sildenafil-citrate and Angina-Pectoris

In less than 20 years, the first selective type 5 phosphodiesterase inhibitor, sildenafil, has evolved from a potential anti-angina drug to an on-demand oral treatment for erectile dysfunction (Viagra), and more recently to a new orally active treatment for pulmonary hypertension (Revatio). Here we describe the key milestones in the development of sildenafil for these diverse medical conditions, discuss the advances in science and clinical medicine that have accompanied this journey and consider possible future indications for this versatile drug.

Topics: Angina Pectoris; Cerebrovascular Circulation; Erectile Dysfunction; Heart Failure; Humans; Hypertension, Pulmonary; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Recent studies have highlighted the relation between erectile dysfunction (ED) and cardiovascular disease. In particular, the role of endothelial dysfunction and nitric oxide in ED and atherosclerotic disease has been elucidated. Given the large number of men receiving medical treatment for ED, concerns regarding the risk for sexual activity triggering acute cardiovascular events and potential risks of adverse or unanticipated drug interactions need to be addressed. A risk stratification algorithm was developed by the First Princeton Consensus Panel to evaluate the degree of cardiovascular risk associated with sexual activity for men with varying degrees of cardiovascular disease. Patients were assigned to 3 categories: low, intermediate (including those requiring further evaluation), and high risk. This consensus study from the Second Princeton Consensus Conference corroborates and clarifies the algorithm and emphasizes the importance of risk factor evaluation and management for all patients with ED. The panel reviewed recent safety and drug interaction data for 3 phosphodiesterase (PDE)-5 inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease. Increasing evidence supports the role of lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease. Special management recommendations for patients taking PDE-5 inhibitors who present at the emergency department and other emergency medical situations are described. Finally, further research on the role of PDE-5 inhibition in treating patients with other medical or cardiovascular disorders is recommended.

Topics: Age Distribution; Aged; Angina Pectoris; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Coronary Disease; Drug Interactions; Erectile Dysfunction; Humans; Incidence; Male; Middle Aged; Piperazines; Prognosis; Purines; Risk Assessment; Severity of Illness Index; Sildenafil Citrate; Sulfones; Survival Rate

Stable angina pectoris is a common condition associated with chest pain predictable for a given level of exercise. Sexual intercourse does not lead to exaggerated heart rate or blood pressure responses and is interpreted by the heart as one of many forms of activity that may take place in a 24-hour period. Stable angina patients optimally treated are not at significantly increased cardiovascular risk during sexual intercourse. Erectile dysfunction (ED) increases with age and shares similar cardiovascular risk factors with stable angina. Sildenafil citrate can be safely prescribed for stable patients with ED providing they are not taking oral, topical, or sublingual nitrates. Sexual relationships should not be constrained by the diagnosis of angina pectoris provided appropriate medical advice is given on risk status. Family physicians and specialists are able to provide this advice based on their knowledge of the patient and the social circumstances. Impersonal advice is potentially dangerous and should be vigorously discouraged.

Topics: Angina Pectoris; Cause of Death; Coitus; Contraindications; Erectile Dysfunction; Humans; Male; Myocardial Infarction; Phosphodiesterase Inhibitors; Piperazines; Purines; Risk Factors; Sildenafil Citrate; Sulfones

Patients with cardiovascular diseases frequently complain of erectile dysfunction especially when treated with beta-blockers. In order to assess whether the effect of beta-blockers on erectile dysfunction is in part related to patient knowledge of the drug side effects, 96 patients (all males, age 52+/-7 years) with newly diagnosed cardiovascular disease and not suffering from erectile dysfunction entered a two phase, single cross over study.. During the first phase of the study patients received atenolol 50mg o.d. (A), 32 patients were blinded on the drug given (group A), 32 were informed on the drug given but not on its side effects (group B) and 32 took A after being informed on its side effects on erectile function (group C). After 3 months the incidence of erectile dysfunction was 3.1% in the group A, 15.6% in group B and 31.2% in group C (P<0.01). All patients reporting ED entered the second phase of the study and were randomised to receive Sildenafil 50mg and placebo in a cross over study. Sildenafil citrate and placebo were equally effective in reversing erectile dysfunction in all but one patient reporting ED with Atenolol.. Our results show that the knowledge and prejudice about side effects of beta-blockers can produce anxiety, that may cause erectile function.

