Prevention of atrial fibrillation in patients with aortic valve stenosis with candesartan treatment after aortic valve replacement.

BACKGROUND: Accumulating data has suggested that treatment with Angiotensin-II receptor antagonists can prevent the new onset of atrial fibrillation (AF). The aim of this study was to evaluate whether treatment with candesartan on top of conventional treatment could prevent new onset AF in patients with aortic valve stenosis (AS) after aortic valve replacement. METHODS AND RESULTS: The study was a single centre, consecutive; investigator initiated study using a prospective randomised blinded endpoint design. 91 patients with severe AS without known AF scheduled for aortic valve replacement (AVR) were randomised to candesartan 32 mg once daily on top of conventional treatment or conventional therapy immediately after AVR. Patients were examined with ECG 3, 6, 9 and 12 months after surgery, and Holter-ECG analysis after 3 and 12 months. Primary endpoint was episode of AF with a duration exceeding 30s, on the ECG or Holter-ECG and/or patients hospitalised due to AF. 14 patients developed new onset AF during follow up. AF-free survival was significantly higher (94% vs 74%, p=0.02) in patients treated with candesartan. CONCLUSION: In patients with symptomatic severe AS undergoing AVR, treatment with candesartan may prevent the new onset of atrial fibrillation.

A randomized clinical trial of chiropractic treatment and self-management in patients with acute musculoskeletal chest pain: 1-year follow-up.

OBJECTIVE: We have previously reported short-term follow-up from a pragmatic randomized clinical trial comparing 2 treatments for acute musculoskeletal chest pain: (1) chiropractic treatment and (2) self-management. Results indicated a positive effect in favor of the chiropractic treatment after 4 and 12 weeks. The current article investigates the hypothesis that the advantage observed at 4 and 12 weeks would be sustained after 1 year. In addition, we describe self-reported consequences of acute musculoskeletal chest pain at 1-year follow-up. METHODS: In a nonblinded, randomized controlled trial undertaken at an emergency cardiology department and 4 outpatient chiropractic clinics, 115 consecutive patients with acute chest pain of musculoskeletal origin were included. After the baseline evaluation, patients were randomized to 4 weeks of either chiropractic treatment or self-management, with posttreatment questionnaire follow-up 52 weeks later. The primary outcome measures were change in pain intensity (11-point box numerical rating scale) and self-perceived change in pain (7-point ordinal scale). RESULTS: Both groups experienced decreases in pain, positive global, self-perceived treatment effect, and increases in the 36-Item Short Form Health Survey scores. No statistically significant differences were observed between groups at the 1-year follow-up, and we could not deduce a common trend in favor of either intervention. CONCLUSIONS: At the 1-year follow-up, we found no difference between groups in terms of pain intensity and self-perceived change in chest pain in the first randomized clinical trial assessing chiropractic treatment vs minimal intervention for patients with acute musculoskeletal chest pain. Further research into health care utilization and use of prescriptive medication is warranted.

Can preoperative myocardial perfusion scintigraphy predict changes in left ventricular perfusion and function after coronary artery bypass graft surgery?

OBJECTIVES We wanted to evaluate whether preoperative myocardial perfusion scintigraphy (MPS) could predict changes in cardiac symptoms and postoperative myocardial perfusion and left ventricular function after coronary artery bypass grafting (CABG). METHODS Ninety-two patients with stable angina pectoris (and at least one occluded coronary artery) underwent MPS before, and 6 months after, undergoing CABG. The result of the MPS was kept secret from the surgeons. RESULTS Before CABG, 90% of the patients had angina. After CABG, 97% of the patients were without symptoms. Overall graft patency was 84%. Before CABG, one patient had normal perfusion; in the rest of them the defects were classified as follows: reversible (60%), partly reversible (27%) and irreversible (12%). Following CABG, 33% had normal perfusion; in the rest the defects were reversible in 29%, partly reversible in 12% and irreversible in 26%. Left ventricular ejection fraction (LVEF), which was normal before operation in 45%, improved in 40% of all patients. The increase in LVEF was not related to the preoperative pattern of perfusion defects. Of 30 patients with normalized perfusion after CABG, 29 (97%) had reversible defects and one patient had partly reversible defects. Of 83 perfusion defects, which were normalized after CABG, 67 were reversible (81%) or partly reversible (12%). Seventy-five percent of all reversible coronary artery territories before CABG were normalized after operation. CONCLUSIONS Our results indicate that reversible or partly reversible perfusion defects at a preoperative MPS have a high chance of normalized myocardial perfusion assessed by MPS 6 months after operation. Normal perfusion is obtained almost exclusively in territories with reversible ischaemia. Symptoms improved in nearly all patients and LVEF in a significant fraction of the patients, not related to preoperative MPS.

