Sylvain Plante

Long-Term Effects of Cholesterol Lowering and Angiotensin-Converting Enzyme Inhibition on Coronary Atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT)

BackgroundThis long-term, multicenter, randomized, double-blind, placebo-controlled, 2×2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. Methods and ResultsThere were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, −0.07 versus −0.14 mm (P =0.004); minimum diameters, −0.09 versus −0.16 mm (P =0.0001); and percent diameter stenosis, 1.67% versus 3.83% (P =0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events;P =0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30;P =0.043) than their respective placebo patients. ConclusionsThis trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.

Myocardial infarction patients in the 1990s—their risk factors, stratification and survival in Canada: The Canadian assessment of myocardial infarction (CAMI) study

OBJECTIVES This study sought to evaluate the in-hospital and postdischarge mortality of patients with an acute myocardial infarction in the 1990s. BACKGROUND The widespread implementation of therapeutic interventions that modify the natural history of coronary artery disease has led to changes in the profile and survival of patients with an acute myocardial infarction. Although data exist for selected subsets of patients with an acute myocardial infarction, at this time there is little recent prospective information on all patients presenting with an acute myocardial infarction, particularly for survival after hospital discharge. METHODS All patients < or = 75 years old presenting with an acute myocardial infarction between July 1, 1990 and June 30, 1992 at nine Canadian hospitals were prospectively evaluated and followed up for 1 year. From November 1991, patients of all ages were included. In two centers, recruitment continued until December 31, 1992. A total of 3,178 patients were recruited. RESULTS The in-hospital mortality rate of patients < or = 75 years old was 8.4%, and that at 1 year after hospital discharge was 5.3%. For patients of all ages recruited after November 1, 1991, the in-hospital mortality rate was 9.9% and 7.1% for 1 year after hospital discharge. For patients < or = 75 years old, age carried an independent in-hospital but no post discharge risk. Female patients had a twofold greater risk of dying in hospital. After hospital discharge, only 1.7% of patients < or = 75 years old and 1.9% of patients of all ages died of a presumed arrhythmic death. Premature ventricular contractions had no independent prognostic value. The relatively low in-hospital (5.3%) and postdischarge (6.1%) reinfarction rate may have contributed to improved survival. A greater reinfarction rate in patients >75 years old (17.4% vs. 9.6%, p < 0.001) may have contributed to their poorer outcome. CONCLUSIONS One-year mortality after acute myocardial infarction continues to decrease, and changes in the prognostic value of traditional methods of risk stratification have occurred.

Comparison of bivalirudin versus heparin on radial artery occlusion after transradial catheterization.

Background: Anticoagulant therapy is required to prevent radial artery occlusion (RAO) after transradial catheterization. There is no data comparing bivalirudin to standard heparin. Methods: We studied 400 consecutive patients. In case of diagnostic angiography‐only (n = 200), they received an intravenous bolus of heparin (70 U kg−1) immediately before sheath removal whereas in case of angiography followed by ad hoc percutaneous coronary intervention (n = 200), they received bivalirudin (bolus 0.75 mg kg−1, followed by infusion at 1.75 mg/kg/h). RAO was assessed 4–8 weeks later using two‐dimensional echography‐doppler and reverse Allens test with pulse oximetry. Results: At follow‐up, 21 of the 400 (5.3%) patients were found to have RAO with no significant difference between the two groups (3.5% bivalirudin vs. 7.0% heparin, P = 0.18). Patients with RAO had a significantly lower weight compared to patients without RAO (78 ± 13 kg vs. 86 ± 18 kg, P = 0.011). By multivariate analysis, a weight <84 kg (OR: 2.78, 95% CI 1.08–8.00, P = 0.032) and a procedure duration ≤20 min (OR: 7.52, 95% CI 1.57–36.0, P = 0.011) remained strong independent predictors of RAO. All cases of radial occlusion were asymptomatic and without clinical sequelae. Conclusion: Delayed administration of bivalirudin or heparin for transradial catheterization provides similar efficacy in preventing RAO. Because of its low cost, a single bolus of heparin can be preferred in case of diagnostic angiography whereas bivalirudin can be contemplated in case of ad hoc percutaneous coronary intervention.

