Olmesartan medoxomil combined with hydrochlorothiazide for the treatment of hypertension

In most patients with hypertension, especially Stage 2 hypertension, adequate control of blood pressure (BP) is only achieved with combination drug therapy. When using combination therapy, antihypertensive agents with complementary mechanisms of action are recommended, for example, an angiotensin receptor blocker (ARB) in combination with hydrochlorothiazide (HCTZ), a beta-blocker + HCTZ, an ACE inhibitor + HCTZ, or a calcium channel blocker + an ACE inhibitor. One such combination is olmesartan medoxomil + HCTZ, which is available as fixed-dose, single-tablet combinations for once-daily administration. In clinical trials, olmesartan medoxomil/HCTZ reduced systolic BP (SBP) and diastolic BP (DBP) to a greater extent than either component as monotherapy. A clinical study in patients with Stage 1 or 2 hypertension showed that olmesartan medoxomil/HCTZ achieved a similar mean reduction in DBP, but a significantly greater mean reduction in SBP and higher rate of BP control (< 140/90 mmHg) than observed with losartan/HCTZ, at US/European-approved starting doses. In a non-inferiority trial, the antihypertensive efficacy of olmesartan medoxomil/HCTZ was comparable to that of atenolol/HCTZ. Furthermore, indirect comparisons have shown that olmesartan medoxomil/HCTZ compares favorably with other antihypertensive combination therapies, including other ARB/HCTZ combinations and amlodipine besylate/ benazepril. Olmesartan medoxomil/HCTZ is generally well tolerated. In conclusion, olmesartan medoxomil/HCTZ is an effective and well-tolerated combination antihypertensive therapy that results in significant BP reductions and BP control in many patients.     

Metoprolol succinate extended release/hydrochlorothiazide combination tablets

Lowering elevated blood pressure (BP) with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events such as stroke and myocardial infarction. Given the heterogeneity of hypertension as a disease, the marked variability in an individual patient's BP response, and low response rates with monotherapy, expert groups such as the Joint National Committee (JNC) emphasize the value of combination antihypertensive regimens, noting that combinations, usually of different classes, have additive antihypertensive effects. Metoprolol succinate extended-release tablet is a beta-1 (cardio-selective) adrenoceptor-blocking agent formulated to provide controlled and predictable release of metoprolol. Hydrochlorothiazide (HCT) is a well-established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubule. The pharmacokinetics, efficacy, and safety/tolerability of the antihypertensive combination tablet, metoprolol extended release hydrochlorothiazide, essentially reflect the well-described independent characteristics of each of the component agents. Not only is the combination product more effective than monotherapy with the individual components but the combination product allows a low-dose multidrug regimen as an alternative to high-dose monotherapy, thereby, minimizing the likelihood of dose-related side-effects.     

Clinical trial update: focus on the ONTARGET study

The renin angiotensin system (RAAS) plays an important role in the pathophysiology of cardiovascular (CV) disease. Modulation of RAAS with angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and aldosterone inhibitors reduces a range of adverse CV outcomes in patients with or at risk of CV disease. Currently, there is incomplete evidence to show all RAAS modulators provide vascular protection by reducing the incidence of myocardial infarction (MI), stroke and CV death. In patients at high risk for CV events, studies with ACEi designed to test for long-term vascular protection, showed benefit. In contrast, studies of ARBs in patients with hypertension, heart failure, and renal disease have not consistently shown a reduction of CV outcomes. However, none of these studies was specifically designed to examine the impact of ARBs on the vascular protective outcomes of CV death, non-fatal MI, and stroke. The ONTARGET and TRANSCEND studies are designed to determine whether the ARB telmisartan is similar (or non-inferior) or superior to the ACEi ramipril in the reduction of CV events in patients with established CV disease or diabetes with target organ damage. The ONTARGET study has enrolled 25,620, and TRANSCEND 5,776 subjects. The subjects in both trials are similar to those studied in the HOPE study, yet there is greater ethnic diversity, a higher proportion of patients with cerebro-vascular disease, and a greater use of beta blockers and lipid-lowering treatment. The studies completed recruitment in 2004, and are due to complete follow-up and report the results in 2008. The ONTARGET and TRANSCEND studies will provide valuable comparative data on the efficacy of telmisartan and ramipril and their combination in patients at high risk for CV events. Although it is possible that enhanced benefits will be observed with dual therapy, the outcomes with ARB monotherapy remain uncertain.     

