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Isidori, associate professor of endocrinology at Sapienza University of Rome. Dosages used for heart ailments are lower than those used for erectile dysfunction, and patients in the study showed few side effects.

“Surprisingly, in over 1600 treated subjects, no increased risk of visual disturbance, photosensitivity and ‘blue haze,’ was observed,” he told NBC News.

The active ingredient in Viagra is sildenafil citrate, which is a phosphodiesterase type 5 inhibitor (PDE5i).

The inhibitor blocks the enzyme PDE5, which prevents relaxation of smooth muscle tissue.

Researchers analyzed randomized trials that had been published between January 2004 and May 2014, choosing 24 involving mixed populations of patients who were treated with PDE5i or a placebo. PDE5i was given to men who had cardiovascular disorders, but who did not necessarily suffer from sexual impotence, according to Isidori. The study found that the inhibitor prevented the heart from changing shape in patients suffering from left ventricular hypertrophy, a condition that causes thickening and enlargement of the heart muscle.

The drug also improved functioning of the heart in patients with a variety of cardiac conditions, with no effect on blood pressure.

In fact, researchers found that the drug improved efficiency when the heart pumped blood into vessels, along with relaxation between beats.

“Very few drugs used in cardiology can actually affect these parameters. For this reason their implications in the treatment and prevention of heart failure are huge.” However, Isidori notes that because these studies were conducted exclusively on men, the next step should be a larger trial on women. This site is protected by recaptcha Privacy Policy | Terms of Service. "A significant number of subjects suffering from erectile dysfunction are much happier to take pills for heart failure or high blood pressure than to improve their erections." “I am not surprised and it’s good news,” said Dr. Kloner, professor of medicine in the cardiovascular division at the Keck School of Medicine at USC in California. “We can always use a new drug for cheap online doctor prescription heart failure." Kloner co-authored the book, “Viagra: How the Miracle Drug Happened & What It Can Do for You.” He said this is not the first time, scientists have looked to Viagra for potential heart benefits.

In 1989, British scientists tested sildenafil citrate as a medication to treat high blood pressure and angina. By the 1990s in early trials of the drug, researchers noticed an interesting side effect — an increase in erections.

In 1996, the pharmaceutical company Pfizer patented it as Viagra, and in just two years, doctors had ordered more than 40,000 prescriptions of the new wonder drug.

“When the drug first came out there was a big scare — is this going to kill people?” said Dr. Kociol, director of the heart failure program at the CardioVascular Institute at Beth Israel Deaconess Medical Center in Boston. “But in all studies, to the best of my knowledge, it’s not shown any increase in cardiac events in patients who take these drugs,” he said.

Past studies have suggested Viagra and other PDE5 inhibitors may have benefits for heart failure by decreasing pulmonary artery resistance and providing cardio-protective effects in settings with low blood flow, according to Kociol.

“They also improve exercise tolerance in patients with heart failure,” he said.

The drug may even reduce the size of a heart attack. But Kociol said scientists have to “temper” their enthusiasm as more studies are necessary. “As interesting as this paper is, there have been conflicting results,” he said. “If there is a silver bullet, it remains to be seen.” Kociol added that researchers also need to “pay more attention” differences between men and women and between racial groups. Some earlier research suggests that drugs like Viagra might interact differently with estrogen, which is known to have naturally protective properties for the heart.

Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension.

In a previous study, 6-minute walk distance (6MWD) improvement with sildenafil was not dose dependent at the 3 doses tested (20, 40, and 80 mg 3 times daily [TID]). This study assessed whether lower doses were less effective than the approved 20-mg TID dosage. Treatment-naive patients with pulmonary arterial hypertension were randomized to 12 weeks of double-blind sildenafil 1, 5, or 20 mg TID; 12 weeks of open-label sildenafil 20 mg TID followed.

Changes from baseline in 6-minute walk distance (6MWD) for sildenafil 1 or 5 mg versus 20 mg TID were compared using a Williams test. Hemodynamics, functional class, and biomarkers were assessed. The study was prematurely terminated for non-safety reasons, with 129 of 219 planned patients treated.

