In a study published in the Journal of the American College of Cardiology in 2021, the Karolinska Institutet in Sweden reported that in a group of patients with erectile dysfunction (abbreviated in English as ED) combined with coronary heart disease, those treated with sildenafil (commonly known as Viagra) appeared to live longer and had a lower risk of developing new-onset Heart disease was lower. The study has been the subject of intense debate among many scholars in the medical field. Because sildenafil has previously been considered a drug with cardiovascular side effects, it is not recommended for patients with erectile dysfunction who have heart disease. Today's article will focus on this issue.
1. First, let's see who the Journal of the American College of Cardiology is
The American Journal of Cardiology, founded in 1958 and sponsored by the American College of Cardiology, is one of the world's most important journals in the cardiovascular field, where many cutting-edge cardiovascular-related theories and advanced treatment techniques have been first disclosed. The American Journal of Cardiology, abbreviated as JACC, is currently one of the four top medical journals in the world, along with the Lancet, the New England Journal of Medicine (NEJM) and the British Medical Journal (BMJ). In the eyes of cardiovascular specialists, to publish a paper in the Journal of the American College of Cardiology is not only a great honor, but also a world-class academic endorsement of one's ability, and the paper itself will receive greater recognition, and the academic theory can also form a better clinical model.
2. Let's take a look at the association between sildenafil and cardiovascular
In 1989, Pfizer developed the "predecessor" of sildenafil, UK92480, targeting cell signaling molecules in the human body, with the main purpose of treating coronary artery disease and pulmonary hypertension. However, between 1989 and 1993, after the Phase I trial in healthy volunteers, Pfizer conducted experimental treatment on a limited number of patients with angina pectoris and found that sildenafil did not have the expected effect on patients with angina pectoris, and therefore terminated the clinical study for the treatment of cardiovascular disease.
Although Pfizer developed sildenafil, for the purpose of treating heart disease failed, but the company found that sildenafil can effectively treat erectile dysfunction (replaced by ED below), after that from 1995 to 1998, sildenafil was studied as a drug for the treatment of erectile dysfunction, successfully passed the phase III clinical trials, and by 1998 that year, sildenafil was approved for marketing by the U.S. FDA, as well as more than 30 other countries, specifically for the treatment of male ED.
After the launch of sildenafil, a large number of multicenter, double-blind, parallel, placebo-controlled trial studies confirmed the safety and efficacy of sildenafil in the treatment of ED. Prior to the launch of sildenafil, there were no effective oral therapeutic drugs for men with ED. Most ED patients were considered to be psychologically ill and could only be treated with psychotherapy or local injections of vasodilators (such as Prostil), which were not only inefficient but also somewhat invasive. So the emergence of sildenafil is a major medical technology innovation in the field of ED treatment, which is a good news for many men with ED. It is for this reason that sildenafil has achieved a superb sales share worldwide as soon as it was launched.
3. Sildenafil has long been considered to be a drug with cardiovascular risks
Although sildenafil has been marketed and proven to be effective in treating men with ED, it has been shown to have certain side effects, especially cardiovascular side effects, including flushing and rapid heartbeat, palpitations and panic, as well as cardiovascular health risks and even death caused by improper use of sildenafil around the world, which has led to strict restrictions on its use in various countries.
In clinical practice, sildenafil is also not recommended, or even prohibited, for use in men with ED who have cardiovascular disease. The instructions for sildenafil also clearly mention that sildenafil should be used with caution in patients with left ventricular outflow tract obstruction (e.g., aortic stenosis, idiopathic hypertrophic subaortic stenosis) and diseases associated with severe impairment of autonomic control of blood pressure, including patients who have had a myocardial infarction, shock, or life-threatening arrhythmia within the last 6 months, patients with heart failure or unstable angina pectoris in coronary artery disease and patients with resting state hypotension or hypertension, because there is a lack of medically controlled data on the safety and efficacy of sildenafil application in such patients, so sildenafil should also be applied with caution in such patients. To date, although there is no direct medically relevant evidence that sildenafil increases health risks in patients with cardiovascular disease, clinicians still do not recommend sildenafil for men with cardiovascular disease combined with ED.