Valsartan in the treatment of heart failure or left ventricular dysfunction after myocardial infarction

The physiological role of the renin angiotensin aldosterone system (RAAS) is to maintain the integrity of the cardiovascular system. The effect of angiotensin II is mediated via the angiotensin type I receptor (AT1 ) resulting in vasoconstriction, sodium retention and myocyte growth changes. This causes myocardial remodeling which eventually leads to left ventricular hypertrophy, dilation and dysfunction. Inhibition of the RAAS with angiotensin converting enzyme (ACE) inhibitors after acute myocardial infarction has been shown to reduce cardiovascular morbidity and mortality. Angiotensin receptor blockers (ARBs) specifically inhibit the AT1 receptor. It has not been known until the performance of the VALIANT (valsartan in acute myocardial infarction trial) whether blockade of the angiotensin receptor with an ARB or combination of an ACE inhibitor and ARB leads to similar outcomes as an ACE inhibitor. The VALIANT trial demonstrated equal efficacy and non-inferiority of the ARB valsartan 160 mg bid compared with captopril 50 mg tds, when administered to high risk patients with left ventricular dysfunction or heart failure in the immediate post myocardial infarction period. The combination therapy showed no incremental benefit over ACE inhibition or an ARB alone and resulted in increased adverse effects. This review examines the role of valsartan in left ventricular dysfunction post myocardial infarction. We also discuss pharmacokinetics, dosing, side effects, and usage in the elderly.     

Clinical update on the therapeutic use of clopidogrel: treatment of acute ST-segment elevation myocardial infarction (STEMI)

The pathogenesis of ST-elevation myocardial infarction (STEMI) involves plaque disruption, platelet aggregation and intracoronary artery thrombus formation. Aspirin is the cornerstone of antiplatelet therapy in patients with STEMI, reducing the risk of recurrent myocardial infarction or death during the acute phase and long term by about one-quarter. Recent large randomized trials have demonstrated that the addition of clopidogrel to aspirin reduces the risk of major ischemic events by up to a further one-third in patients with STEMI treated with fibrinolytic therapy and undergoing percutaneous coronary intervention, with no significant increase in bleeding. Thus, dual antiplatelet therapy with the combination of clopidogrel and aspirin is becoming the new standard of care for the management of patients with STEMI.     

Manidipine-delapril combination in the management of hypertension

High blood pressure (BP) is the major cardiovascular risk factor and the main cause of death around the world. Control of blood pressure reduces the high mortality associated with hypertension and the most recent guidelines recommend reducing arterial BP values below 140/90 mmHg for all hypertensive patients (130/80 in diabetics) as a necessary step to reduce global cardiovascular risk, which is the fundamental objective of the treatment. To achieve these target BP goals frequently requires combination therapy with two or more antihypertensive agents. Although the combination of a diuretic and an angiotensin converting enzyme inhibitor (ACEI) is the most commonly used in the clinical practice, the combination of an ACEI and a calcium channel blocker may have an additive antihypertensive effect, a favorable effect on the metabolic profile, and an increased target organ damage protection. The new oral fixed combination manidipine 10 mg/delapril 30 mg has a greater antihypertensive effect than both components of the combination separately, and in non-responders to monotherapy with manidipine or delapril the average reduction of systolic and diastolic BP is 16/10 mmHg. The combination is well tolerated and the observed adverse effects are of the same nature as those observed in patients treated with the components as monotherapy. However, combination therapy reduces the incidence of ankle edema in patients treated with manidipine.     

