Monthly Archives: July 2010

Lasers vaporised from NICE guideline recommendations for refractory angina 

Br J Cardiol 2010;17:159-60 Leave a comment
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As from May 2009 the National Institute for Health and Clinical Excellence (NICE) have removed transmyocardial laser revascularisation (TMLR) from the list of treatments for refractory angina.1 From their analysis of efficacy they found no evidence of improved myocardial perfusion, ejection fraction or prognosis. There was also no evidence for improvement in exercise tolerance or Canadian Cardiovascular Society (CCS) class when compared with other treatments. Furthermore, looking at the data on safety, randomised controlled trials showed evidence of increased myocardial infarction in the TMLR-treated patient group, as well as evidence of left ventricular perforation. 

There have been reservations regarding this technique for many years and it would seem to be a valid decision on behalf of the specialist advisers. It seems appropriate, therefore, to look at how to best treat this complex group of patients. 

Recommendations

Members of the Canadian Cardiovascular Society have recently issued a position statement on refractory angina (RFA).2 They have produced three recommendations:

  1. Collect accurate data on the incidence and prevalence of RFA in Canada
  2. To have a clear definition of RFA that reflects recent advancements in pain neuropathophysiology
  3. To have joint CCS and Canadian Pain Society (CPS) guidelines.

The group are awaiting the results of a publicly funded study looking at the prevalence of angina six months after percutaneous coronary intervention (PCI). They are also hoping to establish a registry as part of a joint project with the CCS and CPS.

In order to expand on Mannheimer’s widely quoted definition of RFA,3 the authors suggest broadening it to take into account the neurological response to pain similar to that of chronic tissue injury. Angina is a complex somatic response that does not reliably reflect the amount of myocardial ischaemia and, even more confusing, a lot of ischaemia can be silent. To this end the authors suggest adding to the definition “…while the presence of reversible ischaemia must be clinically established to be the root cause, the pain experienced may arise or persist with or without this ischaemia.” Being aware of this must assist healthcare professionals and patients in a better understanding of RFA, and it should also help prevent some inappropriate attempts at revascularisation or increasing anti-anginal medication.

Collaboration

The close collaboration of cardiologists and pain management specialists is an excellent idea and hopefully it will in some way be reflected in the NICE review on stable angina soon to be undertaken.

As we have discussed previously, patients with RFA benefit from coming to a centre specialising in the condition.4 The multi-disciplinary team should include a cardiologist, pain management specialist, cardiac surgeon and interventionalist, specialist nurse and psychologist.

Each case should be reviewed, and consideration given to the possibility that a new lesion is responsible for the symptomatology. Often myocardial perfusion imaging, stress echocardiography or magnetic resonance imaging can be useful in identifying patients who will benefit from intervention. If PCI is recommended for a complex lesion or chronic total occlusion, this should be undertaken by an experienced interventionalist. Coronary artery bypass grafting (CABG) and redo surgery is sometimes a possibility, although patients need to be fully aware of the risks and understand that often the procedure will not affect prognosis, but may relieve symptoms.

Medical therapy

Medical therapy is of course the mainstay of treatment for angina and should not be looked on as the last of all the options. Trials such as Clinical Outcomes Utilising Revascularisation and Aggressive Drug Evaluation (COURAGE) and Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) have helped us understand that medical therapy is a safe, and often preferable option. Heart rate control is important for reducing myocardial oxygen demand and this can be achieved with beta blockade, ivabradine or a non-dihydropyridine calcium channel blocker. Combination of these therapies is possible with careful monitoring of heart rate and symptomatology. The recently introduced ranolazine can also be considered.5 This has been shown in trials to be safe and effective in treating refractory angina, and can be given in combination with other anti-anginal medications. It inhibits the late sodium current resulting in myocardial relaxation and reduces diastolic stiffness.

Pain management also has an important role in controlling symptoms. Patients with chronic pain, such as angina, can develop hypervigilance or an increased sensitivity to pain. The trigger of even a small area of myocardial ischaemia can evoke an exaggerated pain response often lasting one or two hours. Not only is this extremely debilitating for the patient, but there is the additional fear that it could herald a myocardial infarction, and often involves high-speed trips to hospital only to be discharged the next day with very little in the way of treatment or explanation. Pain medicine aims at amelioration of this neurological response and medication, such as tricyclic antidepressants or anti-epileptics, e.g. pregablin, can be effective. Opioids also have a role to play and can help certain patients return to daily activities.

