Can atorvastatin improve the response to sildenafil in men with erectile dysfunction not initially responsive to sildenafil? Hypothesis and pilot trial results. The effect of simvastatin in penile erection: a randomized, double-blind, placebo-controlled clinical trial (Simvastatin treatment for erectile dysfunction—STED TRIAL) Atorvastatin improves the response to sildenafil in hypercholesterolemic men with erectile dysfunction not initially responsive to sildenafil Sexual function, satisfaction, and association of erectile dysfunction with cardiovascular disease and risk factors in cardiovascular high-risk patients: substudy of the ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNT Study in ACE-IN Erectile dysfunction as a predictor of cardiovascular events and death in diabetic patients with angiographically proven asymptomatic coronary artery disease: a potential protective role for statins and 5-phosphodiesterase inhibitors. Effect of statin therapy on early return of potency after nerve sparing radical retropubic prostatectomy. A multicenter, double-blind, placebo-controlled trial to assess the efficacy of sildenafil citrate in men with unrecognized erectile dysfunction. Statin therapy worsens insulin sensitivity in women with polycystic ovary syndrome (PCOS): a prospective, randomized, double-blind, placebo-controlled study. Randomized Trial of a Pharmacist-Delivered Intervention for Improving Lipid-Lowering Medication Adherence among Patients with Coronary Heart Disease Prospective evaluation of the effect of statins on blood pressure control in hypertensive patients in clinical practice. Emotional changes in men treated with sildenafil citrate for erectile dysfunction: a double-blind, placebo-controlled clinical trial. Erectile Dysfunction Predicts Cardiovascular Events in High-Risk Patients Receiving Telmisartan, Ramipril, or Both: The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (ONT Erectile Dysfunction after Therapy with Metoprolol: The Hawthorne Effect Statins, especially atorvastatin, may improve survival following brachytherapy for clinically localized prostate cancer. The effects of quinapril and atorvastatin on the responsiveness to sildenafil in men with erectile dysfunction Association of Statin Therapy with Outcomes of Acute Coronary Syndromes: The GRACE Study A Cluster Randomised Controlled Trial of a Pharmacist-Led Collaborative Intervention to Improve Statin Prescribing and Attainment of Cholesterol Targets in Primary Care
BACKGROUND Erectile dysfunction ( ED ) may be one manifestation of a generalized vascular disorder characterized by endothelial dysfunction . Statin drugs may improve endothelial function , even before altering the lipid profile . OBJECTIVE We sought to determine whether the addition of a statin with sildenafil would improve ED in men who initially responded poorly to sildenafil .  METHODS Men with moderate-to-severe ED despite an adequate sildenafil trial were enrolled in this r and omized , double-blind , placebo-controlled pilot study . ED was defined using a vali date d self-administered question naire as a score of < or=16 on the International Index of Erectile Function ( erectile function domain score range of 6 - 30 ) . Improvement in ED score with sildenafil was reassessed at 6 and 12 weeks of treatment with atorvastatin ( 80 mg daily ) or matching placebo . RESULTS Twelve men ( mean age 58 + /- 13 years ) with a mean domain score of 8.2 + /- 6.9 and a mean duration of ED of 3.7 years were enrolled in the study . Treatment with atorvastatin decreased mean low-density lipoprotein cholesterol by 43 % and result ed in an improvement with  sildenafil in domain score of 7.8 ( P = 0.036 ) ; an effect was apparent by 6 weeks . The increase in domain score in placebo patients was not statistically significant . CONCLUSIONS Treatment with atorvastatin improved sexual function and the response to oral sildenafil  in men who did not initially respond to treatment with sildenafil .  The results of this pilot study support the hypothesis that vascular endothelial dysfunction contributes to ED in sildenafil nonresponders and deserves further testing in a large clinical trial The aim of the study is to evaluate the effect of simvastatin in  erectile dysfunction ( ED ) secondary to endothelial dysfunction . This study is a double-blind , r and omized , placebo-controlled , clinical trial in patients with ED and endothelial dysfunction . Patients were r and omized to receive 20 mg simvastatin  ( n=21 ) or placebo  ( n=20 ) daily for 6 months and subsequently 10 mg of vardenafil on dem and for 4 weeks . Serum cholesterol , hormone profile , ultrasensitive C-reactive protein , the International Index of Erectile Dysfunction ( IIEF ) and the ED Index of Treatment Satisfaction were evaluated . There was a significant reduction in serum cholesterol in the treatment group . The hormonal profile remained unaltered . There was no difference in the IIEF between the groups at follow-up , although , at the beginning , 26 % of the patients of both groups presented with mild ED and 74 % with moderate-to-severe ED ; at the end of the 7th month , all patients from the simvastatin group progressed to mild ED , compared with only 83 % in the placebo group . There was no statistically significant difference in penile erection after intake of simvastatin or placebo . This study does not support the use of simvastatin as erectogenic medication . Further studies are necessary to verify if simvastatin has any beneficial effect on ED Despite the initial enthusiasm , the significant number of patients in whom sildenafil is contraindicated or ineffective is a major challenge to all urologists . Our aim was to determine the safety and efficacy of adjunctive atorvastatin in restoring normal erectile function in hypercholesterolemic ( low-density lipoprotein ( LDL ) cholesterol > 120 mg per 100 ml ) sildenafil nonresponders . The study comprised 131 men with ED not responding to sildenafil citrate .  