4, the current study in the Journal of the American College of Cardiology concluded the opposite
While it has long been the conventional wisdom of most scholars and patients that sildenafil is dangerous for those suffering from cardiovascular disease, this study in the Journal of the American College of Cardiology concludes just the opposite, and even reverses, the long-held perception of sildenafil. According to a study published in March 2021 in. The Journal of the American College of Cardiology, "Association of Phosphodiesterase-5 Inhibitors Versus Alprostadil With Survival in Men with Coronary Artery Disease" (Chinese name: phosphodiesterase-5 inhibitors vs. -5 Inhibitors Versus Alprostadil With Survival in Men with Coronary Artery Disease) showed that men with stable coronary artery disease who took sildenafil for ED may have a longer life expectancy and a lower risk of new heart attacks.
The trial was conducted in such a way that a total of more than 18,000 patients were divided into 2 groups of patients who may have had a heart attack or balloon dilation or coronary artery bypass surgery within 6 months prior to participation in the trial, meaning that these patients had more or less organic cardiovascular pathology, thus confirming during the trial whether sildenafil was beneficial or harmful to patients with pre-existing organic cardiovascular pathology. Patients with pre-existing cardiovascular pathology were identified. Of these patients, 16,548 were treated with sildenafil and another group of 1,994 were treated with prostilol. The study showed that over the 5.8-year follow-up period after the trial, the mortality rate was 14% in the sildenafil-treated patients (2261 deaths) and 26% in the prostilol-treated group (521 deaths), suggesting that the risk of death was 12% lower in the sildenafil-treated patients than in the prostilol-treated patients.
The study also found that patients treated with prostilbestrol were more likely to have stroke, diabetes, heart failure, atrial fibrillation, and peripheral vascular disease compared to patients treated with sildenafil; and that patients treated with sildenafil had a reduced risk of death, new myocardial infarction, heart failure, and risk of hemodialysis compared to patients treated with prostilbestrol. Moreover, this protection was dose-dependent. That is, the more frequent the dose of sildenafil, the lower the above risks.
5. The conclusions of the study in the Journal of the American College of Cardiology, are they credible?
The Journal of the American College of Cardiology, as one of the four top medical journals in the world, has a high authority in cardiovascular clinical research, so there is theoretical truth in the authenticity and practicability of the experiment itself, objectively speaking. Although there is nothing wrong with the experiment itself, there are still some shortcomings in the design of the trial structure, because this study is an "observational study", which means that although the results of the trial show that the mortality rate of patients with coronary heart disease is lower with sildenafil treatment, this does not infer a causal relationship or clinical benefit between sildenafil and coronary heart disease. This does not infer a causal relationship or clinical benefit between sildenafil and coronary heart disease.
This means that this follow-up observational pilot study can only suggest from the trial itself, or from the 2-group trial panel, that mortality was lower in patients with coronary artery disease treated with sildenafil. It does not show that sildenafil is more beneficial for use in patients with coronary artery disease, because this group (16548) treated with sildenafil a class of PDE5 inhibitors, also experienced deaths. It is also not possible to go outside the framework of the trial to affirm that sildenafil is better than prostaglandin, for patients with coronary artery disease. This is because the 2 groups of the trial were not set up with exactly equivalent numbers, and exactly equivalent conditions. For example, some researchers believe that it is possible that patients treated with sildenafil were healthier and therefore had lower risk and lower mortality than those treated with prostaglandin. And to determine if it was sildenafil that reduced the risk, the team is going to conduct the next phase of the study in order to randomize patients into two groups, one with sildenafil and the other with placebo.
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2. Jiang Hui, Dai Yutian, Deng Chunhua, "Chinese Expert Consensus on the 20th Anniversary of the Clinical Application of Sildenafil Citrate (Viagra)
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