Transcutaneous electrical nerve stimulation (TENS) is effective in relieving angina. It works by inhibiting painful stimuli to the brain. It is simple to use, but some patients find them inconvenient to wear, in which case a spinal cord stimulator is an effective alternative involving an internal spinal lead and generator. It is, however, more expensive and requires a day-case admission to have a temporary trial device fitted, followed by a further admission to implant the permanent system. Trials have shown them to be effective in relieving angina, but it would seem from recent experience that Primary Care Trusts remain to be convinced. Again it is hoped that this will be clarified in the updated NICE guidelines. Important contraindications to electrical nerve stimulation are pacemakers and other implanted cardiac devices.

Psychological factors

Finally, but very importantly, the patients need psychological care. Healthcare professionals need to be aware of signs for anxiety and depression, social isolation, fear of mortality, misinformation and many other attendant effects of RFA. We need to be prepared to refer to the appropriate agencies or specialist hospitals. It is a mistake to think of this group of patients as ‘end-stage’. They mostly have moderate-to-good left ventricular function and are, therefore, in a favourable prognostic group; sadly, many are unaware of this fact and live in fear. They need to be offered a comprehensive package of care including opportunities to join a cardiac rehabilitation group or home-based exercise and relaxation. It is often the case that they will have collected maladaptive beliefs about what the pain signifies and these thoughts are often more disabling than the actual pain. By addressing misconceptions about their symptoms, their quality of life can be markedly enhanced. This can often be achieved with a home-care package such as the Angina Plan,6 and the guidance and support of a trained nurse.

The aim of treating these patients is to ameliorate the symptoms, with one or many of the strategies mentioned, such that the quality of life is enhanced, enabling the patient to live a more fulfilled life.

Conflict of interest

None declared.

References

1. Department of Health, Social Services and Public Safety. Interventional procedure programme guideline. Available from: www.dhsspsni.gov.uk/hsc_26-09_ipg302.pdf

2. McGillion M, L’Allier P, Arthur H. Recommendations for advancing the care of Canadians living with refractory angina pectoris. Can J Cardiol 2009;25:399–401.

3. Mannheimer C, Camici P, Chester M et al. The problem of chronic refractory angina. Eur Heart J 2002;23:355–70.

4. Wright C, Towlerton G, Fox K. Optimal treatment for complex coronary disease and refractory angina. Br J Cardiol 2006;13:306–08.

5. Chaitman BR, Pepine CJ, Parker JO et al. Combination assessment of ranolazine in stable angina (CARISA): effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina. JAMA 2004;291:309–16.

6. The Angina Plan. Available from: www.anginaplan.org.uk

Mortality and catheter ablation of atrial fibrillation

Br J Cardiol 2010;17:161-2 Leave a comment
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The prevalence of atrial fibrillation (AF) in the UK alone is estimated to be 1% of the population (approximately 610,000) and rises with age from 1.5% in people in their 60s to more than 10% in those over 90 years old. It is also more common in males than females. Because prevalence increases with age, it is expected to increase over time as the proportion of people aged 65 and over is projected to increase from 16% of the UK population in 2006 to 22% by 2030.1 AF is the most common supraventricular arrhythmia; it is predicted that catheter ablation (CA) as a management strategy will be one of the most commonly performed electrophysiological procedures in the next decade.

Over recent years data have accumulated suggesting that sinus rhythm (SR) is associated with increased survival.2 Whether this association of SR with improved survival is actually a causal relationship is yet to be proven. CA has proven to be an effective curative treatment particularly when used for paroxysmal AF.3 

The risks of catheter ablation

161-img-1The aim of CA, essentially, is to manipulate catheters around the left atrium and cauterise the sources of AF without causing unnecessary damage, a skill that is technically challenging. This requires aggressive anticoagulation, and can be a time-consuming procedure.

Long-term arrhythmia control or cure rates are quoted in excess of 80%, with data from single large-volume centres reporting low complication rates. Whether experience and high volume are associated with a reduction in complication rates is not proven.

Cappato et al.4 recently reported an analysis of a retrospective case series looking at the incidence and cause of peri-procedural death occurring in patients undergoing CA of AF between 1995 and 2006. Out of 546 identified centres worldwide, 262 reported data on safety. A total of 32,569 patients underwent 45,115 procedures with 32 deaths reported (0.98 per 1,000 patients) – 13 of which were intra-operative deaths, another 12 patients died within a month of the index procedure and seven patients after excess of a month. Tamponade was the most common complication but was rarely associated with permanent disability or death.

The authors themselves list the limitations of the study:

  • Volunteer-based retrospective analyses may underestimate true prevalence and under report complication rates.
  • They omit details regarding the questionnaire structure.
  • Relevant medical data surrounding the fatalities, e.g. identifiable precipitants or predictors related to basal clinical status, as well as the type and duration of AF ablated and its relation to morbidity and mortality in the study, are lacking.
  • Although it would prove most useful, the authors were unable to make a comparison with their initial survey to determine whether the risks of AF ablation had changed over time.5 The initial survey sample was considerably smaller and included patients with currently outdated ablation strategies.

