Overall fifty one patients with chronic cardiac insufficiency (ChCI) were studied for changes in parameters characterizing hemodynamics and lipid peroxidation (LPO) under treatment with kapoten and prazosin. Kapoten was found to be capable of exerting an antioxidant effect and working in ways beneficial for the pulmonary circulation, while prazosin is generally indicated to patients with ChCI presenting with increased end diastolic pressure in the left ventricle. Prazosin activates LPO, for which reason its pro-oxidant action needs to be drug-corrected. Because of marked pharmacologic effects of both drugs in dealing with refractory circulatory insufficiency it is advisable that further studies be made in order that we might be able to determine indications for kapoten and prazosin therapy in coronary patients as well as those with arterial hypertension, cardiomyopathies, valvular defects, ChCI with complications more accurately.
The Captopril Prevention Project (CAPPP) is a prospective, randomized, multi-centre intervention trial designed to investigate whether antihypertensive treatment with the angiotensin converting enzyme (ACE) inhibitor captopril may reduce cardiovascular mortality and morbidity more than a therapeutic regimen which does not include an ACE inhibitor. Secondary objectives are to compare total mortality, the development or deterioration of ischaemic heart disease, left ventricular failure, atrial fibrillation, diabetes mellitus and possible differences in renal function in the two groups. Male and female patients with essential hypertension, aged 25-66 years, will be randomly allocated to antihypertensive treatment which will comprise either the use of the ACE inhibitor captopril or will exclude all types of ACE inhibitors. Some 275 hypertension centres and health care centres in Sweden and Finland will take part in this multi-centre trial. A total of 7000 patients will be recruited and studied for an average period of 5 years, the assumption being that a 20% difference in cardiovascular mortality between the two groups can be detected with a power of 80% at the 5% significance level (two-sided test).
The Captopril Prevention Project (CAPPP) is an ongoing intervention study conducted in 11,019 hypertensive patients in Sweden and Finland. Patients have been randomized to receive either conventional antihypertensive therapy (diuretics and/or beta-blockers) or captopril-based treatment. A prospective, randomized, open, blinded-endpoint evaluation (PROBE) study design is used to compare these two therapeutic regimens as regards cardiovascular morbidity and mortality. The rationale for the CAPPP Study are the many observations of beneficial effects of ACE inhibition, as compared to diuretics and beta-blockers, on intermediary endpoints such as insulin sensitivity, serum lipoproteins, left ventricular hypertrophy and renal function. Captopril has also been shown to be markedly effective in the treatment of left ventricular dysfunction as well as congestive heart failure. The hypothesis is that these differences might result in improved risk reduction when ACE inhibitors are used in the treatment of hypertension. The present paper describes the baseline data and the changes in blood pressure during the first year in the total cohort. During the first year the average blood pressure was reduced by 11/8 mm Hg. A number of substudies have been conducted in the CAPPP Study. In one of these insulin sensitivity was compared in a subgroup of the patients using the euglycemic insulin clamp technique. In another substudy the ACE gene was sequenced and some new polymorphisms were discovered. Several other substudies are in progress or in the planning phase. The main results of the CAPPP Study should be available by mid-1998. Some of the intended anayses of the final results as well as other planned substudies are briefly described here.
There are major differences in the organization of the health care systems in Canada and the United States. We hypothesized that these differences may be accompanied by differences in patient care.
To test our hypothesis, we compared the treatment patterns for patients with acute myocardial infarction in 19 Canadian and 93 United States hospitals participating in the Survival and Ventricular Enlargement (SAVE) study, which tested the effectiveness of captopril in this population of patients after a myocardial infarction.
In Canada, 51 percent of the patients admitted to a participating coronary care unit had acute myocardial infarctions, as compared with only 35 percent in the United States (P
Comment In: N Engl J Med. 1993 Mar 18;328(11):805-78437602
Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial.
BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors have been used for more than a decade to treat high blood pressure, despite the lack of data from randomised intervention trials to show that such treatment affects cardiovascular morbidity and mortality. The Captopril Prevention Project (CAPPP) is a randomised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension. METHODS: CAPPP was a prospective, randomised, open trial with blinded endpoint evaluation. 10,985 patients were enrolled at 536 health centres in Sweden and Finland. Patients aged 25-66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions were randomly assigned captopril or conventional antihypertensive treatment (diuretics, beta-blockers). Analysis was by intention-to-treat. The primary endpoint was a composite of fatal and non-fatal myocardial infarction, stroke, and other cardiovascular deaths. FINDINGS: Of 5492 patients assigned captopril and 5493 assigned conventional therapy, 14 and 13, respectively, were lost to follow-up. Primary endpoint events occurred in 363 patients in the captopril group (11.1 per 1000 patient-years) and 335 in the conventional-treatment group (10.2 per 1000 patient-years; relative risk 1.05 [95% CI 0.90-1.22], p=0-52). Cardiovascular mortality was lower with captopril than with conventional treatment (76 vs 95 events; relative risk 0.77 [0.57-1-04], p=0.092), the rate of fatal and non-fatal myocardial infarction was similar (162 vs 161), but fatal and non-fatal stroke was more common with captopril (189 vs 148; 1.25 [1-01-1-55]. p=0.044). INTERPRETATION: Captopril and conventional treatment did not differ in efficacy in preventing cardiovascular morbidity and mortality. The difference in stroke risk is probably due to the lower levels of blood pressure obtained initially in previously treated patients randomised to conventional therapy.
Comment In: ACP J Club. 1999 Jul-Aug;131(1):18
Comment In: Lancet. 1999 Feb 20;353(9153):604-510030320
The aim of the study was evaluation of ACE inhibitors (captopril and ramipril) effect on water-salt homeostasis in the treatment of patients with arterial hypertension (AH) living in the Far North of Russia. 100 male patients with mild and moderate AH were examined 2 weeks, 3 and 6 months after administration of captopril or ramipril. The drugs are shown to correct water-salt metabolism. This is explained by better renal function due to speeding up glomerular filtration and increased sodium excretion with urine, and by activity of humoral mechanisms (inhibited activity of plasma renin, low plasma concentration of aldosterone and its 24-h excretion). Comparison of captopril versus ramipril demonstrates advantages of prolonged ramipril in respect to regulation of water salt metabolism in the treatment of essential hypertension in the Far North.
This study attempted to evaluate whether neurohumoral activation at the time of hospital discharge in postinfarction patients helps to predict long-term prognosis and whether long-term therapy with the angiotensin-converting enzyme inhibitor captopril modifies this relation.
Neurohumoral activation persists at the time of hospital discharge in a large number of postinfarction patients. The Survival and Ventricular Enlargement (SAVE) study demonstrated that the angiotensin-converting enzyme inhibitor captopril improves survival and decreases the development of severe heart failure in patients with left ventricular dysfunction (left ventricular ejection fraction
In 1998 the final results were presented of two large intervention trials in hypertension, the Hypertension Optimal Treatment Study (HOT) and the Captopril Prevention Project (CAPPP). Both were initiated from Sweden although the HOT Study was conducted in 26 countries worldwide and the CAPPP Study in Finland and Sweden. The HOT and CAPPP trials and their principal results will be reviewed briefly here. In addition a brief up-date will be provided of three ongoing intervention trials in hypertension that were also initiated from Sweden: the Swedish Trial in Old Patients with Hypertension-2 (STOP-Hypertension-), the Nordic Diltiazem (NORDIL) Study and the Study on Cognition and Prognosis in Elderly Hypertensives (SCOPE).