Acute myocardial infarction: Sex-related differences in prognosis

Cadralazine is a peripheral arteriolar vasodilator which, unlike hydralazine or dihydralazine, has a protected hydrazino group. In hypertensive patients the optimal effect, based on the antihypertensive efficacy to tolerability ratio, is seen after a 15 mg dose when the drug is administered as monotherapy. When administered in combination with other antihypertensive agents, a 10 mg daily dosage seems appropriate. Noncomparative trials have shown that, in patients who had failed to respond adequately to a beta-blocker and/or diuretic, the addition of cadralazine 10 to 30 mg once daily reduced systolic/diastolic blood pressure by 11 to 19%/13 to 22%. This antihypertensive effect becomes evident over a 2- to 6-week period of therapy and persists during longer term administration. Comparative studies have shown that cadralazine is superior to placebo, and has a similar blood pressure lowering effect to hydralazine, dihydralazine and prazosin in patients not controlled by beta-blocker and/or diuretic but who continued to receive these treatments. Similarly, cadralazine and chlorthalidone were equally effective in reducing blood pressure in resting hypertensive patients but cadralazine shows an advantage in reducing the pressor response in exercising patients. Cadralazine is well tolerated when administered with a beta-blocker or diuretic. Most adverse effects become less frequent and severe with continued use, occur more frequently at dosages of 20 mg/day or more, and do not generally require withdrawal of therapy. Manifestations of the drug's vasodilating properties such as headache, asthenia, dizziness, palpitations and flushing are the most commonly reported symptoms during cadralazine monotherapy, but these may be reduced during combination therapy. The drug does not appear to induce a systemic lupus-like erythematosus syndrome, as may occur with hydralazine, but additional clinical experience is required to completely exclude this possibility. In conclusion, because of its efficacy as a second- or third-line antihypertensive agent, its simple once daily dosage regimen and favourable risk: benefit ratio, cadralazine may have a useful role, particularly in those hypertensive patients who do not respond adequately to established antihypertensive treatments. However, the therapeutic potential of cadralazine cannot be clearly established until the present limited clinical base is expanded to include comparisons with other classes of vasodilating drugs (ACE inhibitors and calcium antagonists), and its utility in the management of other indications such as severe hypertension during pregnancy has been adequately explored.

Cadralazine : a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension

Previous studies on the prognostic value of exercise test variables after acute myocardial infarction (AMI) are limited methodologically and have yielded inconsistent results. This study determined whether 6 exercise test variables (systolic blood pressure, ST-segment depression or elevation, exercise capacity, arrhythmias, and angina pectoris) after controlling for age and sex, enhance 6 clinical variables (digoxin, previous AMI, history of systemic hypertension and angina, Killip class, and stress) as predictors of cardiovascular death and act as independent predictors as well. The present study followed 258 patients for 10.6 years, each of whom had AMI between 1977 and 1980 and an exercise test before hospital discharge. By 1988, 71 of the 258 patients had died, 56 of cardiovascular causes. This study is unique because exposure and outcome variables are clearly defined and follow-up was complete and longer than in previous studies. Multivariate survival analysis using an exponential model was tested to evaluate the conditional effects of the exercise test and clinical variables and to control for confounders. The model combined the exercise test and clinical variables. Results are reported with hazard ratios (HR) and 95% confidence intervals (CI). For important clinical risk predictors, the HRs with CIs are: digoxin use, HR 4.0 (CI 1.8, 8.5); history of prior AMI, HR 2.4 (CI 1.2, 4.7); history of systemic hypertension, HR 2.5 (CI 1.3, 4.5); angina, HR 2.4 (CI 1.3, 4.5); and stress, HR 4.2 (CI 2.2, 7.9). Three exercise test variables—hypotensive blood pressure response, HR 5.1 (CI 1.9,13.6); ST-segment depression, HR 1.8 (CI 0.98, 3.6); and ST-segment elevation, HR 2.4 (CI 0.98, 5.9)—were strong independent predictors of cardiovascular death after controlling for age, sex, and clinical variables. This is the only exercise test study with a complete 10.6-year followup in the U.S., a clearly defined outcome, and showing that 3 exercise test variables—hypotensive blood pressure response, and ST-segment depression and elevation—are strong independent predictors of cardiovascular death after controlling for clinical variables. These results support the use of exercise testing after AMI for predicting long-term prognosis.

Usefulness of exercise testing shortly after acute myocardial infarction for predicting 10-year mortality

Summary: Systemic Sclerosis (SSc) or Scleroderma is a generalized autoimmune disease with variable involvement of the skin and major organs. Etiology and pathogenesis are still largely unknown, but a variety of humoral and cellular autoimmune phenomena can be observed, and a pivotal role of T lymphocytes in SSc pathogenesis is postulated. The rarity of the disease, the wide spectrum of clinical manifestations and severity as well as a variable course render therapy in SSc a major challenge. In view of the immunopathogenesis of SSc, many (presumed) immunomodulatory agents have been used, but no single agent has been proven to be convincingly effective. Trials with extracorporeal therapies (such as photopheresis, plasmapheresis) or even stem cell transplantation are in progress. In contrast to the hitherto unsuccessful therapeutic approaches for the overall disease course, some life-threatening organ manifestations can often be treated successfully, e.g. interstitial pneumonitis with i.v. cyclophosphamide and scleroderma renal crisis with ACE inhibitors and haemodialysis, respectively. Furthermore, pharmacological and supportive treatment of Raynaud's phenomenon and gastrointestinal involvement can alleviate the burden of the disease. Current therapeutic options as well as hitherto investigated immunomodulators are reviewed in this article.




