Characteristics,prognosis and outcome of patients with oesophageal varices in a university hospital in Sweden 1994–1999

Objective. Patients with liver cirrhosis, portal hypertension and oesophageal varices are known to have high morbidity and mortality. The knowledge of incidence, aetiology and outcome in Sweden in recent years is limited. Material and methods. All patients with oesophageal varices diagnosed for the first time at Sahlgrenska University Hospital during the 6-year period 1994–1999 were retrospectively studied. Information about the aetiology of liver cirrhosis and oesophageal varices, as well as about the proportion of bleeding and non-bleeding varices, endoscopic and pharmacological treatment and outcome, was analyszed. Results. 312 patients were retrieved, 297 with liver cirrhosis (197 diagnosed before first bleeding (P), 92 after bleeding (B) and 8 at autopsy) and 15 with portal vein thrombosis without cirrhosis. Fifty-four percent had alcoholic liver disease. Fifty-five percent in group B and 13% in group P had at least one bleeding episode during follow-up (p<0.001). There was no significant difference in survival between groups B and P. Twenty-six percent of the cirrhotics died of liver failure and 19% from variceal bleeding. In a multivariate analysis, variables predicting mortality were: Child-Pugh class, group B, age and bilirubin levels. Conclusions. Variceal bleeding is still a strong risk factor for recurrent bleeding, but few die from their first bleeding. This concurs with studies indicating declining mortality from variceal bleeding. However, this patient group still has a high mortality from other causes.     

Clinical significance of variceal hemorrhage in recent years in patients with liver cirrhosis and esophageal varices

BACKGROUND AND AIMS: Recent progress in the treatment of variceal bleeding might have reduced the impact of variceal bleeding on survival in patients with esophageal varices. We conducted a retrospective cohort study in an attempt to re-evaluate the clinical significance of variceal bleeding. METHODS: A cohort of 304 patients with liver cirrhosis and esophageal varices, who had no previous history of variceal bleeding and no prophylactic therapy, was studied. RESULTS: During a median follow-up period of 32 months, 55 patients (18%) bled from varices and 111 (37%) died. Variceal hemorrhages accounted for 15% of total deaths. The mortality of first variceal bleeding was 25% in the whole group, but was remarkably different depending on liver function at the time of bleeding (0% in grade Child A vs 55% in grade C; P < 0.05). Among the survivors of first bleeding, 30% experienced rebleeding. Form of varix, red color sign and heavy drinking were the independent risk factors for first variceal bleeding. Multivariate analysis revealed that variceal bleeding still had a significant (P < 0.001) impact on death in the whole cohort, when other independent prognostic factors such as age, ascites, encephalopathy, platelet count, serum albumin level and hepatocellular carcinoma were adjusted. Furthermore, in subgroup analyses, variceal bleeding was more strongly (P < 0.001) linked to death in patients with alcoholic cirrhosis than in those with non-alcoholic cirrhosis, and showed a significant association with survival only for the patients in Child grade B. CONCLUSIONS: Variceal bleeding has various prognostic impacts depending on the etiology of cirrhosis or on the degree of liver dysfunction, and this needs to be taken into account in the prophylaxis against first variceal bleeding.     

Oesophageal varices in cirrhotic patients: from variceal screening to primary prophylaxis of the first oesophageal variceal bleeding

Bleeding from oesophageal varices is still a lethal complication in cirrhotic patients with portal hypertension. Approximately 5–10% of patients with cirrhosis will develop oesophageal varices per year, and about 25–30% of cirrhotic patients with oesophageal varices and without previous variceal haemorrhage will bleed from ruptured varices. To date, data on preventing the formation/growth of oesophageal varices (preprimary prophylaxis) are conflicting, with insufficient evidence to use β‐blockers. There is evidence for the need for primary prophylaxis, and both β‐blockers and endoscopic variceal ligation have shown the same efficacy in preventing first bleeding, but which one to prefer is still controversial. The present article reviews the established and potential therapeutic strategies for preventing the development and rupture of oesophageal varices.     

Oesophageal varices: prophylactic treatment?

