Does the response to aspirin and clopidogrel vary over 6 months in patients with ischemic heart disease?

BACKGROUND: Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor, mostly clopidogrel, is the default therapy in both acute coronary syndrome (ACS) and after intracoronary stents. It is well established that responses to antiplatelet therapy (APT), particularly clopidogrel, are subject to considerable interindividual variability. OBJECTIVES: We investigated whether responses to APT in individuals vary significantly over time. METHODS: Simultaneous assay with VerifyNow(™) and short thrombelastography (s-TEG) was performed before and at four time points over 6 months after hospital discharge in 40 patients receiving DAPT. Serum thromboxane B2 levels were also measured. RESULTS: While aspirin response units (ARU) by VerifyNow(™) and serum thromboxane B2 levels remained stable over time, arachidonic acid (AA)-mediated platelet aggregation with s-TEG (i.e. area under the curve at 15 min in AA channel, AUC15AA ) increased at 1 week compared with predischarge (P < 0.008). In addition, platelet reactivity units (PRU) by VerifyNow(™) (P = 0.046) and adenosine diphosphate (ADP)-mediated platelet aggregation with s-TEG (i.e. AUC15ADP ) also increased at 1 week compared with predischarge (P = 0.026). There were no significant changes in either platelet reactivity or rates of high on-treatment platelet reactivity while receiving clopidogrel beyond 1 week. CONCLUSIONS: This study demonstrates important variability in responses to APT within individuals between predischarge and 1 week but not thereafter. The use of a single early (predischarge) platelet function assay as an indicator of future response may therefore be flawed. The design of future strategies to assess individual responses for tailored therapy needs to take this into account.

Transapical perfusion for peri-arrest salvage during transcutaneous aortic valve implantation.

An 80-year-old man developed severe haemodynamic instability during a transapical aortic valve implantation. He was not suitable for a conventional surgical approach due to comorbidities and patent aortocoronary bypass grafts also limited further stabilizing actions. As a bail-out procedure, we demonstrate the feasibility of transapical arterial cannulation by crossing a newly implanted TAVI valve in order to establish an emergency bypass circuit.

The limitations of coronary angiography: identification of a critical coronary stenosis using intravascular ultrasound.

Coronary angiography is considered the gold standard method of imaging coronary stenoses. Quantitative coronary angiography (QCA) has helped to provide information about the degree of stenosis which is used as a surrogate to indicate impaired flow in a coronary bed. QCA however can underestimate disease severity. In this case intravascular ultrasound identifies a critical coronary stenosis not seen on angiography.

Clopidogrel for prevention of major cardiac events after coronary stent implantation: 30-day and 6-month results in patients with smaller stents.

OBJECTIVES: We developed this study to assess the procedural outcome, complications, and clinical follow-up in patients treated with different antiplatelet regimens after intracoronary stent implantation with small stents. Three hundred sixty-one consecutive patients, in whom at least one 3.0-mm intracoronary stent was implanted, were studied. METHODS: The study was a prospective, observational registry of unselected consecutive patients treated in our institution. Patients who underwent stent implantation between December 1997 and July 1998 were treated with aspirin and ticlopidine; those who received stents between August 1998 and February 1999 were treated with aspirin and clopidogrel. RESULTS: In the group treated with ticlopidine, there were 190 patients who had 253 lesions treated with 274 stents. Mean age was 59.1 years, 72% were male, 31% had unstable angina, 64% had 1 stent, 36% had >1 stent, and 23% had multivessel intervention. In the group treated with clopidogrel, there were 171 patients who had 226 lesions treated with 245 stents. Mean age was 60.4 years, 79% were male, 26% had unstable angina, 70% had 1 stent, 30% had >1 stent, and 26% had multivessel intervention. Complications at 30 days in the ticlopidine group were death in 1 (0.5%), stent occlusion in 3 (1. 6%; all reopened with repeat angioplasty), non-Q-wave myocardial infarction in 2 (1%), and urgent revascularization in 4 (2%). Complications at 30 days in the clopidogrel group were noncardiac death in 1 (1.2%), cardiac death in 1 (1.2%), stent occlusion in 0, non-Q-wave myocardial infarction in 3 (1.8%), and urgent revascularization in 0. Follow-up was available in 100% of patients in both groups (mean 253 +/- 75 days in the ticlopidine group, 198 +/- 53 days in the clopidogrel group). Complications at >30 days in the ticlopidine group were death in 1 and clinical restenosis in 11 (5.8%); 1 additional patient had an admission with unstable angina to the local hospital. Hence, recurrent angina as a consequence of target lesion restenosis occurred in 5.8%. Complications at >30 days in the clopidogrel group were death in 0 and clinical restenosis in 8 (4.7%); 2 additional patients were admitted with unstable angina to the local hospital, and 1 patient had a myocardial infarction 164 days after stent implantation. Hence, recurrent angina as a consequence of target lesion restenosis occurred in 4.7%. There were no significant differences in complications between the 2 groups. CONCLUSIONS: Our observations suggest that clopidogrel can be used instead of ticlopidine in patients treated with stents with a diameter of

Intracoronary Multi-link stents: experience in 218 patients using aspirin alone.