Reconstruction of the decision-making process in assessing musculoskeletal chest pain: an exploratory study using recursive partitioning.

OBJECTIVE: The purposes of this study were to identify the most important determinants from the patient history and clinical examination in diagnosing musculoskeletal chest pain (MSCP) in patients with acute noncardiac chest pain when supported by a structured protocol and to construct a decision tree for identification of MSCP in acute noncardiac chest pain. METHODS: Consecutive patients with noncardiac chest pain (n = 302) recruited from an emergency cardiology department were assessed. Using data from self-report questionnaires, interviews, and clinical assessment, patient characteristics were associated with the MSCP diagnosis, and the decision-making process of the clinician was reconstructed using recursive procedures in the tradition of constructing Classification and Regression Trees. RESULTS: Thirty-eight percent of patients had MSCP. There was no single determinant that predicted the condition completely. However, many items with high associations could be identified, mainly with high negative predictive value. The decision-making process was reconstructed giving rise to a 5-step, linear decision tree without branches. CONCLUSIONS: Clinicians use a combination of indicators including systematic palpation of the spine and chest wall and items from the case history to diagnose MSCP. However, the high negative predictive values of the main determinants suggest that the MSCP diagnosis may be a diagnosis by exclusion.

Chiropractic treatment vs self-management in patients with acute chest pain: a randomized controlled trial of patients without acute coronary syndrome.

OBJECTIVE: The musculoskeletal system is a common but often overlooked cause of chest pain. The purpose of the present study is to evaluate the relative effectiveness of 2 treatment approaches for acute musculoskeletal chest pain: (1) chiropractic treatment that included spinal manipulation and (2) self-management as an example of minimal intervention. METHODS: In a nonblinded, randomized, controlled trial set at an emergency cardiology department and 4 outpatient chiropractic clinics, 115 consecutive patients with acute chest pain and no clear medical diagnosis at initial presentation were included. After a baseline evaluation, patients with musculoskeletal chest pain were randomized to 4 weeks of chiropractic treatment or self-management, with posttreatment questionnaire follow-up 4 and 12 weeks later. Primary outcome measures were numeric change in pain intensity (11-point box numerical rating scale) and self-perceived change in pain (7-point ordinal scale). RESULTS: Both groups experienced decreases in pain, self-perceived positive changes, and increases in Medical Outcomes Study Short Form 36-Item Health Survey scores. Observed between-group significant differences were in favor of chiropractic treatment at 4 weeks regarding the primary outcome of self-perceived change in chest pain and at 12 weeks with respect to the primary outcome of numeric change in pain intensity. CONCLUSIONS: To the best of our knowledge, this is the first randomized trial assessing chiropractic treatment vs minimal intervention in patients without acute coronary syndrome but with musculoskeletal chest pain. Results suggest that chiropractic treatment might be useful; but further research in relation to patient selection, standardization of interventions, and identification of potentially active ingredients is needed.

Angiography-based prediction of outcome after coronary artery bypass surgery versus changes in myocardial perfusion scintigraphy.

OBJECTIVES: The present study compared the clinical prediction of the effect of coronary artery bypass grafting (CABG) on coronary blood flow and left ventricular ejection fraction (LVEF) with changes in gated myocardial perfusion scintigraphy. METHODS: A prospective group of 92 patients underwent myocardial perfusion scintigraphy before and 6 months after CABG, the results being kept secret from the surgeon. Based on clinical and angiographic findings, the surgeons filled in a questionnaire indicating the predicted changes in coronary blood flow in each of the three coronary artery territories and in the LVEF. RESULTS: Symptomatic improvement was present in nearly all the patients. Following CABG, the perfusion defects were reduced in around two-thirds and normalized in one-third of the territories clinically predicted to improve. Improved perfusion for territories not predicted to improve was slightly lower, and correlations between predicted and observed regional changes in coronary blood flow and perfusion defects were poor. LVEF increased (by over five ejection fraction units) in almost half of the patients, but with no correlation between the predicted and the observed changes. CONCLUSIONS: Based on clinical and angiographic findings, the marked improvements after CABG in cardiac perfusion and function are poorly predicted.

