Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Coronary Heart Disease (PROSPECTIVE).

AIMS: Although intensive statin therapy reduced cardiovascular risks, cardiovascular events have not been completely prevented. Probucol is a potent antioxidant and reduces tendon xanthomas in familial hypercholesterolemia patients despite reduction of high-density lipoprotein (HDL)-cholesterol (HDL-C). We investigated whether probucol can reduce cardiovascular events on top of conventional lipid-lowering therapy in patients with coronary heart disease (CHD). METHODS: PROSPECTIVE is a multicenter, randomized, prospective study that recruited 876 Japanese patients with CHD and dyslipidemia with a low-density lipoprotein (LDL)-cholesterol (LDL-C) level of ≥ 140 mg/dL without medication or those treated with lipid-lowering drugs. Lipid-lowering agents were administered during the study period in the control group (n=438), and probucol 500 mg/day was added to lipid-lowering therapy in the probucol group (n=438). Patients were randomly assigned to two treatment groups by adjusting the LDL-C level and presence of diabetes and hypertension and followed up for more than 3 years. The primary end point was a composite of cerebrovascular and cardiovascular events (cardiovascular disease death including sudden death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, hospitalization for heart failure, or coronary revascularization). The secondary end point was carotid intima-media thickness in a subset of patients. RESULTS: The incidence of the primary end point showed a trend to be lower in the probucol group compared with that in the control group despite reduced HDL-C without serious adverse events. Anti-atherogenic effects of probucol may be attributed to its potent antioxidative function and enhancement of reverse cholesterol transport. CONCLUSION: Since there was no statistical significance between the probucol and control groups despite a marked reduction of HDL-C, further studies on the clinical outcomes of probucol on top of conventional therapy may be necessary in the future (UMIN000003307).

Beneficial effects of intracoronary nicorandil on microvascular dysfunction after primary percutaneous coronary intervention: demonstration of its superiority to nitroglycerin in a cross-over study.

PURPOSE: In patients undergoing primary percutaneous coronary intervention (PCI) for the treatment of ST-segment elevation myocardial infarction (STEMI), coronary microvascular dysfunction is associated with poor prognosis. Coronary microvascular resistance is predominantly regulated by ATP-sensitive potassium (KATP) channels. The aim of this study was to clarify whether nicorandil, a hybrid KATP channel opener and nitric oxide donor, may be a good candidate for improving microvascular dysfunction even when administered after primary PCI. METHODS: We compared the beneficial effects of nicorandil and nitroglycerin on microvascular function in 60 consecutive patients with STEMI. After primary PCI, all patients received single intracoronary administrations of nitroglycerin (250 µg) and nicorandil (2 mg) in a randomized order; 30 received nicorandil first, while the other 30 received nitroglycerin first. Microvascular dysfunction was evaluated with the index of microcirculatory resistance (IMR), defined as the distal coronary pressure multiplied by the hyperemic mean transit time. RESULTS: As a first administration, nicorandil decreased IMR significantly more than did nitroglycerin (median [interquartile ranges]: 10.8[5.2-20.7] U vs. 2.1[1.0-6.0] U, p=0.0002).As a second administration, nicorandil further decreased IMR, while nitroglycerin did not (median [interquartile ranges]: 6.0[1.3-12.7] U vs. -1.4[-2.6 to 1.3] U, p<0.0001). The IMR after the second administration was significantly associated with myocardial blush grade, angiographic TIMI frame count after the procedure, and peak creatine kinase level. CONCLUSION: Intracoronary nicorandil reduced microvascular dysfunction after primary PCI more effectively than did nitroglycerin in patients with STEMI, probably via its KATP channel-opening effect.

Low levels of serum n-3 polyunsaturated fatty acids are associated with worse heart failure-free survival in patients after acute myocardial infarction.