OBJECTIVES: To assess procedural outcome, complications, and clinical follow up in 218 patients who underwent treatment with 297 Multi-link (Guidant) stents implanted without the use of intravascular ultrasound (IVUS) or quantitative coronary angiography (QCA), and using aspirin alone as antiplatelet therapy. METHODS: The case records and angiograms were reviewed and the patients were contacted by telephone to determine their symptoms and any adverse events at follow up. Data were analysed using Fisher's exact test. RESULTS: Of the 218 patients included in the study, 45 had multivessel intracoronary intervention, and 55 had unstable angina. The mean (SD) length of hospital stay following the procedure was 2.0 (2.1) days. There were two early deaths at less than 30 days, and two deaths during follow up at more than 100 days. Ten patients suffered complications during the first 30 days: four had subacute stent thrombosis, of whom two died and two were treated successfully with coronary artery bypass grafting; five had a non-Q wave myocardial infarction; and one had a femoral false aneurysm. Patient outcome was analysed according to stent diameter (3.0 mm or less, or 3.5 mm or more) and by angina status (stable or unstable). In patients in whom at least one stent was 3.0 mm diameter, four of 86 patients suffered acute stent occlusion, whereas in the 132 patients in whom all stents were at least 3.5 mm diameter there were no cases of stent occlusion (p = 0.02). In the unstable angina group two of 55 patients suffered acute stent occlusion compared to two of 163 patients in the stable angina group (NS). In patients with unstable angina and at least one stent of 3.0 mm diameter, the acute occlusion rate was 7.1% (two of 28 patients). Three of the four patients with stent occlusion had undergone complex procedures. Twenty eight patients were restudied for recurrent symptoms during the follow up period. Of these, eight patients had restenosis within their stent. In seven of these patients the stent size was 3.0 mm diameter, and in the remaining patient the stent size was 4.0 mm diameter. Three of the 28 patients restudied had developed new disease remote from the stented site, and 17 had patent stents and no significant other coronary lesion. CONCLUSIONS: This study suggests that coronary intervention using the Multi-link stent is safe and effective using aspirin alone, without IVUS or QCA, when stent diameter is greater than 3.0 mm. All cases of stent occlusion in this series occurred in patients in whom at least one stent was 3.0 mm diameter, with stent occlusion being higher in patients with unstable angina compared to those with stable angina. Additional antiplatelet therapy may be beneficial in those patients in whom Multi-link stent diameter is less than 3.5 mm, particularly in those with unstable angina, but is not necessary for patients receiving Multi-link stents of 3.5 mm diameter or greater.

Vascular and hormonal responses to arginine: provision of substrate for nitric oxide or non-specific effect?

1. The vascular and hormonal effects of L- and D-arginine were compared in healthy subjects and in patients with insulin-dependent diabetes mellitus or untreated essential hypertension. 2. Infusion of L- or D-arginine (40 mumol/l) in the forearm vascular bed, sufficient to increase the local concentration approximately 20-fold, had no effect on blood flow or the vasodilator response to acetylcholine (30 and 100 nmol/min) in patients with insulin-dependent diabetes (n = 7) or essential hypertension (n = 7), or in age- and sex-matched control subjects (n = 7 in both groups). 3. Systemic infusion of 10 g of L-arginine (n = 5) or D-arginine (n = 3) increased plasma concentration of arginine approximately 20-fold without altering supine or erect haemodynamics. Increases in plasma insulin, prolactin and glucagon were seen with both enantiomers. The stereopurity of arginine was confirmed in a cell-culture assay system. 4. We conclude that, in healthy subjects and patients with essential hypertension or insulin-dependent diabetes, synthesis of nitric oxide within the vasculature is not limited by substrate availability. At high concentrations of arginine, non-stereospecific effects, including alterations in hormone concentration, occur. It remains to be determined whether these non-stereospecific hormonal changes might contribute to certain haemodynamic effects of arginine.

Relative potency and arteriovenous selectivity of nitrovasodilators on human blood vessels: an insight into the targeting of nitric oxide delivery.

The arteriovenous potency of sodium nitroprusside (SNP), linsidomine (SIN-1) and S-nitrosoglutathione (GSNO) was determined in human capacitance (veins) and resistance (arterioles) vessels in vitro and in vivo and compared with the venoselective nitrovasodilator nitroglycerin (GTN). Concentration-response curves were constructed to GTN, SNP, GSNO and SIN-1 (0.001-10 microM) in preconstricted human saphenous vein and to GTN, GSNO and SIN-1 (0.001-10 microM) in omental resistance vessels. In vivo the dilator responses of the dorsal hand vein and the forearm resistance bed were recorded during local infusions of GTN, SNP, GSNO and SIN-1 (1 pmol/min to 160 nmol/min). SNP and SIN-1 had similar arteriovenous profiles to that of GTN. SNP was equipotent with GTN in arterioles and veins but SIN-1 was 10-fold less potent than GTN in vitro and 100-fold less potent in vivo; the potency of SIN-1 was increased after incubation of saphenous vein with superoxide dismutase. GSNO was equipotent with GTN in arterioles but 10-fold less potent in veins in vitro and in vivo. These results demonstrate that most nitrovasodilators are venoselective irrespective of their mechanism of biotransformation to nitric oxide (NO) and suggests that NO itself might be venoselective in vivo. Endogenous carrier molecules, including glutathione, could alter the vascular profile of NO with physiological and therapeutic implications.