Noninvasive assessment of filling pressure and left atrial pressure overload in severe aortic valve stenosis: relation to ventricular remodeling and clinical outcome after aortic valve replacement.

OBJECTIVE: One of the hemodynamic consequences of aortic valve stenosis is pressure overload leading to left atrial dilatation. Left atrial size is a known risk factor providing prognostic information in several cardiac conditions. It is not known if this is also the case in patients with aortic valve stenosis after aortic valve replacement. METHODS: A total of 119 patients with severe aortic valve stenosis scheduled for aortic valve replacement were evaluated preoperatively and divided into 2 groups according to left atrial volume index (≥40 mL/m(2)). Echocardiography was repeated 12 months after surgery. Patients were followed up for 24 months. The primary end point was the composite end point overall mortality and hospitalization due to congestive heart failure. RESULTS: Preoperative left atrial dilation was associated with left ventricular hypertrophy and increased filling pressure. Preoperative left atrial volume index was associated with persistent abnormalities in left ventricular filling pressure and left ventricular mass index at 1 year after surgery. Event-free survival in patients with left atrial volume index of 40 mL/m(2) or more at 1 year was 71% compared with 88% in patients with left atrial volume index less than 40 mL/m(2) (P = .002). Patients with preoperative increased E/e' ratio and left ventricular hypertrophy were at increased risk. In Cox regression analysis after correcting for standard risk factors, left atrial volume index was found to be the only significant predictor of the composite end point. In a forward conditional multivariable model, left atrial volume index 40 mL/m(2) or greater (hazard ratio, 4.2 [1.6-10.7]; P = .003) remained an independent predictor, whereas E/e' was borderline significant (P = .06). CONCLUSIONS: In patients with symptomatic severe aortic valve stenosis undergoing aortic valve replacement, left atrial volume provides important prognostic information beyond standard risk factors.

Effect of candesartan treatment on left ventricular remodeling after aortic valve replacement for aortic stenosis.

In hypertension, angiotensin receptor blockers can augment regression of left ventricular (LV) hypertrophy. It is not known whether this also is the case after aortic valve replacement (AVR) for severe aortic stenosis (AS). To test the hypothesis that treatment with candesartan in addition to conventional treatment is able to augment LV and left atrial (LA) reverse remodeling in patients with AS undergoing AVR, we studied 114 patients scheduled for AVR. Patients were randomized to treatment with candesartan 32 mg 1 time/day or conventional therapy immediately after AVR. Patients were followed with echocardiographic evaluations 3, 6, and 12 months after surgery. Primary end point was change in LV mass index. At baseline and during follow-up no differences in systolic, diastolic, and pulse pressures were seen between groups. Baseline LV mass index was 134 +/- 41 g/m(2) with no difference between groups. Mean decrease in LV mass index in the control group was 12 +/- 28 g/m(2) compared to 30 +/- 40 g/m(2) in the candesartan group (p = 0.015) during follow-up. After 12 months LV mass index was significantly lower in the candesartan group (103 +/- 29 vs 119 +/- 31 g/m(2), p = 0.01). In addition, the candesartan group had greater improvement in longitudinal LV systolic function assessed by tissue Doppler S' wave (0.6 +/- 0.1-cm/s increase in control group vs 1.4 +/- 0.1 cm/s in candesartan group, p = 0.01, p for trend = 0.02) and a decrease in LA volume (p for trend = 0.01). Treatment had no effect on diastolic E/e' ratio or B-type natriuretic peptide. In conclusion, angiotensin receptor blockade with candesartan after AVR in patients with AS is associated with augmented reverse LV and LA remodeling compared to conventional management.

Left ventricular diastolic function in type 2 diabetes mellitus: prevalence and association with myocardial and vascular disease.