Mortality was not decreased in relation to centre experience and volume (35% of centres included in the survey performed less than 20 procedures per year). It may be that this was attributable to the small number of deaths or under reporting.

Mortality was independent of catheter types used, i.e. 4 mm tip catheter versus irrigated tip catheter, and the success rates or complication rates of the centres reporting deaths.

These data highlight that, although rare, deaths are associated with AF ablation procedures and operators should be formally trained to complete all aspects of the procedure, including trans-septal puncture, and be capable of emergency pericardial aspiration. The need for surgical cover for these procedures remains controversial, although anecdotal evidence suggests that, rarely, patients’ lives are saved by early surgical intervention for cardiac perforation.

In data from our own centre at St Bartholomew’s Hospital in London, we report data of 285 patients undergoing wide area circumferential ablation (WACA) (530 procedures) in a prospective database of consecutive cases initiated in 2002 through 2007. No deaths directly resulting from the procedure were reported; the authors concluding that catheter ablation of AF is safe with no late adverse sequelae. In addition, they comment on its efficacy for relief of symptoms and that cure from AF in the majority, for paroxysmal and persistent AF was achieved, with late recurrence being uncommon.6 We have, however, as with the worldwide trend, experienced an exponential increase in the number of AF ablations performed, and, subsequent to the collection of data for this audit, reported three peri-procedural deaths. One of these was intra-operatively in an elderly female related to cardiac perforation, tamponade and retroperitoneal haematoma, the other in a patient sustaining a cerebellar infarct who, thereafter, developed a myocardial infarction secondary to late stent thrombosis on the evening post-ablation, and lastly a man with longstanding ischaemic heart disease who sustained a myocardial infarction six weeks after his procedure.

Though appearing intuitive and predictable that ablation to SR should be associated with a reduction in mortality, it is pertinent to remember that those who have theoretically the most to benefit, e.g. patients in persistent AF or with associated left ventricular dysfunction and heart failure, are the very patients at highest risk for an ablation procedure.

Does catheter ablation reduce morbidity?

There is unquestionably both morbidity and mortality associated with AF ablation as there is with AF itself. Ongoing randomised trials will conclusively answer whether this is offset by mortality/morbidity benefits associated with attaining and maintaining SR. Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation (CABANA), a phase III pilot trial is designed to test the hypothesis that the treatment strategy of percutaneous left atrial CA for the purpose of the elimination of AF is superior to current state-of-the-art therapy with either rate-control or anti-arrhythmic drugs for reducing total mortality (primary end point), and decreasing the composite end point of total mortality, disabling stroke, serious bleeding and cardiac arrest (secondary end point) in patients with untreated or incompletely treated AF warranting therapy.

Therefore, based on the available evidence CA of AF cannot be considered prognostically beneficial and cannot be advocated for minimally or asymptomatic individuals.

Conflict of interest

RJS is a member of the Scientific Advisory Board for Biosense Webster and on the speakers’ bureau for Endocardial Solutions, from whom he has also received speakers’ honoraria. RJS and RG have received travel grants from Guidant, Medtronic, St Jude Medical, Endocardial Solutions and Biosense Webster.

References

1. Department of Health. National Service Framework for Coronary Heart Disease. Chapter 8: arrhythmias and SCD. London: DoH, March 2005.

2. Nademanee K, Schwab MC, Kosar EM et al. Clinical outcomes of catheter substrate ablation for high-risk patients with atrial fibrillation. J Am Coll Cardiol 2008;51:843–9.

3. Pappone C, Rosanio S, Augello G et al. Mortality, morbidity and quality of life after circumferential pulmonary vein ablation for atrial fibrillation: outcomes from a controlled non-randomized long-term study. J Am Coll Cardiol 2003;42:185–97.

4. Cappato R, Calkins H, Chen SA et al. Prevalences and causes of fatal outcome in catheter ablation of atrial fibrillation. J Am Coll Cardiol 2009;19:1798–802.

5. Cappato R, Calkins H, Chen SA et al. Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circulation 2005;111:1100–05.

6. Hunter RJ, Berriman TJ, Diab l et al. Long-term efficacy of catheter ablation for atrial fibrillation: impact of additional targeting of fractionated electrograms. Heart 2010 online.

Report from the 20th Scientific Meeting of the European Society of Hypertension, Oslo, Norway

Br J Cardiol 2010;17:168-170 Leave a comment
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Renal denervation (RDN) revisited

A novel, catheter-based technique is looking promising for the treatment of refractory hypertension. Renal sympathetic hyperactivity is associated with the development of hypertension and its progression, as well as chronic kidney disease (CKD) and heart failure. While sympathectomy procedures have been considered over the past 50 or more years, it is now possible, using a steerable femoral 6F catheter with an RF energy electrode tip, to deliver a series of 2 minute ablations to the renal artery, causing renal denervation (RDN) and blood pressure reduction.

