Statin adherence and LDL cholesterol levels. Should we assess adherence prior to statin upgrade?

BACKGROUND: Adherence to statin therapy has been shown to be suboptimal. In statin-treated patients with residual elevated low density lipoprotein cholesterol (LDL-C) levels the physician must decide whether to switch to a more potent statin or try and achieve better adherence. We examined the association between adherence and LDL-C within low, moderate and high intensity statin groups in a "real world" setting. METHODS: We assessed annual adherence by the mean MPR (Medication Possession Ratio = number of purchased/prescribed daily doses) in unselected patient group. Statins were stratified (ACC/AHA Guideline) into low, moderate and high intensity groups. The impact of adherence on LDL levels was assessed by LOESS (locally weighted scatter plot smoothing). RESULTS: Out of 1183 patients 173 (14.6%) were treated with low, 923 (78.0%) with moderate and 87 (7.4%) with high intensity statins. Statin intensity was inversely associated with adherence (MPR 77±21, 73±22 and 69±21% for low, moderate and high intensity respectively, p=0.018). Non-adjusted LDL levels decreased with higher adherence: a 10% adherence increase resulted in LDL decrease of 3.5, 5.8 and 7.1mg/dL in low, moderate and high intensity groups. Analysis of the adherence effect on LDL levels adjusted for age, DM and ischemic heart disease showed that MPR above 80% was associated with an additional decrease in LDL levels only in the high intensity group. CONCLUSIONS: Increased adherence to statins beyond an MPR of 80% improves LDL levels only among patients given high intensity therapy. Switching from lower to higher intensity therapy may be more effective than further efforts to increase adherence.

Pre-hospital treatment of STEMI patients. A scientific statement of the Working Group Acute Cardiac Care of the European Society of Cardiology.

In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patient's delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patient's baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the effectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.

Myocardial infarction after vascular surgery: the role of prolonged stress-induced, ST depression-type ischemia.

OBJECTIVES: The goal of this study was to investigate the nature of the association between silent ischemia and postoperative myocardial infarction (PMI). BACKGROUND: Silent ischemia predicts cardiac morbidity and mortality in both ambulatory and postoperative patients. Whether silent stress-induced ischemia is merely a marker of extensive coronary artery disease or has a closer association with infarction has not been determined. METHODS: In 185 consecutive patients undergoing vascular surgery, we correlated ischemia duration, as detected on a continuous 12-lead ST-trend monitoring during the period 48 h to 72 h after surgery, with cardiac troponin-I (cTn-I) measured in the first three postoperative days and with postoperative cardiac outcome. Postoperative myocardial infarction was defined as cTn-I >3.1 ng/ml accompanied by either typical symptoms or new ischemic electrocardiogram (ECG) findings. RESULTS: During 11,132 patient-hours of monitoring, 38 patients (20.5%) had 66 transient ischemic events, all but one denoted by ST-segment depression. Twelve patients (6.5%) sustained PMI; one of those patients died. All infarctions were non-Q-wave and were detected by a rise in cTn-I during or immediately after prolonged, ST depression-type ischemia. The average duration ofischemia in patients with PMI was 226+/-164 min (range: 29 to 625), compared with 38+/-26 min (p = 0.0000) in 26 patients with ischemia but not infarction. Peak cTn-I strongly correlated with the longest, as well as cumulative, ischemia duration (r = 0.83 and r = 0.78, respectively). Ischemic ECG changes were completely reversible in all but one patient who had persistent new T wave inversion. All ischemic events culminating in PMI were preceded by an increase in heart rate (delta heart rate = 32+/-15 beats/min), and most (67%) of them began at the end of surgery and emergence from anesthesia. CONCLUSIONS: Prolonged, ST depression-type ischemia progresses to MI and is strongly associated with the majority of cardiac complications after vascular surgery.

Long-distance air travel soon after an acute coronary syndrome: a prospective evaluation of a triage protocol.

BACKGROUND: An increasing number of patients have an acute coronary syndrome while abroad. Such an event may entail significant emotional and financial stress, and patients are usually anxious to return home as soon as possible. The safety of long-distance air travel soon after an acute coronary syndrome is, however, uncertain, and few data exist regarding the evaluation of such patients, the proper timing and conditions of the flight, and short-term complications. METHODS AND RESULTS: We prospectively evaluated 21 tourists who had an acute coronary syndrome in Jerusalem. Patients at high risk were offered angiography; others underwent stress testing. Telephone interviews were conducted a few weeks after the patients returned home, and follow-up information was obtained. Patients flew home 18.2 +/- 11 days (mean +/- SD) after the acute event. Flight duration was substantial (12.5 +/- 3 hours). No patient had cardiac symptoms en route. At follow-up (21.3 +/- 13 days), all but 2 patients were alive and free of cardiac symptoms. CONCLUSIONS: A long-distance flight within 2 to 3 weeks after an acute coronary syndrome is reasonably safe, provided significant ischemia is excluded or treated.

