Ken Kanamasa

Short-Acting Nifedipine and Diltiazem Do Not Reduce the Incidence of Cardiac Events in Patients With Healed Myocardial Infarction

BACKGROUND The administration of calcium antagonists to patients with healed myocardial infarction is a controversial treatment. This study was conducted to elucidate the effect of short-acting nifedipine and diltiazem on cardiac events in patients with healed myocardial infarction. METHODS AND RESULTS A controlled clinical open trial of 1115 patients with healed myocardial infarction was carried out between 1986 and 1994. The patients included 595 who received no calcium antagonist, 341 who received short-acting nifedipine 30 mg/d, and 179 who received short-acting diltiazem 90 mg/d. The primary end points were cardiac events, which were defined as fatal or nonfatal recurrent myocardial infarction; death from congestive heart failure; sudden death; and hospitalization because of worsening angina, congestive heart failure, or premature ventricular contractions. Cardiac events occurred in 51 patients (8.6%) in the no-calcium-antagonist group and 54 (10.4%) in the calcium-antagonist group (odds ratio, 1.24; 95% CI, 0.83 to 1.85), demonstrating that the calcium antagonists did not reduce the incidence of cardiac events. Subgroup analysis revealed no beneficial effects of these drugs for reducing cardiac events in patients with such complications as hypertension or angina pectoris. CONCLUSIONS This study showed that use of short-acting nifedipine and diltiazem in this postmyocardial infarction population was associated with a 24% higher cardiac event rate, but this strong adverse trend did not reach statistical significance.

Long-term, continuous treatment with both oral and transdermal nitrates increases cardiac events in healed myocardial infarction patients

This study was performed to investigate the effects of continuous dosing of oral, trans dermal (patch), and a combination of the two with nitrate treatments on cardiac events in patients with healed myocardial infarction. In total, 1,291 patients with healed myocardial infarction were assigned 2 groups: treatment with nitrates (n = 713) or nontreatment (n = 578). Nitrate treatment was subdivided into 3 groups: patch group (n =149), oral group (n = 504), and combination group (n = 60). The mean observation period was 17.4 ±21.1 months. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. Baseline characteristics were also compared among the 4 groups to determine any effects on outcome. Among the patients with patch, oral, and combination groups, cardiac events occurred 3.4%, 6.7%, 10.0%, respectively, whereas only 2.9% of the patients treated without nitrates had cardiac events. The incidence of cardiac events was significantly greater in patients with oral nitrates and combination groups compared to patients without nitrates (p<0.01, respectively). Continuous dosing of long-term treatment with both oral and transdermal nitrates increased cardiac events in healed myocardial infarction patients.

Comparison of the Effect of Lipophilic and Hydrophilic Statins on Serum Adiponectin Levels in Patients with Mild Hypertension and Dyslipidemia: Kinki Adiponectin Interventional (KAI) Study

The plasma level of adiponectin, which is known as an anti-atherogenic adipocytokine, correlates inversely with the progression of atherosclerosis. An increase in the serum adiponectin level has been reported after the administration of hydrophilic pravastatin, but not after the administration of lipophilic statins thus far. We investigated whether hydrophilic pravastatin acts distinctly from simvastatin, which has the highest lipophilicity, on the favorable effect on adiponectin in dyslipidemic patients. A total of 27 dyslipidemic patients with mild hypertension were enrolled in this study. The patients were initially treated with simvastatin 10 mg/day for six months or more (mean 7.1 months), and then were switched to pravastatin 20 mg/day. The serum adiponectin, cholesterol fractionated components, and C-reactive protein (CRP) were evaluated after six-month intervals. Switching from simvastatin to pravastatin caused little change in the low-density lipoprotein cholesterol levels (103 mg/dl to 104 mg/dl, p = 0.782) and blood pressure (133/70 mmHg to 132/69 mmHg), while the serum adiponectin level significantly increased (11.9 μg/ml to 13.1 μg/ml, p = 0.009, respectively), and the serum CRP significantly decreased (0.078 mg/dl to 0.062 mg/dl, p = 0.040, respectively). Hydrophilic pravastatin increased the serum adiponectin level and decreased the CRP after switching from lipophilic simvastatin in the absence of any difference in the low-density lipoprotein cholesterol level and blood pressure. It remains possible, however, that this difference was due not only to pharmacologic lipophilicity, but also to some other specific characteristics such as the formula of statins, the subject characteristics, race, body size, high-density lipoprotein cholesterol, etc.

