Hypertension Management – Towards Individualisation of Therapy and hypertension in the elderly.2 The reappraisal also discusses
the blood pressure goals and the evidence available for defining lower BP targets of antihypertensive treatment in some groups of patients, for example in diabetics and in patients with a history of cardiovascular disease.
Interestingly, a critical analysis of clinical trials revealed that the evidence in favour of a recommendation to initiate antihypertensive therapy in patients with a low or moderate cardiovascular risk and a blood pressure (BP) of between 140 and 159mmHg systolic and 90 and 99mmHg diastolic remains scant, and hence could be challenged. In this clinical situation, drug therapy should be initiated only after a suitable period of lifestyle changes. Today, there is no evidence to support treatment in patients with a high to normal BP (130–139/85–89mmHg) uncomplicated by diabetes or a previous cardiovascular event. Similarly, there is no argument to treat patients with a previous cardiovascular complication in the absence of hypertension. Finally, the current recommendations on BP values at which one should initiate a treatment in the elderly (i.e >140/90mmHg) are not supported by the results of clinical trials since none of the published studies included patients with such a low starting BP.4 Therefore, the actual recommendations could be questioned and the BP threshold perhaps set at 160mmHg systolic in the elderly.
There are also many discussions about the necessity of starting antihypertensive therapy in patients with diabetes and a high normal blood pressure and to target lower BP goals (
it does not
seem that lowering systolic BP below 120mmHg provides additional clinical benefits in diabetics except perhaps for the prevention of stroke. Thus, it might be sufficient to recommend that in diabetes, systolic BP be reduced well below 140mmHg without additional precision. This critical discussion of BP targets has revived the issue of the J-curve phenomenon, according to which a very low BP may be associated with an increase in coronary events. This phenomenon may particularly relevant in patients with advanced atherosclerotic artery diseases.
When Should We Start a Monotherapy or a Drug Combination?
In contrast to American and British hypertension guidelines, European guidelines are relatively flexible regarding which antihypertensive drug class should be used as first-line therapy in hypertensive patients. This position is based on the principle that the main benefits of antihypertensive therapy reside in the lowering of BP per se. Thus, the five major classes of antihypertensive agents, i.e. diuretics, angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, angiotensin receptor blockers (ARB) and beta-blockers, do not differ in their overall ability to lower BP in hypertension and hence to reduce the cardiovascular risk of patients. In recent years, there have been many discussions concerning the place of beta-blockers, which have been downgraded in the British recommendations based on the results of a meta-analysis suggesting a slight inferiority in preventing stroke. However, beta-blockers are similar to other classes in preventing coronary events and heart failure, and may even be superior to some other classes in patients who have suffered a recent coronary event.6
The reappraisal of the 2007 ESH guidelines recognises the fact that beta-blockers have been found to be less powerful than ACE inhibitors, ARBs and calcium antagonists in
EUROPEAN CARDIOLOGY
reducing left ventricular hypertrophy, aortic stiffness and carotid intima-media thickness, but also consider the fact that beta-blockers are not an homogenous class of antihypertensive drugs. Thus, the majority of the observations have been made with atenolol and the properties of this agent might not be shared by other beta-blockers such as nebivolol or carvedilol,7
although one must admit that there
is clearly less information on the effect of these beta-blockers in hypertension. Today, the main reason why beta-blockers and, to a certain degree, diuretics are less popular as initial therapies is their tolerability profile with an increased incidence of adverse metabolic effects such as new-onset diabetes. With the increased incidence of obesity in the general population, the risk of developing type 2 diabetes is increasing and may be promoted by the use of beta- blockers and diuretics. To avoid this trend, physicians tend to favour the use of blockers of the renin–angiotensin system (RAS) and calcium channel blockers.
Today, considering an equivalent antihypertensive efficacy for the five classes, the main arguments to choose one drug class rather than another one in a given individual are the tolerability profile, the compelling indications and contraindications and the recognised efficacy in specific clinical conditions as illustrated in Tables 1 and 2. Thus, the prescription of the antihypertensive therapy will increasingly be individualised, taking into account not only the tolerability profile but also the associated diseases, the other cardiovascular risk factors and, most importantly, the patient’s expectations and willingness to accept the proposed treatment.
Interestingly, the concept of first-line therapy has rightly been challenged by the 2009 reappraisal of guidelines. A ranking of drugs for management is not really useful for several good reasons. The first is that the response to a monotherapy is highly unpredictable in a given individual. In addition, all classes of drugs have their advantages and possible side effects. Finally, only 30–50% of hypertensive patients will normalise their BP with the administration of a single-drug therapy. Therefore, the likelihood that hypertensive patients will be treated with multiple agents is very high, and hence the concept of first-line therapy becomes irrelevant.
Single-pill Combinations – The Future of Hypertension Management
Clinical trials have clearly demonstrated that to achieve the BP targets defined in the actual guidelines, the majority of hypertensive patients will need more than one antihypertensive agent, and on average between two and three drugs.8
In the 2007 guidelines, the ESH
recognised the possibility of prescribing a single-pill combination as initial therapy. This recommendation was based on several practical arguments. The immediate use of a single-pill combination increases the likelihood of controlling BP in 60% of hypertensive patients. BP will be controlled more rapidly and a more rapid control of BP associated with a simplified therapeutic regimen might result in a lower incidence of treatment discontinuations. The association of drugs with different mechanisms of action enables counter-regulatory processes to be blunted. Finally, the use of combination therapies enables doctors to prescribe lower doses of each agent and hence induces fewer side effects. The only major limitation of this approach would be the loss of flexibility of upward and downward treatment strategies.
In 2007, before the Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial
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