Reduction of congestive heart failure symptoms by very early fibrinolytic therapy in acute myocardial infarction: a long-term follow-up.

BACKGROUND: In patients with acute myocardial infarction (MI), early fibrinolytic therapy results in improved survival and preservation of ventricular function. The purpose of the study was to determine whether very early treatment also reduces the development of congestive heart failure. METHODS AND RESULTS: During the years 1984 to 1989, 358 consecutive patients with acute MI were treated with streptokinase, 161 within the first 1.5 hours from the onset of chest pain (group A) and 197 within 1.5 to 4.0 hours (group B). In 68, fibrinolysis was initiated in the prehospital setting pioneered by our group. Symptoms related to heart failure including dyspnea on exertion, fatigue, orthopnea, paroxysmal nocturnal dyspnea, nocturia, and peripheral edema, in addition to pulmonary edema events, were assessed during 5 years of follow-up. The evaluation was based on medical records and a detailed questionnaire, which was filled in by the investigators. A favorable significant effect of very early thrombolysis on the development of most of these limiting symptoms appeared 3 months after hospital discharge and persisted thereafter (P <.05). During hospitalization, pulmonary edema attacks occurred less frequently in patients from group A (23% vs 36.5%, P <.01). This difference persisted during 4 years of follow-up (13% vs 36%, P <.001). CONCLUSIONS: Our data demonstrate that very early fibrinolytic therapy results in a significant long-term reduction of congestive heart failure-related symptoms and thereby improves the quality of life in patients after MI.

Coronary angioplasty or intravenous thrombolysis: the dilemma of optimal reperfusion in acute myocardial infarction: A critical review of the literature.

Thrombolytic therapy in acute myocardial infarction reduces infarct size and prolongs survival. Coronary reperfusion can also be achieved by direct (primary) percutaneous transluminal coronary angioplasty (PTCA). Whereas thrombolysis has the benefits of simplicity and ease of administration, PTCA achieves high reperfusion rates at a relatively low risk of bleeding and is less frequently contraindicated. These two strategies were evaluated in randomized trials as well as in a number of large registries. In most of the randomized trials, PTCA was found to yield better results than thrombolysis, although the largest randomized trial found only a modest and transient benefit. The registries, on the other hand, found no difference between the two treatment strategies. We analyze the available data and discuss the possible causes for the discrepant results in different studies. PTCA seems to be a better strategy to open occluded coronary arteries, but its clinical benefit is critically dependent on operator experience and on the time to treatment. It is the treatment of choice if the culprit lesion can be crossed within 1 hour of presentation. Home thrombolysis offers the chance of very early reperfusion and may be the most cost-effective way of improving the overall results of reperfusion therapy in the community. Coronary stenting and more effective platelet inhibition may improve the results of medical and interventional reperfusion, and further comparisons of these two strategies will be required.

Thrombolysis in acute myocardial infarction improves prognosis and prolongs life but will increase the prevalence of heart failure in the geriatric population.

This paper will review the hypothesis that early complete thrombolytic therapy in acute myocardial infarction reduces mortality and improves prognosis. ACE inhibitors improve remodelling and anti-platelet drugs or interventional procedures prevent reocclusion of the infarct related coronary artery. Most patients are left with significant myocardial damage and this effect is cumulative with subsequent infarction. The average age of death has increased by 10 years in the last three decades, so that many older patients survive. They have survived acute myocardial infarction and we now have a significant population with important heart failure despite good thrombolytic therapy.

Prevention of congestive heart failure by early, prehospital thrombolysis in acute myocardial infarction: a long-term follow-up study.

The long term impact of pre-hospital thrombolysis in acute myocardial infarction on the subsequent development of heart failure symptoms was investigated in 362 consecutive patients. The pre hospital strategy, used in 61 patients, allowed for very early administration of streptokinase, within 1.2+/-0.6 (mean+/-S.D.) hours from pain onset. In contrast, 294 patients treated in hospital received lytic treatment within 2.0+/-0.9 hours. The pre hospital group showed faster reperfusion, as measured by the time to peak creatine kinase and to ST segment recovery, but only a slightly better ventricular function, as compared to hospital treated patients. Heart failure symptoms were significantly reduced in the pre hospital group during hospitalization and at long term follow up: there were less dyspnea, fatigue, orthopnea, nocturnal dyspnea, nocturia, peripheral edema and episodes of pulmonary edema. Angina was reduced as well. We conclude that the initial benefit of prehospital thrombolysis translates into long term reduction of heart failure symptoms, thus improving quality of life.

Pituitary apoplexy as a first manifestation of pituitary adenomas following intensive thrombolytic and antithrombotic therapy.

Apoplexy of a previously asymptomatic pituitary macroadenoma may occur in the setting of intensive thrombolytic, antithrombotic, or anticoagulant therapy for acute myocardial infarction. Classic clinical findings may initially be nonspecific and a high index of suspicion is therefore required for early diagnosis.

Routine Coronary Arteriography Following Thrombolytic Therapy for Acute Myocardial Infarction: An Unsettled Controversy.

