Olsson et al. conducted a randomised, double-blind, placebo-controlled, parallel group, and flexible dose study in 224 men with ED and one CVD, including IHD (20 %) and hypertension (80 %). This study reported that the sildenafil-treated group showed 71 % improvement in ED compared with the placebo-controlled group (24 %).64 Furthermore, no treatment-related cardiovascular adverse events were reported.65 Conti et al. showed in an early study that sildenafil is an effective treatment for ED in patients with IHD; the majority of patients reported improvement in penile erection with it.66 Another double-blind, placebo-controlled study of patients with ED and stable CAD showed statistically significant improvement with sildenafil versus placebo in both the frequency of penetration and frequency of maintained erections after penetration.67

Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References Sildenafil is taken orally 1 hour before anticipated sexual intercourse and enhances the normal response to sexual stimulation; however, it has no effect on erections in the absence of stimulation.10x10Kloner, RA and Zusman, RM. Cardiovascular effects of sildenafil citrate and recommendations for its use. Am J Cardiol. 1999; 84: 11N–17N
When counseling diabetic men who are considering a PDE-5 inhibitor for ED, it is important to set realistic expectations and explain that studies document that all three agents are less effective in diabetic patients than in the general population of men with ED.45–49 For additional information, readers are referred to the excellent review of the use of PDE-5 inhibitors in diabetic men by Vickers and Satyanarayana.50
Several other facts support the close relationship between sexual dysfunction and CV disease. Endothelial dysfunction mediated by decreased nitric-oxide bioavailability as well as atherosclerotic lesions constitute a common pathophysiologic substrate affecting both CV disease and erectile dysfunction, a disease considered to be primarily of vascular origin[76,80-82]. Several traditional CV risk factors (diabetes mellitus, hypertension, dyslipidemia, and smoking) are frequently found in individuals with erectile dysfunction, conferring a detrimental cardiovascular burden to them. More interestingly, the increased cardiovascular risk observed in those patients is independent of the aforementioned CV risk factors[81-88].
Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Data sources include IBM Watson Micromedex (updated 9 Jan 2019), Cerner Multum™ (updated 14 Jan 2019), Wolters Kluwer™ (updated 7 Jan 2019) and others. Refer to our editorial policy for content sources and attributions.
Although the results provide evidence that PDE5 inhibitors may benefit heart health, the retrospective study design makes it impossible to ascertain direct cause and effect, Andersson noted. It is possible that using erectile dysfunction drugs simply indicates a more active sex life, which could itself contribute to, or be a marker of, a heart-healthy lifestyle overall.
In Western medicine approach, health and disease are clearly divided entities. The emphasis is on protection of the individual body from disease or how to replace the body’s lost functions. Antibiotic therapy is used to combat harmful bacteria during infections, exogenous synthetic hormones are used to replace hormone-deficient individuals and artificial prostheses are applied when an organ loses its functions. This is very different from the holistic Eastern approach where the treatment entity is taken as a whole, and the objective is to seek harmony between different bodily systems.
There’s one more thing to remember: A visit to a physician can be helpful even if a man doesn’t want to go near Viagra or try one of the alternatives. In some cases, a treatable medical condition such as low testosterone or depression could explain a case of ED. “Sexual health should not be viewed as a luxury, but rather as an essential component to wellness,” said urologist Ryan P. Terlecki, MD, of Wake Forest Baptist Health in North Carolina.

