Door-to-balloon: Where do we lose time? Single centre experience in India

Background/AimsTo assess the factors causing delay in attaining DTB time of <90 min.MethodsEighty-five patients who underwent primary PCI from August 2008 to July 2009 were studied. From door-to-balloon, time was divided into 6 stages; any reason for delay was studied.ResultsThe mean DTB time was 80.5 min (SD = 34.4, median time 75 min, range 30–195). DTB time was <90 min in 76.5%, and DTB time >90 min occurred in 23.5%. Mean door to ECG – 6.5 min (SD = 2.7), mean time for the decision of PCI – 7.5 min (SD = 10.5), mean time taken for the patient's consent – 19.6 min (SD = 17.6), for STEMI team activation – 6.7 min (SD = 7.6), average time for financial process – 39.2 min (SD = 22.9). Average time for sheath to balloon – 5.2 min (SD = 1.7). Hospital related delay occurred in 5%, patient related delay in 80%, both together in 15%. 89.5% of patient related delay was due to delay in giving consent and financial reasons. There was no statistically significant delay for patients presented at morning or night and during the weekdays or weekend. Total mortality was 4.7%. Mortality among <90 min was 3.1%, mortality among >90 min was 10% (‘p’ = 0.2).ConclusionsWith effective hospital strategies, the DTB time of 90 min can be achieved in majority of patients. The chief delay in DTB time in this study was due to a delay in obtaining consent and financial reasons.     

Aging might increase myocardial ischemia / reperfusion-induced apoptosis in humans and rats

Previous studies indicated aging results in the significant cardiac function decreasing and myocardial apoptosis increasing in normal humans or rats. Additionally, animal experiments demonstrated aging increased myocardial ischemia / reperfusion (MI/R)-induced apoptosis. However, whether more myocardial apoptosis happen in the old acute myocardial infarction (AMI) patients is unclear. Reperfusion injury-induced apoptosis is an important cause of heart failure. This study determined the effect of aging upon myocardial apoptosis and cardiac function in patients suffering AMI. All enrolled AMI patients received percutaneous coronary intervention therapy. Volunteers and AMI patients were assigned to four groups: adult (age <65, n = 24) volunteers, elderly (age ≥65, n = 21) volunteers, adult (age <65, n = 29) AMI patients, and elderly (age ≥65, n = 36) AMI patients. Blood samples were obtained from all study participants. Plasma apoptotic markers (soluble form of Fas, tumor necrosis factor alpha, and interleukin 6) levels were determined. Cardiac function was evaluated with echocardiogram and Killip class. Due to lack of a direct apoptotic assay method in live human subjects, an additional animal experiment was performed. Both young (2 months) and old (24 months) rats were subjected to 30-min myocardial ischemia and 3 (for TUNEL/caspase activity apoptotic assay) or 24-h (for cardiac function determination) reperfusion. Compared to adult patients, the elderly patients manifested decreased cardiac function and increased plasma apoptotic marker levels significantly. The animal experiment results (cardiac function and plasma apoptotic markers assays) were consistent with the human result data. Animal TUNEL staining and caspase activity measurement revealed a higher myocardial apoptotic ratio in the older rat group. Aging exacerbated MI/R injury in humans and rats. Differential myocardial apoptosis may play a vital role in mediating the observed effects.     

Comparison of benefit and safety between different loading dose of clopidogrel on elderly patients undergoing primary percutaneous cronary intervention for ST-segment elevation myocardial infarction