Although coronary artery disease remains the leading cause of death in industrialized countries, the management of patients recovering from acute myocardial infarction varies significantly. The issue of routine arteriography and revascularization following thrombolytic therapy remains controversial despite substantial evidence associating infarct-related artery patency with improved cardiac function and survival. Randomized trials of routine intervention after myocardial infarction have generally failed to demonstrate advantages of this invasive approach but methodological problems limit their application to current practice. High-risk patients should be referred for arteriography. While awaiting definitive trials addressing the influence of routine arteriography on patient survival and its cost effectiveness, the management of other patient groups must be individualized.

Danaparoid for cardiopulmonary bypass in patients with previous heparin-induced thrombocytopenia.

Anticoagulation for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia requires the use of other anticoagulants. We report a case in whom this was achieved using the heparinoid danaparoid (Orgaran). Based on our experience and a review of the literature, we provide guidelines for managing these rare patients. A danaparoid dose substantially lower than that recommended by the manufacturer may minimize bleeding complications.

Changing paradigms in thrombolysis in acute myocardial infarction.

Acute myocardial infarction occurs when a ruptured coronary artery plaque causes sudden thrombotic occlusion of a coronary artery and cessation of coronary artery blood flow. This paper reviews the underlying coronary pathology in progressive coronary atherosclerosis, mechanisms of plaque rupture and arterial occlusion and the time relationship between coronary occlusion and myocardial necrosis. Reperfusion can be achieved by chemical thrombolysis with different thrombolytic agents. Early lysis is achieved best by prehospital administration, a transtelephonic monitor, a mobile intensive care unit, active general practitioner treatment or by warning the emergency room of impending arrival of a patient. Thrombolytic therapy may be unsuccessful and not achieve Grade III TIMI flow in less than 4 h (or even 2 h) due to inadequate or intermittent perfusion or reocclusion. Adjuvant therapy includes aspirin and platelet receptor antagonists. Bleeding is a constant danger. Direct percutaneous transluminal coronary angioplasty (PTCA) may be as effective or better than chemical thrombolysis. Reperfusion protects the myocardium and salvages viable tissue. It also improves mechanical remodelling of the ventricle. Long-term follow-up has shown that quantum leaps of fresh coronary occlusion causes step-wise progression in patient disability and that further early, prompt reperfusion can salvage myocardium and prevent this inexorable progress of the disease.

Smoking and prognosis after acute myocardial infarction in the thrombolytic era (Israeli Thrombolytic National Survey).

OBJECTIVES: This study sought to compare the relation between smoking and the 30-day and 6-month outcome after acute myocardial infarction in an Israeli nationwide survey. BACKGROUND: Studies before and during the thrombolytic era reported similar or lower early mortality after acute myocardial infarction in smokers than in nonsmokers. This finding is intriguing and may be misleading because numerous epidemiologic studies have clearly shown that smoking is an independent risk factor for atherosclerosis, myocardial infarction and death. METHODS: The study cohort comprised 999 consecutive patients with an acute myocardial infarction from a prospective nationwide survey conducted during January and February 1994 in all coronary care units operating in Israel. The prognosis of 367 patients (37%) who were smokers (current smokers and those who smoked up to 1 month before admission) was compared with that of 632 nonsmokers (past smokers or those who never smoked). RESULTS: Smokers were on average 10 years younger and were more frequently men and patients with a family history of coronary heart disease and inferior infarction and less frequently patients with a previous infarction or a history of angina, hypertension and diabetes than nonsmokers. Smokers also had a lower incidence of congestive heart failure on admission or during the hospital period. Thrombolytic therapy (49% vs. 40%, p < 0.01) and aspirin (89% vs. 80%, p < 0.001) were administered more frequently in smokers than nonsmokers. The crude 30-day (6.0% vs. 15.7%) and cumulative 6-month (7.9% vs. 21.5%) mortality rates were significantly lower (p < 0.0001 for both) in smokers than nonsmokers, respectively. However, after adjustment for age, baseline characteristics, thrombolytic therapy and invasive coronary procedures, the lower 30-day (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.43 to 1.29, p = 0.30) and 6-month (hazard ratio 0.84, 95% CI 0.54 to 1.30, p = 0.42) mortality rates in smokers and nonsmokers were not significantly different. The model had a power of 0.80 for OR 0.50, with alpha 0.1. CONCLUSIONS: In our nationwide survey, the seemingly better prognosis of smokers early after acute myocardial infarction was no longer evident after adjustment for baseline and clinical variables and may be explained by their younger age and a more favorable risk profile. Smokers develop acute myocardial infarction a decade earlier than nonsmokers. Efforts to lower the prevalence of smoking should continue.

Left ventricular free wall rupture as the presenting manifestation of acute myocardial infarction in diabetic patients.

We present 5 diabetic patients with acute myocardial infarction in whom left ventricular free wall rupture was the presenting manifestation. Echocardiography may be indicated in diabetic patients with acute myocardial infarction and in shock, prior to thrombolysis.