BACKGROUND: Although type 2 diabetes mellitus is a risk factor for developing congestive heart failure, the mechanism leading to heart failure is unclear. We examined the prevalence of left ventricular (LV) systolic and diastolic dysfunction in patients with type 2 diabetes mellitus in relation to vascular function and myocardial perfusion. METHODS AND RESULTS: A prospective observational study of 305 patients with type 2 diabetes mellitus (diabetes duration, 4.5+/-5.3 years) referred consecutively to a diabetes clinic were screened for LV systolic and diastolic function by echocardiography. Vascular function was estimated using noninvasive estimation of pulse pressure, carotid arterial compliance, total arterial compliance, and valvulo-arterial impedance. The prevalences of LV diastolic dysfunction and left atrial (LA) volume index >32 mL/m(2) were 40% and 32%, respectively. The prevalence of myocardial ischemia on myocardial perfusion scintigraphy was more frequent in patients with grade 2 diastolic dysfunction and LA volume index >32 mL/m(2) compared with those having normal or grade 1 diastolic dysfunction (P=0.002) or LA volume index < or =32 mL/m(2) (P<0.001), respectively. Predictors of grade 2 diastolic dysfunction and LA dilation were summed stress score on myocardial perfusion scintigraphy, total arterial compliance, and valvulo-arterial impedance, whereas pulse pressure and carotid arterial compliance were not, after adjusting for age, sex, and diabetes duration. On multivariable modeling, summed stress score (P<0.001) and valvulo-arterial impedance (P=0.027) remained predictors of grade 2 diastolic dysfunction, and only summed stress score (P<0.001) was a predictor of LA dilation. CONCLUSIONS: Abnormal LV filling is closely associated with abnormal myocardial perfusion on myocardial perfusion scintigraphy, whereas the association of LV filling with vascular function is less prominent.

Myocardial ischemia, carotid, and peripheral arterial disease and their interrelationship in type 2 diabetes patients.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in type 2 diabetes mellitus (T2DM) patients. We examined the relationship between CVD in different vascular territories. METHODS: T2DM patients without known or suspected CVD (n = 305) referred consecutively to a diabetes clinic for the first time and age-matched nondiabetic reference subjects (n = 40) were screened for myocardial ischemia, carotid, and peripheral arterial disease by means of myocardial perfusion scintigraphy, carotid artery ultrasonography, and peripheral ankle and toe systolic blood pressure measurements. RESULTS: In the T2DM patients, the prevalence of myocardial ischemia, carotid, and peripheral arterial disease was 30%, 42%, and 15%, respectively, almost three times higher than in the reference subjects (P = 0.007, P = 0.001, and P = 0.09, respectively). T2DM patients with myocardial ischemia, carotid, or peripheral arterial disease had a significantly increased risk of CVD in other vascular territories as well (OR: 1.99, 2.09, and 3.09, respectively). However, 40%, 52%, and 22% of the T2DM patients with myocardial ischemia, carotid, or peripheral arterial disease demonstrated exclusively this particular type of CVD manifestation. CONCLUSIONS: In T2DM patients, signs of CVD in one vascular territory carry a significantly increased risk of CVD in other territories, although many patients only presented one manifestation.

Are there long-term benefits in following stable heart failure patients in a heart failure clinic?

OBJECTIVES AND DESIGN: This study describes the long-term outcome of 163 patients with stable mild to moderate heart failure (NYHA II-III), who already were enrolled in a heart failure clinic and now were randomized to continued follow-up in the heart failure (HF) clinic or else to usual care (UC). The primary outcome was unplanned hospitalisations and death, the secondary endpoints were pharmacological therapy, NYHA class, six-minute-walking distances and NT-pro BNP level. RESULTS: At the end of follow-up we found no significant differences in total number of hospitalisation (p = 0.2) or mortality (16% vs. 16%) between the two groups. Patients in the HF clinic cohort achieved a significantly better NYHA score (p < 0.01), significantly longer walking-distances (p = 0.04) and received a significantly higher dose of angiotensin-converting enzyme inhibitors (p < 0.001) and beta-blockers (p < 0.001). No significant difference was found on the level of NT-pro BNP (p = 0.4). CONCLUSIONS: Patients with mild to moderate HF may benefit from long-term follow-up in a HF clinic in terms of pharmacological therapy and functional status, but we found no significant impact on unplanned hospitalisations or death.

Diagnosis and treatment of musculoskeletal chest pain: design of a multi-purpose trial.

