One hundred and eight patients with initial diastolic blood pressure in the range of 100-124 mm Hg while taking hydrochlorothiazide were assigned randomly and double-blind to hydrochlorothiazide plus either bethanidine or guanethidine. The average reduction of the fifth and sixth months' diastolic blood pressure was 18.4 mm Hg for guanethidine and 13.6 mm Hg for bethanidine (P less than 0.01). The distribution of the individual values was such that 68.8% of guanethidine treated patients achieved a diastolic level below 90 mm Hg, compared to only 45.5% of the bethanidine treated group (P less than 0.025). The degree of orthostatic fall in blood pressure was greater with bethanidine than with guanethidine (P less than 0.05). The diurnal variation of blood pressure was slightly greater with bethanidine than with guanethidine. The results significantly favor guanethidine. This study failed to demonstrate that the shorter action of bethanidine confers significantly better control of blood pressure than the longer action of guanethidine.

Twenty-one patients with documented coronary atherosclerotic heart disease were studied to determine the effect of high dose oral isosorbide dinitrate (ISDN) on heart rate, blood pressure, and exercise time until angina pectoris. Patients were tested in two phases, initially with 0.4 mg of sublingual nitroglycerin and with sublingual placebo, and then with oral ISDN, mean dose 29 mg, and oral placebo. Both phases of the study were conducted in a randomized, double-blind, crossover manner. After ISDN was compared to oral placebo, heart rate increased at 30 to 300 min (P less than 0.01) (peak increase 18 beats/min at 60 min), and systolic blood pressure decreased from 45 to 300 min (P less than 0.005) (peak decrease 18 mm Hg at 60 min). Exercise time at 2 min after sublingual nitroglycerin increased 51% as compared to oral placebo, exercise time increased 54% at 1 hr (P less than 0.005), 37% at 3 hr (P less than 0.01), and 12% at 5 hr (NS). Twelve of 21 patients (57%) improved their exercise time until angina larger than or equal to 25% at 1 hr after oral ISDN. The exercise response to sublingual nitroglycerin was a good predictor of this response to oral ISDN.

From a large cooperative prospective randomized study, data relating to a subgroup of 113 patients with angina pectoris and a significant lesion of the left main coronary artery were analyzed. Of these patients, 53 had been randomly allocated to a medical treatment group and 60 to a surgical treatment group. The former group received conventional medical treatment, while the surgical treatment group received one or more aortocoronary saphenous vein bypass grafts. Important risk factors were approximately uniformly distributed between the two groups. Both are being followed up to 60 months (average follow-up, 30 months). To date, 12 of 60 surgical patients (20%) and 19 of 53 medical patients (36%) died (P less than 0.06). The operative (30-day) mortality declined from a rate of 25% for the first 2 years of the study to 7% for the last 3 years. Of patients randomized in the latter 3 years of the study, 12 of 41 medical patients (29%) and three of 42 surgical patients (7%) died (P less than 0.01). The average follow-up period in this group was 24 months. The proportion surviving 24 months was clearly larger in the surgically treated group (P less than 0.02). The difference in the proportion of patients surviving after surgery as compared with medical treatment was greatest in patients with additional significant disease involving the right coronary artery, with or without left ventricular dysfunction. Relief of angina as assessed by an "anginal score" was also better in surgical patients to a significant degree. Graft-patency rates correlated well with relief of angina, but objective studies including treadmill testing are not yet available.

The relative benefits and risks of reserpine and guanethidine were compared in patients with thiazide-treated mild to moderate hypertension (diastolic pressure 95-115 mm Hg). Forty-nine ambulant patients )30 men, 19 women) were treated throughout the study with hydrochlorothiazide, 50 mg/day. In this double blind crossover study each drug was added in graded increments until a predetermined therapeutic response was obtained, blood pressure measurements and side effect scores were evaluated biweekly. Major conclusions of the study were: 1) guanethidine, as well as reserpine, will reduce mild to moderate blood pressures to normal; 2) in most cases, side effects which did occur while taking guanethidine or reserpine were well tolerated and neither drug was clearly superior. Side effects associated with larger doses of guanethidine employed in severe hypertension were absent or only slightly bothersome. Thus, guanethidine apppears to have a good benefit-to-risk ratio in the therapy of mild to moderate hypertension and offers a number of advantages over drugs commonly used in this syndrome. This study refutes the common belief that guanethidine must be reserved only for the treatment of more severe degrees of hypertension.

The effect of timolol versus propranolol on hypertension, hemodynamics, and plasms renin activity was evaluated in 20 men. After two weeks of placebo, 11 men received timolol 30 to 60 mg daily, and nine men received propranolol, 240 to 480 mg daily, for five weeks in a double-blind randomized study. The 20 men then received placebo again for two weeks. Right heart catheterization was performed in all 20 patients after two weeks of the first placebo and after five weeks of timolol or propranolol. Equipotent doses of timolol and propranolol were equally effective in significantly lowering supine and upright systolic and diastolic blood pressure and heart rate recorded on an outpatient basis. Equipotent doses of timolol and propranolol caused similar hemodynamic effects including similar significant depression of cardiac index. Equipotent doses of timolol and propranolol caused similar marked depression of plasma renin activity. The hypotensive action of timolol and of propranolol was unrelated to their effect on plasma renin activity.