At week 12, 6MWD change from baseline was significantly greater for sildenafil 20 versus 1 mg ( P = 0.011) but not versus 5 mg.

At week 24, 6MWD increases from baseline were larger in those initially randomized to 20 versus 5 or 1 mg (74 vs 50 and 47 m, respectively).

At week 12, changes in hemodynamic parameters were generally small and variable between treatment groups; odds ratios for improvement in functional class were not statistically significantly different. Improvements in B-type natriuretic peptide levels were significantly greater with sildenafil 20 versus 1 but not 5 mg.

Sildenafil 20 mg TID appeared to be more effective than 1 mg TID for improving 6MWD; sildenafil 5 mg TID appeared to have similar clinical and hemodynamic effects as 20 mg TID.

ClinicalTrials.gov NCT00430716 (Registration date: January 31, 2007).

Pulmonary arterial hypertension (PAH) is a fatal disease in which increasing pulmonary vascular resistance ultimately culminates in right ventricular failure and death [1, 2].

The phosphodiesterase type 5 (PDE5) inhibitor sildenafil is approved to treat adult patients with PAH [2]; pediatric use is approved in the European Union.

In the 12-week, randomized, double-blind, SUPER-1 study [3], statistically significant improvements in 6-minute walk distance (6MWD) were observed with sildenafil versus placebo in treatment-naive patients at all 3 tested doses (20, 40, and 80 mg 3 times daily [TID]); improvements were similar among groups and did not appear to be dose related.

However, hemodynamic parameters, including mean pulmonary arterial pressure (mPAP), cardiac index, and pulmonary vascular resistance index (PVRI), appeared to improve dose dependently with sildenafil treatment. Sildenafil 20 mg TID

appeared

This multinational, randomized, double-blind study investigated whether low doses of sildenafil (1 and 5 mg TID) were less effective in adult patients with PAH than the currently approved 20-mg TID cheap no prescription cialis dose.

However, before completion of this low-dose study, results from another randomized, double-blind, placebo-controlled study (PACES-1) became available that supported approval of a clinical worsening indication by the FDA [5]. PACES-1 evaluated oral sildenafil in patients with PAH who were receiving stable epoprostenol therapy [6]. In PACES-1, ?75% of patients were titrated from sildenafil 20 mg TID, received during the first 4 weeks, to sildenafil 40 mg TID at week 4, and then to sildenafil 80 mg TID at week 8 (and were maintained on this dose, as patients tolerated). After 16 weeks, 6MWD, hemodynamic parameters, and functional class improved.

There was a significant delay in time to clinical worsening (TTCW) [6], defined as death, lung transplantation, hospitalization due to PAH, initiation of bosentan therapy, or clinical deterioration requiring a change in epoprostenol therapy, with sildenafil compared with placebo. The effect was apparent by week 4, when all patients were receiving sildenafil 20 mg TID ( P = 0.0074) [4].

Following approval of the clinical worsening indication in the United States in 2009, the FDA released Pfizer from the postapproval commitment to conduct a low-dose study.

The study was subsequently terminated (June 2010) based on the recommendation of the data monitoring committee (DMC) because sildenafil 20 mg TID had been shown to reduce time to clinical worsening in PACES-1 and also acknowledging that with recruitment issues the study was unlikely to meet original enrollment targets.

The primary objective of the study was to demonstrate a dose response for 6MWD for 1, 5, and 20 mg TID oral sildenafil.

The hypothesis was that there is a dose that is significantly less effective than sildenafil 20 mg TID. Secondary objectives included assessment of the safety and tolerability of low-dose sildenafil during the 12 weeks of treatment in patients with PAH and evaluation of the effects of sildenafil on perceived PAH-progression biomarkers (B-type natriuretic peptide [BNP]/pro-BNP levels and tricuspid annular plane systolic excursion [TAPSE]).

The study protocol and amendments were reviewed and approved by the Institutional Review Board and/or Independent Ethics Committee at each participating center (Additional file 1); informed consent was obtained from all patients.

