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CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 3, April 2012
AFRICA
South African Hypertension Society 2012 congress report Optimal combination therapy for hypertension Prof Neil Poulter Hypertension is currently the single biggest cause of death globally. In 2000, there were a staggering 1 billion hypertensive individuals worldwide and this is predicted to increase to 1.56 billion by 2025. An increasing prevalence of hypertension is being witnessed in all nations, with numerous risk factors contributing to this upward trend. These sobering statistics formed the introduction to this presentation, which examined optimal combination therapy for hypertension by investigating a variety of guidelines and recent trial data. Prof Neil Poulter, Imperial College, London, listed among the risk factors for hypertension an increasing life expectancy in many nations (hence a larger number of elderly) and a trend towards a sedentary lifestyle. Other factors include decreased fresh fruit and vegetable consumption, an increase in obesity and smoking, and an increased intake of saturated fats, salt and alcohol.
Hypertension guidelines for first-line therapy Prof Poulter emphasised, ‘It is important to get treatment of hypertension right, in order to prevent cardiovascular disease down the line.’ He then compared the Prof Neil Poulter Preventive Cardiovascular Medicine, Imperial College London, currently co-director of the International Centre for Circulatory Health and the Imperial Clinical Trials Unit Prof Poulter has played a senior management role in several international trials, including the AngloScandinavian Cardiac Outcomes Trial (ASCOT) and the ADVANCE study. Other research activities include the optimal investigation and management of essential hypertension and dyslipidaemia, the association between birth weight and various cardiovascular risk factors, the cardiovascular effects of exogenous oestrogen and progesterone, the aetiology and prevention of type 2 diabetes, and ethnic differences in cardiovascular disease.
different guidelines: JNC7, ESH-ESC, WHO-ISH and BHS/NICE2006. They were found to have differing opinions on optimal first-line therapy. BHS states that monotherapy is usually inadequate therapy. Both JNC7 and ESH-ESC recommend two drug combinations (dual therapy), and the 2009 ESH-ESC guidelines selected five preferred combinations: • angiotensin converting enzyme inhibitor (ACE) + diuretic • angiotensin receptor blocker (ARB) + diuretic • calcium channel blocker (CCB) + diuretic • ACE + CCB • ARB + CCB (no trial evidence). ‘The advantages of dual therapy in reduction of stroke and coronary risk is evident in more than one trial’, Prof Poulter noted and he also drew attention to an all-cause mortality benefit of combination therapy. He questioned which agents to use in combination therapy.
Trial evidence on therapeutic agents ‘Although beta-blockers have been recommended as therapy, they have a weak effect on decreasing stroke and there is an absence of effect on coronary heart disease.’ Prof Poulter supported this statement with results of the LIFE comparison between losartan (ARB) and atenolol (beta-blocker), where losartan was found to be superior, with a 25% reduction in stroke. The PROGRESS trial (post-stroke therapy in elderly patients) had significant results for the combination of perindopril (ACE inhibitor) with indapamide (diuretic), showing a 28% decrease in next stroke. Adding perindopril in the HYVET trial of the very elderly showed a 21% decrease in all-cause mortality, with active treatment greatly improving quality of life. Prof Poulter turned his attention to the ASCOT-BPLA trial in which amlodipine (CCB) was found to have stroke protection beyond the benefits of blood pressure management. Beta-blockers (atenolol) only had a benefit on heart rate. Of
particular interest in this trial, Prof Poulter noted, was the relationship between blood pressure variability, stroke and coronary heart disease. It was found that risk of stroke and chronic heart disease increased with increasing blood pressure variability, which was the measure most strongly associated with risk. From this, Prof Poulter concluded that intermittent hypertension is more dangerous than constant hypertension and that the combination of amlodipine and perindopril was found to be better at controlling long-term variability of blood pressure. Mean blood pressure in-trial has minimal association with stroke outcome and no association with coronary heart disease, he pointed out.
Single-pill combinations The advantages of single-combination pills were highlighted by Prof Poulter, referring to the ADVANCE trial where the single-pill combination (ACE inhibitor + diuretic) had good results in type 2 diabetes patients. In the ACCOMPLISH trial, a single-pill combination (ACE inhibitor + CCB) was found to have an advantage in reducing cardiovascular events compared with an ACE inhibitor + thiazide. These benefits were most evident in high-risk subjects, of whom two-thirds were diabetic.
BHS/NICE guidelines for anti-hypertensive therapy Choice of first-line therapy is affected by age. For patients younger than 55 years and of European descent, an ACE inhibitor or ARB is recommended. For patients older than 55 years and all black Africans or people of Caribbean descent, a CCB is recommended. Second-line recommendations are dual therapy of an ACE inhibitor or ARB + CCB, irrespective of age or ancestry. Third-line therapy recommends a tripletherapy combination of ACE inhibitor or ARB + CCB + diuretic. Prof Poulter’s final advice, ‘most patients need two antihypertensive agents with a statin added to the regimen’. J Aalbers, G Hardy