Dr Ray O’Connor takes a look at the latest clinical papers on therapeutics, including Dual Antiplatelet Therapy (DAPT) in Ischaemic Heart Disease among others
1. Drug treatment mild hypertension
This is an update of a Cochrane review published in 2012 of initiation of antihypertensive monotherapy or step-up therapy in people with untreated mild hypertension (systolic blood pressure 140 to 159 mmHg or diastolic blood pressure 90 to 99 mmHg, or both) and no pre-existing cardiovascular disease.
The original review demonstrated no difference in the incidence of all-cause mortality, total cardiovascular events (stroke, myocardial infarction, and congestive heart failure), stroke incidence, coronary heart disease, or withdrawal due to adverse effects (WDAEs).
Dr Ray O’Connor
Evidence for antihypertensive pharmacotherapy in people with mild hypertension for primary prevention remains uncertain in the literature with conflicting studies. The authors of this Cochrane review1 therefore performed an update of the original review.
The objective was to reassess the efficacy and risks of initiating antihypertensive pharmacotherapy in adults with untreated mild hypertension and no pre-existing cardiovascular disease. The primary objective was to reassess the risk of all-cause mortality and total cardiovascular events (defined as fatal and non-fatal strokes, myocardial infarction, and congestive heart failure).
The secondary objectives were to reassess the risk of stroke (fatal and non-fatal), coronary heart disease (fatal and non-fatal myocardial infarction and sudden cardiac death), and WDAEs. The authors searched the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to June 2024.
They included randomized controlled trials (RCTs) of at least one-year duration comparing initiation on antihypertensive monotherapy or step-up therapy, or both, versus placebo or no treatment in participants with mild hypertension and no pre-existing cardiovascular disease. They included individual patient data from five trials involving a total of 9,124 participants, of whom 4,593 received antihypertensives and 4,531 received placebo or no treatment.
All five trials reported all-cause mortality; four trials reported total cardiovascular events and strokes; three trials reported coronary heart disease; and one trial reported WDAEs. Their findings were that there may be little to no reduction in all-cause mortality (RR 0.85, 95 per cent CI 0.64 to 1.14; five trials, 9,124 participants; low-certainty evidence), total cardiovascular events (RR 0.93, 95 per cent CI 0.69 to 1.24; four trials, 7,292 participants; low-certainty evidence), or coronary heart disease (RR 1.12, 95 per cent CI 0.80 to 1.57; three trials, 7,080 participants; low-certainty evidence).
There may be a decreased risk of stroke (RR 0.41, 95 per cent CI 0.20 to 0.84; four trials, 7,292 participants; low-certainty evidence) and an increase in WDAEs (RR 4.80, 95 per cent CI 4.14 to 5.57; one trial, 17,354 participants [aggregate trial-level data; individual patient data unavailable]; low-certainty evidence) with antihypertensives.
The authors downgraded the certainty of evidence for all outcomes due to imprecision, indirectness, and risk of bias. The authors concluded that in people with untreated mild hypertension and no pre-existing cardiovascular disease, initiation of antihypertensive monotherapy or step-up therapy may not reduce all-cause mortality, total cardiovascular events, or coronary heart disease compared to those who received placebo or no treatment. There may be a reduction in stroke, but possibly also an increase in WDAEs.
2. Dual Antiplatelet Therapy (DAPT) in Ischaemic Heart Disease
Two recent papers indicate that DAPT may not need to be used for as long as previously thought necessary. The effect of clopidogrel monotherapy as compared with extended DAPT with clopidogrel and aspirin beyond 12 months after implantation of a drug-eluting stent remains uncertain in patients at high risk for recurrent ischemic events.
This was an open-label noninferiority trial2 conducted in South Korea. The authors enrolled patients with high-risk clinical or lesion characteristics in whom a drug-eluting stent had been implanted 12 months earlier and randomly assigned them, in a 1:1 ratio, to receive clopidogrel monotherapy or extended DAPT (clopidogrel plus aspirin).
The primary end point was net adverse clinical events, a composite of death from any cause, myocardial infarction, stent thrombosis, stroke, or Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 24 months (noninferiority margin, 2.3 percentage points). Key secondary ischemic and bleeding end points were tested in a prespecified hierarchical order.
Of the 3,203 patients who underwent randomization, 1601 were assigned to receive clopidogrel monotherapy and 1,602 to receive extended DAPT. Over the course of 24 months, a primary end-point event occurred in 80 patients (5.0 per cent) in the monotherapy group and in 81 (5.1 per cent) in the DAPT group (risk difference, −0.1 percentage points; 90 per cent confidence interval [CI], −1.3 to 1.2; P = 0.001 for noninferiority).
Death from any cause, myocardial infarction, stent thrombosis, or stroke (the key secondary ischemic end point) occurred in 60 patients (3.7 per cent) in the monotherapy group and in 26 (1.6 per cent) in the DAPT group (hazard ratio, 2.33; 95 per cent CI, 1.47 to 3.69; P<0.001).