BACKGROUND: Intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA), including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is associated with a lower risk of atherosclerotic cardiovascular events, particularly acute myocardial infarction (AMI). However, limited data are available regarding the association between serum n-3 PUFA levels and heart failure (HF) events in survivors of AMI. METHODS AND RESULTS: We evaluated whether serum DHA and EPA levels were associated with HF-free survival and HF hospitalization rates after AMI. A total of 712 patients were divided into 3 groups according to their tertile serum levels of DHA and EPA (Low, Middle, and High). Propensity-score-stratified Cox regression analysis revealed that DHA- and EPA-Low groups presented statistically significant worse HF-free survival (hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.03-2.72, P=0.0358, and HR 1.69, 95% CI 1.05-2.72, P=0.0280, respectively), with the EPA-Low group having a higher risk of HF hospitalization (HR 2.40, 95% CI 1.21-4.75, P=0.0097) than the DHA-Low group (HR 1.72, 95% CI 0.86-3.45, P=0.1224). The relationship between a low DHA or EPA level and decreased HF-free survival was almost common to all subgroups; however, the effect of low serum EPA on HF hospitalization was prominent in male patients, and those with low levels of high-density lipoprotein cholesterol or without statin therapy. CONCLUSIONS: Low levels of circulating n-3 PUFA are associated with decreased HF-free survival in post-AMI patients.

Distal protection during primary coronary intervention can preserve the index of microcirculatory resistance in patients with acute anterior ST-segment elevation myocardial infarction.

BACKGROUND: The objective of this study was to investigate whether a distal protection (DP) device can preserve the index of microcirculatory resistance (IMR) after primary percutaneous coronary intervention (PCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: The study group of 36 consecutive patients with anterior STEMI were randomized into 2 groups of primary PCI with or without DP: stenting without DP (non-DP group, n = 17) and with DP (DP group, n = 19). The DP in all cases was Filtrap (Nipro, Japan). Following final coronary angiography after successful PCI, IMR was measured using PressureWire™ Certus (St Jude Medical, USA) at maximal hyperemia. The averaged IMR of the 36 patients with STEMI after primary PCI was 31.6U. The IMR in the DP group was significantly lower than that in the non-DP group (26.6 ± 25.8U vs. 37.2 ± 23.2U, P = 0.03242). CONCLUSIONS: DP as an adjunctive therapy of PCI for acute anterior STEMI may have beneficial effects on myocardial microcirculation because of preservation of IMR.

A sinus of Valsalva-right atrium fistula without aneurysm formation.

A 61-year-old man was admitted to the hospital because of orthopnea and was diagnosed with heart failure with a continuous heart murmur. A transthoracic echocardiogram revealed turbulent flow from the right coronary sinus of Valsalva to the right atrium throughout the cardiac cycle. Aortography confirmed the presence of a shunt jet from the right coronary sinus of Valsalva to the right atrium. Cardiac catheterization revealed a left-right shunt rate of 47% and a pulmonary to systemic blood flow ratio of 1.81. Transesophageal echocardiography confirmed the existence of the shunt jet and revealed no deformity of the sinus of Valsalva. We report a rare case of sinus of Valsalva-right atrium fistula without typical aneurysmal formation.

High index of microcirculatory resistance level after successful primary percutaneous coronary intervention can be improved by intracoronary administration of nicorandil.

BACKGROUND: Although microvascular dysfunction following percutaneous coronary intervention (PCI) can be evaluated with the index of microcirculatory resistance (IMR), no method of treatment has been established. We hypothesized that intracoronary administration of nicorandil can improve IMR after successful primary PCI in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: In 40 patients with first STEMI after successful primary PCI, IMR was measured using PressureWire(TM) Certus (St. Jude Medical, MN, USA). In 20 of the patients (Group N), IMR was measured at baseline and after intracoronary nicorandil (2 mg/10 ml). In the other 20 patients (Control), IMR was measured at baseline, after intracoronary saline (10 ml) and after intracoronary nicorandil (2 mg/10 ml). In Group N, IMR significantly decreased after intracoronary nicorandil (median IMR, 27.7-18.7 U, P<0.0001). In the Control group, IMR did not change after saline administration (median IMR, 24.3-23.8 U, P=0.8193), but was significantly decreased after intracoronary nicorandil (median IMR, 23.8-14.9 U, P<0.0001). Next, all 40 patients were divided into subgroups by tertile of baseline IMR. In those with intermediate to high IMR (baseline IMR > or =21), intracoronary nicorandil significantly decreased IMR, although it did not change IMR in those with low IMR (baseline IMR <21). CONCLUSIONS: High IMR levels in patients with STEMI after successful primary PCI can be improved by intracoronary administration of nicorandil.