Methodologic sources of inconsistent prognoses for post-acute myocardial infarction.

PURPOSE: To investigate basic methodologic problems that could explain inconsistent and contradictory results for predictor variables in studies of prognosis after myocardial infarction (MI). MATERIALS AND METHODS: Studies on postinfarct prognosis published in English between 1979 and 1991 were identified with a MEDLINE literature search. The key words used for the computer search were: "prognosis" and "myocardial infarction" in the title and "mortality" or "survival" or "outcome" in the title or abstract. Reference lists in the reports captured by the search were examined for pertinent articles, and additional articles were sought in the index pages of two prominent journals. To be included in the analysis, a study had to fulfill the following eligibility criteria: a cohort study or randomized, controlled trial; sample size > or = 50 patients; a clear identification of the time when follow-up began, after the acute phase of MI and either before or at hospital discharge; follow-up for a minimum of 6 months or median/mean of 1 year; and multivariable analysis for intervals no longer than 2 years after the MI. Eight methodologic standards addressing sources of major problems were established and applied to each study. RESULTS: Of 766 reports identified, 111 fulfilled the eligibility criteria. The median number of standards fulfilled was 3, the highest 6. The proportions of studies complying with each of the 8 methodologic standards were: (1) inception cohort, 60%; (2) total death as an unequivocal outcome, 54%; (3) verification of cause-specific deaths (in 62 studies analyzing cardiac death), 37%; (4) analysis of crucial variables describing baseline severity, 13%; (5) indication of quantitative scope of the spectrum of baseline severity, 20%; (6) reproducible classification of candidate predictor variables, 40%; (7) adequate identification of quantitative importance of and boundaries for statistically significant predictor variables, 39%; and (8) evaluation of impact of treatment on predictor variables, 13%. CONCLUSIONS: The results show that studies on postinfarct prognosis have frequently disregarded basic methodologic principles. Suitable adherence to these principles in future research will allow improved interpretation of results and can reduce inconsistent findings, while improving the applicability of the identified predictors.

Effects of antihypertensive treatment on cerebral perfusion.

Antihypertensive treatment reduces the risk of ischemic strokes and cerebral hemorrhage as complications of excessive or long-standing hypertension. However, neurologic dysfunction and brain damage may also accompany short-term, and under certain conditions, even long-term antihypertensive treatment. Therefore, treatment should be instituted restrictively and cautiously. Special regard should be given to the action of antihypertensive drugs on cerebral perfusion in patients with an increased risk for the development of treatment-induced cerebral ischemic complications, such as patients with hypertensive encephalopathy or autonomic dysfunction, and elderly patients with suspected sclerotic stenosis of cerebral or neck arteries. The structural and functional lesions of cerebral vessels observed in acute and chronic hypertension are reviewed, as are the effects of antihypertensive drugs on cerebral blood flow. Calcium channel blockers and angiotensin-converting enzyme inhibitors may have advantages as first-line drugs in the treatment of patients with an elevated risk of cerebral hypoperfusion, because of the selective action of these agents on vasoconstricted vessels and their differential effects in varying regional vascular beds. The excellent efficacy of these drugs in the short- and long-term treatment of hypertension may lead to changes in the traditional management of hypertensive emergencies as well as in management strategies for other patients at risk for treatment-induced complications.

Prognosis of idiopathic membranous nephropathy: a methodologic meta-analysis.

Results in studies on prognosis and treatment of membranous nephropathy are conflicting. The aim of this investigation was to analyze the methodology of the existing research and to identify sources of these conflicting results. Studies published on prognosis of membranous nephropathy from 1970 to 1995 were identified using a Medline database literature search. The criteria for inclusion in the methodologic analysis were: (1) original article; (2) cohort study or clinical trial with > or = 50 adults; (3) zero time near the diagnostic renal biopsy; and (4) follow-up > or = six months. Ten well-accepted methodologic standards for prognostic research were applied to each study and the compliance was evaluated. Among the 26 studies that met the inclusion criteria, the median number of standards fulfilled was 4 and the highest was 7. The proportion of studies adhering to the individual standards was: (1) adequate diagnostic criteria, 35%; (2) definite end point, 46%; (3) adequate analysis of a surrogate end point, 52%; (4) analysis of baseline severity, 0%; (5) indication of baseline frequency for candidate predictors, 35%; (6) reproducible classification of predictors, 85%; (7) multivariable analysis, 50%; (8) identification of the variables' importance in multivariable analysis, 38%; (9) evaluation of the effect of treatment on predictors, 19%; and (10) adequate analysis of censored patients, 58%. We conclude that basic methodologic principles have frequently been disregarded. The consideration of these standards in future research can improve the interpretability and applicability of results and help reconcile conflict when results are compared among different studies.

Hypertensive emergencies.

Hypertensive emergencies are defined as conditions where a seriously elevated blood pressure imposes a substantial threat to a patient's life or vital organ functions. Since acute blood pressure reduction by lowering cardiac output and/or vascular resistance itself has the potential for serious and even life-threatening complications, treatment should be given restrictively based on pathophysiological considerations concerning altered patterns of blood pressure and blood flow regulation in these patients. Ischemic treatment related complications can be avoided by a rational choice of first-line drugs. These include beta-blockers for patients with a compromised myocardial oxygen supply as in acute myocardial infarction and unstable angina as well as for patients with dissecting aneurysms and patients with pronounced catecholamine release. In other types of hypertensive emergencies, calcium antagonists have emerged as the treatment of choice with excellent efficacy and a favorable risk-benefit ratio. Sodium nitroprusside is rarely necessary in treatment failures after calcium channel blockade.