They were r and omized either to 40 mg atorvastatin daily ( n=66 , group 1 ) or matching placebo ( n=65 , group 2 ) for 12 weeks while they were taking on-dem and 100 mg sildenafil . Erectile function was subjectively assessed using the 5-item version of the International Index of Erectile Function ( IIEF-5 ) question naire and response to the global efficacy question ( GEQ ) . Serum biochemical and lipid profile ( total cholesterol , triglycerides , LDL cholesterol and high-density lipoprotein cholesterol ) analyses were performed at baseline and repeated at post-treatment weeks 6 and 12 . Compared with the placebo group ( 59 patients , mean age±s.d . 61.9±6.1 , mean years ED 3.9±1.8 ) , the atorvastatin group ( 59 patients , mean age±s.d . 63.9±6.9 , mean years ED 3.7±1.6 ) had significantly greater improvements in all IIEF-5 questions ( P=0.01 ) and GEQ ( P=0.001 ) . Subgroup analyses did reveal trends in the atorvastatin group to indicate that a change in the IIEF-5 score is affected by age , severity of ED and baseline serum levels of LDL . Patients with moderate ( r=0.28 , P=0.01 ) and severe ( r=0.20 , P=0.01 ) ED had better positive response rates  to adjunctive atorvastatin than patients with mild to moderate ED . None of the patients taking atorvastatin achieved a response of 5 to the IIEF-5 questions and none of the patients regained normal erectile function as defined by the IIEF-5 score > 21 . Subjects experienced a statistically significant but modest improvement in erectile function . Further investigation is needed to test the usefulness of long-term atorvastatin administration to restore erectile function in sildenafil nonresponders BACKGROUND Erectile dysfunction ( ED ) is a common disorder in middle-aged men and is significantly influenced by cardiovascular risk factors ( CVRFs ) and cardiovascular disease . The sub study of the ONTARGET/TRANSCEND trials evaluates the relationship of erectile function to baseline characteristics and current treatment in cardiovascular high-risk patients who have been enrolled in these trials . The effects of treatment with telmisartan and ramipril , alone or in combination , including a telmisartan versus placebo arm will be determined prospect ively during a follow-up of 4 years . METHODS One thous and three hundred fifty-seven patients were evaluated in 13 countries at baseline , 2 years , and 4 years , with ED determined using the ED score of the Cologne Male Survey ( Kölner [ Cologne ] Evaluation of Erectile Dysfunction ) and the 5-item International Index of Erectile Function . Erectile dysfunction scores were related to CVRF and the use of cardiovascular drugs . RESULTS Prevalence of ED was 50.7 % ( Kölner [ Cologne ] Evaluation of Erectile Dysfunction ) and 54.3 % ( 5-item International Index of Erectile Function ) , respectively , with a decline of sexual activity after the diagnosis of cardiovascular disease . In multivariate analysis , diabetes mellitus ( P < .00001 ) , stroke ( P = .00026 ) , pelvic surgery ( P = .025 ) , and age of > 65 years ( P < .00001 ) correlated with the degree of ED . No significant associations were observed for cholesterol levels , hypertension , and smoking status as well as current treatment with angiotensin-converting enzyme inhibitors , angiotensin I antagonists , diuretics , beta-blockers , or calcium-channel blockers . CONCLUSIONS The ONTARGET/TRANSCEND-ED sub study shows a significant influence of cardiovascular disease on erectile function . In contrast to prior smaller studies , drug therapy and CVRF seem to play a minor role in cardiovascular high-risk patients . Follow-up data will provide information whether angiotensin-converting enzyme inhibitors , angiotensin I antagonists , or a combination thereof are able to improve erectile function OBJECTIVES We sought to investigate whether erectile dysfunction ( ED ) is a predictor of future cardiovascular events and death in diabetic patients with silent coronary artery disease ( CAD ) and whether there are predictors of cardiovascular events and death among CAD diabetic patients with ED . BACKGROUND Case-control studies showed that ED is associated with CAD in diabetic patients , but no prospect i ve study is available . METHODS Type 2 diabetic men ( n = 291 ) with silent CAD angiographically documented were recruited .  Erectile dysfunction  was assessed by the International Index Erectile Function-5 question naire .  