Pritor^®/Kinzal^® - News & Views from Warsaw

It was Warsaw, Poland, known among other things for its world famous citizens Frédéric Chopin and Marie Skłodowska Curie, that welcomed on Saturday April 2nd the 7th edition of Bayer HealthCare Pritor^®/Kinzal^® (telmisartan) Stand Alone Symposium. Under the umbrella of the International Cardiovascular and Metabolic Academy (ICMA), close to 500 physicians, predominantly cardiologists and primary care physicians, joined this year’s meeting entitled “Novel Perspectives and Insights into Hypertension Treatment.” Leading international experts in the field of hypertension, cardiology and diabetes provided the audience with a variety of close to practice topics, but also placed emphasis on the importance of early and appropriate treatment of the number one killer worldwide, hypertension. Against the background of the label extension in 2009, the first half of lectures focused on the benefits of ARBs, and in particular Pritor^®/Kinzal^®, in the management of the hypertensive patient with Type 2 diabetes. During the second half, participants gathered more evidence on the need of early attainment of blood pressure (BP) control. One possible way to reach this objective is to combine therapies from different drug classes rather than simply doubling the doses of existing drugs. As the future cannot exist without the past, the final lecture was dedicated to a historical overview and an outlook to the future challenges of hypertension treatment.

In his opening, the meeting Co-Chairman, Zbigniew Gaciong (Warsaw, Poland), placed the meeting straight away in a perspective of global medical importance. Gaciong recalled data from a recently published WHO report on global health risk that show hypertension being the number one risk factor for premature death. Despite the available evidence today and the many different drug classes that have been developed, there is still a great proportion of hypertensive patients, with or without concomitant risk factors, in whom BP is not controlled yet.

“Hypertension along with other risk factors, of which most can be prevented, accounts actually for 61% of premature mortality due to cardiovascular diseases.”

Henry Elliott (Glasgow, UK) discussed the evidence and basic cardiovascular (CV) credentials of angiotensin receptor blockers (ARB) and of telmisartan in particular. However, how to differentiate among ARBs to determine which ARB provides in clinical practice most benefits and that for the broadest possible range of patients? As a starting credential in favour of telmisartan’s antihypertensive profile, Elliott showed that among ARBs, telmisartan has the longest half-life (24-hours), the longest dissociation half-life and provides the greatest BP reductions. Under the umbrella of the PROTECTION Trial program telmisartan has also shown to provide CV benefits beyond its BP reducing efficacy. The ONTARGET Trial Program, which to date is the world’s largest morbidity and mortality trial with an ARB, demonstrated that telmisartan provides the same level of CV protection as the current ‘gold standard’ ramipril for blockade of the Rennin Angiotensin Aldosteron System (RAAS) in high-risk CV patients, but relative to ramipril, telmisartan showed a superior, overall efficacy/tolerability ratio. This, added Elliott, has clear implications for compliance with treatment and, ultimately, for treatment effectiveness. On the basis of this outcome evidence, the existing label of telmisartan for the treatment of essential hypertension has been extended in October 2009 to become the first and only ARB with a broad indication specifically licensed for use in high-risk patients.

“Although there is a basic similarity between ARBs, some of them look a bit more attractive than others because of the available evidence allowing us to make an informed decision as to which is good, better or best”

José Ramón González-Juanatey (Santiago de Compostela, Spain) reminded the audience of the key role that hypertension plays in the development and progression across the CV and renal continuum. Therefore, he stressed, it is crucial to early detect and treat hypertension and that at any time and throughout the cardiovascular continuum. The pathogenic effect of hypertension is influenced by other risk factors, many of which are of metabolic origin. In this context Juanatey recalled the unique pharmacological properties and clinical benefits of telmisartan, alone or in combination with hydrochlorothiazide, as has been demonstrated in the PROTECTION Trial program. In clinical practice, an ARB/diuretic combination as initial therapy is clearly preferred for the vast majority of patients; in particular for those patients with a salt/volume related hypertension, with obesity, type 2 diabetes and/or a metabolic syndrome. Juanatey concluded that in order to reduce the risk of a recurrent CV event in clinical practice a potent antihypertensive drug that offers cardiovascular protection, such as telmisartan, should be considered in the treatment regimen of high-risk patients.

“It is vital to early detect and properly treat hypertension at any stage of the cardiovascular continuum to effectively reduce cardiovascular and cerebrovascular morbidity”

For many years insulin resistance was believed to constitute the major link between hypertension and diabetes. From a dialectologist viewpoint, Antonio Ceriello (Barcelona, Spain), proposed the audience a more modern and “pathophysiologically evidence based” approach, with a special focus on the role of endothelial function. Endothelial dysfunction is now recognized to consistently contribute to the development of diabetes and CV complications. In addition it can also favour the appearance of hypertension. As for the management of hypertension, Ceriello stressed that, early and rigorous glycemic control in both type 1 and 2 diabetic patients is crucial to avoid CV complications. The reason to start treatment as early as possible is based on a relatively new concept, known in diabetology as the “metabolic memory.” This means that even after normalization of glycemia, endothelial function can at best improve, but some dysfunction will usually persist. Ceriello concluded that these findings are of high clinical relevance for diabetic patients as they reflect that the metabolic memory can be switched off leading to a normalization of their endothelial function.

