Achille Gaspardone

Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomised, multicentre trial

BACKGROUND Thrombolysis remains the treatment of choice in ST-segment elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention (PCI) cannot be done within 90 min. However, the best subsequent management of patients after thrombolytic therapy remains unclear. To assess the best management, we randomised patients with STEMI treated by thrombolysis and abciximab at a non-interventional hospital to immediate transfer for PCI, or to standard medical therapy with transfer for rescue angioplasty. METHODS 600 patients aged 75 years or younger with one or more high-risk features (extensive ST-segment elevation, new-onset left bundle branch block, previous myocardial infarction, Killip class >2, or left ventricular ejection fraction < or =35%) in hospitals in France, Italy, and Poland were treated with half-dose reteplase, abciximab, heparin, and aspirin, and randomly assigned to immediate transfer to the nearest interventional centre for PCI, or to management in the local hospital with transfer only in case of persistent ST-segment elevation or clinical deterioration. The primary outcome was a composite of death, reinfarction, or refractory ischaemia at 30 days, and analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number 00220571. FINDINGS Of the 299 patients assigned to immediate PCI, 289 (97.0%) underwent angiography, and 255 (85.6%) received PCI. Rescue PCI was done in 91 patients (30.3%) in the standard care/rescue PCI group. The primary outcome occurred in 13 patients (4.4%) in the immediate PCI group compared with 32 (10.7%) in the standard care/rescue PCI group (hazard ratio 0.40; 95% CI 0.21-0.76, log rank p=0.004). Major bleeding was seen in ten patients in the immediate group and seven in the standard care/rescue group (3.4%vs 2.3%, p=0.47). Strokes occurred in two patients in the immediate group and four in the standard care/rescue group (0.7%vs 1.3%, p=0.50). INTERPRETATION Immediate transfer for PCI improves outcome in high-risk patients with STEMI treated at a non-interventional centre with half-dose reteplase and abciximab.

A Comparison of Coronary-Artery Stenting with Angioplasty for Isolated Stenosis of the Proximal Left Anterior Descending Coronary Artery

BACKGROUND Randomized studies have shown that the use of coronary-artery stenting as the initial treatment for coronary stenosis is associated with a lower risk of restenosis than is standard coronary angioplasty. We prospectively investigated the efficacy of these two approaches in selected patients with isolated stenosis of the proximal left anterior descending coronary artery. METHODS A total of 120 patients with isolated stenosis of the proximal left anterior descending coronary artery were randomly assigned to stent implantation or standard coronary angioplasty. The primary clinical end points were the rate of procedural success (defined as residual stenosis of less than 50 percent and the absence of death, myocardial infarction, and the need for coronary-artery bypass surgery during the hospital stay) and the rate of event-free survival (defined as freedom from death, myocardial infarction, and the recurrence of angina) at 12 months. The angiographic end point was the rate of restenosis 12 months after the procedure. RESULTS The two treatment groups did not differ significantly with respect to demographic, clinical, or angiographic characteristics. The rates of procedural success were similar in the two groups of patients (95 percent in the stenting group vs. 93 percent in the angioplasty group, P = 0.98). The 12-month rates of event-free survival were 87 percent after stenting and 70 percent after angioplasty (P = 0.04). The rates of restenosis were 19 percent after stent implantation and 40 percent after angioplasty (P = 0.02). CONCLUSIONS In patients with symptomatic isolated stenosis of the proximal left anterior descending coronary artery, stenting had advantages over standard coronary angioplasty in that it was associated with both a lower rate of restenosis and a better clinical outcome.

Efficacy of Atorvastatin Reload in Patients on Chronic Statin Therapy Undergoing Percutaneous Coronary Intervention: Results of the ARMYDA-RECAPTURE (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) Randomized Trial