RESULTS During a follow-up period of 47.2 + /- 21.8 months ( range 4 to 82 months ) , 49 patients experienced major adverse cardiac events ( MACE ) . The difference in ED prevalence between patients with and those without MACE was significant ( 61.2 % vs. 36.4 % ; p = 0.001 ) . Cox regression analysis showed that ED predicted MACE ( hazard ratio [ HR ] 2.1 ; 95 % confidence interval [ CI ] 1.6 to 2.6 ; p < 0.001 ) . Among patients with CAD and ED , the Kaplan-Meier method showed that the statin ( Mantel log-rank test : 3.921 ; p = 0.048 ) and 5-phosphodiesterase ( 5-PDE ) inhibitor use ( Mantel log-rank test : 4.608 ; p = 0.032 ) were associated with a lower rate of MACE . Cox regression analysis showed that statin use ( HR 0.66 ; 95 % CI 0.46 to 0.97 ; p = 0.036 ) reduced MACE . Treatment with 5-PDE inhibitors did not enter the model , but its p value was very near to the significant level ( HR 0.68 ; 95 % CI 0.46 to 1.01 ; p = 0.056 ) . CONCLUSIONS Our data first show that ED is a powerful predictor of cardiovascular morbidity and mortality in diabetic patients with silent CAD and that the treatment with statins and 5-PDE inhibitors might reduce the occurrence of MACE among CAD diabetic patients with ED PURPOSE We prospect ively investigated whether postoperative statin use would contribute to earlier recovery of erectile function in men who underwent bilateral nerve sparing radical retropubic prostatectomy for clinical ly localized prostate cancer . MATERIAL S AND METHODS A total of 50 potent men without hypercholesterolemia undergoing bilateral nerve sparing radical retropubic prostatectomy for clinical ly localized prostate cancer were prospect ively r and omized into 2 equal groups . Group 1 patients were instructed to ingest only 50 mg sildenafil per day if needed following hospital discharge after radical retropubic prostatectomy . Group 2 patients were prescribed atorvastatin at a dose of 10 mg daily from postoperative days 1 to 90 and they were also instructed to ingest sildenafil , as in group 1 . Patient status regarding potency and adverse events were assessed 6 months after surgery . RESULTS The 2 groups demonstrated no significant differences regarding various baseline factors , including International Index of Erectile Function-5 scores . Group 2 had a significantly higher postoperative International Index of Erectile Function-5 score than group 1 at 6 months postoperatively ( p = 0.003 ) . Meanwhile , as judged by a preset definition , the incidence of potent patients 6 months after prostatectomy was 26.1 % in group 1 and 55 % in group 2 ( p = 0.068 ) . Also , 17.4 % and 40 % of the men reported achieving intercourse by vaginal penetration without a phosphodiesterase 5 inhibitor in groups 1 and 2 , respectively ( p = 0.172 ) . No serious adverse events associated with medication were reported . CONCLUSIONS Postoperative treatment with atorvastatin in men who report normal erectile function preoperatively may contribute to earlier recovery of erectile function after nerve sparing radical retropubic prostatectomy OBJECTIVE Erectile dysfunction ( ED ) may be present but unrecognized in men with other comorbidities , such as cardiovascular disease ( CVD ) , diabetes , or lower urinary tract symptoms ( LUTS ) . The efficacy of sildenafil citrate treatment for ED in men who did not self-identify with or were unsure about whether they had ED , but had ED based on International Index of Erectile Function Erectile Function domain ( IIEF-EF ) scores , was evaluated . METHODS Men with an ED-associated comorbidity were asked , " Do you have ED ? " Those who answered " no " or " unsure " and were diagnosed with ED ( score of < or=25 IIEF-EF ) were invited to participate in a parallel-group , multicenter , flexible-dose , double-blind , r and omized , placebo-controlled trial , followed by an open-label extension . Erectile function and emotional/psychosocial benefits of sildenafil treatment were assessed . RESULTS Men with ED at baseline were r and omized to sildenafil ( n = 150 ) or placebo ( n = 155 ) . The mean + /- SD number of ED risk factors in the sildenafil and placebo groups was 3.5 + /- 1.8 and 3.3 + /- 1.7 , respectively . Hypertension , hypercholesterolemia , smoking , obesity ( body mass index > or=30 kg/m(2 ) ) , and waist circumference > or=40 inches were the most frequently reported risk factors . Sildenafil-treated men had improved scores on both functional and psychosocial measures . Most adverse events were mild to moderate . CONCLUSIONS Many men do not recognize that they have ED ; sildenafil treatment improved sexual function and satisfaction in these men . Because ED affects quality of life , it should be suspected and assessed in men with risk factors for ED CONTEXT Statins have been shown to improve hyper and rogenism in women with polycystic ovary syndrome ( PCOS ) . However , their use has also been associated with impairment of glucose metabolism and an increased risk of type 2 diabetes mellitus . Because women with PCOS are prone to disturbances in glucose metabolism , statin therapy could also have negative effects . OBJECTIVE Our objective was to explore the effects of atorvastatin therapy on hormonal and metabolic parameters in women with PCOS . DESIGN AND SETTING We conducted a r and omized , double-blind , placebo-controlled 6-month follow-up study conducted at Oulu University Hospital , Finl and . PATIENTS Women with PCOS ( Rotterdam criteria ) were treated with atorvastatin ( 20 mg/d , n = 15 ) or placebo  ( n = 13 ) for 6 months . INTERVENTIONS Fasting serum sample s were collected at baseline and at 3 and 6 