BACKGROUND: Acute chest pain is a major health problem all over the western world. Active approaches are directed towards diagnosis and treatment of potentially life threatening conditions, especially acute coronary syndrome/ischemic heart disease. However, according to the literature, chest pain may also be due to a variety of extra-cardiac disorders including dysfunction of muscles and joints of the chest wall or the cervical and thoracic part of the spine. The diagnostic approaches and treatment options for this group of patients are scarce and formal clinical studies addressing the effect of various treatments are lacking. METHODS/DESIGN: We present an ongoing trial on the potential usefulness of chiropractic diagnosis and treatment in patients dismissed from an acute chest pain clinic without a diagnosis of acute coronary syndrome. The aims are to determine the proportion of patients in whom chest pain may be of musculoskeletal rather than cardiac origin and to investigate the decision process of a chiropractor in diagnosing these patients; further, to examine whether chiropractic treatment can reduce pain and improve physical function when compared to advice directed towards promoting self-management, and, finally, to estimate the cost-effectiveness of these procedures. This study will include 300 patients discharged from a university hospital acute chest pain clinic without a diagnosis of acute coronary syndrome or any other obvious cardiac or non-cardiac disease. After completion of the clinic's standard cardiovascular diagnostic procedures, trial patients will be examined according to a standardized protocol including a) a self-report questionnaire; b) a semi-structured interview; c) a general health examination; and d) a specific manual examination of the muscles and joints of the neck, thoracic spine, and thorax in order to determine whether the pain is likely to be of musculoskeletal origin. To describe the patients status with regards to ischemic heart disease, and to compare and indirectly validate the musculoskeletal diagnosis, myocardial perfusion scintigraphy is performed in all patients 2-4 weeks following discharge. Descriptive statistics including parametric and non-parametric methods will be applied in order to compare patients with and without musculoskeletal chest pain in relation to their scintigraphic findings. The decision making process of the chiropractor will be elucidated and reconstructed using the CART method. Out of the 300 patients 120 intended patients with suspected musculoskeletal chest pain will be randomized into one of two groups: a) a course of chiropractic treatment (therapy group) of up to ten treatment sessions focusing on high velocity, low amplitude manipulation of the cervical and thoracic spine, mobilisation, and soft tissue techniques. b) Advice promoting self-management and individual instructions focusing on posture and muscle stretch (advice group). Outcome measures are pain, physical function, overall health, self-perceived treatment effect, and cost-effectiveness. DISCUSSION: This study may potentially demonstrate that a chiropractor is able to identify a subset of patients suffering from chest pain predominantly of musculoskeletal origin among patients discharged from an acute chest pain clinic with no apparent cardiac condition. Furthermore knowledge about the benefits of manual treatment of patients with musculoskeletal chest pain will inform clinical decision and policy development in relation to clinical practice. TRIAL REGISTRATION: NCT00462241 and NCT00373828.

A randomised trial of a pre-synaptic stimulator of DA2-dopaminergic and alpha2-adrenergic receptors on morbidity and mortality in patients with heart failure.

BACKGROUND: By pre-synaptic stimulation of DA(2)-dopaminergic and alpha(2)-adrenergic receptors, nolomirole inhibits norepinephrine secretion from sympathetic nerve endings. We performed a clinical study with nolomirole in patients with heart failure (HF). METHODS: The study was designed as a multicentre, double blind, parallel group trial of 5 mg b.i.d. of nolomirole (n=501) versus placebo (n=499) in patients with severe left ventricular systolic dysfunction, recently in New York Heart Association (NYHA) class III/IV. The primary endpoint was time to all cause death or hospitalisation for HF, whichever came first. The study was event driven and required 420 primary events. The study was completed as scheduled. RESULTS: Mean age of patients was 70 years, and 73% were male. Heart rate and blood pressure were not different in the two treatment groups. There were no changes in blood pressure. There were 233 primary events in the nolomirole group versus 208 in the placebo group (p=0.1). There were 142/145 deaths and 369/374 all cause hospitalisations in the nolomirole/placebo groups. There were no differences in walking distance, quality of life or NYHA class. CONCLUSION: A dose of 5 mg b.i.d. of nolomirole was not beneficial (or harmful) in patients with heart failure.

How well does standard clinician evaluation identify low likelihood of ischaemic or coronary heart disease?

Guidelines claim that patients with a low likelihood of coronary artery disease can be reliably identified clinically by a simple set of rules. Among 385 patients referred for coronary angiography because of suspected stable angina pectoris we found by myocardial perfusion scintigraphy in three selected low likelihood groups reversible perfusion defects in 23%-29% of male and 11%-17% of female patients. Rates of significant angiographic disease were similar. These data question the validity of current clinical practice for identifying low likelihood of disease in this category of patients.