Background Despite the proven benefit of 600-mg loading dose of clopidogrel in patients with acute ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous cronary intervention (PCI), there is still concern about its benefit and safety on elderly population. Methods Data of 172 consecutive elderly patients (≥75 years) with STEMI who underwent primary PCI at Guangdong Provincial Cardiovascular Institute from January 2008 to December 2011 were retrospectively collected. Patients were divided into 600-mg loading clopidogrel group and 300-mg clopidogrel group accoring to the loading dose of clopidogrel before primary percunaeous coronary intervention(PCI). Enzymatic myocardial infarction size estimated by peak creatine kinase-myocardial band (CK-MB) and patency of the infarct-related artery (IRA) were compared. Thirty-day major adverse cardiac events (MACEs), which consist of death, nonfatal myocardial infarction (MI), nonfatal stroke, target vessel revascularization (TVR) or stent thrombosis (ST) were compared to assess the efficacy of different loading dose. Bleeding information was compared as well to assess the safety of different pretreatment stragety before primary PCI. Results 96 patients were adminstered with 600-mg loading clopidogrel before primary PCI while 76 were administered with 300-mg. Patency of the IRA was significantly higher in patients administered with 600-mg loading clopidogrel therapy as compared with those who received 300-mg loading clopidogrel (94.8% vs. 85.5%, P = 0.038). 600-mg loading dose of clopidogrel was associated with lower incidence of 30-day MACEs compared with 300-mg loading dose of clopidogrel (8.3% vs. 19.7%, P = 0.029) while did not increase the risk of TIMI major (3.1% vs. 3.9%, P = 0.770) and minor bleeding (10.4% vs. 6.6%, P = 0.376). Conclusion 600-mg loading clopidogrel improves final patency of the IRA and clinical outcome as compared with 300-mg loading clopidogrel without increasing bleeding hazard.     

Inequality in access to CABG and PCI

Abstract

Non-inferiority trials are questionable when death and serious complications are included among outcomes. The term itself “non-inferiority” is misleading, since such a study would not demonstrate that a new treatment is non-inferior to a control treatment, but simply that the inferiority would not reach a pre-specified level, deemed as acceptable by the designers of the trial. Group cross-over, assay-sensitivity and the need of a placebo arm are major issues for the reliability of non-inferiority trials.

The SYNTAX trial for severe coronary artery disease was designed on a non-inferiority margin of 6.6%. In this paper we show that the SYNTAX designers were ready to accept up to 30% higher rate of death and major adverse events to claim the non-inferiority of percutaneous coronary intervention versus coronary artery bypass grafting. Eventually the SYNTAX study failed because percutaneous patients sustained an even higher rate of adverse events. We propose major caution in performing non-inferiority randomized trials.     

HRQoL after coronary artery bypass grafting and percutaneous coronary intervention for stable angina

Objectives. To assess the health related quality of life (HRQoL) and the change in the NYHA class after coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in the management of stable coronary artery disease (CAD). The study was non-randomized. CABG group consisted of 240 patients and 229 patients were treated with PCI. HRQoL was measured prospectively by the 15D instrument. Results. Three-year survival was 95.0 and 95.6% (NS). The HRQoL improved statistically in both groups until 6 months after treatment but deteriorated towards the end of the follow-up of 36 months. Clinically evident improvement of the HRQoL and decrease of the NYHA class took place more frequently among CABG patients. Conclusions. Despite initially more serious preoperative state and more demanding procedure CABG patients achieve equal level of HRQoL when compared with PCI patients. CABG patients may also obtain better relief from symptoms in mid-term follow-up. HRQoL cannot be the only factor to determine outcome after invasive treatment of CAD but it has to be placed in the context of the overall situation.     

Platelet Inhibition by Abciximab Bolus-Only Administration and Oral ADP Receptor Antagonist Loading in Acute Coronary Syndrome Patients: The Blocking and Bridging Strategy

Introduction

Current guidelines still recommend the bolus and infusion administration of glycoprotein IIbIIIa inhibitors in patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention. We sought to evaluate the extent of platelet inhibition by a blocking and bridging strategy with intracoronary abciximab bolus-only administration and oral loading of adenosine diphosphate receptor antagonists.

Patients and methods

Fifty-six consecutive high-risk acute coronary syndrome patients with bolus-only abciximab administration (0.25 mg/kg i.c.) and loading with 600 mg clopidogrel (55%) or 60 mg prasugrel (45%) were included in this study. Platelet aggregation induced by thrombin receptor-activating peptide and adenosine diphosphate was measured by multiple electrode aggregometry up to 7 days.