months . Oral and iv glucose tolerance tests were performed at 0 and 6 months . MAIN OUTCOME MEASURES And rogen secretion and glucose metabolism were measured . RESULTS Fasting levels and area under the curve of insulin increased significantly and insulin sensitivity ( insulinogenic and Matsuda indexes ) decreased during 6 months of atorvastatin therapy . Serum levels of dehydroepi and rosterone sulfate decreased in the atorvastatin group , whereas no change was observed in serum testosterone levels . Levels of C-reactive protein , total and low-density lipoprotein-cholesterol , and triglycerides decreased significantly during statin therapy . CONCLUSIONS Atorvastatin therapy improves chronic inflammation and lipid profile , but it impairs insulin sensitivity in women with PCOS . Because women with PCOS have an increased risk of developing type 2 diabetes mellitus , the results suggest that statin therapy should be initiated on the basis of generally accepted criteria and individual risk assessment of cardiovascular disease , and not only because of PCOS A r and omized trial of a pharmacist-delivered intervention ( PI ) versus usual care ( UC ) was conducted ; 689 subjects with known coronary heart disease were recruited from cardiac catheterization laboratories . Participants in the PI condition received 5 pharmacist-delivered telephone counseling calls post-hospital discharge . At one year , 65 % in the PI condition and 60 % in the UC condition achieved an LDL-C level < 100 mg/dL ( P = .29 ) ; mean statin adherence was 0.88 in the PI , and 0.90 in the UC ( P = .51 ) . The highest percentage of those who reached the LDL-C goal were participants who used statins as opposed to those who did not use statins ( 67 % versus 58 % , P = .05 ) . However , only 53 % and 56 % of the patients in the UC and PI conditions , respectively , were using statins . We conclude that a pharmacist-delivered intervention aim ed only at improving patient adherence is unlikely to positively affect outcomes . Efforts must be oriented towards influencing physicians to increase statin prescription rates BACKGROUND AND AIM Some clinical evidence supports a statin antihypertensive effect . Our aim is to evaluate the statin effect on blood pressure control in hypertensive patients in the setting of clinical practice , and the role of some predetermined individual patient characteristics ( age , gender , baseline BP levels , pre-treatment LDL-C levels ) on the supposed statin BP lowering effect . METHODS AND RESULTS Two hundred and fifty-four hypertensive patients with hypercholesterolemia were enrolled in the Ambulatory service of the Hypertension Research Unit of Bologna University Hospital . After 2 - 4 weeks of a run-in period patients were allocated to statin treatment and followed-up for 24 weeks . The blood pressure response to statins was compared in several subgroups of patients according to age , gender , baseline BP and pre-treatment cholesterolemia . In the overall study population , the use of statins was associated with a significant reduction in systolic ( -7.6+/-4 mmHg , p<0.05 ) and diastolic blood pressures ( -5.2+/-3 mmHg , p<0.05 ) in comparison to baseline . The blood pressure decrease was more pronounced in patients younger than 65 years ( p<0.05 ) , with higher baseline systolic blood pressure ( p<0.005 ) , and in those with higher cholesterolemia before statins ( p<0.05 ) . CONCLUSIONS Our study suggests a BP-lowering effect of statins , consistent with some other literature . Some parameters like age , baseline systolic blood pressure and cholesterolemia influence the antihypertensive effect of statins . The lack of consideration for these confounding factors may be one of the reasons for the conflicting results about the BP lowering effects of statins INTRODUCTION Erectile dysfunction ( ED ) has been associated with several comorbidities and can cause significant loss of quality of life and self-esteem . AIM In men with ED , to use the vali date d Self-Esteem and Relationship ( SEAR ) question naire to evaluate changes in self-esteem associated with sildenafil treatment of ED and to assess changes dependent on concomitant comorbid conditions . METHODS This was a 14-week , international , r and omized , parallel-group , double-blind , flexible-dose ( 25 , 50 , or 100 mg ) , placebo-controlled study of sildenafil in men aged > or=18 years with a clinical diagnosis of ED ( score < or= 21 on the Sexual Health Inventory for Men ) . MAIN OUTCOME MEASURES The primary outcome was the change in the SEAR Self-Esteem subscale score from baseline to the end of treatment . Secondary outcomes were the change in SEAR component scores stratified by ED comorbidity , the change in the International Index of Erectile Function ( IIEF ) domain scores and in the intercourse success rate , and the response to the global efficacy assessment and to the global satisfaction assessment . RESULTS A total of 841 patients were included in the intent-to-treat efficacy analysis ( 559 sildenafil , 282 placebo ) . Patients r and omized to sildenafil had significantly greater change scores from baseline to the end of treatment on all components of the SEAR and all domains of the IIEF ( P < 0.0001 ) compared with placebo . This finding was also consistent for all SEAR components when stratified by each ED comorbidity . In