Influence of the menstrual cycle on the timing of acute coronary events in premenopausal women

During their reproductive years, women have a low incidence of coronary artery disease (1,2), which increases markedly 10 to 15 years after menopause (3). It has long been hypothesized that this increased risk is at least in part due to the absence of female hormones, in particular, 17 -estradiol (4). This hypothesis was supported by data from epidemiological studies, which suggested that hormone replacement therapy would protect postmenopausal women from coronary artery disease (5– 8). However, recent placebo-controlled trials designed to test the cardioprotective effects of a regimen of estrogens plus progestin have found no reduction in cardiovascular events or progression of angiographic lesions (9 –12). Nevertheless, acute administration of 17 -estradiol affects the vasculature by modulating the nitric oxide–Larginine pathway (13,14), and improves endothelial function (15) and prolongs the time to ST-segment depression and exercise time, in postmenopausal women with coronary artery disease (16). These data suggest that the acute effects of 17 -estradiol could subside rapidly when levels are low during menses. Therefore, we sought to determine whether premenopausal women would be at greater risk of developing an acute coronary event when blood levels of 17 -estradiol levels are low during the menstrual cycle.

Comparison of Propafenone Versus Procainamide for the Acute Treatment of Atrial Fibrillation After Cardiac Surgery

A prospective, randomized, double-blind study to compare the efficacy in terminating postoperative atrial fibrillation of the class Ic drug propafenone versus class Ia drug procainamide was conducted. Intravenous propafenone was superior to procainamide in achieving rapid cardioversion and a better rate control with a lower incidence of symptomatic hypotension.

PTCA of chronically occluded coronary arteries

The occlusion of a coronary artery does not necessarily imply the existence of nonviable myocardium of that flow-dependent region, because the presence of a well developed collateral circulation may be a sufficient nutrient source. During an episode of increased demand for myocardial oxygen, this collateral blood supply may become insufficient, and symptoms of myocardial ischemia may arise. PTCA of the occluded vessel appears to be an attractive approach to relieve ischemia in this situation. The primary success of dilatation of totally occluded segments depends largely on the duration of the occlusion but also on anatomic factors such as total or functional occlusion, the length of the occluded segment, and good angiographic visualization of the coronary artery distal to the occlusion by collaterals. The primary success rate (+/- 60%) of PTCA of occluded vessels is lower than the success rate (greater than 90%) of PTCA of nonocclusive stenoses. Also the restenosis rate (+/- 40%) and subsequent recurrence rate of angina pectoris is higher, compared to the 30% restenosis rate after dilatation of conventional lesions. Newer percutaneous techniques such as lasers, newly designed guide wires, and intravascular imaging devices are necessary to increase the primary success rate. Whether these techniques will also improve the long-term results remains uncertain.

The sPLA2 Inhibition to Decrease Enzyme Release After Percutaneous Coronary Intervention (SPIDER-PCI) Trial

Background— Secretory phospholipase A2 (sPLA2) may play a role in myonecrosis after elective percutaneous coronary intervention (PCI). Inhibition of this enzyme may have a beneficial effect. The central hypothesis of this study was that treatment with varespladib, a small-molecule inhibitor of sPLA2 would reduce postprocedural release of cardiac biomarkers after elective percutaneous coronary intervention. Methods and Results— Between October 2007 and June 2009, 144 stable patients were randomized in a phase II trial to receive varespladib 500 mg PO BID or placebo 3 to 5 days before and for 5 days after elective percutaneous coronary intervention. The primary end point was elevation of troponin I or creatine kinase-MB above the upper limit of normal at 6 to 8 or 18 to 24 hours after percutaneous coronary intervention. Mean age was 63±10 and 64±10 years, with 38% and 42% with diabetes mellitus and 29% and 28% with prior myocardial infarction for the varespladib and placebo groups, respectively. The primary end point occurred in 75% of varespladib and 63% of placebo patients (P=0.14). Troponin I 3 times the upper limit of normal was observed in 57% and 50% (P=0.39) and creatine kinase-MB 2 times the upper limit of normal in 14% and 3% (P=0.018). Median (first and third quartiles) change in high-sensitivity C-reactive protein in these 2 groups was 0.65 mg/L (−0.18 and 1.48) and 0.70 mg/L (0.00 and 1.50) at 18 to 24 hours (P=0.81) and 0.20 mg/L (−0.70 and 1.40) and 0.60 mg/L (−0.12 and 1.72) at 3 to 5 days (P=0.23), whereas change in sPLA2 activity at 3 to 5 days in a subset was −2.85 ng/ml (−3.40 and −1.85) and 0.25 ng/ml (−0.20 and 0.85) (P<0.001). Conclusions— Inhibition of sPLA2 by varespladib administered for 3 to 5 days before the procedure does not reduce periprocedural myonecrosis associated with elective percutaneous coronary intervention. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00533039.

