This recently published paper describes an open label, randomised controlled trial conducted at (n=102) sites in the US and Puerto Rico. The study aimed to answer the question of the optimal systolic blood pressure (SBP) strategy (target) in the prevention of cardiovascular events.
The study assessed 14 692 participants for eligibility, of which 9 361 were randomised, between November 2010 and March 2013, to either standard or intensive blood pressure lowering therapy. Standard treatment (n=4683) was defined as a target SBP of <140 mmHg, whereas intensive treatment (4 678) set an SBP of <120 mmHg.
Eligibility criteria were: 50 years or older, an SBP of between 130–180 mmHg and an increased risk of cardiovascular events. Increased cardiovascular risk was defined by one or more of the following: a Framingham risk score of 15% or over in relation to a 10-year risk of cardiovascular disease; age 75 years or older; existing clinical or subclinical cardiovascular disease other than stroke; chronic kidney disease. Patients with diabetes mellitus or previous stroke were excluded.
The study hypothesised that intensive SBP treatment would reduce the number of clinical events; primary outcomes were defined as myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure or death from a cardiovascular cause.
What is extremely interesting about this study is that it was stopped early on 20 August 2015 such was the superiority of the intensive treatment arm; a primary outcome occurred in 562 participants: 243 in intensive treatment versus 319 receiving standard therapy. A total of 365 deaths with 155 in the intensive arm versus 210 in the standard arm; the median follow up was 3.26 years rather than a planned median of 5 years. Overall, the relative risk of death from cardiovascular cause was assessed as 43% lower in the intensive treatment arm (p=0.005).
There were a total of 1793 serious adverse events in the intensive treatment group including syncope, electrolyte abnormalities, hypotension, acute kidney injury or renal failure in the intensive arm versus 1736 in standard treatment. Orthostatic hypotension was less common in the intensive arm when assessed on clinic visits.
The paper states that the study encouraged but did not mandate which drug classes should be used. Interestingly chlorthalidone (a thiazide-like diuretic) was encouraged, as was amlodipine (calcium channel blocker). Azilsartan (angiotensin receptor blocker) and a combination of azilsartan and chlorthalidone were donated to the study by Takeda and Arbor Pharmaceuticals; neither played any further role in the study according to the paper.
This paper represents a profound shift from current UK guidance (National Institute for Health and Care Excellence (NICE), 2011) with data suggesting a targeting of SBP to <120 mmHg. How this converts to clinical practice remains to be elucidated; it is possible that the number of antihypertensive drugs will increase with concomitant problems of medication concordance, cost and side effects.
Furthermore, this study does not include, for example, younger patients with stage 1 hypertension who represent an increased lifetime risk than older patients for hypertensive complications (Brown et al, 2012). Undoubtedly there is considerable evidence that treating hypertension is both cost effective and efficacious, the SPRINT trial has challenged much of the existing evidence around the subject and it will be interesting to see how this is taken up by NICE and other interested groups. I would strongly recommend this paper given the weight of its findings and its potential implications for practice.