168-img-1An initial proof of principle study was reported in The Lancet (Krum H et al. Lancet 2009;373:1275–81) by Dr Henry Krum (Monash University, Melbourne, Australia) and co-investigators who, using the newly developed Symplicity® catheter system, performed RDN in 45 patients with resistant hypertension (systolic blood pressure [SBP] ≥160 mmHg on three antihypertensive agents); the procedure lasting a median of 38 minutes. The primary end points were office blood pressure (BP) and safety data at one, three, six, nine and 12 months, and patient’s renal angiography and magnetic resonance angiography during follow-up. BP was significantly reduced by, -14/-10, -21/-10, -22/-11, -24/-11 and -27/-17 mmHg at these pre-specified time points compared with five non-treated patients who had elevations in BP. Renal function (estimated glomerular filtration rate [GFR] and creatinine) was sustained and there were no renovascular complications. One intraprocedural renal artery dissection occurred before the ablation without sequelae.

The same team reported the two-year ‘durability’ of BP reduction among the cohort after RDN, during the ESH Congress. In all, 117 patients were treated at 17 centres. BPs were reduced by -20/-11, -24/-10, -24/-12, -25/-12, -29/-17 and -33/-14 mmHg at, one, three, six, 12, 18 and 24 months respectively. One patient required renal artery stenting for a lesion present at baseline, otherwise there were no adverse late events. Catheter-based RDN therefore appears to produce substantial reduction in BP sustained to at least two years and changes in eGFR “are better than the natural history reported in similar patients” say the authors. UK workers, notably at Barts & the London Hospital, are involved in further assessment of RDN as a treatment for resistant hypertension.

ROADMAP: olmesartan delays progression to microalbuminuria in type 2 diabetes

Can the presence of microalbuminuria act as a sensitive surrogate end point to identify early stages of preventable disease? This was the question posed by the ROADMAP study, which was presented at the meeting.

Explaining the rationale for the trial, the study’s lead investigator Dr Hermann Haller (Hannover Medical School, Hannover, Germany) said: “We are treating our patients too late and every diagnostic criteria we have to be able to treat early is important”. He called microalbuminuria an early window into a person’s vasculature: “Microalbuminuria is very strongly associated with future cardiovascular events and it is relatively easy to measure,” he added, saying he thought that of all the measurements for organ damage, microalbuminuria should, at the moment, be “number one”.

ROADMAP (Randomised Olmesartan and Diabetes Microalbuminuria Prevention) was set up to determine whether the angiotensin receptor blocker (ARB), olmesartan, could delay the onset of microalbuminuria in normoalbuminuric patients with type 2 diabetes and at least one additional cardiovascular risk factor, who had not received an ACE inhibitor or an ARB within the last six months.

The double-blind, randomised, controlled study was carried out in 262 centres in 19 European countries. Some 4,447 patients (mean age 57.7 +/- 8.72 years, mean systolic blood pressure 136 +/- 15 mmHg, mean diastolic blood pressure 81 +/- 10 mmHg) with type 2 diabetes (mean duration 6.1 +/- 6.0 years, BMI 31.0 +/- 14.91 kg/m2, HbA1c 7.65 +/- 1.62%) were randomised to either treatment with olmesartan 40 mg (n = 2,232) or placebo (n=2,215).

To reach the target blood pressure of < 130/80 mmHg, other antihypertensive agents were used with the exception of drugs affecting the renin-angiotensin- system. Follow-up was for 3.2 years and urinary albumin to creatinine ratio (UACR) was determined every six months. The primary end point was time to onset of microalbuminuria and secondary end points were cardiovascular and renal morbidity and mortality.

Results showed that patients in the olmesartan group had a significant 23% risk reduction (p= 0.01) in time to onset of microalbuminuria, the study’s primary end point (table 1). Blood pressure was very well controlled in the study with more than 75% of all patients achieving the blood pressure target of < 130/80 mmHg.

Table 1. ROADMAP: primary end point result
Table 1. ROADMAP: primary end point result

Safety

Results for secondary end points in the hypertensive sub population are summarised in table 2. Although results for the secondary end points were similar between the two groups, there was an increase in the numbers of cardiovascular deaths in the olmesartan group compared to the placebo group. This was also seen in the total study population where there were 15 cardiovascular deaths in the olmesartan group compared to three in the placebo group. Dr Haller maintained these numbers were low and not a cause for concern. He said analysis of the data had shown the higher cardiovascular mortality occurred only in those patients with existing cardiovascular disease and a low systolic blood pressure (i.e. < 120/mmHg). “This fits very nicely with the recommendations of the European guidelines that target blood pressure in patients with cardiovascular disease should be between systolic 130 and 140 mmHg,” he said.