Trandolapril/verapamil combination in hypertensive diabetic patients

Cardiovascular diseases are directly affected by arterial hypertension. When associated with diabetes mellitus, the potential deleterious effects are well amplified. Both conditions play a central role in the pathogenesis of coronary artery disease, heart failure, stroke, and renal insufficiency. Prevalence of hypertension is much higher among diabetic than non-diabetic patients, and the hypertensive patient is more likely to develop type 2 diabetes. Current international guidelines recommend aggressive reductions in blood pressure (BP) in hypertensive patients with additional risk factors, including cardiovascular risk factors, and emphasize the relevance of intensive reduction in patients with diabetes mellitus; a goal of 130/80 mm Hg is required. To achieve BP target a combination of antihypertensives will be needed, and the use of long-acting drugs that are able to provide 24-hour efficacy with a once-daily dosing confers the noteworthy advantages of compliance improvement and BP variation lessening. Lower dosages of the individual treatments of the combination therapy can be administered for the same antihypertensive efficiency as that attained with high dosages of monotherapy. Angiotensin-converting enzyme inhibitors and calcium-channel blockers as a combination have theoretically compelling advantages for vessel homeostasis. Trandolapril/verapamil sustained release combination has showed beneficial effects on cardiac and renal systems as well as its antihypertensive efficacy, with no metabolic disturbances. This combination can be considered as an effective therapy for the diabetic hypertensive population.     

Management of Hypertension in Patients with Diabetes Mellitus

Hypertension and diabetes mellitus are significant and independent risk factors for cardiovascular disease.Antihypertensive therapy reduces cerebrovascular and cardiovascular morbidity and mortality in patients with hypertension. Tight blood pressure (BP) control [target diastolic BP (DBP) ≤80mm Hg] reduced the incidence of major cardiovascular events by 51% compared with less tight control (DBP ≤90mm Hg) in patients with diabetes mellitus in the Hypertension Optimal Treatment (HOT) study. Similarly, in the UK Prospective Diabetes Study (UKPDS), tight BP control [mean systolic BP (SBP)/DBP = 144/82mm Hg] with captopril or atenolol reduced diabetes mellitus-related morbidity and mortality by 24% compared with less tight control (mean SBP/DBP = 154/87mm Hg). Importantly, the frequency of microvascular disease (including retinopathy) was reduced by 37% among those randomised to tight BP control in the UKPDS.In the diabetic subgroup in the Heart Outcomes Prevention Evaluation (HOPE) study, there was a 25% reduction in the composite end-point of death due to cardiovascular causes, or myocardial infarction or stroke during 5 years of treatment with ramipril 10 mg/day relative to placebo.Lisinopril is an ACE inhibitor indicated for use in hypertension, heart failure and post-myocardial infarction. As an antihypertensive agent the drug is effective and generally well tolerated in patients with type 1 or 2 diabetes mellitus and in those with early or overt nephropathy.In the Swedish Treatment of Old People (STOP) Hypertension 2 trial, there was no difference in the relative risk of cardiovascular death between those assigned to ACE inhibitors (lisinopril or enalapril), calcium channel blockers (felodipine or isradipine) or ‘conventional’ antihypertensive therapy (thiazide diuretics or β blockers); treatment effects did not differ significantly between diabetic and nondiabetic patients (10.9% of the 6614 patients had diabetes mellitus). Importantly, lower frequencies of nonfatal or fatal myocardial infarction [relative risk (RR) 0.77; 95% confidence interval (CI) 0.61 to 0.96] and congestive heart failure (RR 0.78; CI 0.83 to 0.97) were detected during 4 years’ treatment with lisinopril or enalapril than felodipine or isradipine in this study.Lisinopril reduced albumin excretion rates in patients with type 1 or 2 diabetes mellitus. In the 2-year EURODIAB Controlled Trial of Lisinopril in IDDM (EUCLID) study, albumin excretion rates decreased by 49.7% relative to placebo in normotensive patients with type 1 diabetes mellitus and microalbuminuria during treatment with lisinopril 10 to 20 mg/day. Progression of retinopathy was attenuated in normotensive patients with type 1 diabetes mellitus during treatment with lisinopril in this study.In conclusion, lisinopril, like other ACE inhibitors should be considered a first-line agent for reducing BP and attenuating nephropathy in patients with type 1 or 2 diabetes mellitus.     

The practice guideline 'Hypertension' (third revision) from the Dutch College of General Practitioners; a response from the perspective of general practice

In the revised practice guideline on hypertension from the Dutch College of General Practitioners, some changes have been made in the areas of diagnosis and therapy in comparison to the previous edition. Finding people with hypertension is a major goal for the prevention of cardiovascular disease. A systolic blood pressure > 140 mmHg (> 160 mmHg in patients > 60 years) necessitates non-pharmaceutical advice and antihypertensive therapy with diuretics, beta-blockers, angiotensin-converting-enzyme (ACE) inhibitors or calcium antagonists, either as monotherapy or in combination. In view of the ever-increasing importance of ACE inhibitors in antihypertensive therapy, we expect that the next revision of the practice guideline will soon be necessary.     