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Anxiety; Attitude to Health; Awareness; Cardiovascular Diseases; Cross-Over Studies; Humans; Hypertension; Impotence, Vasculogenic; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Placebos; Purines; Sildenafil Citrate; Sulfones

The aim of this study was to evaluate whether sildenafil, used for treatment of erectile dysfunction (ED), affects the exercise tolerance and ischaemic threshold in men with exercise-induced angina not taking nitrates.. This was a double-blind placebo-controlled study in men with ED and chronic stable angina, assessing the effect of sildenafil on time to limiting angina during incremental treadmill exercise. Patients remained on their antianginal therapy and received a 100-mg dose of sildenafil or placebo 1h prior to treadmill exercise. Other measurements included times to onset of angina, 1-mm ST-segment depression, and total exercise time.. Adjusted treatment differences for the time to limiting angina, time to onset of angina, total exercise time, and time to 1-mm ST-segment depression were (mean+/-SE) 20+/-10s (95% CI, 1-39; P=0.040), 32+/-11s (95% CI, 11-53; P=0.004), 20+/-10s (95% CI, 0-39; P=0.049), and 12+/-17s (95% CI, -21 to 45, P=0.48), respectively, in favour of sildenafil. There were no serious treatment-related adverse events.. Sildenafil was well tolerated and did not adversely affect any exercise parameter in men with coronary artery disease and ED. Favourable trends in total exercise duration and times to onset of angina and limiting angina were recorded with sildenafil use.

Topics: Adolescent; Adult; Aged; Angina Pectoris; Chronic Disease; Double-Blind Method; Erectile Dysfunction; Exercise Test; Exercise Tolerance; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

It has been suggested that phosphodiesterase 5 (PDE5) inhibition is potentially hazardous and that it increases the risk of cardiac events in patients with coronary artery disease. This study sought to evaluate whether PDE5 inhibition with sildenafil exerts any effect on exercise-induced myocardial ischemia in patients on beta-blockers.. Fourteen patients underwent a baseline exercise test off-therapy and were then started on atenolol (100 mg once daily). After a run-in phase of 1 week, patients underwent a second exercise test and were randomized to receive either sildenafil (50 mg) or placebo given in a random order on two different occasions, 2 days apart. Exercise test was repeated 2 hours after the administration of sildenafil or placebo.. All patients had a > 1 mm ST-segment depression while off-therapy. Eight patients had a negative exercise test response after atenolol, which was unaltered by the adjunct of either sildenafil or placebo. In the remaining subjects, atenolol significantly prolonged the time to 1 mm ST-segment depression and the exercise time. Sildenafil and placebo did not reverse the beneficial effect of atenolol upon exercise-induced myocardial ischemia.. PDE5 inhibition does not worsen exercise capacity and exercise-induced myocardial ischemia in patients with chronic stable angina whose symptoms and exercise test response are well controlled by beta-blocker therapy.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angina Pectoris; Atenolol; Blood Pressure; Chronic Disease; Contraindications; Drug Interactions; Exercise Test; Heart Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

We sought to study the effects of a single oral dose of sildenafil citrate (50 mg) on blood pressure (BP) in men taking the nitric oxide (NO) donor drugs isosorbide mononitrate (ISMN) or glyceryl trinitrate (GTN) for stable angina.. Sildenafil, a selective phosphodiesterase type 5 inhibitor, is an orally effective treatment for erectile dysfunction. The presence of phosphodiesterases in the vasculature suggests the possibility of an interaction between sildenafil and NO donor drugs.. Two double-blind, placebo-controlled, randomized, two-way crossover trials were undertaken. Sixteen male patients received oral ISMN (20 mg twice a day) for five to seven days before their dose of sildenafil or placebo and continued receiving ISMN daily until administration of the alternate drug seven days later. For the second study, 15 male patients received sublingual GTN (500 microg) 1 h after sildenafil or placebo on each of two study days, which were seven days apart. Sitting or standing BP was measured before and for 6 h after the administration of the study drug.. The effects of sildenafil plus ISMN on BP (standing mean maximum reductions from baseline in systolic/diastolic BP, -52/-29 mm Hg) were greater than the effects of placebo plus ISMN on BP (-25/-15 mm Hg; p < 0.001). Sildenafil plus GTN also resulted in greater sitting mean maximum reductions from baseline in systolic/diastolic BP (-36/-21 mm Hg) compared with placebo plus GTN (-26/-12 mm Hg; p < 0.01).. Coadministration of sildenafil with ISMN or GTN produced significantly greater reductions in BP than ISMN or GTN alone. Based on these data, sildenafil should not be administered to patients taking nitrates.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Oral; Aged; Angina Pectoris; Blood Pressure; Contraindications; Cross-Over Studies; Delayed-Action Preparations; Double-Blind Method; Drug Interactions; Drug Synergism; Drug Therapy, Combination; Humans; Isosorbide Dinitrate; Male; Middle Aged; Nitric Oxide Donors; Nitroglycerin; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Chest pain is a common complaint in patients with pulmonary arterial hypertension (PAH). Left main coronary artery (LMCA) compression by an enlarged pulmonary artery trunk (PAT) has been associated with angina, but appropriate diagnostic and treatment approaches remain poorly defined. We present two cases of angina caused by LMCA compression from an enlarged pulmonary artery, one of which also presented with new, severe left ventricular systolic dysfunction attributed to myocardial ischemia. Diagnosis of LMCA stenosis was made via coronary angiography followed by computed tomography-gated coronary angiography (CT-CA), which confirmed pulmonary artery enlargement as the source of extrinsic compression. Restoring LMCA patency with percutaneous intervention and/or aggressive treatment of pulmonary hypertension led to significant improvement in angina, cardiac function and quality of life. Given the negative impact on cardiac function, prompt diagnosis and treatment of extrinsic LMCA compression should be considered a priority.