He added that predictors for a better response to treatment with olmesartan were those with a higher baseline systolic blood pressure (>135 mmHg), a high UACR (> 4 mg/g), a low HbA1c (< 7.3%) and a low estimated glomerular filtration rate of 83.79. The majority of the effect on microalbuminuria appeared to be blood pressure independent.

Table 2. ROADMAP: secondary end point in the hypertensive subpopulation
Table 2. ROADMAP: secondary end point in the hypertensive subpopulation

Atrial fibrillation and hypertension

“Hypertension is the most prevalent risk factor leading to the development of atrial fibrillation (AF), the most common arrhythmia,” according to Dr I Grundvold (University of Oslo, Norway). In the ATHENA study with dronederone, for example, 86% of patients had hypertension. It is assumed that this risk increases with increasing blood pressure (BP) levels, but it is not known at which level systolic BP imposes a risk for AF.

He presented data from 2,014 apparently healthy men aged 45–59 years who were included in the Oslo Ischemia Study, between 1972–75 and who were followed for 35 years. By this time some 272 men (14% of total) had a diagnosis of AF. The adjusted risk of developing AF was increased by 63% for study participants with baseline BP >128 mmHg (p=0.0003) compared to participants with systolic BP <128 mmHg. This, therefore, represented a “strong, independent long-term predictor of AF” according to these investigators.

Salt controversy, the spice of life

High blood pressure is “the biggest cause of death in the world… and we must do something about it”, said Professor Graham MacGregor (Wolfson Institute of Preventive Medicine, Barts & The London School of Medicine and Dentistry, London).

A well-known advocate for dietary salt restriction, he said that the problem is predominantly one of salt intake, 80% of which is “hidden” in foods. Less is now used for food preservation, with the exception of anchovies and smoked salmon. Salt is also used as a binding agent, to hold water in meat and thus increase its weight and sales price. Similarly, salt is used to make “inedible things edible” and it is, of course, a major driver of thirst, leading to increases in soft sugar-containing drinks, to which children become addicted, leading to weight gain.

The goals in Professor MacGregors view are to get the UK population blood pressure down and to treat those with high blood pressure. He believes the adverse effects of dietary salt are overwhelming and we need to halve our intake to 4 g a day. This is “the most efficient and cheapest thing you can do for public health” he said.

The pressure group, Consensus Action on Salt and Health (CASH; www.actiononsalt.org.uk) for which he is Chairman, has been very successful in influencing the UK Department of Health and the Food Standards Agency in changing policy, and gaining public advocacy and support to bring pressure to bear on the food industry to reduce added salt levels. It issues a press release every six weeks. “The public in the UK know that salt is dangerous but they don’t know what to do about it,” he said. He is pleased with progress and major food manufacturers in the UK have been gradually reducing salt in their products at a rate of about 10–20% per year without rejection or public outcry. He believes that a 6 g a day salt target will be reached in the UK in the next four years.

This is in harmony with the recently launched UK National Institute for Health and Clinical Excellence (NICE) public health guidance on prevention of cardiovascular disease which recommends reducing mean salt intakes by 3 g a day for adults (to achieve a target of 6 g a day) and which would, in the UK, lead to around 14–20,000 fewer annual cardiovascular deaths each year (see page 163).

Professor MacGregor, with help from World Health Organisation, is rolling his message out worldwide. (See review; He FJ, MacGregor GA. Reducing population salt intake worldwide; from evidence to implementation. Prog Cardiovasc Dis 2010;52:363–82.
[www.onlinepcd.com]).

Leg over and blood pressure

170-img-1Crossing your leg over may not be good for your blood pressure! A team from Radboud University Medical Centre, Nijmegen, The Netherlands, has shown, in a study of 25 subjects, that the mere act of crossing their ankle over their knee, in the sitting position, caused considerable haemodynamic changes. For example, compared to the ‘uncrossed position’, blood pressure rose +11.4/+3.8 mmHg, mean arterial pressure (MAP) rose 7.0 mmHg and heart rate by 1.7 beats per minute. There were also increases in cardiac output and stroke volume. The authors recommend that all those who measure blood pressure should be aware of these effects and patients advised to keep their feet on the floor during measurements. They also suggest that, “the position of the legs should be mentioned in all guidelines and publications regarding blood pressure”.