Adequate cavernosal arterial inflow is necessary for penile erection. Arterial morphology,28 flow,29 and diameter30 differ between diabetic and nondiabetic populations with ED. BB and STZ-induced diabetic rats exhibit impairment of endothelium-mediated vascular smooth muscle relaxation, and proposed mechanisms include changes in the expression, activity, or post-translational modification of endothelial NOS.31
Several other facts support the close relationship between sexual dysfunction and CV disease. Endothelial dysfunction mediated by decreased nitric-oxide bioavailability as well as atherosclerotic lesions constitute a common pathophysiologic substrate affecting both CV disease and erectile dysfunction, a disease considered to be primarily of vascular origin[76,80-82]. Several traditional CV risk factors (diabetes mellitus, hypertension, dyslipidemia, and smoking) are frequently found in individuals with erectile dysfunction, conferring a detrimental cardiovascular burden to them. More interestingly, the increased cardiovascular risk observed in those patients is independent of the aforementioned CV risk factors[81-88].
Obesity is a strong predictor of ED as it is associated with other risk factors, such as diabetes, hyperlipidaemia and hypertension.4 Obesity increases the risk of ED by 30–90 % and acts as an independent risk factor for CVD. Obese men with ED have greater impairment in endothelial function than non-obese men with ED.5 Moreover, high BMI causes low testosterone levels, which in turn leads to ED, as observed in a prospective trial involving 7,446 participants.50
The development of PDE5-inhibitors is a clear example of how Western medicine approached the problem of ED differently from Eastern medicine. The erectogenic effect of sildenafil (Viagra®) was discovered by accident when patients undergoing heart clinical trials reported better erections as a side effect after taking sildenafil. This observation led to further elucidation of the NO/cGMP signalling pathway and development of PDE5-inhibitors as a first-line therapy in ED (5).
The discovery in 1992 of the second messenger of cavernosal smooth muscle relaxation was the critical step that led to the era of nonhormonal oral drug therapy for ED. In 1998, the multicenter trial of sildenafil in the treatment of ED was published in the New England Journal of Medicine, and the era of the phosphodiesterase type 5 (PDE-5) inhibitor began.1 For 5 years, sildenafil was the primary therapy for men with EDDM. Recently, 2 new PDE-5 inhibitors, vardenafil and tadalafil, were introduced.
Crossref | PubMed | Google ScholarSee all References Risk factors for cardiovascular disease include diabetes mellitus, obesity, physical inactivity, hyperlipidemia, tobacco use, and hypertension. Often, the relative risk of each of these factors in the development of ED is difficult to assess because many patients with ED and cardiovascular disease have more than 1 risk factor. Another important consideration is the effect of cardiac disease itself on erectile function. A history of a prior myocardial infarction was not found to be a significant independent risk factor for ED in a study comparing sexual function in 50 patients who had a prior myocardial infarction with a control group of 50 patients.14x14Dhabuwala, CB, Kumar, A, and Pierce, JM. Myocardial infarction and its influence on male sexual function. Arch Sex Behav. 1986; 15: 499–504
Towards this direction, several sufficiently powered studies have demonstrated a higher incidence of erectile dysfunction in patients with coronary artery disease, either asymptomatic or overt. At the same time, patients with erectile dysfunction are more prone to have established coronary artery stenosis of more than 50% and consequently evident CV disease[75]. This is in conformity with the “artery size hypothesis” according to which smaller arteries (e.g., penile arteries) are the first to undergo a vascular lesion prior to the larger ones (e.g., coronary arteries). Moreover, in such patients erectile dysfunction is connected to the number of occluded vessels and more interestingly occurs over three years before coronary artery disease becomes apparent[76-80].
Guidelines recommend that phosphodiesterase type 5 (PDE5) inhibitors are the first-line drug for the treatment of ED (Table 1). Sildenafil citrate was the first oral drug approved for ED in the US.59 The newer PDE5 inhibitors include vardenafil, tadalafil and avanafil. The inhibition of PDE5 enhances cyclic guanosine monophosphate (cGMP)-NO-mediated vasodilatation by preventing PDE5 catabolism of cGMP and so delaying detumescence. PDE5 inhibitors increase the number and duration of erections, as well as the percentage of successful sexual intercourse.60
Crossref | PubMed | Google ScholarSee all References In study patients taking these medications compared with controls, significant decreases in total cholesterol and low-density lipoprotein cholesterol levels were found, as well as significant increases in length of maximal tumescence per nocturnal penile tumescence testing at 2 weeks. Hypoglycemia secondary to the use of insulin or hypoglycemic agents may result in ED or orgasmic dysfunction.4x4Feldman, HA, Goldstein, I, Hatzichristou, DG, Krane, RJ, and McKinlay, JB. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994; 151: 54–61
Testosterone therapy in hypogonadism modulates metabolic components associated with CV risk. The majority of prospective clinical studies indicates that treatment achieving testosterone levels within physiological limits has beneficial or neutral effects on a lipid profile other than HDL-C, beneficial or neutral effects on inflammatory mediators, and generally beneficial effects on glycaemic state.25 The lean body mass is typically increased in hypogonadal subjects, and visceral adiposity is decreased in several studies and unchanged in the remainder. Such metabolic effects have raised interest on the potential impact on cardiovascular health. Regarding symptoms in patients with pre-existing cardiovascular conditions (angina or heart failure) TTh has been either neutral or beneficial.25 Regarding CVD risk, available clinical trial data indicate that the use of testosterone in middle-aged to elderly men does not increase cardiovascular risk25 with the exception of one study in very frail (substantial limitation of mobility and a high rate of comorbidities) elderly subjects that used an off-label high, and rapid escalation, dosing regimen.46 Prospective data from large, well-designed, long-term trials of TTh are warranted.