Hypertensive encephalopathy in patients with chronic renal failure caused by stopping antihypertensive agents: a report of two cases.

We herein report two cases of patients with chronic kidney disease who developed hypertensive encephalopathy, which occurred after a sudden discontinuance of antihypertensive agents. Both patients underwent care at our hospital after experiencing neurological abnormalities. In both patients, magnetic resonance imaging (MRI) revealed edema in the cerebral white matter and cortices, basal ganglia, brainstem, and cerebellum. Though recently the number of reports about hypertensive encephalopathy has decreased, we describe two case reports and also review the pertinent literature.

Incidence of cancer in postmyocardial infarction patients treated with short‐acting nifedipine and diltiazem

Recent reports suggest a possible link between nifedipine (but not diltiazem) and an increased risk of cancer in patients being treated with calcium antagonists.

Suppression of cell proliferation by tissue plasminogen activator during the early phase after balloon injury minimizes intimal hyperplasia in hypercholesterolemic rabbits.

Thrombus formation is a key component of the pathogenesis of restenosis after arterial balloon injury. The purpose of this study was to determine whether intimal hyperplasia could be attenuated by infusion of recombinant tissue plasminogen activator (tPA). Forty-two Kurosawa and Kusanagi hypercholesterolemic rabbits were divided into tPA (n = 20) and control (n = 22) groups, the former receiving 7 days of continuous tPA infusion (0.6 mg/kg/day) via ear veins. The walls of the common iliac arteries were injured using 2.5-mm balloon catheters and then examined histologically 7, 14, 21, and 28 days later. Cell proliferation was assessed by immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), and transforming growth factor (TGF)-β immunohistochemistry was carried out to estimate cell proliferation and differentiation. It was observed that 28 days after balloon injury, intimal cross-sectional areas in the tPA group were significantly smaller than in controls (0.11 ± 0.03 mm2 vs. 0.57 ± 0.08 mm2, p < 0.01), as were ratios of the cross-sectional areas of the intima and media (0.21 ± 0.07 vs. 1.06 ± 0.18, p < 0.05). In addition, the numbers of PCNA-positive medial cells were significantly lower (0.06 ± 0.01 vs. 0.36 ± 0.08, p < 0.05) and TGF-β-positive vessel wall areas were significantly smaller in tPA-treated animals 7 days after balloon injury (0.47 ± 0.28% vs. 4.55 ± 1.44%, p < 0.05). Thus infusion of tPA after arterial balloon injury appears to decrease medial cell proliferation and suppress intimal hyperplasia.

tPA via infusion catheters followed by continuous IV infusion for 3 days prevents intimal hyperplasia after balloon injury.

A rabbit model was used to examine the effects of tissue plasminogen activator (tPA) on development of intimal hyperplasia following balloon injury. Thirty-two hereditary hypercho lesterolemic (KHC) rabbits underwent percutaneous transluminal coronary artery balloon catheterization and injury to the common iliac artery, after which they were divided into four groups: untreated (control); Dispatch catheterized-30 minutes local saline delivery [D(+)- tPA(-)]; D(+)-30 minutes local tPA delivery (0.6 mg/kg) [D(+)-tPA(30 min)]; and D(+)-30 minutes local tPA + 3 days intravenous infusion (0.6 mg/kg/24 h) [(D(+)-tPA(30 min + 3 d)]. Twenty-eight days later, the intimal cross-sectional areas of all three Dispatch catheterized groups were significantly smaller than those of control groups, as were the intimal/medial area ratios. Moreover, the intima/media ratios of the D(+)-tPA(30 min + 3 d) group were significantly smaller than those of the D(+)-tPA(-) group. Thus, local delivery of tPA via Dispatch catheters followed by continuous intravenous infusion of tPA for 3 days prevented intimal hyperplasia after angioplasty.

Protective effect of PEG-SOD against early coronary reperfusion injury assessed in reperfused and non-reperfused ischaemic areas of the same heart.