Hypertension trial round up

TALENT

It is important to achieve blood pressure control quickly. But is it more beneficial to start with combination antihypertensive therapy than to start with monotherapy and then add another drug, i.e. stepped care? This was the key question addressed in the TALENT study (a multicentre study evaluating Efficacy of Nifedipine GITS-Telmisartan Combination in blood pressure control and beyond:Comparison of two strategies).

The study recruited 405 high risk hypertensive patients in 40 centres in Spain and Italy. “The primary end point of TALENT, to assess 24-hour mean systolic blood pressure by ambulatory blood pressure monitoring (ABPM) after 16 weeks compared with baseline, was met,” according to Professor Luis Ruilope, Octuber Hospital, Madrid, Spain.

After eight weeks of treatment, the combination of nifedipine GITS 20 mg/telmisartan 80 mg reduced office blood pressure from a baseline of 153/90 mmHg to 138/83 mmHg, with a blood pressure-lowering effect evident at two weeks. The effect was achieved earlier than with monotherapy and the addition of another drug after eight weeks, leading Professor Ruilope to conclude that the message from this is: “don’t be afraid to use two drugs up front”.

ESPORT

Professor Gulianno Tocci (Rome, Italy) presented findings for a team of Italian and French investigators, looking at the efficacy and safety of olmesartan versus ramipril in 351 elderly hypertensive patients. The eight-week active treatment phase showed that olmesartan provided greater blood pressure normalisation compared to ramipril, and that this ARB should be considered a good first-line treatment in these patients. Similar findings were shown in the larger ESPORT study of 1,320 patients.

Commenting on the initial study, Professor Gordon McInnes (Glasgow) suggested that the findings may be explained by using ramipril as a comparator, which he believes is a less effective drug, which should be taken twice a day rather than once daily.

TEAMSTA

Professor M Volpe (Rome) presented the TEAMSTA study results. This looked at the combination of telmisartan 80 mg/amlodipine 10 mg versus their single components in over 800 patients with severe hypertension (blood pressure ≥180/95 mmHg). Again the combination was superior to monotherapies and 80% of the effect was seen early in the eight-week active treatment phase.

Antihypertensive combinations

In a review of which antihypertensive combination to use (ACE inhibitors or angiotensin receptor blockers with calcium channel blockers, when treating hypertension, Professor McInnes reminded delegates of the adage, “it’s the blood pressure, stupid” and he suggested we avoid “woolly thinking”.

Antihypertensives were probably much the same, he said, and what is most important is to use agents, which provide efficacious and sustained reduction of blood pressure.

In a discussion session, mention was made of a recent meta-analysis, which purported to show an increase in cancer in patients taking angiotensin receptor blockers. The view from Oslo was that this represented ‘junk science’ and looked selectively at data, out of context, and that it should be dismissed.

SHARE

Failure to reach blood pressure targets is often blamed on poor patient compliance with antihypertensive medication but it now seems that physician inertia must also be overcome.

Results from the SHARE (New Supporting Hypertension Awareness and Research Europe-wide) study showed that in a survey of 2,629 physicians in Europe, most (76%) felt the European Society of Hypertension guidelines blood pressure targets of 140/90 mmHg were ‘about right’. But the study highlighted the mean blood pressure that physicians became ‘concerned with’ was 149/92 mmHg and most physicians (78% and 61%, respectively) would not consider taking any action in general hypertensive patients until systolic and diastolic blood pressures were above 140 and 90 mmHg, respectively. Some (50%) would not take any action until blood pressure was higher than 168/100 mmHg.

The results also showed that physicians underestimate the number of challenging patients they treat. Challenging patients were defined as those not reaching a blood pressure goal of <140/90 mmHg – physicians estimated 34% of their patients were not at goal, while in reality, this number was 47%.

New NICE guidance on prevention of cardiovascular disease at the population level 

Br J Cardiol 2010;17:163-5 Leave a comment
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The National Institute for Health and Clinical Excellence (NICE) has published a new guidance on prevention of cardiovascular disease at the population level.

The guidance sets out a range of evidence-based recommendations for effective action to help reduce cardiovascular disease and make it easier to enable individuals to make healthy choices. It focuses mainly on food production and its influence on the nation’s diet, and it aims to change the cardiovascular risk factors faced by the UK population through regulation, legislation, subsidy and taxation or by rearranging the physical layout of communities.

Dr Simon Capewell (University of Liverpool, UK) who is also vice-chair of the NICE Guidance Development Group, said: “There was a feeling that dietary interventions have been largely neglected, yet have a big potential to deliver CVD benefits. The guidance shows how by introducing simple changes at the population level, huge gains could be made in reducing the death toll from cardiovascular disease. This is no longer an optional discussion, but an issue that governments and the rest of society have to confront.” He added: “The idea is to kick-start a debate, and persuade politicians to set both short-term and long-term goals for change”.

