This week in General Medicine

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Welcome to This Week in General Medicine. This week we're covering 10 notable papers spanning when to intervene in heart disease, tighter control of cardiometabolic risk, and the gaps in prevention and recovery that land in general practice.

Three cardiovascular trials this week ask whether doing more procedurally, or prescribing more afterwards, actually helps patients. In the New England Journal of Medicine, Généreux and colleagues report the PROGRESS trial, which randomized 744 patients with moderate aortic stenosis and at least one at-risk feature, such as symptoms or a structural or functional abnormality, to transfemoral TAVR or to the guideline approach of echocardiographic surveillance [1]. The patients averaged 78 years old, and just under half of the patients were at low surgical risk. At two years, death or a heart-failure event occurred in about 17 percent of the TAVR group and about 24 percent of the surveillance group, an absolute difference of roughly seven points. All-cause death was similar in both arms, so the benefit came from heart-failure events, which fell from about 19 percent to about 11 percent. The trial was open-label and funded by the valve manufacturer, and a heart-failure event did not require hospitalization, which matters when the endpoint is partly judged by clinicians who know the allocation. It is a single trial that challenges current surveillance guidance for this group, and guidelines have not yet changed. In JAMA, Hochman and colleagues extend the ISCHEMIA trial to a median of nine years in 5,179 patients with stable coronary disease and moderate or severe ischemia [2]. At eleven years, all-cause mortality was about 26 percent with an initial invasive strategy and about 27 percent with initial medical therapy, a difference that was not statistically significant. Restricted mean survival differed by about two weeks, and a Bayesian analysis put the probability of even a one-point survival gain from routine invasive management at under one in five. Cardiovascular and noncardiovascular deaths also did not differ significantly. For patients without left main disease, unacceptable angina or reduced ejection fraction, this long follow-up strengthens the evidence that routine revascularization does not extend life. The third trial, SIMPLAAFY in JAMA from Reddy and colleagues, randomized 1,857 patients after successful left atrial appendage closure to dual antiplatelet therapy, a reduced-dose direct oral anticoagulant, or aspirin alone [3]. Both simpler regimens were noninferior for the composite of death, stroke, systemic embolism or major bleeding at six months, and with aspirin alone that composite occurred in about 3 percent of patients against about 7 percent with dual antiplatelet therapy. Major bleeding was lowest with aspirin alone, although the bleeding and device-thrombus comparisons were exploratory. Device-related thrombus at 45 days was least frequent with the reduced-dose anticoagulant. Follow-up was six months, so the evidence supports lighter therapy after uncomplicated closure in the short term. Rounding out this theme, Grotta reviews intravenous thrombolysis in the New England Journal of Medicine, covering the shift from alteplase to tenecteplase, how thrombolysis fits alongside thrombectomy for large vessel occlusion, broadening indications, and adjunctive drugs under study [4].

Two trials address cardiometabolic risk factors that general physicians manage daily. In JAMA, Lopez-Lopez and colleagues ran a pragmatic cluster randomized trial across 40 primary care clinics in Colombia and Jamaica, enrolling 1,706 adults with uncontrolled hypertension [5]. Intervention clinics combined single-pill combination therapy with team-based care: clinician training, health coaching, home monitoring, and audit and feedback. Over 18 months, systolic pressure fell about 10 millimetres of mercury more in the intervention group than with standard care. Roughly 70 percent of intervention patients reached a target below 130 over 80, compared with about 29 percent of standard care patients. Serious adverse events were similar. Because the intervention bundled several components, the trial cannot say how much came from the pill itself, but it supports this package as a scalable model in resource-constrained primary care. In the New England Journal of Medicine, Watts and colleagues pooled two placebo-controlled trials of plozasiran, a small interfering RNA against APOC3, in 757 adults with severe hypertriglyceridemia [6]. Quarterly injections lowered median triglycerides by about 80 percent from baseline, and placebo-adjusted reductions were in the mid-forties of percentage points. More than nine in ten treated patients fell below 500 milligrams per decilitre, against about half of placebo patients. Acute pancreatitis occurred at about one per hundred patient-years with plozasiran and five with placebo, roughly a fifth of the rate. Adverse events were equally common in both groups. This is the first randomized evidence in this report linking triglyceride lowering with fewer pancreatitis episodes, though event numbers were modest and follow-up was one year.

The last group of papers concerns prevention gaps, recovery and conservative care, where much of the decision-making sits with generalists. In The Lancet, Caskey and colleagues randomized 445 older adults with kidney failure, median age 82, to prepare for conservative kidney management or prepare for dialysis across 31 centres in the United Kingdom [7]. Over about four and a half years, quality-adjusted life-years did not differ significantly between the groups, though the point estimate slightly favoured dialysis preparation. Dialysis access complications were lower with conservative management. Deaths occurred in about 69 percent of the conservative group and about 63 percent of the dialysis group. Only a small share of screened patients enrolled, so the result applies to older adults willing to be randomized, and it supports conservative management as a reasonable option to discuss rather than establishing either approach as superior. In JAMA, Scott and colleagues used electronic health records from more than five million infants in the United States and found that nonreceipt of newborn vitamin K rose from about 3 percent to about 7 percent between 2017 and 2025 [8]. Infants who did not receive it had roughly half again the risk of bleeding by six months, more than double the risk of intracranial bleeding, and higher mortality with concurrent bleeding. The design is retrospective and relies on diagnosis codes, but the size and consistency of the association give clinicians firm data for conversations with families who decline prophylaxis. Measles is the subject of a clinical review by Lo in Annals of Internal Medicine, written for internists and hospitalists who may now meet adults with measles in places where it had been eliminated [9]. The review covers epidemiology, prevention, diagnosis and management, and stresses prompt suspicion, infection control and notification of public health departments. Also in Annals of Internal Medicine, Reeder and colleagues followed 1,019 adults in the RECOVER cohort who still had likely long COVID a year after infection [10]. About half of these patients no longer met the long COVID threshold by 36 months, and about a quarter reported complete remission. Patients who still had symptoms at 18 or 24 months improved on a similar relative timeline. The study is observational and cannot identify causes of recovery, but it gives clinicians figures to use when discussing prognosis, and the authors call for placebo-controlled treatment trials.

If you only have time for one paper this week, make it the single-pill combination trial from Lopez-Lopez and colleagues in JAMA [5]. Uncontrolled hypertension is the most common problem in general practice, and this trial tests whether a pragmatic, team-delivered strategy can more than double control rates in routine clinics, which is a question of implementation more than of drug efficacy.

That's your roundup for This Week in General Medicine. The full transcript and references are available on the episode page. See you next week.

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