BARC type 2, 3, or 5 bleeding (the key secondary bleeding end point) occurred in 28 patients (1.8 per cent) in the monotherapy group and in 65 (4.1 per cent) in the DAPT group (hazard ratio, 0.43; 95 per cent CI, 0.27 to 0.67; P<0.001). The incidence of serious adverse events was similar in the two groups.
The authors concluded that among patients at high risk for ischemic events 12 months after drug-eluting stent implantation, clopidogrel monotherapy was noninferior to extended DAPT with respect to net adverse clinical events at 24 months. Extended DAPT was associated with fewer ischemic events and deaths but with more bleeding events than clopidogrel monotherapy.
The objective of this next study3 was to evaluate the efficacy DAPT for three months versus 12 months in saphenous vein graft occlusion while reducing bleeding risk. The study was a Multicentre, non-inferiority, double blind, randomised controlled trial.
The setting was 13 cardiac surgery centres in China, with enrolment between February 2023 and July 2024. Some 2,300 participants aged 18 to 80 years who underwent elective primary coronary artery bypass grafting with ≥1 saphenous vein graft were studied. Participants were randomly assigned (1:1) to receive DAPT (ticagrelor 90 mg twice daily plus aspirin 100 mg once daily) for 12 months or the same dual antiplatelet regimen for the first three months, followed by placebo plus aspirin for nine months.
The primary outcomes were saphenous vein graft occlusion at one year (non-inferiority) and BARC type 2, 3, or 5 bleeding (superiority). Secondary outcomes were major adverse cardiovascular events (MACCE), saphenous vein graft failure, venous or arterial graft stenosis, and venous or arterial graft occlusion. 2,290 patients (mean age 61.5 years), 20.6 per cent (n=472) women) were included in the modified intention-to-treat set.
The mean number of saphenous vein graft segments was 2.5 (SD 0.8). Some 2,070 patients (90.4 per cent) with a total of 5,125 saphenous vein graft segments were assessed at one year. Saphenous vein graft occlusion occurred in 280 of 2,596 (10.8 per cent) in the three month DAPT group and 283 of 2,529 (11.2 per cent) in the 12 month DAPT group (absolute difference −0.31 per cent, 95 per cent confidence interval (CI) −3.13 per cent to 2.52 per cent; P=0.008 for non-inferiority).
During a median follow-up of 368 days, BARC type 2, 3, or 5 bleeding occurred in 95 patients (8.3 per cent) in the three month DAPT group and 149 patients (13.2 per cent) in the 12 month DAPT group (absolute difference −4.67 per cent, 95 per cent CI −7.18 per cent to −2.16 per cent; P<0.001).
The number needed to treat to prevent one bleeding event was 21 (95 per cent CI 13 to 46). MACCE occurred in 26 (2.3 per cent) patients in the three month DAPT group and 27 (2.7 per cent) in the 12 month DAPT group (absolute difference −0.11%, 95 per cent CI −1.48 per cent to 1.26 per cent). The findings for other secondary outcomes were also similar between the two groups.
The authors concluded that a three month DAPT strategy was non-inferior to the 12 month DAPT strategy in saphenous vein graft occlusion and was superior in reducing bleeding risk.
3. Secondary prevention after ischaemic stroke.
Ischemic stroke, defined as a central nervous system injury caused by loss of blood flow, is most often due to arterial thromboembolism. Globally, the incidence of stroke was estimated at almost 12 million in 2021, with 94 million prevalent cases worldwide. Stroke was the third leading cause of death and the fourth leading cause of healthy life-years lost.
Each year, approximately 795,000 persons in the United States have a stroke, which is ischemic in 87 per cent. However, the incidence of ischemic and haemorrhagic stroke varies internationally, with almost 30 per cent of all strokes in low- and middle-income countries being due to intracerebral or subarachnoid haemorrhage.
This review article4 summarises the latest updates in secondary prevention after ischaemic stroke. The article provides detailed advice, based on the exact mechanism of the stroke which is difficult to summarise in a short article. The key essential points highlighted by the authors are as follows:
After ischemic stroke, the risk of recurrence can be reduced by modifying risk factors related to the specific mechanism of stroke.
Diagnostic studies help identify the mechanism of stroke and provide targets for intervention.
Strategies for secondary prevention should be instituted as early as possible to improve adherence to therapy and prevent recurrence.
Poststroke monitoring of risk metrics, lifestyle behaviours, and medication recommendations is of key importance. 
References:
Wang D et al. Pharmacotherapy for mild hypertension. Cochrane Database of Systematic Reviews 2026, Issue 4. Art. No.: CD006742. DOI: 10.1002/14651858.CD006742.pub4
Lee SJ et al. Clopidogrel or Dual Antiplatelet Therapy in High-Ischemic-Risk Patients. N Engl J Med. Published August 29, 2026, at NEJM.org. DOI: 10.1056/NEJMoa2608533
Yuan X et al. Efficacy of dual antiplatelet therapy for three months versus 12 months after coronary artery bypass grafting: multicentre, double blinded, randomised controlled trial. BMJ 2026;393:e088939. http://dx.doi.org/10.1136/bmj-2025‑088939
Furie K et al. Secondary Prevention after Ischemic Stroke. N Engl J Med 2026;394:784-92. DOI: 10.1056/NEJMcp2415601