Aims
The aim of this study was to determine the outcome benefits in those originally assigned atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial-8 years after closure of the lipid-lowering ...arm (LLA) of the trial (ASCOT-LLA) among the UK population.
Methods and results
ASCOT-LLA was a factorially designed double-blind placebo-controlled trial of atorvastatin in 10 305 hypertensive patients enrolled into the ASCOT-Blood Pressure Lowering Arm (BPLA) of the trial and with total cholesterol concentrations, at baseline, of <6.5 mmol/L. ASCOT-LLA was stopped prematurely after a median 3.3-year follow-up because of a 36% relative risk reduction (RRR) in non-fatal myocardial infarction and fatal coronary heart disease (CHD) (the primary outcome) in favour of atorvastatin and a non-significant reduction in CV deaths (16%) and all-cause mortality (13%). After a further 2.2 years at the end of ASCOT-BPLA, despite extensive crossovers from and to statin usage, the RRR in all endpoints remained essentially unchanged. A median 11 years after initial randomization and ∼8 years after closure of LLA, all-cause mortality (n= 520 and 460 in placebo and atorvastatin, respectively) remained significantly lower in those originally assigned atorvastatin (HR 0.86, CI 0.76-0.98, P= 0.02). CV deaths were fewer, but not significant (HR 0.89, CI 0.72-1.11, P= 0.32) and non-CV deaths were significantly lower (HR 0.85, CI 0.73-0.99, P= 0.03) in those formerly assigned atorvastatin attributed to a reduction in deaths due to infection and respiratory illness.
Conclusion
Legacy effects of those originally assigned atorvastatin may contribute to long-term benefits on all-cause mortality. An explanation for long-term benefits on non-CV deaths has not been established.
Abstract
Uncontrolled blood pressure (BP) and therapeutic inertia pose significant challenges in effectively managing hypertension. This study objective was to quantify levels of uncontrolled BP and ...therapeutic inertia among patients treated for hypertension in primary care. This retrospective cohort study used data recorded by general practitioners from the UK Clinical Practice Research Datalink database. Adults with primary hypertension who received a recorded prescription for any antihypertensive drug between January 2015 and June 2017 (index date) were included, with a follow‐up of 18 months. Primary outcomes included the percentage of patients with uncontrolled BP (defined as systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) and of apparent therapeutic inertia (defined as two consecutive uncontrolled BP records without treatment change) during follow‐up. Finally, of 581 260 patients receiving antihypertensive drug(s), 37.2% (
n
= 216 014) had uncontrolled BP at the index date and 30.3% (
n
= 175 955) had no record of BP at this date. During follow‐up, 59.2% had ≥1 record of uncontrolled BP, in 22% all records showed uncontrolled BP, and 12.8% had no record of BP. Among those with uncontrolled BP at the index date, 72.9% had ≥1 record of uncontrolled BP during follow‐up, and in 28.3% all records showed uncontrolled BP. Therapeutic inertia was observed in 33.1% of patients overall, and in 55.7% of those with uncontrolled BP at the index date. In conclusion, BP recording was infrequent, possibly reflecting both a low frequency of measurement and potential under‐recording. Uncontrolled BP and therapeutic inertia appear to be widespread in UK general practice.
Hypertension remains the leading cause of global mortality, with elevated systolic blood pressure (BP) leading to 10.8 million deaths each year. Despite this, only around 50% of individuals with ...hypertension are aware of their condition. Alongside low awareness rates, lack of patient adherence to medication and therapeutic inertia have been identified as factors contributing to the lack of hypertension control worldwide. This report summarizes presentations from the “one of a kind” Servier-sponsored symposium,
Improving the Management of Hypertension: Acting on Key Factors
, which was conducted as part of the European Society of Hypertension (ESH)-International Society of Hypertension (ISH) 2021 ON-AIR meeting. The symposium focused on how low awareness, therapeutic inertia, and nonadherence can be addressed by combining the experience of a patient with the expertise of physicians. May Measurement Month, the ongoing global BP measurement program, is raising awareness of hypertension in over 90 countries, and the 2018 European Society of Cardiology/ESH guidelines and the 2020 ISH guidelines now include recommendations that specifically address low adherence and therapeutic inertia, including involving patients in a shared decision-making process and the use of single-pill combination therapy. Understanding the role of emotion in decision making and addressing the different psychological states and attitudes in the patient’s “cycle of change” are key to effective shared decision making and improving adherence.