One hundred and twenty patients undergoing aortocoronary bypass procedures were randomly placed into control and digitalized groups. All were initially in normal sinus rhythm and without evidence of congestive heart failure. Supraventricular arrhythmias occurred in 17 of 66 controls and in only three of 54 digitalized patients (P less than 0.01). There was no evidence of digitals toxicity. Based on this evidence we recommend prophylactic digitalization for patients having aortocoronary bypass operations.

The effect of sulfinpyrazone on the incidence of thrombosis of arterio-venous shunts was investigated in a double-blind crossover study in 45 patients on chronic hemodialysis over a period of 12 months. The incidence of thrombosis was reduced from 0.64 thrombi per patient month when on placebo to 0.21 thrombi per patient month when on sulfinpryazone (P less than 0.001). The therapeutic effect was more striking in men than in women and became evident within a week of starting the drug. The side effects were minimal, requiring withdrawal from the study of only one patient. This crossover study strengthens the findings in the previous report that sulfinpyrazone is of value in the prevention of thrombosis.

Vasodilators are known to be effective in improving the hemodynamics of congestive heart failure by increasing cardiac output and reducing left ventricular filling pressure (LVFP). Long acting agents are needed to augment the practicality and availability of chronic vasodilator therapy. In the present study the vascular effects of chewable isosorbide dinitrate (CHIS), sublingual nitroglycerin (NTG) and placebo (P) were compared in eight patients with high LVFP due to heart failure. Patients with LVFP (pulmonary wedge pressure) over 14 mm Hg were given CHIS, 10 mg, NTG, 0.6 mg, and P, two chewable tablets, in random fashion. Heart rate (HR), blood pressure (BP) and LVFP were monitored for three hours after each drug. HR was not significantly affected by any drug, although it rose slightly after NTG and fell after CHIS. Significant reduction of BP occurred only after NTG, with peak effect at five minutes, but lasting only 15 minutes. NTG reduced LVFP 5.1 mm Hg (19.5%, P, less than 0.05), at peak effect, but LVFP was no longer significantly lower by 20 minutes after NTG. After CHIS, LVFP fell significantly within five minutes, reached a peak reduction of 8.6 mm Hg (32;7%, P less than 0.01) at 15 minutes, and remained significantly lower through three hours. Thus CHIS provides a nitrate action of rapid onset and sustained effect that may be useful for chronic vasodilator therapy of heart failure.

In a prospective study to evaluate surgery for angina pectoris, 50 patients randomized to surgery and 50 treated medically have completed 8 to 34 months' follow-up (median, 24 months). Anginal symptoms improved in both groups (88%, 72%), but more operated patients are currently asymptomatic (70%, 8%) and using fewer medications (nitrates, 18%, 96%; propranolol, 8%, 72% of patients). Exercise tests with treadmill revealed increased exercise tolerance time in both groups, more so in the operated group (+ 89%, + 42%), and angina could not be provoked in 70% and 20% of patients, respectively. During the follow-up, fewer cardiac complications developed in the operated group (19 vs. 44; P = less than 0.02); there was no difference in mortality. Repeat catheterization in 83 of 84 survivors at 1 year did not reveal any significant differences in the progression of disease. Atrial pacing studies revealed improvement in anginal threshold in 70% of operated and 48% of nonoperated patients. The study suggests that although subjective and objective improvement occurs with surgical as well as nonsurgical treatment, the frequency and magnitude are higher with surgery. The quality of life appears to be better in the operated patients during the first 24 months. Further follow-up is necessary to determine the duration of such improvement and to assess the influence of surgery on the natural life history of this disease.

Cardiac output and pressure-flow measurements were made in left internal mammary artery-to-left anterior descending coronary artery grafts and left subclavian artery-to-left circumflex coronary artery vein grafts after proximal coronary artery ligation. Similar measurements were also made in left internal mammary artery-to-left anterior descending coronary artery grafts and aortocoronary saphenous vein grafts in patients with coronary artery disease. Hemodynamic parameters and graft blood flows were measured during control baseline conditions and after pharmacological interventions using isoproterenol, phenylephrine, and epinephrine in random order. Blood flow through vein grafts and internal mammary artery grafts was similar under basal conditions and increased similarly with each of these vasoactive agents. Other hemodynamic parameters changed variably with the various pharmacological agents used. There was no close correlation between mammary artery or vein graft blood flow and arterial mean pressure and cardiac output over the wide range observed with the different drugs was associated with either an increase in perfusion pressure or a decrease in coronary vascular resistance. If the percentage increase in coronary blood flow above the basal control value in response to pharmacological stress is considered as a reflection of coronary vascular reserve, these studies suggest that coronary vascular reserve in patients with coronary artery disease is less than that of the normal dog heart.