Prehospital diagnosis and triage of ST-elevation myocardial infarction by paramedics without advanced care training

BACKGROUND Prehospital triage of ST-elevation myocardial infarction (STEMI) for primary percutaneous coronary intervention (PCI) reduces treatment times. Prehospital triage and transport of STEMI patients have traditionally been undertaken in emergency medical service systems with Advanced Care Paramedics (ACPs). However, ACPs are not available in many regions. A pilot study was conducted to determine the feasibility of prehospital STEMI triage in a region with only Primary Care Paramedics. METHODS Hemodynamically stable patients with chest pain and suspected STEMI were brought directly to a catheterization laboratory for primary PCI. End points included accuracy of prehospital STEMI identification, complications during transfer, and treatment times. RESULTS One hundred thirty-four consecutive patients with suspected STEMI were triaged for primary PCI. Only 1 patient developed complications during transport (rapid atrial flutter) that required ACP skills. One hundred thirty-three patients underwent urgent angiography, and 105 patients underwent PCI. Based on physician interpretation of the prehospital electrocardiogram, there was agreement with triage decision for 121 (90%) of the 134 cases. The final diagnosis based on the angiogram and cardiac markers was true STEMI for 106 patients and false positive for 28 patients. The median first medical contact to balloon time was 91 (81-115) minutes. CONCLUSIONS Hemodynamically stable patients with suspected STEMI can be safely and effectively transported directly for primary PCI by paramedics without advanced care training. Prehospital STEMI triage for primary PCI can be extended to regions that have few or no paramedics with advanced care training.

The ACE-DD genotype is associated with endothelial dysfunction in postmenopausal women.

Objective: To evaluate the effects of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D), the angiotensinogen M235T and the angiotensin II type 1 receptor A1166C polymorphisms, and hormone therapy used on endothelial function in postmenopausal women without manifestation of coronary artery disease. Design: Sixty-four postmenopausal women (42 hormone therapy users and 22 hormone therapy nonusers) without clinical manifestation of coronary artery disease were evaluated using external vascular ultrasonography to measure endothelium-dependent (hyperemic response, flow-mediated dilatation) and -independent (nitroglycerin) dilatation. Genotypes were determined by polymerase chain reaction amplification. Results: Women with the ACE-DD genotype displayed a lower flow-mediated dilatation compared to those with the ACE-II genotype (8.4% ± 3.9% vs 12.6% ± 5.4%, P = 0.04). Endothelial function was not associated with the angiotensinogen M235T and anglotensin II type 1 receptor A1166C polymorphisms. ACE polymorphism seems to modulate endothelial function among postmenopausal women without hormone therapy (8.2% ± 5.1% vs 18.4% ± 5.9% for the DD and the II genotype, respectively, P = 0.02). However, in hormone therapy users, flow-mediated dilatation was similar according to the ACE genotypes. Conclusions: Our findings suggest that ACE-I/D polymorphism is related to endothelial dysfunction in postmenopausal women. Furthermore, a potential interaction between estrogen users and ACE polymorphism on endothelial function may be present.

Symptoms of disturbed sleep predict major adverse cardiac events after percutaneous coronary intervention.

BACKGROUND Disturbed sleep is associated with atherosclerosis in native coronary arteries and may be associated with adverse cardiac events after percutaneous coronary intervention (PCI). We sought to determine the association between symptoms of disturbed sleep and adverse cardiovascular events after PCI. METHODS Outpatients who were stable after successful PCI were assessed for symptoms of disturbed sleep with 10 true/false questions. Follow-up was performed at least 4 years after PCI. The primary outcome was a composite of death, myocardial infarction (MI), and repeated revascularization. RESULTS Three hundred eighty-eight patients (mean age, 66 ± 11 years) reported on average 3.1 ± 2.1 sleep disturbance symptoms. Follow-up was performed on average 4.4 years after the incident PCI. The primary outcome occurred in 25% of patients. An association was seen between the number of sleep disturbance symptoms and the occurrence of the primary end point. Patients with zero symptoms had a 4-year event rate of 12% compared with a 67% event rate for those with 9 symptoms. On multivariable analysis, sleep symptoms, diabetes mellitus, and the number of diseased coronary vessels were independently associated with the primary end point. Each additional sleep symptom was associated with a hazard ratio (HR) of 1.2 (P = 0.001). The results were driven primarily by the association between symptoms of disturbed sleep and the need for repeated revascularization (repeated PCI HR, 1.9; P = 0.003; coronary artery bypass grafting (CABG) HR, 1.5; P = 0.001). CONCLUSIONS Symptoms of disturbed sleep were associated with increased risk of long-term adverse cardiovascular outcomes after successful PCI.