Patients were aged >18 years with idiopathic or heritable PAH or PAH associated with connective tissue disease or surgical repair (?5 years before enrollment) of atrial septal defect, ventricular septal defect, patent ductus arteriosus, or aorto-pulmonary window and 6MWD 100 to 450 m. PAH, defined as mPAP ?25 mmHg and pulmonary artery wedge pressure ?15 mmHg at rest (or a left ventricular end diastolic pressure 3 and 6 h, and >6 and 8 h postdose), week 1 (immediately after BNP/pro-BNP sampling), weeks 4 and 8 (immediately before 6MWD), and week 12 (between 15 min and 3 h and between >3 and 6 h postdose, immediately before 6MWD, between >6 and 8 h postdose, and during RHC assessment).

Adverse events (AEs) were monitored throughout the study. Laboratory testing and physical examinations were performed at screening, baseline, and weeks 4, 8, and 12. The relationship between 6MWD and sildenafil exposure could not be modeled because 6MWD had reached a plateau across all SUPER-1 dose groups [3]. Therefore, the relationship between PVRI and exposure was used to select doses predicting exposures from the population pharmacokinetic/pharmacodynamic model. The average sildenafil plasma concentration required to achieve 50% effect (EC 50 ) on PVRI was approximately 3 ng/mL; at a 20-ng/mL concentration, sildenafil appeared to have a 90% maximal effect (EC 90 ) on PVRI [4].

Therefore, after receipt of 20 mg TID, sildenafil concentrations were anticipated to be > EC 90 for the entire 8-hour dosing interval; for 5 mg TID, above EC 50 for the entire 8-hour dosing interval but.

The study was conducted at 34 centers in Europe, Asia, Russia, the United States, and Brazil.

Of the planned 219 patients, 169 were screened, 130 were randomized, and 129 were treated (1 patient [sildenafil 1 mg] did not meet entry criteria).

Treated patients were mostly female and mostly Asian; baseline cardiac index was significantly higher in the sildenafil 20-mg group versus the 1- and 5-mg groups ( P = 0.0328 and 0.0030, respectively; Table 1). Two patients died during the double-blind phase (pneumonia [1 mg TID; death was the reason for discontinuation] and acute exacerbation of idiopathic pulmonary fibrosis [5 mg TID; patient was enrolled in error and received 4 days of treatment]), neither of which was considered to be treatment related; no deaths were reported in the open-label phase (Fig.

Legend: TID = 3 times daily; SIL = sildenafil.*Right ventricular failure. † Drug hypersensitivity ( n = 1) and rash ( n = 1) Sildenafil concentration. Overall, 129 patients provided 1068 sildenafil concentrations. A 1-compartment pharmacokinetic model adequately described the sparse data.

From this model, the estimated apparent clearance was 43.9 (95% CI, 39.3–48.6) L/h, the apparent volume of distribution was 458 (95% CI, 393–523) L, and the absorption rate constant was 2.16 (95% CI, 1.48–2.84) h ?1 . Coadministration of weak or moderate CYP3A4 inhibitors ( n = 12 patients/110 samples) reduced CL/F by 40.4% (95% CI, 19.2%–61.6%).

The model cheap online doctor prescription supported dose proportionality of exposures.

The limit of quantification of the pharmacokinetic assay was 1 ng/mL; 134 samples were below the limit of quantification (BLQ).

The majority of BLQ samples (approximately 75%) were measured at the 1-mg TID sildenafil dose, but had little effect on the population pharmacokinetic parameter estimates. Figure 3 represents the sildenafil concentration data.

Because a small accumulation existed between the first (at baseline visit) and subsequent doses, only concentrations after the second and subsequent doses are shown (for data including baseline visit, see Additional file 3).

Concentrations after concomitant administration of CYP3A4 inhibitors were adjusted for the estimated effect.

Visual inspection of observed concentration distribution across each dose indicated consistency of the observed data with the model.