Treatment of ED which was previously confined to invasive procedures, cavernosal injections or to rather ineffective oral medications was revolutionized in 1999 with the introduction of the orally administered PDE5 inhibitor sildenafil. Phosphodiesterase type 5 inhibitors are the first-line therapy for ED of organic aetiology unless there is a specific contraindication to their use. This class of agents is widely used because of its effectiveness and safety.38 Interactions with cardiovascular drugs have been minimal with the exception of nitrates and other nitric oxide (NO) donors (such as nicorandil), where co-administration may result in severe vasodilation and hypotension. However, nitrates are often overused in clinical practice; therefore, the option of their discontinuation should be considered. A strong body of clinical data shows that all three agents (sildenafil, tadalafil, and vardenafil) do not increase the risk of non-fatal myocardial infarction, stroke, or cardiovascular deaths. These drugs do not exacerbate ischaemia or worsen exercise tolerance in patients with known CAD who achieve levels of exercise comparable or greater than that achieved during sexual intercourse.38,39 Phosphodiesterase type 5 is expressed throughout the human body, including the pulmonary and systemic vasculature and hypertrophied myocardium. While currently their only additional indication, beyond ED, is idiopathic pulmonary hypertension (for sildenafil and tadalafil), they show potential to be of benefit in several other conditions, such as CAD and systolic heart failure.39 Mechanisms of benefit of PDE5 inhibitors include pulmonary and systemic vasodilation, increased myocardial contractility, reduced large artery stiffness and wave reflections, improved endothelial function, and reduced apoptosis, fibrosis and hypertrophy through mechanisms involving NO, cyclic guanosine monophosphate, protein kinase G and Rho kinase.39 A very important issue is whether treatment of ED per se (and not of its risk factors and comorbidities) will have an impact on cardiovascular risk. While this applies to all therapeutic modalities of ED, it is particularly pertinent for PDE5 inhibitors, since they represent the mainstay of ED therapy. Data are limited to date. Gazzaruso et al.21 showed a trend of PDE5 inhibitors to reduce cardiovascular morbidity and mortality in diabetic patients with silent CAD and ED, while Frantzen et al.40 showed that 2 years after the introduction of sildenafil, the relative risk of the incidence of CVD among men with ED compared with healthy men significantly decreased from 1.7 to 1.1.
Abstract | Full Text | Full Text PDF | PubMed | Scopus (95) | Google ScholarSee all References, 56x56Wallis, RM, Corbin, JD, Francis, SH, and Ellis, P. Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol. 1999; 83: 3C–12C
Testosterone cypionate and testosterone enanthate injections are used for replacement therapy in patients with low testosterone. Other formulations, such as gels and patches, are recommended in older patients with chronic conditions.57 Serum prostate specific antigen should be measured before starting testosterone replacement, then 3–6 months after starting the treatment, followed by annual measurement.74

If you have been diagnosed with heart disease or have already had a heart attack and are experiencing erectile dysfunction, it is critical that you discuss erectile dysfunction medication with your physician before considering taking it. Popular erectile dysfunction medications such as Viagra (sildenafil), Cialis (tadalafil) and Levitra (vardenafil) can interact with a range of cardiovascular disease medications. Interactions are possible with blood pressure medications; blood thinners such as Coumadin (warfarin), nitrates for the treatment of chest pain, and antiarrhythmia medication for the treatment of irregular heart rhythms.
Crossref | PubMed | Google ScholarSee all References Patients with vascular risk factors (diabetes mellitus, hypertension, heart disease, and hyperlipidemia) had significantly decreased peak systolic velocities and increased end-diastolic velocities. Patients with diabetes mellitus had increased end-diastolic velocities and decreased resistive indices, indicating a disorder of venous trapping during erections. Another study examined corpora cavernosal tissue removed at penile prosthesis placement in 21 diabetic men and 42 nondiabetic controls.23x23Saenz de Tejada, I, Goldstein, I, Azadzoi, K, Krane, RJ, and Cohen, RA. Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. N Engl J Med. 1989; 320: 1025–1030