Oesophageal varices: prophylactic treatment? Patients with oesophageal varices as a result of liver cirrhosis are at risk of bleeding from these varices. Because of the high mortality, specially from the first variceal haemorrhage, it would seem justified to pose the question: does prophylactic treatment of oesophageal varices reduce the risk of bleeding and improve life expectancy? A review of the literature shows that until now no mode of prophylactic therapy has succeeded in accomplishing these goals. It is not, therefore, possible at this time to advise the use of prophylactic treatment of oesophageal varices as a routine therapy.     

The role of the transjugular intrahepatic portosystemic stent shunt (TIPSS) in the management of bleeding gastric varices: clinical and haemodynamic correlations

BACKGROUND: The transjugular intrahepatic portosystemic stent shunt (TIPSS) is effective in the management of both oesophageal and gastric variceal bleeding. Although it has been reported that gastric varices can bleed at pressures of < or = 12 mm Hg, this phenomenon has been little studied in the clinical setting. AIMS: To assess the efficacy of TIPSS on rebleeding and mortality following gastric and oesophageal variceal bleeding, and the importance of portal pressure in both groups. METHODS: Forty eligible patients who had bled from gastric varices and 232 from oesophageal varices were studied. Patients were also subdivided into those whose portal pressure gradients (PPG) prior to TIPSS were < or = 12 mm Hg (group 1) and >12 mm Hg (group 2). RESULTS: There was no difference in Child-Pugh score, age, sex, or alcohol related disease between patients bleeding from gastric or oesophageal varices. Patients who bled from gastric varices had a lower PPG pre-TIPSS (15.8 (0.8) v 21.44 (0.4) mm Hg; p<0.001). There was no difference in the rebleeding rate (20.0% v 14.7%; NS). There was a significant difference (p<0.05) in favour of the gastric varices group in the one year mortality (30.7% v 38.7%) and five year mortality (49.5% v 74.9%), particularly in those patients in group 2. Gastric variceal bleeding accounted for significantly more cases in group 1 than in group 2 (36.8% v 10.2%; p<0.001). Most patients in group 2 who rebled had a PPG post-TIPSS of >7 mm Hg. CONCLUSIONS: TIPSS is equally effective in the prevention of rebleeding following gastric and oesophageal variceal bleeding. A significant proportion of gastric varices bleed at a PPG < or = 12 mm Hg. The improved mortality in patients with gastric variceal bleeding is seen only in those that bleed at a PPG >12 mm Hg, and warrants further study.     

非选择性β受体拮抗剂在肝硬化门静脉高压患者中的合理应用

曲张静脉出血是肝硬化门静脉高压患者最常见和最严重的并发症之一。近三十余年来,尽管对其治疗取得了进展,但其相关病死率仍达15%～20%左右。不仅如此,曲张静脉出血常导致肝功能进一步的恶化,也是诱发肝硬化其他并发症的共同启动因素。因此,预防曲张静脉首次出血与再出血是提高失代偿期肝硬化和食管曲张静脉患者生存率的重要措施。非选择性β受体阻滞剂（nonselective beta-blockers,NSBB）因具有明确地降低肝静脉压力剃度的作用,被推荐用于预防曲张静脉首次出血和再出血。尽管该类药物具有耐受性好、口服方便和经济实惠的优点,但在使用过程中因存在副作用和潜在的不良作用,一般推荐应有选择地用于那些高危的曲张静脉患者。     

Update on gastric varices

Although less common than oesophageal variceal haemorrhage, gastric variceal bleeding remains a serious complication of portal hypertension, with a high associated mortality. In this review we provide an update on the aetiology, classification and management of gastric varices, including acute bleeding, prevention of rebleeding and primary prophylaxis. We describe the optimum management strategies for gastric varices including drug, endoscopic and radiological therapies, focusing on recent published evidence.     

Comparative efficacy of emergency endoscopic sclerotherapy for active variceal bleeding due to cirrhosis of the liver, non-cirrhotic portal fibrosis and extrahepatic portal venous obstruction