OBJECTIVES This study was designed to investigate whether an acute atorvastatin reload before percutaneous coronary intervention (PCI) protects patients receiving chronic statin therapy from periprocedural myocardial damage. BACKGROUND Previous ARMYDA (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) studies demonstrated that short-term pre-treatment with atorvastatin reduces myocardial infarction during PCI in statin-naïve patients with both stable angina and acute coronary syndromes. METHODS A total of 383 patients (age 66 +/- 10 years, 305 men) with stable angina (53%) or non-ST-segment elevation acute coronary syndromes (47%) and chronic statin therapy (55% atorvastatin) undergoing PCI were randomized to atorvastatin reload (80 mg 12 h before intervention, with a further 40-mg pre-procedural dose [n = 192]) or placebo (n = 191). All patients received long-term atorvastatin treatment thereafter (40 mg/day). The primary end point was 30-day incidence of major adverse cardiac events (cardiac death, myocardial infarction, or unplanned revascularization). RESULTS The primary end point occurred in 3.7% of patients treated with atorvastatin reload and in 9.4% in the placebo arm (p = 0.037); this difference was mostly driven by reduction in periprocedural myocardial infarction. There was lower incidence of post-procedural creatine kinase-myocardial band and troponin-I elevation greater than the upper limit of normal in the atorvastatin arm (13% vs. 24%, p = 0.017, and 37% vs. 49%, p = 0.021, respectively). Multivariable analysis identified atorvastatin reload as a predictor of decreased risk of 30-day incidence of major adverse cardiac events (odds ratio: 0.50, 95% confidence interval: 0.20 to 0.80; p = 0.039), mainly in patients with acute coronary syndromes (82% relative risk reduction; p = 0.027). CONCLUSIONS The ARMYDA-RECAPTURE trial suggests that reloading with high-dose atorvastatin improves the clinical outcome of patients on chronic statin therapy undergoing PCI. These findings may support a strategy of routine reload with high-dose atorvastatin early before intervention even in the background of chronic therapy.

Predictive value of C-reactive protein after successful coronary-artery stenting in patients with stable angina

Plasma levels of C-reactive protein were measured 72 hours after successful coronary artery stenting in 76 patients with stable angina pectoris. At 12-month follow-up, the cumulative event rate was higher in patients with abnormal levels of C-reactive protein than that observed in patients with normal C-reactive protein who were event free.

Immunosuppressive therapy for the prevention of restenosis after coronary artery stent implantation (IMPRESS study)

OBJECTIVES This study tested the effect of oral prednisone on clinical and angiographic restenosis rate after successful stent implantation in patients with persistent elevation of systemic markers of inflammation after the procedure. BACKGROUND Experimental studies have shown that corticosteroids have the potential to reduce the inflammatory response associated with stent implantation. METHODS Eighty-three patients undergoing successful stenting with C-reactive protein (CRP) levels >0.5 mg/dl 72 h after the procedure were randomized to receive oral prednisone or placebo for 45 days. The primary clinical end point was 12-month event-free survival rate (defined as freedom from death, from myocardial infarction, and from recurrence of symptoms requiring additional revascularization). The angiographic end points were restenosis rate and late loss at six months. RESULTS Twelve-month event-free survival rates were 93% and 65% in patients treated with prednisone and placebo, respectively (relative risk [RR] 0.18, 95% confidence intervals [CI], 0.05 to 0.61, p = 0.0063). Six-month restenosis rate and late loss were lower in prednisone-treated than in placebo-treated patients (7% vs. 33%, p = 0.001, and 0.39 +/- 0.6 mm vs. 0.85 +/- 0.6 mm, p = 0.001, respectively). CONCLUSIONS In patients with persistently high CRP levels after successful coronary artery stent implantation, oral immunosuppressive therapy with prednisone results in a striking reduction of clinical events and angiographic restenosis rate.

Predictive value of C-reactive protein in patients with unstable angina pectoris undergoing coronary artery stent implantation.

This study was aimed at establishing the relation between baseline C-reactive protein levels and 12-month outcome in patients with unstable angina successfully treated with coronary artery stent implantation. Our results suggest that in patients with unstable angina and 1-vessel coronary disease successfully treated with coronary artery stent implantation, normal baseline serum levels of C-reactive protein identify a subgroup of patients at low risk of cardiac events during follow-up.

Effects of Naloxone on Myocardial Ischemic Preconditioning in Humans

OBJECTIVES We attempted to establish whether naloxone, an opioid receptor antagonist, abolishes the adaptation to ischemia observed in humans during coronary angioplasty after repeated balloon inflations. BACKGROUND Experimental studies indicate that myocardial opioid receptors are involved in ischemic preconditioning. METHODS Twenty patients undergoing angioplasty for an isolated stenosis of a major epicardial coronary artery were randomized to receive intravenous infusion of naloxone or placebo during the procedure. Intracoronary electrocardiogram and cardiac pain (using a 100-mm visual analog scale) were determined at the end of the first two balloon inflations. Average peak velocity in the contralateral coronary artery during balloon occlusion, an index of collateral recruitment, was also assessed by using a Doppler guide wire in the six patients of each group with a stenosis on the left anterior descending coronary artery. RESULTS In naloxone-treated patients, ST-segment changes and cardiac pain severity during the second inflation were similar to those observed during the first inflation (12+/-6 vs. 11+/-7 mm, p = 0.3, and 58+/-13 vs. 56+/-12 mm, p = 0.3, respectively), whereas in placebo-treated patients, they were significantly less (6+/-3 vs. 13+/-6 mm, p = 0.002 and 31+/-21 vs. 55+/-22 mm, p = 0.008, respectively). In both naloxone- and placebo-treated patients, average peak velocity significantly increased from baseline to the end of the first inflation (p = 0.04 and p = 0.02, respectively), but it did not show any further increase during the second inflation. CONCLUSIONS The adaptation to ischemia observed in humans after two sequential coronary balloon inflations is abolished by naloxone and is independent of collateral recruitment. Thus, it is due to ischemic preconditioning and is, at least partially, mediated by opioid receptors, suggesting their presence in the human heart.