Zusammenfassung: Die systemische Sclerose (SSc) oder Sklerodermie ist eine generalisierte Autoimmunerkrankung mit Beteiligung der Haut und innerer Organe. Die Atiologie und Pathogenese sind weitgehend unbekannt, obwohl eine Vielzahl humoraler und zellularer Autoimmunvorgange beobachtet werden kann und eine entscheidende Rolle der T-Lymphozyten vermutet wird. Die Seltenheit der Erkrankung, das weite Spektrum an klinischen Manifestationen und Schweregraden, sowie ein variabler Verlauf machen die Therapie der SSc zu einer Herausforderung. Zahlreiche immunomodulatorische Medikamente wurden bisher ohne eindeutigen Erfolg erprobt. Therapieversuche mit extrakorporalen Verfahren, wie der Photopherese und der Plasmapherese, bis hin zur Stammzelltransplantation sind im Gange. Im Gegensatz zu den bisher erfolglosen Versuchen, die Sklerodermie selbst zu behandeln, konnen potentiell lebensbedrohliche Organmanifestationen suffizient therapiert werden: Darunter fallen die Cyclophosphamid-Therapie der interstitiellen Pneumonitis und die Behandlung der renalen Krise mit ACE-Hemmern bzw. mittels Hamodialyse. Daruber hinaus konnen medikamentose und palliative Behandlungen des Raynaud-Phanomens und der gastrointestinalen Beteiligung die Last der Erkrankung mildern. Empfohlene Therapien sowie bisherige Behandlungsversuche mit Immunomodulatoren werden in dieser Arbeit zusammengefast.

Current treatment options in systemic Sclerosis (Scleroderma).

The antihypertensive efficacy of a new long-lasting vasodilator, cadralazine, and the diuretic chlorthalidone have been compared in hypertensive patients receiving concurrent treatment with atenolol. After a 4-week run-in period with atenolol alone 100 mg/day, two groups of 10 patients whose diastolic blood pressure exceeded 100 mm Hg were given for a period of 65 days either cadralazine 15 mg/day or chlorthalidone 25 mg/day, according to a randomized, double-blind, between-patients design. Compared to atenolol alone, both cadralazine and chlorthalidone induced a statistically and clinically significant decrease in blood pressure. The antihypertensive effect did not differ significantly between groups. Good compensation of the atenolol-induced decrease in heart rate was obtained with cadralazine, whereas during atenolol + chlorthalidone treatment at times the standing heart rate was significantly lower than during treatment with atenolol + cadralazine. Side-effects, many of which were already present during atenolol treatment, occurred with a similar frequency in both groups. It is concluded that atenolol + cadralazine and atenolol + chlorthalidone are equally well tolerated, acceptable and effective in the treatment of hypertension, but that further studies are warranted to explore the potential haemodynamic advantages of the cadralazine + atenolol combination.

Controlled clinical trial of cadralazine as a second-step drug in the treatment of hypertension.

[Effects of cadralazine (ISF 2469) on water-sodium balance and on essential arterial hypertension].

The prognostic value of early clinical history, exercise testing and ambulatory electrocardiography was assessed in 263 men (mean age 50 years) recovering from an uncomplicated myocardial infarction (MI). During a mean follow-up period of 31 months, 11 patients died of cardiac causes, 22 developed a non fatal recurrent MI, 16 unstable angina (UA) and 16 underwent coronary artery bypass surgery. The appearance at the exercise stress test of an ischemic S-T segment depression of 0.2 mV or greater (P less than 0.001) as well as the achievement of a work load of 360 Kg-m/m' or less (P less than 0.01) and of a rate-pressure product of 200 Units or less (P less than 0.01), were found to be predictive of the future development of UA, but neither of cardiac death nor of non fatal recurrent MI. The ischemic response was also seen to be predictive of cardiac death (P less than 0.05). S-T segment depression of 0.1 mV or greater, angina and ventricular ectopic activity during the stress test and clinical history were not of predictive value. Complex ventricular ectopic activity (multiform extrasystoles, couplets and ventricular tachycardia) recorded during 24 hour ambulatory electrocardiogram was seen to be predictive of death and non fatal MI. Whereas some parameters such as the ejection fraction and the extension of coronary artery disease are generally accepted as good predictors for cardiac events, others, such as those derived from exercise testing, history and ambulatory electrocardiography may change their predictive value from one survey to another. These discrepancies are due to differences in patient characteristics, in methodology and in medical management.(ABSTRACT TRUNCATED AT 250 WORDS)

The prognostic significance of clinical history, exercise testing and ambulatory electrocardiography in patients with uncomplicated myocardial infarction.

Open pilot study of the activity and tolerability of cadralazine in hypertensive patients resistant to other therapy

Indications for temporary electrostimulation in acute myocardial infarct

Retrospective analysis in patients hospitalized in a coronary unit for acute myocardial infarct

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