Patients with continued variceal bleeding due to portal hypertension (n = 202) were treated by endoscopic injection sclerotherapy after resuscitation. Portal hypertension was due to hepatic cirrhosis in 123, non-cirrhotic portal fibrosis (NCPF) in 49 and extrahepatic portal venous obstruction (EHO) in 30 patients. Polidocanol 1% was injected intravariceally. An adequate sclerotherapy was carried out in 97% of patients. Immediate haemostasis was achieved in 177 (88%) patients. Rebleeding occurred in 31 (17.5%) of 177 patients. By reinjection of varices, definitive control of bleeding occurred in 160 (79%) patients. There was no significant difference in terms of immediate control of bleeding in patients with different aetiologies of portal hypertension and hepatic functional status (Child's grade). Rebleeding episodes were lower in patients with EHO than cirrhosis of the liver and NCPF. Similarly, the Child's status significantly influenced the recurrence of bleeding which was lower in Child's A than B and B than C. The in-hospital mortality was 18.6%. This was also significantly related to Child's status and aetiology of portal hypertension. Minor complications occurred in 10.4% of patients. It is concluded that endoscopic sclerotherapy as the first line of treatment is an effective and technically feasible procedure for the control of active variceal bleeding, regardless of the cause of portal hypertension. Furthermore, the results were influenced by the aetiology of portal hypertension and hepatic functional status.     

Prognosis in patients with cirrhosis and mild portal hypertension

OBJECTIVE: Sixty to 70% of upper gastrointestinal bleeding episodes in patients with cirrhosis are caused by oesophageal varices. Prophylaxis is indicated in patients with varices and a hepatic venous pressure gradient (HVPG) above 12 mmHg. The study of the natural history of patients with lower HVPG has been sparse. In this study, long-term survival and the risk of complications in mild portal hypertension were analysed. MATERIAL AND METHODS: Sixty-one patients with cirrhosis and HVPG below 10 mmHg were included in the study. Data were collected from medical files and National Patient Registries. Variceal bleeding, hepatic encephalopathy and death related to cirrhosis were registered. Thirty-nine patients were graded as Child class A, 19 as class B and 3 as class C. Median survival time was 11 years. RESULTS: Twenty-eight patients (46%) developed one or more complications: variceal bleeding in 10 (16%) and hepatic encephalopathy in 18 patients (30%). Twenty-three patients (38%) died from complications of cirrhosis. Two patients (3%) died from variceal bleeding, another two (3%) from gastrointestinal bleeding of unidentified source. Survival rate was significantly decreased compared with that in the background population. CONCLUSIONS: The frequency of complications in patients with mild portal hypertension is considerable, and guidelines for follow-up or medical prophylaxis are warranted. The risk of bleeding from oesophageal varices is low and bleeding-related deaths rare.     

乙型肝炎肝硬化并发食管胃底静脉曲张破裂出血患者临床特征及影响因素分析

目的 探讨乙型肝炎肝硬化并发食管胃底静脉曲张破裂出血患者的临床特征及其影响因素。方法 2015年6月～2020年6月我院收治的乙型肝炎肝硬化并发食管胃底静脉曲张破裂出血患者90例和同期乙型肝炎肝硬化未出血患者90例,收集患者临床资料,分析乙型肝炎肝硬化并发食管胃底静脉曲张破裂出血患者的临床特征,并采用多因素Logistic回归分析影响出血的因素。结果 单因素分析结果显示,出血组病程长、有消化道出血史、使用非甾体类药物、Child-Pugh分级差、食管静脉曲张程度严重、胃左静脉内径和门静脉内径宽、PT延长、有腹水和血清白蛋白水平低与未出血组比,存在显著性统计学差异(P<0.05);多因素Logistic回归分析结果显示,肝硬化病程长、应用非甾体类药物、Child-Pugh分级差、食管静脉曲张程度严重、胃左静脉内径增宽、门静脉内径增宽、PT延长和有腹水是乙型肝炎肝硬化并发食管胃底静脉曲张破裂出血的独立危险因素(OR=3.145;3.171;2.190;2.672;2.363;3.142;3.083;3.062,P<0.05),而血清白蛋白增加是出血的保护因素(OR=0.288,P<0.05)。结论 乙型肝炎肝硬化并发食管胃底静脉曲张患者存在一些可能诱发曲张静脉破裂出血的危险因素,临床应予以重视,以预防曲张静脉破裂出血的发生。     

Hemorrhagic ascites from spontaneous ectopic mesenteric varices rupture in NASH induced cirrhosis and successful outcome: A case report

Bleeding from gastro-esophageal varices can often present as the first decompensating event in patients with cirrhosis. This can be a potentially life threatening event associated with a 15%-20% early mortality. We present a rare case of new onset ascites due to intra-abdominal hemorrhage from ruptured mesenteric varices; in a 37 years old male with newly diagnosed nonalcoholic steatohepatitis induced cirrhosis as the first decompensating event. The patient was successfully resuscitated with emergent evacuation of ascites for diagnosis, identification and control of bleeding mesenteric varices and eventually orthotopic liver transplantation with successful outcome. Various clinical presentations, available treatment options and outcomes of ectopic variceal bleeding are discussed in this report.     