Key goals in the NICE document include:

Reducing mean salt intakes to achieve a target of 6 g per day per adult by 2015 and 3 g by 2025, which would lead to around
14–20,000 fewer annual deaths from cardiovascular disease each year.  Reducing salt added during the manufacturing process is considered especially important since this is estimated to represent 70 to 90% of the population’s total salt intake.

  • Reducing saturated fat intakes from 14% to 7% of energy intake (to reach the levels seen in Japan), which could prevent up to 30,000 cardiovascular deaths annually.
  • Banning the use of trans fats, which could save 4,500–7000 lives each year.
  • Restrictions on advertising for foods high in saturated fats, salt
    and sugar.
  • Making healthy food alternatives cheaper than junk food.
  • More extensive use of the traffic light food labelling systems, which indicates whether food or drink contains a high, medium or low level of salt, fat or sugar.
  • Giving local authorities powers to limit fast food outlets.
  • Ensuring young people under 16 are protected from all forms of marketing, advertising and promotions which encourage an unhealthy diet.
  • Ensure government funding supports physically active modes of travel.

The European Society of Cardiology says the new guidance “delivers important messages for the rest of Europe”. ESC spokesman Dr Lars Rydén (Karolinska Institute, Sweden) added: “This is an extremely strong document that clearly underlines how much can be gained from society by introducing legislative changes protecting the content of diets.”

The full NICE guidance can be found at: http://guidance.nice.org.uk/PH25

Testosterone trial stopped due to cardiovascular events 

Br J Cardiol 2010;17:163-5 Leave a comment
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A trial testing testosterone gel in older men with mobility limitations has been stopped early because of an increased risk of cardiovascular events in the treated group.

The trial, supported by the US National Institute on Aging, was being conducted to investigate whether testosterone treatment would increase muscle mass and strength in older men with limited mobility.

In the trial, 209 men were randomly assigned to receive 10 g of a transdermal gel, containing either placebo or 100 mg of testosterone, to be applied to the skin once daily for six months. The men in the trial were an average 74 years old and had high rates of chronic diseases such as diabetes and cardiovascular disease.

The trial was stopped after a review by the study’s data and safety monitoring board, which found that 23 of the 106 men who had received testosterone experienced adverse cardiovascular-related events during the study, compared with five of the 103 men who received placebo. In addition, seven men in the testosterone group and one in the placebo group had atherosclerosis-related events. The cardiovascular-related events included myocardial infarction (MI), arrhythmias, hypertension, and one death from a suspected MI. The testosterone group did show significantly greater improvements in muscle strength.

Reporting the findings in a paper published online on June 30, 2010, in The New England Journal of Medicine, the trial investigators say that chance may have played a role in the outcomes observed and that the diversity of the adverse cardiac events that were seen makes them less easily explained by a single mechanistic explanation. They also caution against extrapolating the findings to other doses and formulations of testosterone or to other populations, particularly young men who have hypogonadism, without cardiovascular disease or limitations in mobility.

Apixaban beneficial in atrial fibrillation 

Br J Cardiol 2010;17:163-5 Leave a comment
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A study of a new drug for atrial fibrillation, apixaban (Pfizer/Bristol-Myers Squibb), has been stopped early because of benefit.

The trial was stopped after a predefined interim analysis by the independent data monitoring committee “revealed clear evidence of a clinically important reduction in stroke and systemic embolism”, a company statement announced.

The AVERROES (Apixaban Versus Acetylsalicylic Acid to Prevent Strokes) study included 5,600 patients with all types of atrial fibrillation who were intolerant of or unsuitable for warfarin. They were randomised to 5 mg of apixaban or 81–324 mg of aspirin for up to 36 months.

The primary efficacy outcome is the time from the first dose of the study drug to the first occurrence of ischaemic stroke, haemorrhagic stroke, or systemic embolism. The secondary efficacy outcome includes the time to the first occurrence of ischaemic stroke, haemorrhagic stroke, systemic embolism, myocardial infarction, or vascular death.

Full results from the AVERROES study will be presented at the European Society of Cardiology 2010 Congress in Stockholm, Sweden.

Eplerenone beneficial in mild heart failure 

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Another trial stopped early because of benefit is EMPHASIS-HF (Eplerenone in Mild Patients Hospitalisation And SurvIval Study in Heart Failure) which looked at the aldosterone inhibitor, eplerenone, in mild heart-failure patients.

According to Pfizer, an interim analysis of the trial showed that patients treated with eplerenone in addition to current standard of care experienced a significant reduction in risk of cardiovascular death or heart failure hospitalisation compared with those in the placebo arm of the trial. 