Combination therapy (interferon alfa and ribavirin) in the treatment of chronic hepatitis C: a rapid and systematic review

BACKGROUND: Hepatitis C is a viral disease of the liver, which frequently causes few or no symptoms at first infection but has a high probability of becoming an insidious chronic disease. Treatment has traditionally been with interferon alfa but only a small proportion of patients have been cured by this method. The recent introduction of ribavirin, given in combination, has led to a re-appraisal of the management of chronic hepatitis C. The current report considers the additional benefit of combination therapy (interferon alfa and ribavirin) compared with monotherapy (interferon alfa alone) for the treatment of patients with chronic hepatitis C. It supersedes two reports of combination therapy conducted by the Scottish Health Purchasing Information Centre and the Wessex Institute for Health Research and Development. OBJECTIVE: To review the clinical effectiveness and cost-effectiveness of combination therapy with interferon alfa and ribavirin in patients with chronic hepatitis C. METHODS - EFFECTIVENESS: Electronic databases were searched from 1993 to the end of 1999, to identify randomised controlled trials (RCTs) or systematic reviews of RCTs that evaluated interferon alfa in combination with ribavirin compared with interferon alfa alone (or placebo) in patients with chronic hepatitis C. Bibliographies from previous studies were also examined. METHODS - ECONOMIC ANALYSIS: The economic evaluation is based on the three largest RCTs of combination therapy, and a pooled analysis of two of these trials. Sustained virological response rates were entered into a spreadsheet model incorporating a hypothetical cohort of 1000 patients who were followed over a 30-year period. RESULTS - EFFECTIVENESS: Nineteen RCTs and two meta-analyses were identified. The methodological quality of the included studies was variable, though the larger RCTs and meta-analyses were considered to be of high quality. Results of these trials indicate that combination therapy produces larger sustained response rates than monotherapy. For patients naive to interferon treatment, sustained virological response rates were: 33% (95% confidence interval (CI), 29 to 37) for combination therapy compared with 6% (95% CI, 3 to 10) for monotherapy, based on 24 weeks of treatment; and 41% (95% CI, 36 to 45) compared with 16% (95% CI, 13 to 19), respectively, for 48 weeks of treatment. For patients who had relapsed following a previous course of interferon, sustained virological response rates were 49% (95% CI, 42 to 57) compared with 5% (95% CI, 2 to 9), respectively, based on 24 weeks of treatment. Two groups of chronic hepatitis C patients are expected to benefit from combination therapy: interferon-naive patients and relapse patients. RESULTS - ECONOMIC ANALYSIS: A 4-week cycle of interferon alfa at 3 mU three times a week costs pound 194; ribavirin costs pound 543. Thus, ribavirin substantially increases drug costs compared with interferon monotherapy. Six months of combination therapy will cost pound 4422 (excluding monitoring costs). For interferon alfa-naive patients, the additional discounted cost per quality-adjusted life-year (QALY) gained from treatment with combination therapy for 6 months compared with no active treatment is pound 7578. For patients who have relapsed after a previous course of interferon alfa, the additional discounted cost per QALY gained from treatment with combination therapy for 6 months compared with monotherapy for 6 months is pound 3503. A subgroup analysis was conducted to examine the sensitivity of the cost per QALY based on the response rates of different patient subgroups (chronic hepatitis C patients with between none and five favourable response factors). This shows it is worth treating all patients with combination therapy as first-line treatment for 6 months, but only worth treating those with one or two response factors for a further 6 months. Those with three or four factors do well by 6 months, but gain very little from furt     

Moexipril and left ventricular hypertrophy

Angiotensin-converting enzyme (ACE) inhibitors today are the standard therapy of patients with myocardial infarction and heart failure due to their proven beneficial effects in left ventricular remodeling and left ventricular function. ACE inhibitors have also been demonstrated to lead to regression of left ventricular hypertrophy (LVH). It is believed that the mechanism of action of LVH regression with ACE inhibitors arises from more than simple blood pressure reduction. LVH is an important risk factor for cardiovascular disease morbidity and mortality independent of blood pressure. Moexipril hydrochloride is a long-acting, non-sulfhydryl ACE inhibitor that can be taken once daily for the treatment of hypertension. Moexipril has now also been demonstrated to have beneficial effects on LVH and can lead to LVH regression.     