Plain Language Summary
Raised blood pressure (hypertension) is involved in the death of around 10.8 million people throughout the world each year. However, only about half of the people with hypertension are aware of their condition. In addition, many patients who are prescribed blood pressure-lowering medications do not take their pills regularly (intentional or nonintentional low adherence). Many doctors are not as strict as they should be in ensuring blood pressure control of their hypertensive patients (therapeutic inertia). This report presents ideas and data from a “first of its kind” symposium sponsored by Servier as part of the European Society of Hypertension (ESH)-International Society of Hypertension (ISH) 2021 ON-AIR meeting involving both patient and physicians. The report summarizes the ways in which low awareness, therapeutic inertia, and lack of adherence can be addressed and includes insights into patients’ perspectives. An ongoing global blood pressure screening program called May Measurement Month was discussed, which has detected almost a million people with untreated or inadequately treated hypertension worldwide since 2017. Recent ESH and ISH guidelines for managing hypertension now include recommendations on how to address low adherence and therapeutic inertia. Crucially, doctors should involve their patients with hypertension in decisions about their own treatment, which will help improve adherence to medication and ultimately reduce hypertension-related serious adverse events (e.g. heart attacks, strokes and deaths).
Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication. We evaluated the effect among 1411 participants in the ...Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm who received spironolactone mainly as a fourth-line antihypertensive agent for uncontrolled blood pressure and who had valid BP measurements before and during spironolactone treatment. Among those who received spironolactone, the mean age was 63 years (SD: +/-8 years), 77% were men, and 40% had diabetes. Spironolactone was initiated a median of 3.2 years (interquartile range: 2.0 to 4.4 years) after randomization and added to a mean of 2.9 (SD: +/-0.9) other antihypertensive drugs. The median duration of spironolactone treatment was 1.3 years (interquartile range: 0.6 to 2.6 years). The median dose of spironolactone was 25 mg (interquartile range: 25 to 50 mg) at both the start and end of the observation period. During spironolactone therapy, mean blood pressure fell from 156.9/85.3 mm Hg (SD: +/-18.0/11.5 mm Hg) by 21.9/9.5 mm Hg (95% CI: 20.8 to 23.0/9.0 to 10.1 mm Hg; P<0.001); the BP reduction was largely unaffected by age, sex, smoking, and diabetic status. Spironolactone was generally well tolerated; 6% of participants discontinued the drug because of adverse effects. The most frequent adverse events were gynecomastia or breast discomfort and biochemical abnormalities (principally hyperkaliemia), which were recorded as adverse events in 6% and 2% of participants, respectively. In conclusion, spironolactone effectively lowers blood pressure in patients with hypertension uncontrolled by a mean of approximately 3 other drugs. Although nonrandomized and not placebo controlled, these data support the use of spironolactone in uncontrolled hypertension.
More data regarding effects of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes (T2D) and heart failure (HF) are required.
The purpose of this study was to investigate the ...effects of liraglutide on cardiovascular events and mortality in LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) participants, by HF history.
In the multinational, double-blind, randomized LEADER trial, 9,340 patients with T2D and high cardiovascular risk were assigned 1:1 to liraglutide (1.8 mg daily or maximum tolerated dose up to 1.8 mg daily) or placebo plus standard care, and followed for 3.5 to 5 years. New York Heart Association (NYHA) functional class IV HF was an exclusion criterion. The primary composite major adverse cardiovascular events outcome was time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Post hoc Cox regression analyses of outcomes by baseline HF history were conducted.
At baseline, 18% of patients had a history of NYHA functional class I to III HF (liraglutide: n = 835 of 4,668; placebo: n = 832 of 4,672). Effects of liraglutide versus placebo on major adverse cardiovascular events were consistent in patients with (hazard ratio HR: 0.81 95% confidence interval (CI): 0.65 to 1.02) and without (HR: 0.88 95% CI: 0.78 to 1.00) a history of HF (p interaction = 0.53). In both subgroups, fewer deaths were observed with liraglutide (HR: 0.89 95% CI: 0.70 to 1.14 with HF; HR: 0.83 95% CI: 0.70 to 0.97 without HF; p interaction = 0.63) versus placebo. No increased risk of HF hospitalization was observed with liraglutide, regardless of HF history (HR: 0.98 95% CI: 0.75 to 1.28 with HF; HR: 0.78 95% CI: 0.61 to 1.00 without HF; p interaction = 0.22). Effects of liraglutide on the composite of HF hospitalization or cardiovascular death were consistent in patients with (HR: 0.92 95% CI: 0.74 to 1.15) and without (HR: 0.77 95% CI: 0.65 to 0.91) a history of HF (p interaction = 0.19).
Based on these findings, liraglutide should be considered suitable for patients with T2D with or without a history of NYHA functional class I to III HF. (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results LEADER; NCT01179048)
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DEVOTE was designed to evaluate the cardiovascular safety of insulin degludec (IDeg) vs insulin glargine U100 (IGlar) in patients with T2D at high risk of cardiovascular events. DEVOTE is a phase 3b, ...multicenter, international, randomized, double-blind, active comparator-controlled trial, designed as an event-driven trial that would continue until 633 positively adjudicated primary events were accrued. The primary end point was the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Patients with T2D at high risk of cardiovascular complications were randomized 1:1 to receive either IDeg or IGlar, each added to background therapies. This trial was designed to demonstrate statistical noninferiority of IDeg vs IGlar for the primary end point. DEVOTE enrolled 7,637 patients between October 2013 and November 2014 at 436 sites in 20 countries. Of these, 6,506 patients had prior cardiovascular disease or chronic kidney disease, and the remainder had multiple cardiovascular risk factors. DEVOTE was designed to provide conclusive evidence regarding the cardiovascular safety of IDeg relative to IGlar in a high-risk population of patients with T2D.
