Medicine Top Ten: New Treatment for At-Risk Patients with Aortic Stenosis

March 2012

The first trans-catheter aortic valve implantation (TAVI) was performed 10 years ago in a 57-year-old man for whom the experimental procedure was a “last resort.” The valve functioned well but the patient, who already had noncardiac complications, died 17 weeks later. Since then, TAVI has taken off, and towards the end of 2011 there had been some 20,000 of these procedures. A seminal multicenter controlled trial appeared in the fall of 2010, and that important paper, surprisingly perhaps, has dropped a place in the bimonthly citation rankings of medicine’s most-cited papers published over the last two years, from #11 last time to #12 in the current listings (M.B. Leon, et al., New Engl. J. Med., 363[17]: 1597-607, 2010; 32 citations this period, 125 overall). The patients were all deemed unsuitable for surgical management (the average age was 83). There were several reasons for ineligibility, and although over 3,000 patients were screened, only 358 were randomized to TAVI or to standard nonsurgical treatment, which was usually a balloon aortic valvuloplasty. All-cause mortality at one year was significantly lower for TAVI (30.7%) than for the controls (50.7%).

TAVI has taken off, and towards the end of 2011 there had been some 20,000 of these procedures.

Strokes and vascular complications were more common with TAVI. However, there have been improvements in the technology (e.g., smaller, less traumatic devices). An excellent review of the state of play as of last year is coauthored by Dr. Alain Cribier, a pioneer of this form of interventional cardiology (J. Webb, A. Cribier,  Eur. Heart J., 32[2]:140-47, 2011).

Besides saving lives, TAVI also significantly improved quality of life. This was looked at separately within the controlled trial known as PARTNER (see M.R. Reynolds, et al., Circulation, 124[18]: 1964-72, 2011). Paper #12 was concerned with patients not suitable for surgery, but there is another group for whom surgical replacement would be risky but not impossible, and the place for TAVI in such cases has been explored in a later study with non-inferiority as the null hypothesis (C.R. Smith, et al., New Engl. J. Med., 364[23]: 2187-98, 2011). The risk of major stroke with TAVI was a concern here as in the earlier study, but the mortality outcomes were very similar at one year, showing that TAVI was at least not inferior to surgical management. PARTNER II (NCT 0131413), with about 600 patients, is due for completion by the end of 2017. This compares two delivery systems.

Controlling Tuberculosis

What’s Hot in Medicine
Rank Paper Citations This Period
(Sept-Oct 11)
Rank Last Period
(Jul-Aug 11)
1 K.M. Flegal, et al., "Prevalence and trends in obesity among US adults,1999-2008," JAMA, 303(3): 235-41, 20 January 2010. [Ctrs. Disease Control & Prevent., Hyattsville, MD] 104 1
2 C.L. Ogden, et al., "Prevalence of high body mass index in US children and adolescents, 2007-2008," JAMA, 303(3): 242-9, 20 January 2010. [Ctrs. Disease Control & Prevent., Hyattsville, MD] 67 +
3 S. Rerks-Ngarm, et al., "Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand," New Engl. J. Med., 361(23): 2209-20, 3 December 2009. [10 Thailand and U.S. institutions] 55 +
4 K.T. Flaherty, et al., "Inhibition of mutated, activated BRAF in metastatic melanoma," New Engl. J. Med., 363(9): 809-19, 26 August 2010. [9 U.S. and Australian institutions] 50 +
5 P.W. Kantoff, et al., "Sipuleucel-T immunotherapy for castration-resistant prostate cancer," New Engl. J. Med., 363(5): 411-22, 29 July 2010. [11 U.S. institutions] 42 9
6 F.S. Hodi, et al., "Improved survival with ipilimumab in patients with metastatic melanoma," New Engl. J. Med., 363(8): 711-23, 19 August 2010. [Reprint address: Dana-Farber Cancer Inst., Boston, MA] 41 3
7 S. Jain, et al., "Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009," New Engl. J. Med., 361(20): 1935-44, 12 November 2009. [Ctrs. for Disease Control & Prevent., Atlanta, GA] 37 7
8 Q.A. Karim, et al., "Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women," Science, 329(5996): 1168-74, 3 September 2010. [5 South African and U.S. institutions] 37 +
9 E.L. Kwak, et al., "Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer," New Engl. J. Med., 363(18): 1693-1703, 28 October 2010. [10 institutions worldwide] 36 +
10 K.K. Kumarasamy, et al., "Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study," Lancet, 10(9): 597-602, September 2010. [10 institutions worldwide] 35 +

SOURCE: Thomson Reuters Hot Papers Database

NB. Only papers indexed by Thomson Reuters since November 2009 are tracked. A dagger indicates that the paper was not ranked in the Top Ten during the last period. In the event that two or more papers collected the same number of citations in the most recent bimonthly period, total citations to date determine the rankings.

Elsewhere among medicine’s most-cited papers, the topic of tuberculosis emerges. If the disease is to be controlled worldwide, a simple diagnostic test that can be done on the spot and that will yield a result quickly is essential. Is Xpert MTB/RIF the answer? MTB stands for Mycobacterium tuberculosis and RIF refers to the antituberculosis drug rifampin, resistance to which can be tested at the same time. A result can be had in two hours. The test has been developed as a public-private partnership, and the World Health Organization has been monitoring its use. Data supplied by one of the partners, the Foundation for Innovative New Diagnostics, show that in the first 12 months, to 30 September 2011, over 300,000 test cartridges for this automated molecular test had been ordered. These are inserted into the GeneExpert device. The package is not cheap, and access to it in countries most in need is a concern. The test is unquestionably sensitive and specific. In a study conducted in five sites in Peru, Azerbaijan, South Africa, and India) 98.1% of smear-positive tuberculosis cases (and 72.5% of smear-negative ones) were correctly identified and 99.2% of patients not having tuberculosis were correctly identified (C.C. Boehme, et al. New Engl. J. Med., 363[11]: 1005-15, 2010; currently at #11, with 34 citations this period and 141 total).

Gel Against HIV

Besides saving lives, TAVI also significantly improved quality of life.

The journal Science in 2010 awarded “breakthrough” status to an investigation reported in paper #8, into the use of 1% tenofovir gel to prevent HIV infection in women. The research was done by the Centre for the AIDS Program of Research in South Africa (CAPRISA). In this randomized trial in 889 sexually active, HIV-negative women, the rates of subsequent HIV infection were 5.6 per 100 woman-years in the tenofovir arm and 9.1 in the controls (placebo). Tenofovir gel had been promised fast-track assessment by the U.S. Food and Drug Administration, so the announcement late in 2011 that an interim analysis of another trial had revealed an HIV rate of 6% in gel users and that the tenofovir gel arm of that study (VOICE) had been abandoned came as great disappointment to CAPRISA and elsewhere. A coauthor on #8 and the director of CAPRISA is Salim Abdool Karim, who said that this result had been “totally unexpected.” Nonetheless, research into this type of approach to preventing HIV infection continues (R.J. Shattock, Z. Rosenberg, Cold Spring Harbor Perspect. Med., 2[2]: a007385, 2012).

A former deputy editor of The Lancet, David W. Sharp, M.A. (Cambridge), is a freelance writer living in Minchinhampton, Gloucestershire, U.K.

The data and citation records included in this report are from Thomson Reuters Web of ScienceTM. Web of ScienceTM is a registered trademark of Thomson Reuters. All rights reserved.