Objective — In order to investigate the salvage of ischaemic myocardium by polyethylene glycolconjugated superoxide dismutase (PEG-SOD), we compared reperfused and non-reperfused regions in the same canine heart and measured regional myocardial blood flow (RMBF) and myocardial CPK during coronary occlusion and reperfusion using non-radioactive, coloured microspheres. Methods and results — The chests of 17 mongrel dogs were opened under anaesthesia, and the left circumflex coronary artery was occluded for 90 min and then reperfused for 5 min. During this procedure, polystyrene microspheres of different colours were infused at four different times: prior to occlusion (orange), 10 min (red) and 90 min (blue) after occlusion, and 5 min after reperfusion (yellow). Thereafter, the heart was excised, cut in slices along the left circumflex coronary artery, and flow rates at the various times were assessed as a function of microsphere counts. In the control group (n=9), there are significant differences in the myocardial CPK level between reperfused and non-reperfused areas.The myocardial CPK level in reperfused area was significantly reduced compared to non-reperfused area in the outer layers (54 ± 8 IU/g vs. 74 ± 9 IU/g, P < 0.05), and also reduced in the inner layers (59 ± 9 IU/g vs. 74 ± 13 IU/g), however, it was not significantly different. In the PEG-SOD group (n=8), there was no significant difference in the myocardial CPK level between reperfused and non-reperfused areas in both inner and outer layers (inner layers; 68 ± 11 IU/g vs. 68 ± 6 IU/g, outer layer; 69 ± 17 IU/g vs. 67 ± 18 IU/g), indicating a significant protective effect of PEG-SOD. In the control group, transmural necrosis of the reperfused areas was 22.4 ± 10.0%, which showed no significant difference compared with non-reperfused areas (23.1 ± 9.9%). In the PEG-SOD group, transmural necrosis of the reperfused areas by TTC staining was 8.1 ± 8.1%, which showed no significant difference compared with non-reperfused areas (8.5 ± 7.1%). Conclusions — PEG-SOD prevents infarct extension during early coronary reperfusion.

Haziness on coronary angiogram after percutaneous transluminal coronary angioplasty evaluated with angioscopy.

Coronary angiograms obtained after percutaneous transluminal coronary angioplasty are often hazy due to uneven distribution of contrast medium at the angioplasty site. In this study, structural changes resulting in haziness after percutaneous transluminal coronary angioplasty were identified angioscopically. The affected coronary arteries of 35 patients who underwent successful percutaneous transluminal coronary angioplasty were examined with angioscopy. Coronary angioscopic examination of the sites subjected to percutaneous transluminal coronary angioplasty revealed large surface disruptions in 17 cases, small surface disruptions in four cases, and thrombi in 24 cases. Angiographic haziness was recognized in 24 of 35 patients after percutaneous transluminal coronary angioplasty. Haziness on angiography was more significant in patients who exhibited large surface disruption (88% vs 50%, p < 0.05), and was significantly greater in patients who exhibited white thrombus (100% vs 56%, p < 0.05). Moreover, it appears that percutaneous transluminal coronary angioplasty-induced large surface disruption and white thrombus likely play an important role in increasing haziness.

Chronic Use of Continuous Dosing of Long-Term Nitrates Does Not Prevent Cardiac Events in Patients with Severe Acute Myocardial Infarction

This study was performed to investigate the effects of the chronic use of continuous, not eccentric, dosing of nitrates on cardiac events in patients with severe acute myocardial infarction. A total of 1,303 patients with healed myocardial infarction were divided into two groups: treatment with nitrates or nontreatment. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure and sudden death. Among the 725 patients treated with nitrates, 45 patients (6.2%) experienced cardiac events during the observation period, whereas only 17 of the 578 patients treated without nitrates (2.9%) had cardiac events. This difference was statistically significant (p < 0.01; odds ratio 2.18, 95% confidence interval 1.24–3.86). In Killip class II–IV patients, the incidence of cardiac events in patients with nitrates was significantly greater than in patients without nitrates (18.8 vs. 3.5%, p < 0.05). The chronic use of continuous, not eccentric, dosing of nitrates did not prevent cardiac events in patients with severe acute myocardial infarction.