Evaluation of endoscopic variceal ligation in prophylactic therapy for bleeding of oesophageal varices: a prospective, controlled trial compared with endoscopic injection sclerotherapy

BACKGROUND: To evaluate the efficacy of endoscopic variceal ligation (EVL) in prophylactic therapy for oesophageal varices, we performed a randomized prospective trial to compare the recurrence of oesophageal varices treated by EVL with those treated by endoscopic injection sclerotherapy. METHODS: Fifty patients with liver cirrhosis were divided into two groups at random, after informed consents were obtained, to receive prophylactic therapy for bleeding of oesophageal varices. Group 1 patients underwent sessions of sclerotherapy with 5% ethanolamine oleate used as the sclerosant. Group 2 patients underwent EVL followed by one or two sessions of sclerotherapy. RESULTS: During the 18 month follow-up period, both the recurrence rate in group 2 (56%) and the incidence of bleeding (20%) were significantly higher compared with group 1 (recurrence rate 16%, bleeding 0%). CONCLUSIONS: This result indicates that EVL is not effective for prophylactic therapy for oesophageal varices in liver cirrhosis.     

Frequency and factors influencing portal hypertensive gastropathy and duodenopathy in cirrhotic portal hypertension

Portal hypertensive gastropathy and duodenopathy are distinct clinical and endoscopic entities. Data on factors influencing the development of these lesions are still emerging. Data on portal hypertensive duodenopathy are scarce. We prospectively studied 230 patients with liver cirrhosis and oesophageal varices attending the liver clinic of the Sanjay Gandhi Post Graduate Institute of Medical Sciences. One hundred and forty-two patients had no history of upper gastrointestinal bleeding, while the remainder had bled in the past. Endoscopic appearances were recorded before starting patients on a sclerotherapy programme. Forty-four patients were re-evaluated after variceal eradication. The frequency of portal hypertensive gastropathy (PHG) and duodenopathy (PHD) was 61 and 14%, respectively. Mild PHG was present in 85% and was severe in the rest. Portal hypertensive duodenopathy was mild in 50%, while in the other half it was severe. There was no relationship of PHG and PHD to: (i) a history of upper gastrointestinal bleed; (ii) size of oesophageal varices; (iii) aetiology of liver cirrhosis; or (iv) liver function status as assessed by Child Pugh's scores (P=NS for all). The prevalence of PHG was higher in those patients with oesophagogastric varices (74 of 107; 69%) compared with patients with oesophageal varices alone (68 of 123; 55%; P<0.05). However, no such increase in frequency of PHD was noted in patients with oesophagogastric varices. Sclerotherapy increased the frequency of PHG. Twenty-four patients had PHG before starting sclerotherapy, while it was noted in 33 patients 1–3 months after variceal eradication (P< 0.05). In contrast, there was no increase in the prevalence of portal hypertensive duodenopathy after sclerotherapy (P=NS). There was no correlation between endoscopic and histological changes of PHG and PHD. In conclusion, PHG is quite frequent in patients with cirrhosis and its frequency increases with the presence of oesophagogastric varices and after sclerotherapy. However, the frequency of PHD is low and is not affected by the factors studied.     

