPI use with heparin (RR 0.44, 95% CI 0.23-0.81, P = .009) vs bailout (RR 0.73, 95% CI 0.42-1.25, P = .252), predominantly radial access (RR 0.54, 95% CI 0.25-1.15, P = .114) vs non-radial access (RR 0.60, 95% CI 0.36-0.99, P = .049), and second-generation P2Y12 inhibitor use with bivalirudin (RR 0.70, 95% CI 0.40-1.24, P = .226) vs clopidogrel use (RR 0.39, 95% CI 0.18-0.85, P = .018). CONCLUSIONS In primary PCI, relative to heparin, bivalirudin reduces the risk for all-cause mortality, cardiac mortality, and major bleeding but yields similar rates of major adverse cardiac event and net adverse clinical event at 30 days. However, the benefit of a reduction in bleeding with bivalirudin appears to be modulated by the concurrent administration of second-generation P2Y12 inhibitors with bivalirudin, using radial access, and avoiding routine GPI use with heparin.

Ticagrelor as an alternative in clopidogrel-associated neutropenia.

Abstract Aspirin in combination with platelet P2Y12 receptor blocker has become the mainstay antiplatelet treatment strategy for the prevention of stent thrombosis. Ticlopidine was the first widely used P2Y12 receptor blockers, but clopidogrel has mostly replaced the use of ticlopidine due to its more favorable adverse event profile on bone marrow. However, when clopidogrel induced bone marrow toxicity occurs, little is known about the efficacy and safety of alternative treatments, and thus, in these cases, medical decisions may be very difficult. We report a case of clopidogrel-induced severe neutropenia in a patient treated with coronary stent and safety of alternative treatment with ticagrelor.

Radial versus femoral access for cardiac catheterisation

1 Valgimigli M, Gagnor A, Calabró P, et al, for the MATRIX Investigators. Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial. Lancet 2015; 385: 2465–76. clinical events compared with femoral access, and that this benefit is most pronounced in centres that manage a high proportion (80·0–98·0%) of cases via the radial approach. However, in centres that manage a low-to-intermediate proportion (14·9–79·0%) of cases via the radial approach, almost identical outcomes were seen between radial and femoral access for major adverse cardiovascular events, net adverse clinical events, and all-cause mortality. By contrast, in centres that manage a high proportion of cases via the radial approach, a significant difference was reported between radial and femoral access for major adverse cardiovascular events (10% vs 15%; p=0·00014), net adverse clinical events (11% vs 17%; p<0·0001) and all-cause mortality (2% vs 3%; p=0·006). Centres that manage a high proportion of cases via the radial approach do not achieve superior outcomes with radial access compared with centres that manage a low-to-intermediate proportion of cases via this approach; rather, a significant excess of events was reported in their femoral access group (table). The study’s positive outcomes in favour of radial access are probably driven by excess events after femoral access in centres that manage a low proportion of cases via James E Bennett, Guangquan Li, Vasilis Kontis, Kyle Foreman, *Majid Ezzati majid.ezzati@imperial.ac.uk

Meta-Analysis of the Relative Efficacy and Safety of Oral P2Y12 Inhibitors in Patients With Acute Coronary Syndrome

A cornerstone of medical therapy for patients with acute coronary syndrome (ACS) is dual antiplatelet therapy, which includes aspirin and a P2Y12 inhibitor. Randomized controlled trials (RCTs) have shown that prasugrel and ticagrelor are superior to clopidogrel, but none directly compared these 3 commonly used oral P2Y12 inhibitors for safety and efficacy. Therefore, we performed a Bayesian network meta-analysis of RCTs to compare the efficacies and safeties of 3 commonly used oral P2Y12 inhibitors in patients with ACS. Scientific databases and websites were searched for relevant RCTs. We included data from 9 RCTs that enrolled 106,288 patients. Clopidogrel decreased the rates of major adverse cardiac event, recurrent myocardial infarction, and all-cause mortality compared with placebo. Both ticagrelor and prasugrel decreased the rates for major adverse cardiac event and recurrent myocardial infarction compared with clopidogrel, but there was no difference between the 2. Both also decreased the stent thrombosis rate compared with clopidogrel, but prasugrel was more effective than ticagrelor. Ticagrelor use was also associated with improved all-cause and CV mortalities compared with clopidogrel. There was no difference in CV mortality or all-cause mortality between clopidogrel and prasugrel. Prasugrel use was also associated with significantly increased risk of major bleeding compared with clopidogrel but showed a nonsignificant trend toward increasing the risk of bleeding compared with ticagrelor. In treatment ranking, ticagrelor was the most efficacious, and prasugrel was the least safe. In conclusion, this meta-analysis shows that in patients with ACS, adding P2Y12 inhibitors to aspirin and other standard treatments reduces ischemic events and all-cause mortality. Among the commonly used oral P2Y12 inhibitors, ticagrelor has the best net efficacy and safety profile.