Frequent change of procedure during coronary artery bypass surgery suggests insufficient preoperative diagnostic strategy.

We sought to evaluate how often and in what way surgeons change peroperatively their preoperative coronary artery bypass grafting strategy and to what degree these changes affect postoperative graft patency. A series of 109 patients with stable angina pectoris and at least one occluded coronary artery participated. The surgeon filled in a questionnaire pertaining to the planned localization and number of grafts. These estimates were compared to procedures actually performed and with the angiographic outcome six months after bypass surgery. Planned and actually inserted grafts disclosed a discrepancy in 22% of the patients, resulting in a lower or higher number of grafts than pre-operatively estimated. The difference in shift rates between the three sites, left anterior descending, left circumflex, and right coronary artery, was significant (P=0.014). Patency rates were highest when only preoperatively planned grafts were inserted. When shifts occurred, no matter in which direction, it resulted in a decreased patency rate of the inserted grafts. This finding was significant for LAD (P=0.037). Our findings might indicate the necessity of future studies with the use of scintigraphy or fractional flow reserve as physiological adjuncts to angiography for more targeted revascularization.

High probability of disease in angina pectoris patients: is clinical estimation reliable?

BACKGROUND: According to most current guidelines, stable angina pectoris patients with a high probability of having coronary artery disease can be reliably identified clinically. OBJECTIVES: To examine the reliability of clinical evaluation with or without an at-rest electrocardiogram (ECG) in patients with a high probability of coronary artery disease. PATIENTS AND METHODS: A prospective series of 357 patients referred for coronary angiography (CA) for suspected stable angina pectoris were examined by a trained physician who judged their type of pain and Canadian Cardiovascular Society grade of pain. Pretest likelihood of disease was estimated, and all patients underwent myocardial perfusion scintigraphy (MPS) followed by CA an average of 78 days later. For analysis, the investigators focused on the approximate groups of patients with more severe disease, ie, typical angina (n=187), Canadian Cardiovascular Society grade 2 pain or higher (n=176) or high (higher than 85%) estimated pretest likelihood of disease (n=142). RESULTS: In the three groups, 34% to 39% of male patients and 65% to 69% of female patients had normal MPS, while 37% to 38% and 60% to 71%, respectively, had insignificant findings on CA. Of the patients who had also an abnormal at-rest ECG, 14% to 21% of men and 42% to 57% of women had normal MPS. Sex-related differences were statistically significant. CONCLUSIONS: Clinical prediction appears to be unreliable. Addition of at-rest ECG data results in some improvement, particularly in male patients, but it makes the high probability groups so small that the addition appears to be of limited clinical relevance.

Revascularization compared to medical treatment in patients with silent vs. symptomatic residual ischemia after thrombolyzed myocardial infarction--the DANAMI study.

AIMS: The aim was to compare the effect of revascularization to conservative treatment in patients with residual silent and with residual symptomatic ischemia following acute myocardial infarction (AMI). The study was a subanalysis of the DANAMI (DANish AMI) randomized study of invasive vs. conservative treatment in patients with inducible ischemia after thrombolysis in AMI. METHODS AND RESULTS: One thousand and eight patients were randomized to invasive or conservative treatment, stratified by the type of ischemia: silent, i.e. ST depression during an exercise test prior to discharge in 56%, or symptomatic, i.e. chest pain occurring either spontaneously during admission or during the exercise test, with or without ST changes, in 44%. Compared to a conservative strategy, invasive treatment reduced the incidence of nonfatal reinfarction, after in median 2.4 years, in both symptomatic patients (13.3-7.2%, p < 0.006) and patients with silent ischemia (10.1 vs. 5.7%, p < 0.05), and of admissions with unstable angina in symptomatic (44.5-27.6%, p < 0.0001) and silent ischemia (21.6-13.3%, p < 0.0006). CONCLUSIONS: Compared to conservative strategy, invasive treatment reduces the risk of nonfatal reinfarction and hospital admissions for unstable angina in thrombolyzed post-AMI patients with silent as well as symptomatic exercise-induced ischemia.

Prevalence of aspirin resistance in patients with an evolving acute myocardial infarction.