Coronary artery stent placement in patients with variant angina refractory to medical treatment

We performed a prospective study to establish the efficacy of coronary stent placement in a highly selected group of patients with focal coronary artery spasm in whom anginal attacks could not be prevented by full medical therapy. The results of this study indicate that intracoronary stent placement may represent an alternative and feasible treatment for patients with vasospastic angina refractory to aggressive medical therapy.

Mechanisms of cardiac pain during coronary angioplasty

OBJECTIVES This study was conducted to establish whether the cardiac pain patients experience during coronary angioplasty is modulated by 1) the stretching of the coronary artery wall, and 2) the mechanisms responsible for the ischemic preconditioning. BACKGROUND Anecdotal experimental observations indicate that stretching of the coronary artery wall is a stimulus adequate to cause cardiac pain. Furthermore, recent experimental studies indicate that adenosine, a mediator of the anginal pain, appears to play an important role in the genesis of ischemic preconditioning. METHODS We randomly allocated 48 consecutive patients undergoing coronary angioplasty into two groups. In Group A the second balloon inflation was performed at a higher level than the first; in Group B the first two inflations were performed at the same level of balloon pressure. The mean values (+/- 1 SD) of ST segment shift on the surface 12-lead electrocardiogram (ECG) and the intracoronary ECG were measured at the end of each inflation period. Severity of cardiac pain was also obtained at the same time by using a visual analog scale. RESULTS The mean ST segment shift during the second balloon inflation was significantly less than that during the first inflation in both groups of patients (12.8 +/- 9.3 vs. 18.5 +/- 11.9 mm, p < 0.001 and 13.7 +/- 10.1 vs. 21.3 +/- 13.9 mm, p < 0.001, respectively, in Groups A and B). Yet, the severity of cardiac pain during the second inflation was greater than that during the first inflation in Group A (40.8 +/- 32.7 vs. 26.9 +/- 27.2 mm, p < 0.01), whereas it was lesser in Group B (23.1 +/- 20.7 vs. 32.9 +/- 29.6 mm, p < 0.05). However, in the latter group, pain severity after normalization for the mean ST segment shift was similar during the first and second inflations (2.1 +/- 2.4 vs. 2.7 +/- 3.6, p = NS). CONCLUSIONS During coronary angioplasty, the cardiac pain experienced by patients is caused in part by stretching of the coronary artery wall. If the stretching is maintained at a constant level during repeated coronary occlusions, the cardiac pain is entirely predicted by the severity of myocardial ischemia and therefore does not appear to be directly modulated by the mechanisms responsible for the ischemic preconditioning.

A Prospective Randomized Trial Comparing Stenting to Internal Mammary Artery Grafting for Proximal, Isolated De Novo Left Anterior Coronary Artery Stenosis: The SIMA Trial

OBJECTIVE To compare coronary artery bypass grafting (CABG) with percutaneous transluminal coronary angioplasty (PTCA) in patients with proximal, isolated de novo left anterior descending coronary artery disease and left ventricular ejection fraction of 45%. PATIENTS AND METHODS In the multicenter Stenting vs Internal Mammary Artery (SIMA) study, patients were randomly assigned to PTCA and stent implantation or to CABG (using the internal mammary artery). The primary clinical composite end point was event-free survival, including death, myocardial infarction, and the need for additional revascularization. Secondary end points were functional class, antianginal treatment, and quality of life. Analyses were by intention to treat. RESULTS Of 123 patients who accepted randomization, 59 underwent CABG, and 62 were treated with stent implantation (2 patients were excluded because of protocol violation). At a mean ± SD follow-up of 2.4±o.9 years, a primary end point had occurred in 19 patients (31%) in the stent group and in 4 (7%) in the CABG group (P P =.90). The functional class, need for antianginal drug, and quality-of-life assessment showed no significant differences. CONCLUSIONS Both stent implantation and CABG are safe and highly effective treatments to relieve symptoms in patients with isolated, proximal left anterior descending coronary artery stenosis. Both are associated with a low and comparable incidence of death and myocardial infarction. However, similar to PTCA alone, a percutaneous approach using elective stent placement remains hampered by a higher need for repeated intervention because of restenosis.