Olsson et al. conducted a randomised, double-blind, placebo-controlled, parallel group, and flexible dose study in 224 men with ED and one CVD, including IHD (20 %) and hypertension (80 %). This study reported that the sildenafil-treated group showed 71 % improvement in ED compared with the placebo-controlled group (24 %).64 Furthermore, no treatment-related cardiovascular adverse events were reported.65 Conti et al. showed in an early study that sildenafil is an effective treatment for ED in patients with IHD; the majority of patients reported improvement in penile erection with it.66 Another double-blind, placebo-controlled study of patients with ED and stable CAD showed statistically significant improvement with sildenafil versus placebo in both the frequency of penetration and frequency of maintained erections after penetration.67

In most men, ED is recognised as sharing vascular aetiology with IHD.17 ED and IHD share common risk factors, such as hypertension, hyperlipidaemia, diabetes, obesity, lack of physical exercise, cigarette smoking, poor diet, excess alcohol consumption and psychological stress, including depression.30 Endothelial dysfunction has been implicated as a common mechanism between CAD and ED and it has an important role in the development of atherosclerosis.31


The Massachusetts Male Aging Study of 1,290 men, aged 40–70 years, has documented the extraordinarily high prevalence of erectile dysfunction among aging men: 50% of men at 50 years of age, and 70% by age 70 have erectile dysfunction.2 Furthermore, a recent Italian study of men with severe heart disease has uncovered an astounding 93% with erectile dysfunction 24 months before their heart attack or onset of heart disease symptoms.3
If the cause is believed to be organic but not hormonal, or if the patient defers psychological intervention, he can be offered the VCD or oral drug therapy. EDDM patients on organic nitrates or who have experienced or are concerned about potential adverse reaction to PDE-5 inhibitors are suitable candidates for the VCD. The VCD induces functional rigidity in 75% of patients with diabetes with autonomic neuropathy. Some patients or their partners may reject or discontinue the use of the VCD because it induces an unnatural erection, causes bruising and numbness of the penis, and or inhibits antegrade ejaculation.8
Erectile dysfunction is frequent in patients with established CAD with prevalence rates ranging between 47 and 75% in studies.2,4,14 The AssoCiatiOn Between eRectile dysfunction and coronary Artery disease (COBRA) trial tested the hypothesis that the ED rate differs in CAD patients according to the clinical presentation (acute vs. chronic coronary syndromes) and the extent of vessel involvement (one vs. two to three vessel disease)15 (Figure 3). The overall ED prevalence in CAD patients was 47%, whereas in the normal coronary angiography group the ED rate was 24%. When separately considered, the ED rate was 22% in patients with acute coronary syndromes (ACS) and one-vessel disease and 55 and 65% in patients with ACS and multi-vessel disease and with chronic coronary syndrome, respectively. The study also showed that both severity (IIEF <10) and duration (>24 months) of ED were predictive of severe coronary involvement at angiography. This study offers pathophysiological and mechanistic explanations related to the clinical setting. In patients with multi-vessel disease, regardless of the clinical presentation, the advanced coronary and systemic atherosclerosis is the reason for the high rate of ED. However, in the setting of acute myocardial infarction with one-vessel disease, ED is far less frequent because the atherosclerotic burden is modest (i.e. abrupt occlusion of a single non-obstructing plaque in the absence of extensive atherosclerosis) in both the coronary and penile circulations.15,16
In men without cardiovascular disease, erectile dysfunction (ED) pills are very safe. The three rivals -- Viagra, Cialis, and Levitra -- have similar side effects, including headache, facial flushing, nasal congestion, diarrhea, backache, and, in a few Viagra or Levitra users, temporary impaired color vision (men with retinitis pigmentosa, a rare eye disease, should check with their ophthalmologists before using these medications).
Surgery for erectile dysfunction is usually considered only after all other options have failed. The two surgical options include the insertion of a semi-rigid rod or the implantation of a three-piece inflatable prosthesis. Penile prosthesis implantation has low infection, complication, and malfunction rates. However, since placement of an implant requires permanent injury to the erectile tissue of the penis, implant treatment is considered irreversible.
×