the sildenafil group , the improvement in the mean Self-Esteem subscale score correlated with improvements in the mean Erectile Function domain score ( r = 0.6338 , P < 0.0001 ) . CONCLUSIONS The physiologic and emotional benefits of sildenafil in the treatment of ED were confirmed , overall and in men with comorbid hypertension , hyperlipidemia , benign prostatic hypertrophy , and /or depression . Using both the IIEF and the SEAR question naires provides a more complete assessment of ED Background — Although erectile dysfunction ( ED ) is associated with cardiovascular risk factors and atherosclerosis , it is not known whether the presence of ED is predictive of future events in individuals with cardiovascular disease . We evaluated whether ED is predictive of mortality and cardiovascular outcomes , and because inhibition of the renin-angiotensin system in high-risk patients reduces cardiovascular events , we also tested the effects on ED of r and omized treatments with telmisartan , ramipril , and the combination of the 2 drugs ( ONTARGET ) , as well as with telmisartan or placebo in patients who were intolerant of angiotensin-converting enzyme inhibitors ( TRANSCEND ) . Methods and Results — In a prespecified sub study , 1549 patients underwent double-blind r and omization , with 400 participants assigned to receive ramipril , 395 telmisartan , and 381 the combination thereof ( ONTARGET ) , as well as 171 participants assigned to receive telmisartan and 202 placebo ( TRANSCEND ) . ED was evaluated at baseline , at 2-year follow-up , and at the penultimate visit before closeout . ED was predictive of all-cause death ( hazard ratio [ HR ] 1.84 , 95 % confidence interval [ CI ] 1.21 to 2.81 , P=0.005 ) and the composite primary outcome ( HR 1.42 , 95 % CI 1.04 to 1.94 , P=0.029 ) , which consisted of cardiovascular death ( HR 1.93 , 95 % CI 1.13 to 3.29 , P=0.016 ) , myocardial infa rct ion ( HR 2.02 , 95 % CI 1.13 to 3.58 , P=0.017 ) , hospitalization for heart failure ( HR 1.2 , 95 % CI 0.64 to 2.26 , P=0.563 ) , and stroke ( HR 1.1 , 95 % CI 0.64 to 1.9 , P=0.742 ) . The study medications did not influence the course or development of ED . Conclusions — ED is a potent predictor of all-cause death and the composite of cardiovascular death , myocardial infa rct ion , stroke , and heart failure in men with cardiovascular disease . Trial treatment did not significantly improve or worsen ED . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT 00153101 Aims : It is often assumed that β-blockers , e.g. metoprolol ( METO ) , induce erectile dysfunction ( ED ) in men . However , cardiovascular diseases can also induce ED and there is also the possibility that psychological factors , such as fear of the disease and side effects of the prescribed drug , may also induce ED . Thus , it is often assumed that β-blockers induce ED in a large percentage of men , but this statement is not well vali date d and the role of the pharmacologic effect of METO per se on the occurrence of ED is largely unknown . To get an answer we selected 114 men ( age 57 ± 4.7 years ) without ED but with newly diagnosed arterial hypertension , and who could be treated with METO . Methods : METO ( 100 mg/day ) was given as a retard formulation . The hypertensive men were r and omized into 3 groups . In group 1 patients were fully informed ( they knew that the drug was METO and that it might induce ED ) . In group 2 patients were partially informed ( they knew that the drug was METO , but were not informed that it might induce ED ) . In group 3 patients were not informed either about the drug used or about the possible occurrence of ED . The first phase of the study lasted 60 days . After 60 days the incidence of ED was 32 % in group 1 , 13 % in group 2 , and 8 % in group 3 ( p < 0.01 ) . All patients with ED entered the second , cross-over , double-blind phase of the study . METO was continued at unchanged dosage , and tadalafil ( 20 mg ) and a placebo were given to treat ED . Results : Both treatments were equally effective . Conclusion : Prejudice about the possible occurrence , i.e. the Hawthorne effect , of ED with METO facilitates the occurrence of this side effect in hypertensive men . Since the etiology of this ED is largely psychological , it is not surprising that placebo is as effective as tadalafil in reversing this side effect This is the largest and longest clinical study to date to examine statin usage and overall patient survival following clinical ly localized prostate cancer . In a retrospective examination of 938 consecutive patients with early-stage prostate cancer treated with brachytherapy , 191 patients were documented to be taking statin medications .  