OBJECTIVE: To study the prevalence and importance of aspirin resistance in patients with an evolving acute myocardial infarction (AMI) by use of the Platelet Function Analyzer-100. INTRODUCTION: Previous studies have demonstrated the existence of aspirin resistance, but the clinical relevance of the phenomenon remains to be clarified. If aspirin resistant patients comprise a high-risk subgroup, it might be expected that the prevalence of aspirin resistance in patients with AMI would be higher than in patients without AMI. We hypothesized that the prevalence of aspirin resistance in patients with AMI was twice the prevalence in patients without AMI. METHODS: We included 298 consecutive patients with known cardiovascular disease who were admitted to hospital with symptoms suggestive of an AMI. All had been taking aspirin 150 mg/day for at least 7 days prior to hospital admission. Platelet function was measured immediately at admission, and aspirin resistance was defined as a collagen/epinephrine Closure Time (CT(CEPI))<165 s. RESULTS: We found that 70 (23.5%) patients were aspirin resistant, and 70 (23.5%) patients ended up with the diagnosis of an AMI. The prevalence of aspirin resistance was significantly higher in patients with AMI as compared to patients without (36% versus 20%, OR 2.26, CI 95% 1.19-4.22, p=0.0058). The CT(CEPI) measured at admission was an independent factor associated with an AMI. CONCLUSIONS: Aspirin resistance is present in almost one fourth of patients admitted to hospital with symptoms suggestive of an AMI, and aspirin resistance is significantly associated with the diagnosis of a definite AMI.

Using the Platelet Function Analyzer-100 for monitoring aspirin therapy.

INTRODUCTION: The aim of the study was to evaluate the test characteristics of the Platelet Function Analyzer-100 (PFA-100) in patients treated with aspirin. METHODS AND RESULTS: The study consisted of two sub-studies. In study 1, 10 patients with ischemic heart disease (IHD) and 10 controls had platelet function assessed by optical platelet aggregation and the PFA-100 method in two 5-week periods. Patients with IHD were treated with aspirin 150 mg/day (first 5-week period), and 300 mg/day (second 5-week period), whereas the controls only received aspirin (150 mg/day) during the second 5-week period. From the results of study 1, we found that a cut-off value for the PFA-100 collagen/epinephrine cartridge <165 s identified patients not taking aspirin (sensitivity 0.91, specificity 1.00). A good agreement between the PFA-100 method and optical platelet aggregation was found. Within-subject variation for the PFA-100 collagen/epinephrine cartridge was +/-28%, as compared to +/-17% for the optical platelet aggregation. Study 2 included 298 aspirin treated patients who were admitted with symptoms suggestive of an acute myocardial infarction. Platelet function was assessed in duplicate by the PFA-100 collagen/epinephrine cartridge, and a 95% Limit of Agreement interval at [-65%, 65%] indicated a limited precision. CONCLUSION: We defined a cut-off value below which patients not taking aspirin can be identified. However, due to imprecision of the PFA-100 method repeated duplicate assessment of the collagen/epinephrine Closure Time is recommended.

Variation and importance of aspirin resistance in patients with known cardiovascular disease.

AIM: To investigate whether aspirin resistance is a persistent condition, and to evaluate if aspirin resistance affects one-year clinical outcome. METHODS AND RESULTS: Previously we studied 298 patients admitted to hospital with symptoms suggestive of an acute myocardial infarction (MI) despite treatment with aspirin, and 70 patients (23.5%) were aspirin resistant. In the present study, platelet function was reassessed by use of a Platelet Function Analyzer-100 one year later. A total of 187 patients were re-examined, and 17 (9.1%) demonstrated aspirin resistance. Of these 17 patients, 12 also exhibited aspirin resistance at baseline resulting in a 6% (12/187) prevalence of persistent aspirin resistance. A total of 34 patients had changed from aspirin resistant at baseline to aspirin sensitive at follow-up. We found a significant decrease in the prevalence of aspirin resistance from baseline (43%) to follow-up (11%) in patients with MI at baseline (p=0.0018). Furthermore, a significant decrease was found for patients without MI at baseline (20% to 9%, p=0.0009). During follow-up, 17% (12/70) of the patients with aspirin resistance at baseline suffered death, MI or stroke compared to 16% (37/227) of aspirin sensitive patients (p=0.868). CONCLUSION: The prevalence of aspirin resistance varies with the clinical status of the patients, and indeed an acute MI is associated with temporary aspirin resistance. We also found that 6% of patients demonstrate persistent aspirin resistance. The presence of aspirin resistance did not affect one-year clinical outcome.