Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?

PURPOSE: We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT). METHODS: This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure. RESULTS: The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan-Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82-1.86)]; there were no significant differences in secondary endpoints. CONCLUSION: Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT00212017.

Effects of moderate-to-severe obstructive sleep apnea on the clinical manifestations of plaque vulnerability and the progression of coronary atherosclerosis in patients with acute coronary syndrome.

AIMS: It is unclear whether obstructive sleep apnea (OSA) increases the recurrence of acute coronary syndrome (ACS) in patients with acute myocardial infarction (MI). We hypothesized that moderate-to-severe OSA increased the number of adverse cardiovascular events in patients who underwent primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: This study included 272 patients with acute MI. Polysomnography at first admission determined that 124 patients suffered from moderate-to-severe OSA. The main study outcome measures were cardiac death, recurrence of ACS, and re-admission for heart failure. Major adverse cardiac events (MACEs) were defined as composite end points of individual clinical outcomes. Follow-up coronary angiograms were obtained in 222 patients. PCI-related measures were target vessel revascularization and newly necessitated PCI for progressive lesions. The moderate-to-severe OSA patients had increased ACS recurrence and MACEs compared with patients with mild OSA or without sleep apnea (16% vs. 7%, p = 0.014; 22% vs. 11%, p = 0.014, respectively). PCI for progressive lesions was also higher in the moderate-to-severe OSA patients (28% vs. 15%, p = 0.015). Cox regression analysis showed that moderate-to-severe OSA was an independent predictor of ACS recurrence (hazard ratio = 2.30, p = 0.040). In addition, moderate-to-severe OSA was an independent predictor of PCI for progressive lesions, with a hazard ratio of 2.38 (p = 0.015). CONCLUSIONS: Moderate-to-severe OSA increased the risk of ACS and the incidence of PCI for progressive lesions. Increased plaque vulnerability might be related to these clinical manifestations.

Obstructive sleep apnoea increases the incidence of morning peak of onset in acute myocardial infarction.

AIMS: There exists a discrepancy regarding the relationship between obstructive sleep apnoea (OSA) and circadian variation during the onset of acute myocardial infarction (MI). We hypothesized that OSA patients show a characteristic circadian variation and that the severity of OSA significantly affects this variation. METHODS AND RESULTS: The present study included 288 patients with first acute MI who underwent percutaneous coronary intervention within 12 h of symptom onset. The diagnosis of OSA required an apnoea-hypopnoea index (AHI) of ≥5 events/h. A total of 216 patients fulfilled the OSA criteria. The incidence of MI onset between 06:00 and 11:59 hours was significantly higher in OSA patients than in control patients (38 vs. 25%, p=0.039). Circadian variation in the morning peak of MI onset was attenuated in mild OSA (as defined by AHI, 5.0-14.9 events/h; 33 vs. 25%, p=0.240). Moderate-to-severe OSA (as defined by AHI ≥15.0 events/h) clearly increased the incidence of MI onset between 06:00 and 11:59 hours (43 vs. 25%, p=0.014). Multiple logistic regression adjusting for AHI (≥15.0 events/h), age, body mass index, hypertension, and current smoking showed that moderate-to-severe OSA significantly contributed to MI onset between 06:00 and 11:59 hours (odds ratio 2.00, p=0.010). CONCLUSIONS: OSA showed a morning peak with regard to MI onset, and moderate-to-severe OSA significantly enhanced this circadian variation.

Impact of obstructive sleep apnea on myocardial tissue perfusion in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Vascular endothelial dysfunction has been recognized as an essential feature of obstructive sleep apnea (OSA). This study was designed to examine the hypothesis that OSA may impair the coronary microcirculation in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: The present study included 100 patients with a first STEMI who underwent primary percutaneous coronary intervention (PCI) within 12h from onset. Coronary flow velocity at baseline and at maximum hyperemia was measured using a Doppler guidewire following PCI. Total ST-segment elevation was calculated at baseline and 30 min after PCI. All patients underwent polysomnography at 14 days to diagnose OSA. Coronary flow velocity reserve (CFVR) was used for quantitative analysis of myocardial tissue perfusion. Systolic retrograde flow (SRF) and ST-segment resolution (STR) <50% were used as an index of microvascular injury. Forty-eight patients presented with OSA. CFVR was comparable between the 2 groups. The incidence of SRF was higher in OSA patients than in the control patients (6% vs. 31%, P=0.005). Patients with OSA had a higher incidence of STR <50% (31% vs. 60%, P=0.003). Multiple logistic regression showed that OSA was an independent positive predictor of SRF and STR <50% (odds ratio=4.46, P=0.044; odds ratio=3.79, P=0.010). CONCLUSIONS: OSA may impair myocardial tissue perfusion following primary PCI.