Variceal hemorrhage

Opinion statement Reducing morbidity and mortality from esophageal varices remains a challenge for physicians managing patients with chronic liver disease. For patients who have never bled from varices, prophylactic therapy with nonselective beta-blockers reduces the risk of initial variceal bleeding and bleeding-related death. Thus, patients with newly diagnosed cirrhosis should be considered for endoscopic variceal screening. All patients with Child’s class B and C cirrhosis should be offered endoscopic screening, whereas those with Child’s class A with evidence of portal hypertension (eg, platelet count less than 140,000 per milliliter, portal vein diameter larger than 13 mm, evidence of splenic varices on ultrasound) should be screened. The principal risk factors for variceal bleeding are variceal size, the presence of color changes on the variceal wall (indicative of decreased wall thickness), and degree of liver dysfunction. Patients with moderate or large sized varices and those with varices exhibiting color changes (eg, red wale marks, cherry red spots) should be treated with beta-blockers. Individuals without varices and those with small varices should undergo repeat endoscopy at approximately 2-year intervals. Patients unwilling or unable to take beta-blockers do not need to be screened. For patients with acute variceal bleeding, the combination of pharmacologic therapy plus endoscopic therapy is superior to either therapy alone. Octreotide is the drug most often used as initial therapy in the United States. Terlipressin is the preferred agent; however, it is not available in the United States. Endoscopy is performed as early as possible, and endoscopic injection sclerotherapy or endoscopic variceal band ligation is employed if variceal bleeding is confirmed or suspected. Endoscopic therapy should be repeated until the varices are obliterated completely. The addition of beta-blockers to endoscopic sclerotherapy or ligation may decrease the rate of rebleeding compared with receiving endoscopic treatment alone. Patients with bleeding refractory to combined medical plus endoscopic therapy should be considered for transjugular intrahepatic portosystemic shunts or shunt surgery.     

Long-term follow-up study of adult patients with non-cirrhotic obstruction of the portal system: comparison with cirrhotic patients.

Thirty-two patients with non-cirrhotic portal system obstruction and oesophageal varices of non-malignant etiology were recruited over 13 years. Diagnosis was based on the presence of oesophageal varices at endoscopy, minor alterations in liver function tests and liver histology, a low hepatic venous pressure gradient, and pertinent angiographic patterns. Twenty-three had portal vein thrombosis, nine had splenic vein thrombosis. Twenty-one had idiopathic portal vein obstruction, 11 had secondary obstruction. The outcome was compared with a group of 32 patients with cirrhosis and portal hypertension, matched for age, Child-Pugh class, previous history of gastrointestinal bleeding, and size of oesophageal varices. Patients with non-cirrhotic obstruction of the portal system were followed for up to 171 months (mean 94 months). During follow-up ten patients had gastrointestinal bleeding, and eight died (five of gastrointestinal bleeding). After 6 years of follow-up, the cumulative risk of gastrointestinal bleeding was 24%, the cumulative risk of death was 17%, and the cumulative risk of death from gastrointestinal bleeding was 14%. Cumulative probability of death by any cause and the probability of gastrointestinal bleeding were significantly lower in patients with non-cirrhotic obstruction of the portal system than in patients with cirrhosis comparable for liver function and portal hypertension (p = 0.04 for both). The cumulative probability of death by gastrointestinal bleeding was not significantly different. In conclusion, the prognosis for non-cirrhotic obstruction of the portal system is significantly better than for patients with cirrhosis with comparable levels of liver function impairment and severity of portal hypertension.     

Natural history of portal hypertension in patients with cirrhosis

All patients with cirrhosis will eventually develop portal hypertension and esophagogastric varices. Bleeding from ruptured esophagogastric varices is the most severe complication of cirrhosis and is the cause of death in about one third of patients. The rate of development and growth of esophageal varices is poorly defined but in general seem to be related to the degree of liver dysfunction. Once varices have formed, they tend to increase in size and eventually to bleed. In unselected patients, the incidence of variceal bleeding is about 20% to 30% at 2 years. Variceal size is the single most important predictor of a first variceal bleeding episode. Several prognostic indexes based on endoscopic and clinical parameters have been developed to predict the risk of bleeding; however, their degree of accuracy is unsatisfactory. Death caused by uncontrolled bleeding occurs in about 6% to 8% of patients; the 6-week mortality rate after a variceal hemorrhage is 25% to 30%. There are no good prognostic indicators of death caused by uncontrolled bleeding or death within 6 weeks. Untreated patients surviving a variceal hemorrhage have a 1- to 2-year risk of rebleeding of about 60% and a risk of death of about 40% to 50%. The risk of bleeding is greatest in the first days after a bleeding episode and slowly declines thereafter. All patients surviving a variceal hemorrhage must be treated to prevent rebleeding. Varices can also be found in the stomach of cirrhotic patients, alone or in association with esophageal varices. Gastric varices bleed less frequently but more severely than esophageal varices. Portal hypertensive gastropathy is a common feature of cirrhosis, and its prevalence parallels the severity of portal hypertension and liver dysfunction. Portal hypertensive gastropathy can progress from mild to severe and vice-versa or even disappear completely. Acute bleeding from portal hypertensive gastropathy seems to be relatively uncommon, and less severe than bleeding from varices.     