The company says it is now working to ensure that all patients are informed of this decision, and an amendment to the protocol will be requested to allow all consenting patients to start treatment with eplerenone in an open-label extension of the study, after completing a close-out visit ending the double-blind, placebo-controlled phase. 

Eplerenone is currently approved for hypertension and for use in addition to optimal medical therapy early after acute myocardial infarction in patients with congestive heart failure.

The routine use of oxygen in the treatment of myocardial infarction (MI) patients is questioned in a new analysis in the Cochrane Database of Systematic Reviews. 

The authors, led by Dr Juan Cabello (Hospital General Universitario de Alicante, Spain) and Professor Tom Quinn (University of Surrey, Guildford) say there is no conclusive evidence from randomised controlled trials to support the routine use of inhaled oxygen in patients with acute MI, and the available clinical trial data suggest that oxygen might actually be harmful. 

A definitive randomised controlled trial is urgently required given the mismatch between trial evidence suggestive of possible harm from routine oxygen use and recommendations for its use in clinical practice guidelines, they add. 

For the review, published on June 16, 2010, the authors pooled the results of three randomised trials involving 387 MI patients. Results showed that oxygen use was associated with a relative risk of death of 2.88 in an intention-to-treat analysis and 3.03 in patients with confirmed MI. While suggestive of harm, the small number of deaths (14) meant that this could be a chance occurrence, they point out. 

They note that as long ago as 1950, it was demonstrated that the administration of pure oxygen not only failed to reduce the duration of angina pain but also prolonged the electrocardiographic changes indicative of an MI, adding that: “It is surprising that a definitive study to rule out the possibility that oxygen may do more harm than good has not been done”. 

Treat individual risk factors not ‘metabolic syndrome’ 

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A new study suggests that patients with metabolic syndrome are no more at risk of future myocardial infarction (MI) than those with diabetes or hypertension alone, and that doctors should focus on treating individual risk factors.

The study, published in the May 25, 2010 issue of the Journal of the American College of Cardiology, analysed data from the INTERHEART study, a case control study of incident acute MI, to investigate whether the risk of MI associated with the metabolic syndrome is greater than that conferred by its constituent components (such as abdominal obesity, elevated glucose, abnormal lipids, and elevated blood pressure).Results showed that metabolic syndrome was associated with a two- to three-times increased risk of MI, but the same risk was conferred by having either hypertension or diabetes alone. 

The authors explain that supporters of the metabolic syndrome concept believe that when the component risk factors occur together this would have an additive or greater effect on risk. They add that their results do not support this idea, and therefore adds to the evidence that a diagnosis of metabolic syndrome is not useful.

The British Valve Group – a new special interest group

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The influence and importance of valve disease is increasing and yet the subject remains under-represented. There is, for example, no group affiliated to the British Cardiovascular Society and no National Services Framework on valve disease. A number of interested individuals have recently convened to discuss the formation of a specialist group suggesting it could issue comments on topical issues, plan collaborative research and organise study days. The group will bring together all disciplines interested in valve disease and will be concerned with wider issues like variations in care as well as those more immediately related to clinical practice.

Its first study day will be held on 25 October 2010 at the Royal Society of Medicine in London. Topics will include: the epidemiology, health economics, bioengineering, biology and genetics of valve disease; temporal and regional variations in valve surgery; advances in techniques of repair; exercise-testing, the use of neurohormones, and risk-stratification for valve surgery; the case for specialist clinics and for screening. The day will appeal to all interested in valve disease including cardiologists and surgeons, nurses and sonographers, anatomists, bioengineers and geneticists and epidemiologists. The group welcomes registrants (Becky West on [email protected]) and also expressions of interest ([email protected]).

Lp(a) screening recommended by European Atherosclerosis Society 

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Patients at moderate to high risk of cardiovascular disease should be screened for elevated Lp(a) and take niacin to lower levels to under 50 mg/dL (1.3 mmol/L), according to a consensus statement from the European Atherosclerosis Society (EAS).

A preview of the EAS statement was announced during the EAS 2010 Congress held in June in Hamburg, Germany, by Dr Børge Nordestgaard (University of Copenhagen, Denmark). He said bringing a patient’s Lp(a) level under 50 mg/dL should be a treatment priority, after the management of LDL cholesterol.

It is thought that about 20% of people have plasma Lp(a) levels over
50 mg/dL, with no gender differences, but there are some racial differences, with whites and Asians having lower levels while black and Hispanics generally have somewhat higher levels.

Since lifestyle appears to have little impact on Lp(a) level, the EAS recommends that 1 to 3 g of niacin daily is the best treatment. But it notes that further studies are needed in both primary- and secondary-prevention settings to better define which patients should be targeted for treatment and what the target level of Lp(a) should be.