Topics: Adult; Angina Pectoris; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Stenosis; Echocardiography; Epoprostenol; Humans; Hypertension, Pulmonary; Male; Middle Aged; Myocardial Ischemia; Piperazines; Pulmonary Artery; Purines; Sildenafil Citrate; Stents; Sulfones; Tomography, X-Ray Computed; Ultrasonography, Interventional; Vasodilator Agents

Effects of ranolazine on isosorbide dinitrate- and on sildenafil-induced changes in mean arterial pressure and heart rate were assessed in conscious dogs. Dogs (n = 7) were chronically instrumented for measurements of mean arterial pressure and heart rate. Bolus intravenous injections of either isosorbide dinitrate (0.2 mg/kg) or sildenafil (0.5 mg/kg) caused biphasic changes in mean arterial pressure and heart rate: a transient (approximately 20 s) decrease in mean arterial pressure and an increase in heart rate, followed by prolonged (10-15 min) decreases in mean arterial pressure by 11 +/- 1.6 and 11 +/- 2.2 mm Hg, respectively. Infusion of ranolazine alone (plasma concentrations = 4 or 8 microM) for 10 min did not significantly affect mean arterial pressure and heart rate. The transient hypotension and tachycardia caused by isosorbide dinitrate were not altered by ranolazine. The sildenafil-induced transient tachycardia (Delta change: 114 +/- 10 beats/min) was significantly (P < 0.05) blunted by either 4 (Delta change: 71 +/- 8 beats/min) or 8 (Delta change: 66 +/- 9 beats/min) microM ranolazine. However, the sildenafil-induced transient decrease in mean arterial pressure was not altered by ranolazine. During ranolazine infusion (4-5 or 8-10 microM), isosorbide dinitrate and sildenafil caused prolonged decreases in mean arterial pressure. These results indicate that except for a blunting of the transient tachycardia caused by sildenafil, ranolazine at concentrations up to 10 microM does not alter changes in mean arterial pressure and heart rate induced by either isosorbide dinitrate or sildenafil in conscious dogs.

Topics: Acetanilides; Angina Pectoris; Animals; Blood Pressure; Dogs; Enzyme Inhibitors; Heart Rate; Hypotension; Injections, Intravenous; Isosorbide Dinitrate; Male; Piperazines; Purines; Ranolazine; Sildenafil Citrate; Stimulation, Chemical; Sulfones; Vasodilator Agents

Recently the new specific phosphodiesterase-5 inhibitor sildenafil was introduced into therapy for erectile dysfunction. The hemodynamic effects of sildenafil may be potentially hazardous for patients with cardiac disease. Sildenafil has been reported to augment the hypotensive effects of nitrates. There is sparse information regarding the systemic and pulmonary hemodynamic effects of a single oral dose of sildenafil in patients with stable angina.. Male patients referred for coronary angiography with diagnosis of chronic stable angina were enrolled in this study to assess the acute hemodynamic effects of sildenafil. Patients receiving long-acting or sublingual nitrates for the last 6 h before the study were excluded. Hemodynamic measurement were taken during right and left heart catheterization in the basal state and 60 min after 50 mg of oral sildenafil.. Twelve patients (age 53+/-7 years) were studied. All had stable angina CCS class II or III. Four had previous myocardial infarction. By coronary angiography, seven patients had at least one coronary artery with >70% stenosis, four had at least one with 50-70% stenosis, and one had only intimal irregularities. There were no significant effects of sildenafil on systemic or pulmonary arterial pressure, left ventricle end diastolic pressure, cardiac output, and systemic or pulmonary vascular resistance (P>0.05 for all). No adverse events were observed.. A single oral dose of sildenafil had no significant hemodynamic effect in supine patients with stable angina. Isolated administration of sildenafil does not appear to be associated to adverse cardiovascular effects.

Topics: Adult; Aged; Angina Pectoris; Coronary Angiography; Hemodynamics; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Aged; Angina Pectoris; Drug Synergism; Emergency Treatment; Family Practice; Fatal Outcome; Humans; Male; Malingering; Nitroglycerin; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Suicide; Sulfones; Vasodilator Agents

Topics: Aged; Angina Pectoris; Coronary Angiography; Diltiazem; Humans; Hypotension; Male; Nitrates; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones

Topics: Angina Pectoris; Blood Pressure; Contraindications; Drug Therapy, Combination; Erectile Dysfunction; Humans; Male; Molsidomine; Nicorandil; Nitrates; Nitric Oxide Donors; Piperazines; Purines; Sildenafil Citrate; Sulfones