Summary Background Up to 50% of patients with acute stroke are taking antihypertensive drugs on hospital admission. However, whether such treatment should be continued during the immediate ...post-stroke period is unclear. We therefore aimed to assess the efficacy and safety of continuing or stopping pre-existing antihypertensive drugs in patients who had recently had a stroke. Methods The Continue Or Stop post-Stroke Antihypertensives Collaborative Study (COSSACS) was a UK multicentre, prospective, randomised, open, blinded-endpoint trial. Patients were recruited at 49 UK National Institute for Health Research Stroke Research Network centres from January 1, 2003, to March 31, 2009. Patients aged over 18 years who were taking antihypertensive drugs were enrolled within 48 h of stroke and the last dose of antihypertensive drug. Patients were randomly assigned (1:1) by secure internet central randomisation to either continue or stop pre-existing antihypertensive drugs for 2 weeks. Patients and clinicians who randomly assigned patients were unmasked to group allocation. Clinicians who assessed 2-week outcomes and 6-month outcomes were masked to group allocation. The primary endpoint was death or dependency at 2 weeks, with dependency defined as a modified Rankin scale score greater than 3 points. Analysis was by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Register , number ISRCTN89712435. Findings 763 patients were assigned to continue (n=379) or stop (n=384) pre-existing antihypertensive drugs. 72 of 379 patients in the continue group and 82 of 384 patients in the stop group reached the primary endpoint (relative risk 0·86, 95% CI 0·65–1·14; p=0·3). The difference in systolic blood pressure at 2 weeks between the continue group and the stop group was 13 mm Hg (95% CI 10–17) and the difference in diastolic blood pressure was 8 mm Hg (6–10; difference between groups p<0·0001). No substantial differences were observed between groups in rates of serious adverse events, 6-month mortality, or major cardiovascular events. Interpretation Continuation of antihypertensive drugs did not reduce 2-week death or dependency, cardiovascular event rate, or mortality at 6 months. Lower blood pressure levels in those who continued antihypertensive treatment after acute mild stroke were not associated with an increase in adverse events. These neutral results might be because COSSACS was underpowered owing to early termination of the trial, and support the continuation of ongoing research trials. Funding The Health Foundation and The Stroke Association.
Results of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) show significantly lower rates of coronary and stroke events in individuals allocated an ...amlodipine-based combination drug regimen than in those allocated an atenolol-based combination drug regimen (HR 0·86 and 0·77, respectively). Our aim was to assess to what extent these differences were due to significant differences in blood pressures and in other variables noted after randomisation.
We used data from ASCOT-BPLA (n=19 257) and compared differences in accumulated mean blood pressure levels at sequential times in the trial with sequential differences in coronary and stroke events. Serial mean matching for differences in systolic blood pressure was used to adjust HRs for differences in these events. We used an updated Cox-regression model to assess the effects of differences in accumulated mean levels of various measures of blood pressure, serum HDL-cholesterol, triglycerides and potassium, fasting blood glucose, heart rate, and bodyweight on differences in event rates.
We noted no temporal link between size of differences in blood pressure and different event rates. Serial mean matching for differences in systolic blood-pressure attenuated HRs for coronary and stroke events to a similar extent as did adjustments for systolic blood-pressure differences in Cox-regression analyses. HRs for coronary events and stroke adjusted for blood pressure rose from 0·86 (0·77–0·96) to 0·88 (0·79–0·98) and from 0·77 (0·66–0·89) to 0·83 (0·72–0·96), respectively. Multivariate adjustment gave HRs of 0·94 (0·81–1·08) for coronary events (HDL cholesterol being the largest contributor) and 0·87 (0·73–1·05) for stroke events.
Multivariate adjustment accounted for about half of the differences in coronary events and for about 40% of the differences in stroke events between the treatment regimens tested in ASCOT-BPLA, but residual differences were no longer significant. These residual differences could indicate inadequate statistical adjustment, but it remains possible that differential effects of the two treatment regimens on other variables also contributed to the different rates noted, particularly for stroke.
In the UK, most adults with hypertension are managed in Primary Care. Referrals to Secondary Care Hypertension Specialists are targeted to patients in whom further investigations are likely to change ...management decisions. In this position statement the British and Irish Hypertension Society provide clinicians with a framework for referring patients to Hypertension Specialists. Additional therapeutic advice is provided to optimise patient management whilst awaiting specialist review. Our aim is to ensure that referral criteria to Hypertension Specialists are consistent across the UK and Ireland to ensure equitable access for all patients.
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