Valsartan in the treatment of heart attack survivors

Survivors of myocardial infarction (MI) are at high risk of disability and death. This is due to infarct-related complications such as heart failure, cardiac remodeling with progressive ventricular dilation, dysfunction, and hypertrophy, and arrhythmias including ventricular and atrial fibrillation. Angiotensin (Ang) II, the major effector molecule of the renin-angiotensin-aldosterone system (RAAS) is a major contributor to these complications. RAAS inhibition, with angiotensin-converting enzyme (ACE) inhibitors were first shown to reduce mortality and morbidity after MI. Subsequently, angiotensin receptor blockers (ARBs), that produce more complete blockade of the effects of Ang II at the Ang II type 1 (AT1) receptor, were introduced and the ARB valsartan was shown to be as effective as an ACE inhibitor in reducing mortality and morbidity in high-risk post-MI survivors with left ventricular (LV) systolic dysfunction and and/or heart failure and in heart failure patients, respectively, in two major trials (VALIANT and Val-HeFT). Both these trials used an ACE inhibitor as comparator on top of background therapy. Evidence favoring the use of valsartan for secondary prevention in post-MI survivors is reviewed.     

Secondary prevention in coronary heart disease

After myocardial infarction, beta-blockers, aspirin and (in selected patients) ACE inhibitors all reduce substantially the risk of further myocardial infarction or coronary death. With regard to life-style changes, giving up cigarette smoking reduces coronary risk by about 50%. Weight reduction and regular exercise are advised, although the effect of these measures on prognosis is uncertain. Recently, two major trials, the Scandinavian Simvastatin and West of Scotland Pravastatin studies, have radically changed ordinary medical practice. In these trials HMG CoA reductase inhibitor (statin) treatment reduced coronary events by 30–40%, reduced all-cause mortality, and proved safe and well-tolerated. The accepted policy now is to treat all patients with coronary heart disease, who have a cholesterol concentration 5.5 mmol/l or higher, with a statin. Where does this leave cholesterol-lowering dietary advice in secondary prevention? The benefits of statin treatment were attained by reducing serum cholesterol by an average of 25%. Diet change rarely attains such a fall in cholesterol and should therefore be used only as an adjunct to drug therapy. When recommending a lipid-lowering diet there is a danger that patients may be denied highly-effective drug treatment because of the «threshold» effect. A decision on the need for cholesterol reduction should be made before diet change is advised. Once the decision is made the target is a 25% cholesterol reduction, which will require drug therapy in addition to diet changes.     

Should patients receive secondary prevention medications for free after a myocardial infarction? An economic analysis

Taken in combination, aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins (combination pharmacotherapy) greatly reduce cardiac events. These therapies are underused, even among patients with drug insurance. Out-of-pocket spending is a key barrier to adherence. We estimated the impact of providing combination pharmacotherapy without cost sharing ("full coverage") to insured patients after a myocardial infarction (MI). Under base-case assumptions, compared to standard coverage, three years of full coverage will reduce mortality and reinfarction rates and will save 5,974 per patient. Our analysis suggests that covering combination therapy for such patients will save both lives and money.     

Drug treatment considerations for the hypertensive black patient

In prior years the major differences noted between hypertension in black and white patients have been mostly epidemiological, with some suggestion that the differences were primarily quantitative and probably not qualitative. Recently, certain pathophysiological aberrations in hypertensive patients have been shown to be different in blacks and whites. Whether these differences are primary (genetic) or secondary has yet to be resolved. Nevertheless, certain racial differences may have therapeutic implications. Diuretics remain the mainstay of therapy for most hypertensive black patients. beta-Blockers and angiotensin-converting enzyme (ACE) inhibitors have not shown great efficacy when used as monotherapy in black hypertensive patients. The combination of a diuretic with beta-blockers or ACE inhibitors, however, has been shown to abolish black-white differences in drug response. More recently, the calcium channel blockers have been shown to be potentially effective in black hypertensive patients. In spite of the effective drug therapy that is available for hypertensive patients in general, economic and social considerations continue to contribute to the low rate of detection, treatment, and control of hypertension in the black population.     

Calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors: effectiveness in combination with diuretics or beta-blockers for treating hypertension

This retrospective database analysis compared the effectiveness of dihydropyridine calcium channel blockers (DHPs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) added to diuretics or beta-blockers. Adults with hypertension treated with diuretic or beta-blocker monotherapy between 1998 and 2001 were identified from a large US electronic medical records database of primary care practices. Patients were required to have a baseline blood pressure (BP) > or =140/90 mmHg (> or =130/80 mmHg for diabetes mellitus) and recorded BP measurements within 6 months before and 1-12 months following index date. Patients were matched 1:1:1 by propensity score to correct for differences in baseline characteristics. 1875 patients met study criteria and 660 (220 in each cohort) were matched based on propensity scores. Matched cohorts had no significant differences in baseline characteristics. Mean changes in systolic/diastolic BP were -17.5/-8.8, -15.7/-6.3, and -13.0/-8.0 mmHg with DHPs, ACE inhibitors, and ARBs, respectively. Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High BP 6/7 goal attainment for each regimen was 47.3%, 40.0%, and 32.2%, respectively. DHPs, ACE inhibitors, and ARBs improved BP when added to patients' beta-blocker or diuretic therapy. The greatest benefits were observed with DHPs, followed by ACE inhibitors, then ARBs.     

急性心肌梗死患者医院获得性肺炎危险因素分析

目的 探讨急性心肌梗死患者发生医院获得性肺炎(HAP)的危险因素及防治措施.方法 回顾性调查分析328例急性心肌梗死住院患者,应用logistic回归模型,分析吸烟、介入治疗、泵功能、慢性阻塞性肺疾病(COPD)、糖尿病、心肌梗死类型、性别、年龄、住院时间等因素对HAP的影响.结果 急性心肌梗死患者医院获得性肺炎感染率为11.6％,住院时间为急性心肌梗死患者,发生HAP的主要危险因素,其OR值为10.192;而其余因素均与HAP无显著相关.结论 住院时间为急性心肌梗死患者发生HAP的主要危险因素;临床上宜采取综合措施,以预防为主、缩短住院时间、合理应用抗菌药物.     

An Update on Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health

Interest in the potential cardiovascular (CV) benefits of omega-3 polyunsaturated fatty acids (Ω-3) began in the 1940s and was amplified by a subsequent landmark trial showing reduced CV disease (CVD) risk following acute myocardial infarction. Since that time, however, much controversy has circulated due to discordant results among several studies and even meta-analyses. Then, in 2018, three more large, randomized trials were released—these too with discordant findings regarding the overall benefits of Ω-3 therapy. Interestingly, the trial that used a higher dose (4 g/day highly purified eicosapentaenoic acid (EPA)) found a remarkable, statistically significant reduction in CVD events. It was proposed that insufficient Ω-3 dosing (<1 g/day EPA and docosahexaenoic acid (DHA)), as well as patients aggressively treated with multiple other effective medical therapies, may explain the conflicting results of Ω-3 therapy in controlled trials. We have thus reviewed the current evidence regarding Ω-3 and CV health, put forth potential reasoning for discrepant results in the literature, highlighted critical concepts such as measuring blood levels of Ω-3 with a dedicated Ω-3 index and addressed current recommendations as suggested by health care professional societies and recent significant scientific data.     

Drug-eluting stents: a review of current evidence on clinical effectiveness and late complications

Drug-eluting stent (DES) use has increased greatly as a result of early trial evidence of a reduction in restenosis. However, thet are expensive and do not improve patient survival. Therefore their use has been rationed in some countries. There is a paucity of clinical evidence for some patient groups such as non-ST elevation myocardial infarction and multi-vessel disease. Recent studies suggest that the early benefits of drug-eluting stents may be offset by an increased risk in late stent thrombosis which is a potentially fatal complication. However, the absolute risk appears low and, as yet, there is no evidence of an increased risk of stent-thrombosis related myocardial infarction or death in patients studied in randomised clinical trials. Long-term use of anti-platelet therapy may protect against the risk of late stent thrombosis but the optimal treatment strategy is currently unclear. The aim of this paper is to provide an up-to-date review of the current evidence on DES; including clinical effectiveness, the limitations of existing trials, the emerging evidence on late stent thrombosis and the potential role of clopidogrel.