The Fuzzy Math of Anticoagulation and Access Site: When 1 + 1 Does Not Always Equal 2

Performing percutaneous coronary intervention (PCI) involves choices. The operator must choose the access site, the guide catheter, the guidewire, the antithrombotic therapy, the general approach, the stent type, and the closure method. Some of these decisions can affect the success of the procedure

Contrast use in relation to the arterial access site for percutaneous coronary intervention: A comprehensive meta-analysis of randomized trials

AIM To compare the amount of contrast used during percutaneous coronary intervention (PCI) via trans-radial access (TRA) vs trans-femoral access (TFA). METHODS Scientific databases and websites were searched for:randomizedcontrolledtrials (RCTs). Data were extracted by two independent reviewers and was summarized as the weighted mean difference (WMD) of contrast used with a 95%CI using a random-effects model. RESULTS The meta-analysis included 13 RCTs with a total of 3165 patients. There was no difference between the two strategies in the amount of contrast used (WMD = - 0.65 mL, 95%CI: -10.94-9.46 mL; P = 0.901). CONCLUSION This meta-analysis shows that in patients undergoing PCI, the amount of contrast volume used was not different between TRA and TFA.

Mortality and operator experience with vascular access for percutaneous coronary intervention in patients with acute coronary syndromes: A pairwise and network meta-analysis of randomized controlled trials

BACKGROUND Recently, several meta-analyses of randomized controlled trials (RCTs) have shown that transradial access (TRA) reduces mortality compared to transfemoral access (TFA). However, a critical appraisal of these RCTs suggests that the findings could have resulted from a greater incidence of adverse events in the TFA groups rather than a beneficial effect of TRA. METHODS Scientific databases and websites were searched for RCTs. Patients were divided into groups based on access type and whether the operator was a radial expert (RE) or non-radial expert (NRE). The groups were TFA-RE, TFA-NRE, TRA-RE, and TRA-NRE. Both a traditional meta-analysis and a network meta-analysis using mixed-treatment comparison models were performed. RESULTS Data from 13 trials including 15,615 patients were analyzed. The mortality rate for TFA-RE (3.54%) was more than double compared to TFA-NRE (1.61%). In pairwise meta-analysis, TFA-RE was associated with increased risk of mortality (RR: 1.72, 95% CI: 1.13-2.62; p=0.011) compared to TFA-NRE. In subgroup analysis, TFA-RE was associated with increased mortality (RR: 1.70, 95% CI: 1.24-2.34; p=0.001) compared to TRA, but TRA-NRE was not. Similarly, in mixed comparison models, TFA-RE was associated with increased mortality compared to TRA-NRE, TRA-RE, and TFA-NRE, but TFA-NRE was not, compared to TRA-RE and TRA-NRE. CONCLUSION Recently-reported survival differences between TRA and TFA may have been driven by adverse events in the TFA groups of the RCTs rather than a beneficial effect of TRA. This issue needs further investigation before labeling radial access a lifesaving procedure in invasively-managed patients with ACS.

Bivalirudin in Acute Coronary Syndromes.

To the Editor: Valgimigli et al. (Sept. 10 issue)1 report that prolongation of the bivalirudin infusion after the completion of coronary intervention did not significantly reduce the risk of early stent thrombosis with bivalirudin as compared with the periprocedural use of unfractionated heparin. The rapid and opposing endothelial effects of bivalirudin and heparin have been described previously.2 Bivalirudin enhances the vascular sequestration of neutrophil-derived myeloperoxidase, which has the effect of accelerating the consumption of nitric oxide and depressing its bioavailability.2 In contrast, heparin liberates vessel-bound myeloperoxidase and improves endothelial function.2 The bivalirudin–myeloperoxidase–nitric oxide interaction may predispose patients to early stent thrombosis during acute myocardial infarction. First, neutrophil activation is an early event in acute myocardial infarction.3 Second, interactions between activated platelets and neutrophils stimulate the formation of so-called neutrophil extracellular traps (chromatin filaments released from neutrophils) bearing active tissue factor in the infarct-related artery,4 which further induces thrombin generation and platelet activation. Third, blockade of the platelet P2Y12-receptor boosts the capacity of nitric oxide to inhibit thrombin-stimulated platelet activation and aggregation by a factor of 1000 to 100,000.5 Thus, the bivalirudin-mediated vascular immobilization of neutrophil-derived myeloperoxidase might contribute to early stent thrombosis during acute myocardial infarction as a result of the inactivation of endogenous nitric oxide that occurs before there is fully effective platelet inhibition, just after loading doses of oral P2Y12 antagonists have been administered. Andrzej Surdacki, M.D., Ph.D.