Results

Thrombin receptor-activating peptide induced platelet aggregation was significantly suppressed for a minimum of 48 h (45 ± 17 U) and returned to a normal range (> 84 U) after 6 days (90 ± 26 U; p < 0.001). Co-medication with prasugrel significantly reduced adenosine diphosphate-induced (p = 0.002) and thrombin receptor-activating peptide-induced (p = 0.02) platelet aggregation compared with clopidogrel throughout the observation period. No stent thrombosis or repeat myocardial infarction occurred at 30-day follow-up.

Conclusions

Immediate blocking of platelet aggregation in high-risk acute coronary syndrome patients by intracoronary abciximab bolus-only administration and bridging to prolonged inhibition via oral blockade of ADP receptors effectively inhibited overall platelet reactivity for at least 48 h, questioning the value of continuous abciximab infusion. Co-medication with prasugrel vs. clopidogrel synergistically augmented platelet inhibition.     

Paraoxonase-1 activity affects the clopidogrel response in CYP2C19 loss-of-function carriers

Background

The impact of paraoxonase-1 (PON1) activity on the response to clopidogrel may differ in patients treated with drug-eluting stents (DES) in association with CYP2C19 loss-of-function (LOF) polymorphisms.

Methods

This study included 112 Japanese patients receiving clopidogrel (75 mg/day) and aspirin (100 mg/day) who underwent optical coherence tomography (OCT) examination 9 months after DES implantation. The CYP2C19 genotype was analyzed and LOF carriers (*1/*2, *1/*3, *2/*2, *3/*3, *2/*3) were identified. At the 9-month follow-up, platelet reactivity was determined by measuring the P2Y12 reactivity unit (PRU) using a VerifyNow P2Y12 assay, PON1 activity was evaluated and intra-stent thrombus was evaluated by OCT.

Results

Of the 112 Japanese patients, 75 were LOF carriers (67.0%). The patients were divided into tertiles according to the PON1 activity (tertile 1; < 230 U/L, tertile 2; 230–283 U/L, tertile 3; > 283 U/L). In the VerifyNowP2Y12 analysis, tertile 1 had a higher PRU than tertiles 2 and 3 in LOF carriers, and there was no difference among tertiles in non-carriers. The highest incidence of intra-stent thrombus was observed in tertile 1 followed by tertiles 2 and 3 in LOF carriers, whereas there was no such difference in non-carriers. Multivariate analysis revealed that LOF carriers and PON1 activity tertile 1 were independent predictors of intra-stent thrombus in all patients. In LOF carriers, tertile 1 was the only independent predictor for intra-stent thrombus.

Conclusion

Low PON1 activity is associated with a low response to clopidogrel and a high frequency of intra-stent thrombus only in LOF carriers.     

Platelet reactivity evaluated with the VASP assay following ticagrelor loading dose in acute coronary syndrome patients undergoing percutaneous coronary intervention

Background

The level of platelet reactivity (PR) inhibition obtained after P2Y12-ADP receptor antagonist loading dose (LD) is associated with the ischemic and bleeding risk following percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS).

Objective

We aimed to evaluate the level of PR inhibition achieved by a 180 mg LD of ticagrelor and the rate of high on-treatment platelet reactivity (HTPR) in ACS patients undergoing PCI.

Methods

We performed a multicentre prospective observational study enrolling ACS patients undergoing PCI. Patients were included if they were admitted for ST-elevation myocardial infarction or non ST-elevation ACS. To assess PR, a VASP index was measured at least 6 and within 24 hours following a 180 mg LD of ticagrelor. HTPR was defined as a VASP index ≥ 50%.

Results

One hundred and fifteen patients were included: 31.3% of STEMI, 49.6% of NSTEMI and 19.1% of unstable angina. Following ticagrelor LD the mean VASP index was 17 ± 14%. However the response to ticagrelor was not uniform with a small inter-individual variability: inter quartile range: 7.6–22.8% and a rate of HTPR of 3.5%. A high number of patients, 65.6%, had a VASP index < 16%. None of the baseline characteristics of the study population was associated with PR. In addition, PR was similar in STEMI, NSTEMI and unstable angina (p = 0.9).

Conclusion

In ACS patients the level of PR inhibition achieved by a 180 mg loading dose of ticagrelor is not uniform and the rate of HTPR is 3.5%. A high proportion of patients exhibited a VASP index < 16%.