“Due to its anti-oxidant properties, telmisartan is able to switch off the metabolic memory in diabetic patients”

Prevention of diabetes represents an important therapeutic goal in current cardiovascular risk reduction strategies. Blockade of the RAAS, either by ACEIs or ARBs, has been shown in large clinical trials to markedly reduce the incidence of new-onset diabetes (NOD) in different patient populations. Ulrich Kintscher (Berlin, Germany), recalled the outcomes of the subgroup analyses of diabetic patients in the HOPE study which showed an antidiabetogenic action of the ACE inhibitor ramipril on CV events. However, until recently there was only limited evidence for diabetic patients treated with an ARB and as to whether an ARB could provide the same effect as an ACE inhibitor in diabetic patients. The recent results from the ONTARGET Trial demonstrated that telmisartan was as effective as the ACE inhibitor ramipril in reducing NOD. Kintscher also explained the “ticking-clock-hypothesis” which means that in the pre-diabetic state, before the clinical diagnosis of diabetes has been established, macrovascular disease or cardiovascular damage is already occurring. Kintscher concluded that to obtain long-term cardiovascular risk reduction RAAS blockade should be considered for the prevention of NOD.

“In contrast to other ARBs, telmisartan has a specific mode of action by bimodally acting on the AT1 and PPAR-γ receptors. This provides beneficial effects on the diabetic continuum with protective effects against macrovascular end organ damage.”

From a primary care viewpoint Carlos Brotons (Barcelona, Spain) shared with the audience personal research data on hypertension and associated risk factors. He pointed out that despite the improvement of hypertension management over the past decade, still a huge proportion of hypertensive patients remains uncontrolled (>140/90 mmHg). From his own research Brotons showed data on file of the EUROPREVIEW SURVEY that examined self-reported hypertension in 7947 patients from 22 European countries. Preliminary data show that on average 30% of patients reported to be aware of having hypertension and most patients considered that hypertension is an important issue for their health. He also noticed that the increased use of combination therapy over the last decade can probably explain the increase in control rates. Brotons laid emphasis on the usefulness of risk assessment tools, such as the HeartScore, for daily practice. As the key issues in the management of hypertensive patients in general practice Brotons concluded that physicians should aim to not only focus on hypertension, but also to assess and manage all CV risk factors.

“Patients’ compliance is one of the major issues we have to consider and we have to deal with in daily clinical practice”

Roland Asmar (Paris, France), illustrated that the BP goal of <140/90 mmHg can be reached in approximately 70% of patients when using a mean of 2.7 drugs as combination therapy. The use of fixed dose (or single pill) combinations should be preferred over free drug combinations, as they might lead to a simplification of treatment and consequent compliance to treatment. He also demonstrated that irrespective of the drug class used, adding a drug from another class is 3 to 4 times more effective in reducing BP than just doubling the dose of the existing drug. Asmar also stressed the importance of early initiation of BP-lowering treatments before the onset of target organ damage and the occurrence of CV events. Asmar explained that the incidence of drug related side effects of combination therapy is lower than the sum of symptoms induced by the individual drugs. Whether all combination therapies with diuretics and calcium channel blockers are equipotent remains to be demonstrated in a head-to-head comparison trial, Asmar concluded.

“The rationale behind combination therapy “higher efficacy, less side-effects” is true”

Giuseppe Mancia, (Monza, Milan, Italy) recalled the history of antihypertensive treatment and gave an outlook to the future challenges in the treatment of hypertension. The concept that hypertension is a risk factor and that antihypertsensive treatment is beneficial goes back to only a few decades. With the Framingham Heart Study it became obvious that hypertension leads to increased risk of CV events when compared to normotensive patients. Over the last 20 years, a huge amount of knowledge has been gathered and in particular with regard to the beneficial effects of adding treatments for other pathologies, such as statins and antiplatelet agents, to antihypertensive treatment. Another concept that became clear over the last years is that blood pressure, by any means, has to be lowered per se in order to protect against CV events. With regard to the future Mancia raised a number of issues that should be considered properly for investigation. He also stressed that treatment should be initiated before or latest at the beginning of organ damage. Mancia concluded by emphasizing that to optimize treatment of hypertension and to increase patients’ compliance, drugs with a favorable safety profile, such as ARBs should be preferred and if possible be prescribed as combination therapy.

“Blood pressure control, even beyond research, is probably the most important unmet medical need we have in hypertension”