Prediction in idiopathic membranous nephropathy.

BACKGROUND: Results of the prognosis of idiopathic membranous nephropathy are conflictive and prevent an effective risk stratification. These conflicts are explained in part by insufficient consideration of methodological principles for prognostic research. This cohort study is aimed at identifying clinical predictors for risk stratification while paying particular attention to methodology. METHODS: We studied 120 patients with idiopathic membranous nephropathy. Baseline data were extracted at the time of diagnostic renal biopsy, and patients were followed prospectively. Predictors were identified for the end points end-stage renal failure (ESRF) and ESRF or death. RESULTS: From the 120 patients followed for a median of five years (1 to 24 years), 19% developed end-stage renal failure or deterioration of renal function. Proteinuria of more than 3.5 g/day persisted in 34%, and 47% were in complete or partial remission. The Kaplan-Meier estimated probability of renal survival was 91 +/- 3% at five years and 75 +/- 6% at ten years. The predictors for the primary outcome, ESRF, identified in a Cox proportional hazards model, were histological stage (Ehrenreich-Churg) III-IV (hazard ratio 5.3, CI 1.9 to 15.0, P = 0.002) and nephrotic syndrome (hazard ratio 7.9, CI 1.1 to 61.5, P = 0.04); the predictors for the secondary outcome, ESRF or patient death, were histological stage III-IV (hazard ratio 2.8, CI 1.3 to 6.0, P = 0.008), nephrotic syndrome (hazard ratio 3.0, CI 1.1 to 8.0, P = 0.003) and comorbidity (hazard ratio 2.8, CI 1.3 to 5.9, P = 0.007). Nephrotic syndrome and histological stage III-IV allowed the demarcation of the high-risk group from the remaining patients (P < 0.0001). CONCLUSION: Histological stage, nephrotic syndrome, and comorbidity predict end-stage renal failure or death in idiopathic membranous nephropathy. Identification of the high-risk group at the time of diagnostic renal biopsy will permit appropriate treatment to be targeted to the patients who might benefit the most from the therapy in future clinical trials.

Late recurrent ischemia in infarct patients with a normal predischarge exercise test after thrombolysis.

We investigated the prognostic value of normal predischarge exercise test in 109 patients after myocardial infarction treated with i.v. thrombolysis within 4 h. In 29 of these 109 patients, elective PTCA or bypass surgery was performed for prognostic reasons after coronary angiography; 80 patients were treated conservatively with drug therapy. Recurrent postinfarct angina early after hospital discharge was the reason in 4 of 80 for PTCA or bypass surgery. Twenty-three of the remaining 76 conservatively treated patients developed recurrent ischaemia during long-term follow-up of 12.0 +/- 6.2 months, including one patient with reinfarction. Late recurrent ischaemia during long-term follow-up was observed in one third of the conservatively treated patients with a normal predischarge exercise test, although a high percentage (30%) of patients in this subgroup had been treated with PTCA or bypass surgery mainly for prognostic reasons. Predischarge exercise test is therefore of limited value for detection of still viable myocardium at risk of further ischaemic events after acute myocardial infarction and thrombolysis.

[Fibrinolysis in acute myocardial infarct. Treatment rate, assessment and follow-up treatment in the Zürich hospitals]. / Fibrinolyse bei akutem Myokardinfarkt. Behandlungsquote, Abklärung und Nachbehandlung in Zürcher Spitälern.

We report the results of i.v. fibrinolysis in patients with acute myocardial infarction treated in four major hospitals in Zürich. Between 1986 and 1988 only 96 (9%) of 1069 patients admitted to intensive care units with acute myocardial infarction received thrombolytic therapy (less than 3 hours after onset of symptoms), 7% (50/703) during the first treatment period (streptokinase for 14 months), 13% (46/306) during the second treatment period (rt-PA for 8 months). The hospital mortality was 4% and severe complications of fibrinolytic therapy occurred in 4%. Coronary angiography was performed in 60% of patients in 1986/87 and in 87% in 1987/88. Despite this significant increase in invasive diagnostic procedures the percentage of patients after thrombolysis qualifying for invasive therapy remained unchanged at 53%. The indications for PTCA or bypass surgery were postinfarct angina in 41%, silent ischemia in 5%, left main coronary artery stenosis or multivessel disease with reduced left ventricular ejection fraction in 16%, and residual high grade stenosis with preserved contractility of the infarct-related myocardium in 38%. The mean in-hospital stay was 16 days, with significant variation from 13 to 22 days between the different hospitals (p less than 0.05). In the follow-up of 65 men aged below 65 years, 75% of the patients undergoing invasive therapy and 65% of those treated medically had returned to work 6 months after myocardial infarction. Due to the limited possibility of detecting viable myocardium by non-invasive methods, and the high rate of invasive therapy necessary in our patients, further management after thrombolysis should generally include large scale coronary angiography.(ABSTRACT TRUNCATED AT 250 WORDS)