The patients taking statin medications had significantly lower prostate-specific antigen values , percent positive biopsies , and prostate volume than those patients not taking statin medications . Statin usage result ed in a nonstatistical improvement in all survival parameters with the results most pronounced for atorvastatin . Improving prostate cancer survival with statins could have important treatment implication s and could potentially limit or even improve the role of supplemental therapies . A prospect i ve trial of statin medications in conjunction with definitive local treatment for prostate cancer is recommended Phosphodiesterase-5 ( PDE-5 ) inhibitors are an effective therapy for the majority of men with erectile dysfunction ( ED ) . However , many men with ED still report a suboptimal or partial response even after an adequate trial of oral PDE-5 therapy . Since ED is associated with impaired vascular function and both atorvastatin and quinapril have been previously shown to improve vascular function , we examined the effects of adjunctive treatment with these medications in men with vasculogenic ED who were suboptimal responders to 100 mg of sildenafil . Men with ED and suboptimal response to sildenafil  were r and omly assigned to 3 months of treatment with atorvastatin 40 mg ( n = 12 ) , quinapril 10 mg ( n = 10 ) , or placebo ( n = 13 ) , along with continued adjunctive sildenafil use . Measured variables included : International Index of Erectile Function ( IIEF ) question naire , brachial artery flow-mediated dilation ( FMD ) , endothelium-independent dilation ( EID ) via nitroglycerin , penile Doppler blood flow , blood pressure ( BP ) , lipids , and C-reactive protein ( CRP ) . Compared to placebo , quinapril ( p < 0.01 ) significantly improved symptoms of ED as measured by the IIEF-5 question naire . There was a trend toward a significant improvement in IIEF-5 with atorvastatin . Similarly , quinapril significantly improved the IIEF ED Domain ( p < 0.05 ) . Other peripheral and penile vascular parameters were unchanged with drug therapy as compared to placebo . In conclusion , treatment with quinapril , in combination with sildenafil , improved ED in men with suboptimal response to sildenafil alone . Atorvastatin demonstrated a trend toward improved ED in this group Context While the benefits of statins in the primary and secondary prevention of coronary artery disease are clear , the value of statin therapy in acute coronary syndromes is uncertain . Contribution Analyzing data from a large , international observational study of acute coronary syndromes , these investigators identified associations between statin use before and during acute coronary events and favorable outcomes . Caution s While these data suggest a potential benefit of statins during acute coronary events , trials are necessary to determine the most appropriate use of statins in the treatment of acute coronary events . The Editors Data from r and omized clinical trials support the efficacy of lipid-lowering medications , particularly statins , in the primary and secondary prevention of coronary artery disease ( 1 - 3 ) . The benefits of statins , however , were not readily apparent until after several months of therapy , suggesting that the drugs ' lipid-lowering capabilities were largely responsible . In vitro work has suggested that statins may have an abundance of pleiotropic effects ( 4 ) . These include modulation of inflammation , inhibition of platelet function and thrombosis , and enhancement of endothelial cell function . The demonstrated ability of statins to immediately affect basic pathophysiologic mechanisms has result ed in increased interest in their potential role in the setting of acute coronary syndromes . The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering ( MIRACL ) trial found that early treatment with high-dose atorvastatin modestly reduced event rates of recurrent ischemia in statin-naive patients presenting with an acute coronary syndrome ( 5 ) . These observations , while intriguing , did not conclusively establish the role of statins in patients with acute coronary syndromes . In the MIRACL trial , the failure of statins to significantly affect more concrete trial end points ( for example , death or recurrent myocardial infa rct ion [ MI ] ) was disappointing . Whether this reflected a true lack of physiologic impact of early statin treatment or merely indicated that the study was underpowered to detect differences in these end points remains unclear . In a sub study using data from the Platelet Receptor Inhibition for Ischemic Syndrome Management ( PRISM ) trial in patients with acute coronary syndromes , patients already taking statins  had better short-term outcomes ( decreased risk for death or nonfatal MI ) than those not previously receiving statin therapy , unless statin therapy was discontinued in the hospital ( 6 ) . Initiation of statin therapy after the onset of an acute coronary syndrome appeared to be less effective than treatment with statins before symptom onset . Using data from the Global Registry of Acute Coronary Events ( GRACE ) project , a large , multinational , observational study of patients with acute coronary syndromes , we examined the association between previous statin therapy  , presentation characteristics of acute coronary syndromes , and hospital outcomes . We also examined the effect of early in-hospital statin therapy ( or withdrawal of statins ) on important hospital outcomes , including death or the development of recurrent MI or stroke . Methods Full details of the GRACE rationale and methods have been published elsewhere and are outlined below ( 7 - 9 ) . Site Selection The GRACE project is design ed to reflect an unbiased population of patients with acute coronary syndromes , regardless of geographic region . Currently , 94 hospitals located in 14 countries ( Argentina , Australia , Austria , Belgium , Brazil , Canada , France , Germany , Italy , New Zeal and , Pol and , Spain , the United Kingdom , and the United States ) are participating in this observational study . Patients entered in the registry must be at least 18 years of age and alive at the time of hospital presentation ; be admitted with an acute coronary syndrome as a presumptive diagnosis ( that is , have symptoms consistent with acute ischemia ) ; and have at least 1 of the following : electrocardiographic changes consistent with an acute coronary syndrome , serial increases in serum biochemical markers of cardiac necrosis , or documentation of coronary artery disease ( 7 - 9 ) . The qualifying acute coronary syndrome must not be precipitated by a significant noncardiovascular comorbid condition ( for example , trauma or surgery ) . To ensure the enrollment of an unbiased sample , the first 10 to 20 consecutive patients ( depending on each site 's patient volume ) are recruited from each site on a monthly basis . Where required , study investigators received approval from their local hospital ethics or institutional review board . Data Collection At each site , a trained coordinator collected data using a st and ardized case-report form . Data on demographic characteristics , medical history , presenting symptoms , duration of prehospital delay , biochemical and electrocardiographic findings , treatment practice s , and hospital outcome were collected . St and ardized definitions of all patient-related variables and clinical diagnoses were used . All cases were assigned to 1 of the following categories : ST-segment elevation MI , nonST-segment elevation MI , unstable angina , and other cardiac or noncardiac diagnoses that have been previously described ( 7 - 9 ) . St and ardized definitions were also used for selected hospital complications and outcomes . Patient Sample For the current study , patients who were subsequently found to have noncardiac or other cardiac ( nonacute coronary syndrome ) primary diagnoses and those who transferred into or out of GRACE registry hospitals were excluded from further consideration . Treatments defined as previous use were those taken by the patient on a long-term basis at home and within 7 days of the presenting event , based on the review of information contained in medical records and abstract ed by trained study physicians and nurses . Treatments received in the hospital ( within the first 24 hours or thereafter ) were categorized as within hospital . Agents prescribed for use after discharge from participating hospitals were categorized as at discharge . Patient treatment categories were defined according to the following groupings : no previous treatment with statins and no treatment with statins during hospitalization , no previous therapy with statins but statin therapy  instituted during hospitalization , previous therapy with statins and statin therapy continued during hospitalization , and previous  therapy with statins but statin therapy not continued during the index hospitalization . Statistical Analysis We used the chi-square tests for discrete variables to analyze differences in demographic and clinical characteristics , treatment practice s , clinical presentation ( ST-segment elevation vs. nonST-segment elevation , large infa rct [ creatine phosphokinase level > 2 times the upper limit of normal ] vs. small infa rct ) , subsequent diagnosis ( ST-segment elevation MI , nonST-segment elevation MI , unstable angina ) , and hospital complications ( death , congestive heart failure or pulmonary edema , cardiogenic shock , stroke , ventricular tachycardia or ventricular fibrillation , and cardiac arrest ) in relation to statin use . The Wilcoxon rank-sum test was used to analyze differences between respective comparison groups for continuous variables . While controlling for potentially confounding variables , we performed multivariate regression analyses to examine the association between previous statin therapy and hospital presentation ( ST-segment elevation vs. no ST-segment elevation , creatine phosphokinase level 2 times normal vs. creatine phosphokinase level < 2 times the upper limit of normal ) , as well as any association between previous or in-hospital statin therapy and hospital outcomes ( death , recurrent MI or MI after 24 hours , and stroke ) or a composite end point of all 3 outcomes . C and i date variables for inclusion in the regression models evaluating previous statin use and hospital presentation included patient age , sex , smoking status , diabetes , history of vascular disease ( previous MI , stroke , positive angiogram , peripheral vascular disease , percutaneous coronary intervention , or coronary artery bypass graft surgery ) , hypertension , hyperlipidemia , and previous therapies ( aspirin , angiotensin-converting enzyme [ ACE ] inhibitors , -blockers , and other lipid-lowering agents ) . C and i date variables for regression models evaluating previous or in-hospital statin use and hospital outcomes included all of the previously listed characteristics plus characteristics present at the time of hospital admission ( heart rate , systolic blood pressure , Killip class , ST-segment elevation or left bundle-branch block pattern , and positive cardiac enzymes ) and receipt of in-hospital therapies ( aspirin and other antiplatelet agents , -blockers , unfractionated heparin , low-molecular-weight heparin , glycoprotein IIb/IIIa inhibitors , cardiac catheterization , percutaneous coronary intervention , or coronary artery bypass graft surgery ) . C and i date variables possibly associated with the outcomes of interest ( P < 0.25 after univariate analysis ) were included in the multivariate models . Variables for which the P value exceeded 0.05 were eliminated in a stepwise fashion so that only those that had a statistically significant association with the outcome of interest were included in the final regression models . Because of their clinical relevance and potential importance , age , sex , and history of hyperlipidemia were retained in the final multivariable models for clinical outcomes regardless of statistical significance . Final models were evaluated for goodness of fit by the HosmerLemeshow test . Because between-hospital variation in use of statin treatment could be considerable and potentially affect our study results , we adjusted for hospital r and om effects on the observed outcomes . We used a generalized estimating equation modeling technique , assuming patients were repeated measures within each hospital . Variable Background Small trials with short term follow up suggest pharmacists ’ interventions targeted at healthcare professionals can improve prescribing . In comparison with clinical guidance , contemporary statin prescribing is sub-optimal and achievement of cholesterol targets falls short of accepted st and ards , for patients with atherosclerotic vascular disease who are at highest absolute risk and who st and to obtain greatest benefit . We hypothesised that a pharmacist-led complex intervention delivered to doctors and nurses in primary care , would improve statin prescribing and achievement of cholesterol targets for incident and prevalent patients with vascular disease , beyond one year . Methods We allocated general practice s to a 12-month Statin Outreach Support ( SOS ) intervention or usual care . SOS was delivered by one of 11 pharmacists who had received additional training . SOS comprised academic detailing and practical support to identify patients with vascular disease who were not prescribed a statin at optimal dose or did not have cholesterol at target , followed by individualised recommendations for changes to management . The primary outcome was the proportion of patients achieving cholesterol targets . Secondary outcomes were : the proportion of patients prescribed simvastatin 40 mg with target cholesterol achieved ; cholesterol levels ; prescribing of simvastatin 40 mg ; prescribing of any statin and the proportion of patients with cholesterol tested . Outcomes were assessed after an average of 1.7 years ( range 1.4–2.2 years ) , and practice level simvastatin 40 mg prescribing was assessed after 10 years . Findings We r and omised 31 practice s ( 72 General Practitioners ( GPs ) , 40 nurses ) . Prior to r and omisation a subset of eligible patients were identified to characterise practice s ; 40 % had  cholesterol levels  below the target threshold . Improvements in data collection procedures allowed identification of all eligible patients ( n = 7586 ) at follow up . Patients in practice s allocated to SOS were significantly more likely to have cholesterol at target ( 69.5 % vs 63.5 % ; OR 1.11 , CI 1.00–1.23 ; p = 0.043 ) as a result of improved simvastatin prescribing . Subgroup analysis showed the primary outcome was achieved by prevalent but not incident patients . Statistically significant improvements occurred in all secondary outcomes for prevalent patients and all but one secondary outcome ( the proportion of patients with cholesterol tested ) for incident patients . SOS practice s prescribed more simvastatin 40 mg than usual care practice s , up to 10 years later . Interpretation Through a combination of educational and organisational support , a general practice based pharmacist led collaborative intervention can improve statin prescribing and achievement of cholesterol targets in a high-risk primary care based population . Trial Registration International St and ard R and omised Controlled Trials Register IS RCT
RESULTS For the comparison of statins ( + /- sildenafil ) with placebo ( + /- sildenafil ) , the mean International Index of Erectile Function ( IIEF-5 ) ( the st and ardized mean difference [ SMD ] = 3.23 , 95 % confidence interval [ CI ] = -1.65 to 4.80 , P < 0.0001 ) indicated that statins ( + /- sildenafil ) showed statistically significantly greater improvements in the mean IIEF-5 compared with placebo ( + /- sildenafil ) .
For the comparison of statins plus sildenafil with placebo plus sildenafil , the mean IIEF-5 ( SMD = 3.60 , 95 % CI = 2.64 to 4.56 , P < 0.00001 ) , the IIEF domain ( SMD = 4.88 , 95%CI = 3.01 to 6.74 , P < 0.00001 ) , and the global efficacy question ( odds ratio = 6.44 , 95 % CI = 2.92 to 14.23 , P < 0.00001 ) showed that compared with placebo plus sildenafil , statins plus sildenafil clearly improved erectile function .
CONCLUSIONS This meta- analysis indicates that statins ( + /- sildenafil ) may improve ED compared with placebo ( + /- sildenafil )
INTRODUCTION It is not known if statins will improve symptoms in patients with established erectile dysfunction ( ED ) .
AIM We carried out a systematic review and meta- analysis to assess the effect of statins on ED .