In particular, in the 8 h after drug administration, most of the determinations in the 1-mg TID group had a concentration below 3 ng/mL, whereas in the 5-mg TID and 20-mg TID groups, most of the determinations had a concentration above 3 ng/mL, which is the average sildenafil plasma concentration required to achieve 50% effect (EC 50 ) on PVRI [4].

An exploratory assessment (see Additional files 4 and 5) of the relationship between 6MWD, PVR, and steady-state concentrations revealed a significant relationship for 6MWD, whereas only a small trend could be seen for PVR across the concentration range observed (Additional files 6 and 7).

Plot of observed plasma sildenafil concentrations vs time after sildenafil dosing.

Legend: Plasma sildenafil concentrations ( open circles ), sildenafil doses of 1 mg (left ), 5 mg ( cheap online doctor prescription middle ), and 20 mg ( right ).

Median ( solid line ) and 90% prediction intervals ( dashed lines ) from simulations are overlaid.

Tick marks on the horizontal time axis indicate concentration measures below the limit of quantification. The shaded area shows the concentration range between 3 ng/mL and 20 ng/mL, which are the average sildenafil plasma concentrations required to achieve 50% effect (EC 50 ) and 90% effect (EC90) on PVRI, respectively. At week 12, compared with baseline, the increase in 6MWD was of a magnitude consistent with estimates of clinical significance [7, 8] in 5- and 20-mg TID groups and smaller although statistically significant in the 1-mg TID group. Among dose groups, the mean change in 6MWD from baseline was statistically significantly different only for the sildenafil 20- versus 1-mg group (Fig. Legend: Mean (SE) overall change from double-blind baseline in 6MWD in double-blind (week 12) and open-label (week 24) phases of the study ( a ), and change from baseline to week 12 in 6MWD by baseline 6MWD ( b ).

All patients received sildenafil 20 mg TID in the open-label phase of the study (weeks 13–24).

6MWD = 6-minute walk distance; TID = 3 times daily. Analysis of change from baseline in 6MWD at week 12 showed a statistically significant ( P = 0.011) difference between sildenafil 1 mg and 20 mg, but not sildenafil 5 mg and 20 mg (Table 2). The results were confirmed by an analysis of variance; the mean treatment difference between sildenafil 20 mg and 1 mg was 23 (3–43) m and between 20 mg and 5 mg was –3 (–23 to 17) m ( P = 0.02 and 0.76, respectively). Mean change from baseline in 6MWD assessed by race. Legend: Mean (SE) overall change from double-blind baseline in 6MWD in the double-blind (week 12) phase of the study ( a ) and change from baseline to week 12 in 6MWD by baseline 6MWD ( b ) assessed by race (Asian vs non-Asian). 6MWD = 6-minute walk distance; TID = 3 times daily. During the open-label period (cheap online doctor prescription weeks 12 to 24), in which all patients received sildenafil 20 mg TID, patients who received sildenafil 1 mg TID during the double-blind phase (weeks 0 to 12) had a larger increase in 6MWD than patients who received sildenafil 5 mg TID (mean change, 31 vs 6 m, respectively); the magnitude of change was similar between patients who received sildenafil 1 mg and 20 mg TID in the double-blind phase (mean change, 31 vs 26 m; Fig. Compared with baseline, there was a trend toward reduction in pulmonary vascular resistance (PVR) at week 12 in all groups; the mean reduction was statistically significantly different from 0 only in the 20-mg TID group (ie, 95% CIs do not include 0). There were no statistically significant differences among treatment groups for change in PVR (Table 3).

Changes at week 12 in the additional hemodynamic parameters were generally small and variable between groups. Most patients in each treatment group remained in the same functional class from baseline to week 12; the same was true through week 24 (Table 4).

Odds ratios (ORs) showed no significant differences for functional class between sildenafil 20 mg and the 5-mg (OR, 1.08 [95% CI, 0.35–3.32]; P = 0.897) or 1-mg (OR, 1.55 [95% CI, 0.50–7.78]; P = 0.448) dose at week 12.