Primary prophylaxis of variceal bleeding in cirrhosis

Variceal bleeding is the result of portal hypertension, which is a major complication of liver cirrhosis and carries a high mortality rate. Because of the mortality associated with variceal bleeding, strategies for prevention of the first bleed is important. Risk stratification is important in determining those at risk of bleeding from varices and current data suggest that patients with large varices with red signs, severe underlying liver disease and those who have a hepatic venous pressure gradient of greater than 12 mmHg are at high risk of bleeding. Surveillance for varices in patients with cirrhosis is therefore important. The current review evaluates the role of various treatments in the primary prophylaxis of variceal bleeding. The current first choice treatment is non-selective beta-blockers; which is cheap, easy to administer, and reduces the risk of first variceal haemorrhage significantly. Combination of beta-blockers and nitrates looks promising but needs further evaluation. Endoscopic variceal band ligation compares favourably with non-selective beta-blockers in preventing the first bleeding episode in cirrhotic patients and may be an alternative for patients who cannot tolerate, or have contraindications to beta-blockers. The role of monitoring the hepatic venous pressure gradient in those being treated with pharmacological agents, the role of newer drugs such as non-selective beta-blockers with intrinsic alpha-adrenergic activity and angiotensin receptor blockers require further evaluation.     

Sclerotherapy versus sclerotherapy and propranolol in the prevention of rebleeding from oesophageal varices: a randomised study.

BACKGROUND--This trial was carried out to assess the value of propranolol in the prevention of recurrent variceal bleeding when combined with longterm endoscopic sclerotherapy. PATIENTS AND METHODS--Two hundred patients (161 male, 39 female, age range 20-68 years) with portal hypertension resulting mainly from schistosomal periportal fibrosis or posthepatitic cirrhosis presenting with their first episode of haematemesis or melena, or both were included. This was confirmed endoscopically to result from ruptured oesophageal varices. After initial control of bleeding, patients were randomised into two groups: group 1 treated with endoscopic sclerotherapy alone and group 2 treated with sclerotherapy plus propranolol. They were followed up for two years. RESULTS--Group (2) had a lower rebleeding rate (14.3% v 38.6% in group 1), lower variceal recurrence after obliteration (17% v 34% in group 1), longer period between variceal obliteration and recurrence (36 weeks v 21 weeks in group 1); but no change in mortality (12% in both groups). CONCLUSIONS--Patients treated with sclerotherapy should be given propranolol for longterm management.     

Portal hypertension in primary biliary cirrhosis

Evidence of portal hypertension was found in 50 out of 109 patients (47%) with primary biliary cirrhosis, and of these 32 bled from oesophageal varices. In four patients portal hypertension was the initial manifestation of the disease and this complication was recognized in a further 17 within two years of the first symptom of primary biliary cirrhosis. The development of portal hypertension was associated with a poor prognosis and death could frequently be attributed to variceal bleeding; the mean duration of survival from the time that portal hypertension was recognized was 14.9 months. Portal decompression operations may have improved the immediate prognosis in some patients but did not otherwise influence the progression of the disease. In 47 patients the histological findings in wedge biopsy or necropsy material were correlated with the presence or absence of varices. An association between nodular regeneration of the liver and varices was confirmed, but, in the absence of nodules, no other histological cause for portal venous obstruction could be found.     

Acute variceal bleeding: pharmacological treatment and primary/secondary prophylaxis

Variceal bleeding is one of the most severe complications of portal hypertension related to liver cirrhosis. Primary prophylaxis is considered mandatory in patients with cirrhosis and high-risk oesophageal varices, and once varices have bled, every effort should be made to arrest the haemorrhage and prevent further bleeding episodes. In acute variceal bleeding, vasoactive drugs that lower portal pressure should be started even before endoscopy, and should be maintained for up to 5 days. The choice of vasoactive drug should be made according to local resources. Terlipressin, somatostatin and octreotide can be used; vasopressin plus transdermal nitroglycerin may be used if no other drug is available. In variceal bleeding, antibiotic therapy is also mandatory. In primary and secondary prophylaxis, beta-blockers are the mainstay of therapy. In secondary prophylaxis (but not in primary prophylaxis) these drugs can be combined with organic nitrates.